Hematology Times

Doctor using a smartphone
Photo by Daniel Sone

Cancer survivors report a range of benefits and detriments related to telehealth, according to research published in the Journal of Medical Internet Research.
 
Telehealth is the use of technology to provide remote, personalized healthcare to patients.

Telehealth services allow patients to have meetings and follow-up consultations with healthcare professionals either on the phone or through online services at a time that suits the patients.

Anna Cox, PhD, of the University of Surrey in the UK, and her colleagues examined 22 studies, published between 2006 and 2016, that reported cancer patients’ direct views on their experience of telehealth.

Some of the cancer survivors studied reported their appreciation of the flexibility and convenience of telehealth, which enabled them to engage with healthcare providers with minimum disruption to their lives and in a comfortable, familiar environment.

“Our research found that cancer survivors wanted to get back to their daily lives as quickly as possible,” Dr Cox said. “Telehealth helped facilitate this, as it removed the often burdensome visits to hospital and enabled the integration of care into daily routines.”

However, not all subjects viewed telehealth as a convenience. Of the Internet-based interventions studied, 2 were perceived as an extra burden, and 1 was considered too time-consuming.

In addition, some study participants viewed telehealth as an impersonal service that did not allow them to meet their healthcare team in person.

On the other hand, the invisibility and perceived anonymity that telehealth provided sometimes reduced cancer survivors’ sense of vulnerability and enabled them to raise concerns remotely that they would not have wanted to discuss face-to-face.

And, in 8 different studies, subjects said telehealth had educated them about ways they could improve or manage their symptoms, or it had raised their awareness of potential issues they might experience.

Unfortunately, some of the cancer survivors studied said they were unable to use telehealth due to personal circumstances, such as hearing issues and lack of computer literacy skills.

“For many cancer survivors, telehealth supported their independence and offered them reassurance,” Dr Cox noted. “However, it is all down to personal preference, as some cancer survivors still preferred traditional methods of care.”

Doctor using a smartphone
Photo by Daniel Sone

Cancer survivors report a range of benefits and detriments related to telehealth, according to research published in the Journal of Medical Internet Research.
 
Telehealth is the use of technology to provide remote, personalized healthcare to patients.

Telehealth services allow patients to have meetings and follow-up consultations with healthcare professionals either on the phone or through online services at a time that suits the patients.

Anna Cox, PhD, of the University of Surrey in the UK, and her colleagues examined 22 studies, published between 2006 and 2016, that reported cancer patients’ direct views on their experience of telehealth.

Some of the cancer survivors studied reported their appreciation of the flexibility and convenience of telehealth, which enabled them to engage with healthcare providers with minimum disruption to their lives and in a comfortable, familiar environment.

“Our research found that cancer survivors wanted to get back to their daily lives as quickly as possible,” Dr Cox said. “Telehealth helped facilitate this, as it removed the often burdensome visits to hospital and enabled the integration of care into daily routines.”

However, not all subjects viewed telehealth as a convenience. Of the Internet-based interventions studied, 2 were perceived as an extra burden, and 1 was considered too time-consuming.

In addition, some study participants viewed telehealth as an impersonal service that did not allow them to meet their healthcare team in person.

On the other hand, the invisibility and perceived anonymity that telehealth provided sometimes reduced cancer survivors’ sense of vulnerability and enabled them to raise concerns remotely that they would not have wanted to discuss face-to-face.

And, in 8 different studies, subjects said telehealth had educated them about ways they could improve or manage their symptoms, or it had raised their awareness of potential issues they might experience.

Unfortunately, some of the cancer survivors studied said they were unable to use telehealth due to personal circumstances, such as hearing issues and lack of computer literacy skills.

“For many cancer survivors, telehealth supported their independence and offered them reassurance,” Dr Cox noted. “However, it is all down to personal preference, as some cancer survivors still preferred traditional methods of care.”

Doctor using a smartphone
Photo by Daniel Sone

Cancer survivors report a range of benefits and detriments related to telehealth, according to research published in the Journal of Medical Internet Research.
 
Telehealth is the use of technology to provide remote, personalized healthcare to patients.

Telehealth services allow patients to have meetings and follow-up consultations with healthcare professionals either on the phone or through online services at a time that suits the patients.

Anna Cox, PhD, of the University of Surrey in the UK, and her colleagues examined 22 studies, published between 2006 and 2016, that reported cancer patients’ direct views on their experience of telehealth.

Some of the cancer survivors studied reported their appreciation of the flexibility and convenience of telehealth, which enabled them to engage with healthcare providers with minimum disruption to their lives and in a comfortable, familiar environment.

“Our research found that cancer survivors wanted to get back to their daily lives as quickly as possible,” Dr Cox said. “Telehealth helped facilitate this, as it removed the often burdensome visits to hospital and enabled the integration of care into daily routines.”

However, not all subjects viewed telehealth as a convenience. Of the Internet-based interventions studied, 2 were perceived as an extra burden, and 1 was considered too time-consuming.

In addition, some study participants viewed telehealth as an impersonal service that did not allow them to meet their healthcare team in person.

On the other hand, the invisibility and perceived anonymity that telehealth provided sometimes reduced cancer survivors’ sense of vulnerability and enabled them to raise concerns remotely that they would not have wanted to discuss face-to-face.

And, in 8 different studies, subjects said telehealth had educated them about ways they could improve or manage their symptoms, or it had raised their awareness of potential issues they might experience.

Unfortunately, some of the cancer survivors studied said they were unable to use telehealth due to personal circumstances, such as hearing issues and lack of computer literacy skills.

“For many cancer survivors, telehealth supported their independence and offered them reassurance,” Dr Cox noted. “However, it is all down to personal preference, as some cancer survivors still preferred traditional methods of care.”

Markus Müschen, MD, PhD

Photo from Business Wire

A pair of transcription factors protect B cells from malignant transformation by keeping the cells’ glucose and energy levels low, according to research published in Nature.

“While transformation to cancer and childhood leukemia takes large amounts of energy, we discovered that low energy levels in B cells protects from malignant transformation toward leukemia and cancer,” said study author Markus Müschen, MD, PhD, of City of Hope Comprehensive Cancer Center in Duarte, California.

“The low energy levels in normal B cells are simply too low to allow transformation to leukemia.”

Dr Müschen and his colleagues found that PAX5 and IKZF1, transcription factors that are critical for early B-cell development, “enforce a state of chronic energy deprivation” that results in constitutive activation of the energy-stress sensor AMPK.

However, dominant-negative mutants of PAX5 and IKZF1 reverse this effect.

Past research has suggested that mutations and deletions in the PAX5 and IKZF1 genes occur in more than 80% of cases of pre-B-cell acute lymphoblastic leukemia (ALL).

In the current study, Dr Müschen and his colleagues found that heterozygous deletion of Pax5 in a mouse model of pre-B ALL greatly increased glucose uptake and ATP levels.

Similarly, when they reconstituted PAX5 and IKZF1 in samples from patients with pre-B ALL, the investigators observed “an energy crisis” that prompted leukemic cell death.

Dr Müschen and his colleagues also performed a CRISPR/Cas9-based screen of PAX5 and IKZF1 transcriptional targets. They said this revealed that NR3C1, TXNIP, and CNR2 are central effectors of B-lymphoid restriction of glucose and energy.

To build upon this finding, the investigators tested TXNIP and CNR2 agonists as well as a small-molecule AMPK inhibitor. They found these compounds synergized with glucocorticoids in patient-derived pre-B ALL cells.

The team therefore concluded that TXNIP, CNR2, and AMPK are potential therapeutic targets for pre-B ALL.

The investigators also said the results of this study support a previous finding that obese children with high blood sugar levels are much more likely to develop drug-resistant leukemia than children who are not overweight. So dieting could be an important consideration for children who have survived leukemia.

“Avoiding obesity and excessive energy supply may help to decrease the risk of leukemia relapse,” said study author Lai Chan, PhD, also of City of Hope.

To test that theory, Drs Chan and Müschen and their colleagues plan to perform experiments in animal models to evaluate the efficacy of dietary restriction on patient-derived childhood leukemia cells, and to assess the activity of drugs that reduce leukemia cells’ glucose and energy supply.

“Based on the outcome of these studies, we plan to introduce dietary restriction and/or glucose-restricting drugs into a clinical trial for children who are at risk to develop leukemia relapse,” Dr Müschen said.

Markus Müschen, MD, PhD

Photo from Business Wire

A pair of transcription factors protect B cells from malignant transformation by keeping the cells’ glucose and energy levels low, according to research published in Nature.

“While transformation to cancer and childhood leukemia takes large amounts of energy, we discovered that low energy levels in B cells protects from malignant transformation toward leukemia and cancer,” said study author Markus Müschen, MD, PhD, of City of Hope Comprehensive Cancer Center in Duarte, California.

“The low energy levels in normal B cells are simply too low to allow transformation to leukemia.”

Dr Müschen and his colleagues found that PAX5 and IKZF1, transcription factors that are critical for early B-cell development, “enforce a state of chronic energy deprivation” that results in constitutive activation of the energy-stress sensor AMPK.

However, dominant-negative mutants of PAX5 and IKZF1 reverse this effect.

Past research has suggested that mutations and deletions in the PAX5 and IKZF1 genes occur in more than 80% of cases of pre-B-cell acute lymphoblastic leukemia (ALL).

In the current study, Dr Müschen and his colleagues found that heterozygous deletion of Pax5 in a mouse model of pre-B ALL greatly increased glucose uptake and ATP levels.

Similarly, when they reconstituted PAX5 and IKZF1 in samples from patients with pre-B ALL, the investigators observed “an energy crisis” that prompted leukemic cell death.

Dr Müschen and his colleagues also performed a CRISPR/Cas9-based screen of PAX5 and IKZF1 transcriptional targets. They said this revealed that NR3C1, TXNIP, and CNR2 are central effectors of B-lymphoid restriction of glucose and energy.

To build upon this finding, the investigators tested TXNIP and CNR2 agonists as well as a small-molecule AMPK inhibitor. They found these compounds synergized with glucocorticoids in patient-derived pre-B ALL cells.

The team therefore concluded that TXNIP, CNR2, and AMPK are potential therapeutic targets for pre-B ALL.

The investigators also said the results of this study support a previous finding that obese children with high blood sugar levels are much more likely to develop drug-resistant leukemia than children who are not overweight. So dieting could be an important consideration for children who have survived leukemia.

“Avoiding obesity and excessive energy supply may help to decrease the risk of leukemia relapse,” said study author Lai Chan, PhD, also of City of Hope.

To test that theory, Drs Chan and Müschen and their colleagues plan to perform experiments in animal models to evaluate the efficacy of dietary restriction on patient-derived childhood leukemia cells, and to assess the activity of drugs that reduce leukemia cells’ glucose and energy supply.

“Based on the outcome of these studies, we plan to introduce dietary restriction and/or glucose-restricting drugs into a clinical trial for children who are at risk to develop leukemia relapse,” Dr Müschen said.

Markus Müschen, MD, PhD

Photo from Business Wire

A pair of transcription factors protect B cells from malignant transformation by keeping the cells’ glucose and energy levels low, according to research published in Nature.

“While transformation to cancer and childhood leukemia takes large amounts of energy, we discovered that low energy levels in B cells protects from malignant transformation toward leukemia and cancer,” said study author Markus Müschen, MD, PhD, of City of Hope Comprehensive Cancer Center in Duarte, California.

“The low energy levels in normal B cells are simply too low to allow transformation to leukemia.”

Dr Müschen and his colleagues found that PAX5 and IKZF1, transcription factors that are critical for early B-cell development, “enforce a state of chronic energy deprivation” that results in constitutive activation of the energy-stress sensor AMPK.

However, dominant-negative mutants of PAX5 and IKZF1 reverse this effect.

Past research has suggested that mutations and deletions in the PAX5 and IKZF1 genes occur in more than 80% of cases of pre-B-cell acute lymphoblastic leukemia (ALL).

In the current study, Dr Müschen and his colleagues found that heterozygous deletion of Pax5 in a mouse model of pre-B ALL greatly increased glucose uptake and ATP levels.

Similarly, when they reconstituted PAX5 and IKZF1 in samples from patients with pre-B ALL, the investigators observed “an energy crisis” that prompted leukemic cell death.

Dr Müschen and his colleagues also performed a CRISPR/Cas9-based screen of PAX5 and IKZF1 transcriptional targets. They said this revealed that NR3C1, TXNIP, and CNR2 are central effectors of B-lymphoid restriction of glucose and energy.

To build upon this finding, the investigators tested TXNIP and CNR2 agonists as well as a small-molecule AMPK inhibitor. They found these compounds synergized with glucocorticoids in patient-derived pre-B ALL cells.

The team therefore concluded that TXNIP, CNR2, and AMPK are potential therapeutic targets for pre-B ALL.

The investigators also said the results of this study support a previous finding that obese children with high blood sugar levels are much more likely to develop drug-resistant leukemia than children who are not overweight. So dieting could be an important consideration for children who have survived leukemia.

“Avoiding obesity and excessive energy supply may help to decrease the risk of leukemia relapse,” said study author Lai Chan, PhD, also of City of Hope.

To test that theory, Drs Chan and Müschen and their colleagues plan to perform experiments in animal models to evaluate the efficacy of dietary restriction on patient-derived childhood leukemia cells, and to assess the activity of drugs that reduce leukemia cells’ glucose and energy supply.

“Based on the outcome of these studies, we plan to introduce dietary restriction and/or glucose-restricting drugs into a clinical trial for children who are at risk to develop leukemia relapse,” Dr Müschen said.

Child receiving RTS,S

Photo by Caitlin Kleiboer

Researchers say they have identified molecular signatures that could potentially be used to predict whether the malaria vaccine RTS,S will be effective.

The group says the research, published in PNAS, could inform decisions on how RTS,S or other malaria vaccines are deployed or modified.

RTS,S (also known as RTS,S/AS01 or Mosquirix) has been shown to provide partial protection against malaria in phase 2 and phase 3 trials.

The vaccine is scheduled for roll-out through pilot projects in 3 African countries next year, according to the World Health Organization.

With the current study, researchers used a systems biology approach to identify molecular signatures induced after subjects were vaccinated with RTS,S.

The team looked at 2 groups of subjects:

• Individuals vaccinated with the standard RTS,S vaccination regimen, which consists of 3 RTS,S immunizations (RRR)
• Individuals vaccinated first with recombinant adenovirus 35 (Ad35) expressing the circumsporozoite malaria antigen, followed by 2 immunizations with RTS,S (ARR).

Vaccinated subjects were exposed to mosquitoes infected with Plasmodium falciparum 3 weeks after their final immunization.

Both vaccination regimens resulted in about 50% protection from malaria infection. And the researchers identified markers in each group that were associated with protection.

In the RRR group, circumsporozoite protein-specific antibody titers, prior to the challenge with infected mosquitoes, were associated with protection from malaria infection.

In addition, molecular signatures of B and plasma cells detected in peripheral blood mononuclear cells were associated with pre-challenge antibody titers and protection from malaria infection in the RRR group.

In the ARR group, protection from infection was associated with polyfunctional CD4+ T-cell responses 2 weeks after priming with Ad35, early signatures of innate immunity, and dendritic cell activation.

In both groups, natural killer (NK) cell signatures were negatively correlated with protection.

“Many of the genes contained in the predictive signatures are known to be expressed in natural killer cells, which mediate critical immune functions against viruses,” said study author Bali Pulendran, PhD, of Emory University School of Medicine in Atlanta, Georgia.

“It was a surprise to see such a robust ‘NK cell signature’ in predicting success of vaccination against the malaria parasite and raises the hypothesis that such cells may be playing a vital role in orchestrating immunity against malaria.”

Dr Pulendran and his colleagues said the results of this research suggest protective immunity against P falciparum can be achieved via multiple mechanisms.

“The extent to which these candidate signatures of protection can successfully predict vaccine efficacy in other field trials remain to be determined,” Dr Pulendran noted.

Child receiving RTS,S

Photo by Caitlin Kleiboer

Researchers say they have identified molecular signatures that could potentially be used to predict whether the malaria vaccine RTS,S will be effective.

The group says the research, published in PNAS, could inform decisions on how RTS,S or other malaria vaccines are deployed or modified.

RTS,S (also known as RTS,S/AS01 or Mosquirix) has been shown to provide partial protection against malaria in phase 2 and phase 3 trials.

The vaccine is scheduled for roll-out through pilot projects in 3 African countries next year, according to the World Health Organization.

With the current study, researchers used a systems biology approach to identify molecular signatures induced after subjects were vaccinated with RTS,S.

The team looked at 2 groups of subjects:

• Individuals vaccinated with the standard RTS,S vaccination regimen, which consists of 3 RTS,S immunizations (RRR)
• Individuals vaccinated first with recombinant adenovirus 35 (Ad35) expressing the circumsporozoite malaria antigen, followed by 2 immunizations with RTS,S (ARR).

Vaccinated subjects were exposed to mosquitoes infected with Plasmodium falciparum 3 weeks after their final immunization.

Both vaccination regimens resulted in about 50% protection from malaria infection. And the researchers identified markers in each group that were associated with protection.

In the RRR group, circumsporozoite protein-specific antibody titers, prior to the challenge with infected mosquitoes, were associated with protection from malaria infection.

In addition, molecular signatures of B and plasma cells detected in peripheral blood mononuclear cells were associated with pre-challenge antibody titers and protection from malaria infection in the RRR group.

In the ARR group, protection from infection was associated with polyfunctional CD4+ T-cell responses 2 weeks after priming with Ad35, early signatures of innate immunity, and dendritic cell activation.

In both groups, natural killer (NK) cell signatures were negatively correlated with protection.

“Many of the genes contained in the predictive signatures are known to be expressed in natural killer cells, which mediate critical immune functions against viruses,” said study author Bali Pulendran, PhD, of Emory University School of Medicine in Atlanta, Georgia.

“It was a surprise to see such a robust ‘NK cell signature’ in predicting success of vaccination against the malaria parasite and raises the hypothesis that such cells may be playing a vital role in orchestrating immunity against malaria.”

Dr Pulendran and his colleagues said the results of this research suggest protective immunity against P falciparum can be achieved via multiple mechanisms.

“The extent to which these candidate signatures of protection can successfully predict vaccine efficacy in other field trials remain to be determined,” Dr Pulendran noted.

Child receiving RTS,S

Photo by Caitlin Kleiboer

Researchers say they have identified molecular signatures that could potentially be used to predict whether the malaria vaccine RTS,S will be effective.

The group says the research, published in PNAS, could inform decisions on how RTS,S or other malaria vaccines are deployed or modified.

RTS,S (also known as RTS,S/AS01 or Mosquirix) has been shown to provide partial protection against malaria in phase 2 and phase 3 trials.

The vaccine is scheduled for roll-out through pilot projects in 3 African countries next year, according to the World Health Organization.

With the current study, researchers used a systems biology approach to identify molecular signatures induced after subjects were vaccinated with RTS,S.

The team looked at 2 groups of subjects:

• Individuals vaccinated with the standard RTS,S vaccination regimen, which consists of 3 RTS,S immunizations (RRR)
• Individuals vaccinated first with recombinant adenovirus 35 (Ad35) expressing the circumsporozoite malaria antigen, followed by 2 immunizations with RTS,S (ARR).

Vaccinated subjects were exposed to mosquitoes infected with Plasmodium falciparum 3 weeks after their final immunization.

Both vaccination regimens resulted in about 50% protection from malaria infection. And the researchers identified markers in each group that were associated with protection.

In the RRR group, circumsporozoite protein-specific antibody titers, prior to the challenge with infected mosquitoes, were associated with protection from malaria infection.

In addition, molecular signatures of B and plasma cells detected in peripheral blood mononuclear cells were associated with pre-challenge antibody titers and protection from malaria infection in the RRR group.

In the ARR group, protection from infection was associated with polyfunctional CD4+ T-cell responses 2 weeks after priming with Ad35, early signatures of innate immunity, and dendritic cell activation.

In both groups, natural killer (NK) cell signatures were negatively correlated with protection.

“Many of the genes contained in the predictive signatures are known to be expressed in natural killer cells, which mediate critical immune functions against viruses,” said study author Bali Pulendran, PhD, of Emory University School of Medicine in Atlanta, Georgia.

“It was a surprise to see such a robust ‘NK cell signature’ in predicting success of vaccination against the malaria parasite and raises the hypothesis that such cells may be playing a vital role in orchestrating immunity against malaria.”

Dr Pulendran and his colleagues said the results of this research suggest protective immunity against P falciparum can be achieved via multiple mechanisms.

“The extent to which these candidate signatures of protection can successfully predict vaccine efficacy in other field trials remain to be determined,” Dr Pulendran noted.

Doctor examines SCD patient

Photo courtesy of St. Jude

Children’s Research Hospital

Population-based surveillance data has revealed patterns of emergency department (ED) visits among Californians with sickle cell disease (SCD).

Previous research suggested that between one-half and two-thirds of SCD patients’ ED visits end in a discharge from the ED, called a treat-and-release visit.

The remainder result in admission to a hospital or other treatment facility.

The purpose of the current study was to use data from the Sickle Cell Data Collection program to describe patterns of ED use for treat-and-release visits by California’s SCD population and compare these new findings with results of previous studies.

The current study was published in Pediatric Blood and Cancer.

Researchers looked at ED and hospital discharge data in California from 2005 to 2014. This included 4636 patients with SCD.

The data showed that 88% of patients had 1 or more treat-and-release ED visits during the 10-year study period.

This group of 4100 patients had 90,904 treat-and-release ED visits. The average number of visits each year was 2.1 (rage, 0-185).

In a single year (2005):

• 53% of patients had no treat-and-release ED visits (no ED use)
• 35% had between 1 and 3 visits (low ED use)
• 9% had between 4 and 10 visits (medium ED use)
• 3% had 11 or more visits (high ED use).

The youngest patients (age 0 to 9.9) and the oldest patients (80 and older) were the least likely to have at least 1 treat-and-release ED visit.

The proportion of patients with at least 1 ED visit over the study period was:

• 68% among patients age 0 to 9.9 at the close of the study
• 80% among patients age 10 to 19.9
• 92% among patients age 20 to 29.9
• 94% among patients age 30 to 39.9
• 93% among patients age 40 to 49.9
• 92% among patients age 50 to 59.9
• 92% among patients age 60 to 69.9
• 85% among patients age 70 to 79.9
• 73% among patients age 80 and older.

The researchers said this study highlights the utility of a multisource, longitudinal data collection effort for SCD. And further study of patients with the highest ED utilization may highlight areas where changes could improve and extend the lives of patients with SCD.

Doctor examines SCD patient

Photo courtesy of St. Jude

Children’s Research Hospital

Population-based surveillance data has revealed patterns of emergency department (ED) visits among Californians with sickle cell disease (SCD).

Previous research suggested that between one-half and two-thirds of SCD patients’ ED visits end in a discharge from the ED, called a treat-and-release visit.

The remainder result in admission to a hospital or other treatment facility.

The purpose of the current study was to use data from the Sickle Cell Data Collection program to describe patterns of ED use for treat-and-release visits by California’s SCD population and compare these new findings with results of previous studies.

The current study was published in Pediatric Blood and Cancer.

Researchers looked at ED and hospital discharge data in California from 2005 to 2014. This included 4636 patients with SCD.

The data showed that 88% of patients had 1 or more treat-and-release ED visits during the 10-year study period.

This group of 4100 patients had 90,904 treat-and-release ED visits. The average number of visits each year was 2.1 (rage, 0-185).

In a single year (2005):

• 53% of patients had no treat-and-release ED visits (no ED use)
• 35% had between 1 and 3 visits (low ED use)
• 9% had between 4 and 10 visits (medium ED use)
• 3% had 11 or more visits (high ED use).

The youngest patients (age 0 to 9.9) and the oldest patients (80 and older) were the least likely to have at least 1 treat-and-release ED visit.

The proportion of patients with at least 1 ED visit over the study period was:

• 68% among patients age 0 to 9.9 at the close of the study
• 80% among patients age 10 to 19.9
• 92% among patients age 20 to 29.9
• 94% among patients age 30 to 39.9
• 93% among patients age 40 to 49.9
• 92% among patients age 50 to 59.9
• 92% among patients age 60 to 69.9
• 85% among patients age 70 to 79.9
• 73% among patients age 80 and older.

The researchers said this study highlights the utility of a multisource, longitudinal data collection effort for SCD. And further study of patients with the highest ED utilization may highlight areas where changes could improve and extend the lives of patients with SCD.

Doctor examines SCD patient

Photo courtesy of St. Jude

Children’s Research Hospital

Population-based surveillance data has revealed patterns of emergency department (ED) visits among Californians with sickle cell disease (SCD).

Previous research suggested that between one-half and two-thirds of SCD patients’ ED visits end in a discharge from the ED, called a treat-and-release visit.

The remainder result in admission to a hospital or other treatment facility.

The purpose of the current study was to use data from the Sickle Cell Data Collection program to describe patterns of ED use for treat-and-release visits by California’s SCD population and compare these new findings with results of previous studies.

The current study was published in Pediatric Blood and Cancer.

Researchers looked at ED and hospital discharge data in California from 2005 to 2014. This included 4636 patients with SCD.

The data showed that 88% of patients had 1 or more treat-and-release ED visits during the 10-year study period.

This group of 4100 patients had 90,904 treat-and-release ED visits. The average number of visits each year was 2.1 (rage, 0-185).

In a single year (2005):

• 53% of patients had no treat-and-release ED visits (no ED use)
• 35% had between 1 and 3 visits (low ED use)
• 9% had between 4 and 10 visits (medium ED use)
• 3% had 11 or more visits (high ED use).

The youngest patients (age 0 to 9.9) and the oldest patients (80 and older) were the least likely to have at least 1 treat-and-release ED visit.

The proportion of patients with at least 1 ED visit over the study period was:

• 68% among patients age 0 to 9.9 at the close of the study
• 80% among patients age 10 to 19.9
• 92% among patients age 20 to 29.9
• 94% among patients age 30 to 39.9
• 93% among patients age 40 to 49.9
• 92% among patients age 50 to 59.9
• 92% among patients age 60 to 69.9
• 85% among patients age 70 to 79.9
• 73% among patients age 80 and older.

The researchers said this study highlights the utility of a multisource, longitudinal data collection effort for SCD. And further study of patients with the highest ED utilization may highlight areas where changes could improve and extend the lives of patients with SCD.

Researchers have developed a
portable technology, Seq-Well, that
can prepare the RNA of many cells
for simultaneous sequencing.
Photo courtesy of Alex K. Shalek
and his colleagues

Researchers say they have developed a portable, low-cost platform for high-throughput, single-cell RNA sequencing.

The

team believes the technology, known as Seq-Well, could allow

scientists to more easily identify different cell types in blood and tissue

samples, helping them study how cancer cells respond to treatment, among other applications.

“Rather than trying to pick one marker that defines a cell type, using single-cell RNA sequencing, we can go in and look at everything a cell is expressing at a given moment,” said Alex K. Shalek, PhD, of the Massachusetts Institute of Technology in Cambridge.

“By finding common patterns across cells, we can figure out who those cells are.”

Dr Shalek and his colleagues have spent the past several years developing single-cell RNA sequencing strategies.

Now, they’ve created a new version of the technology that, they say, can rapidly analyze large numbers of cells using simple equipment.

“We’ve combined [Dr Shalek’s] technologies with some of ours in a way that makes it really accessible for researchers who want to do this type of sequencing on a range of different clinical samples and settings,” said J. Christopher Love, PhD, also of the Massachusetts Institute of Technology.

“It overcomes some of the barriers that are facing the adoption of these techniques more broadly.”

Drs Love and Shalek are the senior authors of a paper describing Seq-Well in Nature Methods.

Improving analysis

Key to sequencing RNA from large populations of cells is keeping track of which RNA transcripts came from which cell. The earliest techniques for this required sorting the cells into individual tubes or compartments of multiwell plates and then separately transforming each into a sequencing library.

That process works well but can’t handle large samples containing thousands of cells, such as blood samples or tissue biopsies, and costs between $25 and $35 per cell.

Dr Shalek and others have recently developed microfluidic techniques to help automate and parallelize the process considerably, but the amount of equipment required makes it impossible to be easily transported.

Drs Shalek and Love realized that technology Dr Love had previously developed to analyze protein secretions from single cells could be adapted to do single-cell RNA sequencing rapidly and inexpensively using a portable device.

Over the past several years, Dr Love’s lab has developed a microscale system that can isolate individual cells and measure the antibodies and other proteins that each cell secretes. The device resembles a tiny ice cube tray, with individual compartments for each cell.

Dr Love also developed a process known as microengraving that uses these trays, which can hold tens of thousands of cells, to measure each cell’s protein secretions.

To use this approach for sequencing RNA, the researchers created arrays of nanowells that each capture a single cell plus a barcoded bead to capture the RNA fragments.

The nanowells are sealed with a semipermeable membrane that allows the passage of chemicals needed to break the cells apart, while the RNA stays contained.

After the RNA binds to the beads, it is removed and sequenced. Using this process, the cost per cell is less than $1.

Uncovering unknowns

Similar to previous single-cell RNA sequencing techniques, the Seq-Well process captures and analyzes about 10% to 15% of the total number of RNA transcripts per cell.

“That is still a very rich set of information that maps to several thousand genes,” Dr Love said. “If you look at sets of these genes, you can start to understand the identity of those cells based on the sets of genes that are expressed in common.”

The researchers used Seq-Well to analyze macrophages infected with tuberculosis, allowing them to identify different pre-existing populations and responses to infection.

Dr Shalek and members of his lab also brought the technology to South Africa and analyzed tissue samples from tuberculosis- and HIV-infected patients there.

“Having a simple system that can go everywhere, I think, is going to be incredibly empowering,” Dr Shalek said.

Dr Love’s lab is now using this approach to analyze immune cells from people with food allergies, which could help researchers determine why some people are more likely to respond well to therapies designed to treat their allergies.

“There are still a lot of unknowns in chronic diseases, and these types of tools help you uncover new insights,” Dr Love said.

The research team has also joined forces with clinical investigators at Dana-Farber/Harvard Cancer Center to apply this technology toward the discovery of new combination immunotherapies for cancers.

Researchers have developed a
portable technology, Seq-Well, that
can prepare the RNA of many cells
for simultaneous sequencing.
Photo courtesy of Alex K. Shalek
and his colleagues

Researchers say they have developed a portable, low-cost platform for high-throughput, single-cell RNA sequencing.

The

team believes the technology, known as Seq-Well, could allow

scientists to more easily identify different cell types in blood and tissue

samples, helping them study how cancer cells respond to treatment, among other applications.

“Rather than trying to pick one marker that defines a cell type, using single-cell RNA sequencing, we can go in and look at everything a cell is expressing at a given moment,” said Alex K. Shalek, PhD, of the Massachusetts Institute of Technology in Cambridge.

“By finding common patterns across cells, we can figure out who those cells are.”

Dr Shalek and his colleagues have spent the past several years developing single-cell RNA sequencing strategies.

Now, they’ve created a new version of the technology that, they say, can rapidly analyze large numbers of cells using simple equipment.

“We’ve combined [Dr Shalek’s] technologies with some of ours in a way that makes it really accessible for researchers who want to do this type of sequencing on a range of different clinical samples and settings,” said J. Christopher Love, PhD, also of the Massachusetts Institute of Technology.

“It overcomes some of the barriers that are facing the adoption of these techniques more broadly.”

Drs Love and Shalek are the senior authors of a paper describing Seq-Well in Nature Methods.

Improving analysis

Key to sequencing RNA from large populations of cells is keeping track of which RNA transcripts came from which cell. The earliest techniques for this required sorting the cells into individual tubes or compartments of multiwell plates and then separately transforming each into a sequencing library.

That process works well but can’t handle large samples containing thousands of cells, such as blood samples or tissue biopsies, and costs between $25 and $35 per cell.

Dr Shalek and others have recently developed microfluidic techniques to help automate and parallelize the process considerably, but the amount of equipment required makes it impossible to be easily transported.

Drs Shalek and Love realized that technology Dr Love had previously developed to analyze protein secretions from single cells could be adapted to do single-cell RNA sequencing rapidly and inexpensively using a portable device.

Over the past several years, Dr Love’s lab has developed a microscale system that can isolate individual cells and measure the antibodies and other proteins that each cell secretes. The device resembles a tiny ice cube tray, with individual compartments for each cell.

Dr Love also developed a process known as microengraving that uses these trays, which can hold tens of thousands of cells, to measure each cell’s protein secretions.

To use this approach for sequencing RNA, the researchers created arrays of nanowells that each capture a single cell plus a barcoded bead to capture the RNA fragments.

The nanowells are sealed with a semipermeable membrane that allows the passage of chemicals needed to break the cells apart, while the RNA stays contained.

After the RNA binds to the beads, it is removed and sequenced. Using this process, the cost per cell is less than $1.

Uncovering unknowns

Similar to previous single-cell RNA sequencing techniques, the Seq-Well process captures and analyzes about 10% to 15% of the total number of RNA transcripts per cell.

“That is still a very rich set of information that maps to several thousand genes,” Dr Love said. “If you look at sets of these genes, you can start to understand the identity of those cells based on the sets of genes that are expressed in common.”

The researchers used Seq-Well to analyze macrophages infected with tuberculosis, allowing them to identify different pre-existing populations and responses to infection.

Dr Shalek and members of his lab also brought the technology to South Africa and analyzed tissue samples from tuberculosis- and HIV-infected patients there.

“Having a simple system that can go everywhere, I think, is going to be incredibly empowering,” Dr Shalek said.

Dr Love’s lab is now using this approach to analyze immune cells from people with food allergies, which could help researchers determine why some people are more likely to respond well to therapies designed to treat their allergies.

“There are still a lot of unknowns in chronic diseases, and these types of tools help you uncover new insights,” Dr Love said.

The research team has also joined forces with clinical investigators at Dana-Farber/Harvard Cancer Center to apply this technology toward the discovery of new combination immunotherapies for cancers.

Researchers have developed a
portable technology, Seq-Well, that
can prepare the RNA of many cells
for simultaneous sequencing.
Photo courtesy of Alex K. Shalek
and his colleagues

Researchers say they have developed a portable, low-cost platform for high-throughput, single-cell RNA sequencing.

The

team believes the technology, known as Seq-Well, could allow

scientists to more easily identify different cell types in blood and tissue

samples, helping them study how cancer cells respond to treatment, among other applications.

“Rather than trying to pick one marker that defines a cell type, using single-cell RNA sequencing, we can go in and look at everything a cell is expressing at a given moment,” said Alex K. Shalek, PhD, of the Massachusetts Institute of Technology in Cambridge.

“By finding common patterns across cells, we can figure out who those cells are.”

Dr Shalek and his colleagues have spent the past several years developing single-cell RNA sequencing strategies.

Now, they’ve created a new version of the technology that, they say, can rapidly analyze large numbers of cells using simple equipment.

“We’ve combined [Dr Shalek’s] technologies with some of ours in a way that makes it really accessible for researchers who want to do this type of sequencing on a range of different clinical samples and settings,” said J. Christopher Love, PhD, also of the Massachusetts Institute of Technology.

“It overcomes some of the barriers that are facing the adoption of these techniques more broadly.”

Drs Love and Shalek are the senior authors of a paper describing Seq-Well in Nature Methods.

Improving analysis

Key to sequencing RNA from large populations of cells is keeping track of which RNA transcripts came from which cell. The earliest techniques for this required sorting the cells into individual tubes or compartments of multiwell plates and then separately transforming each into a sequencing library.

That process works well but can’t handle large samples containing thousands of cells, such as blood samples or tissue biopsies, and costs between $25 and $35 per cell.

Dr Shalek and others have recently developed microfluidic techniques to help automate and parallelize the process considerably, but the amount of equipment required makes it impossible to be easily transported.

Drs Shalek and Love realized that technology Dr Love had previously developed to analyze protein secretions from single cells could be adapted to do single-cell RNA sequencing rapidly and inexpensively using a portable device.

Over the past several years, Dr Love’s lab has developed a microscale system that can isolate individual cells and measure the antibodies and other proteins that each cell secretes. The device resembles a tiny ice cube tray, with individual compartments for each cell.

Dr Love also developed a process known as microengraving that uses these trays, which can hold tens of thousands of cells, to measure each cell’s protein secretions.

To use this approach for sequencing RNA, the researchers created arrays of nanowells that each capture a single cell plus a barcoded bead to capture the RNA fragments.

The nanowells are sealed with a semipermeable membrane that allows the passage of chemicals needed to break the cells apart, while the RNA stays contained.

After the RNA binds to the beads, it is removed and sequenced. Using this process, the cost per cell is less than $1.

Uncovering unknowns

Similar to previous single-cell RNA sequencing techniques, the Seq-Well process captures and analyzes about 10% to 15% of the total number of RNA transcripts per cell.

“That is still a very rich set of information that maps to several thousand genes,” Dr Love said. “If you look at sets of these genes, you can start to understand the identity of those cells based on the sets of genes that are expressed in common.”

The researchers used Seq-Well to analyze macrophages infected with tuberculosis, allowing them to identify different pre-existing populations and responses to infection.

Dr Shalek and members of his lab also brought the technology to South Africa and analyzed tissue samples from tuberculosis- and HIV-infected patients there.

“Having a simple system that can go everywhere, I think, is going to be incredibly empowering,” Dr Shalek said.

Dr Love’s lab is now using this approach to analyze immune cells from people with food allergies, which could help researchers determine why some people are more likely to respond well to therapies designed to treat their allergies.

“There are still a lot of unknowns in chronic diseases, and these types of tools help you uncover new insights,” Dr Love said.

The research team has also joined forces with clinical investigators at Dana-Farber/Harvard Cancer Center to apply this technology toward the discovery of new combination immunotherapies for cancers.

EBV-infected cell (green/red)

among uninfected cells (blue)

Image courtesy of

Benjamin Chaigne-Delalande

New research published in Nature Communications appears to explain how Epstein-Barr virus (EBV) reprograms cells into cancer cells.

Investigators said they discovered a mechanism by which EBV particles induce chromosomal instability without establishing a chronic infection, thereby conferring a risk for the development of tumors that do not necessarily carry the viral genome.

“The contribution of the viral infection to cancer development in patients with a weakened immune system is well understood,” said study author Henri-Jacques Delecluse, MD, PhD, of the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) in Heidelberg.

“But in the majority of cases, it remains unclear how an EBV infection leads to cancer development.”

With their research, Dr Delecluse and his colleagues found that BNRF1, a protein component of EBV, promotes the development of cancer. They said BNRF1 induces centrosome amplification, which is associated with chromosomal instability.

When a dividing cell comes in contact with EBV, BNRF1 frequently prompts the formation of an excessive number of centrosomes. As a result, chromosomes are no longer divided equally and accurately between daughter cells—a known cancer risk factor.

In contrast, when the investigators studied EBV deficient of BNRF1, they found the virus did not interfere with chromosome distribution to daughter cells.

The team noted that EBV normally remains silent in a few infected cells, but, occasionally, it reactivates to produce viral offspring that infects nearby cells. As a consequence, these cells come in close contact with BNRF1, thus increasing their risk of transforming into cancer cells.

“The novelty of our work is that we have uncovered a component of the viral particle as a cancer driver,” Dr Delecluse said. “All human-tumors viruses that have been studied so far cause cancer in a completely different manner.”

“Usually, the genetic material of the viruses needs to be permanently present in the infected cell, thus causing the activation of one or several viral genes that cause cancer development. However, these gene products are not present in the infectious particle itself.”

Dr Delecluse and his colleagues therefore suspect that EBV could cause cancers other than those that have already been linked to EBV. Certain cancers might not have been linked to the virus because they do not carry the viral genetic material.

“We must push forward with the development of a vaccine against EBV infection,” Dr Delecluse said. “This would be the most direct strategy to prevent an infection with the virus.”

“Our latest results show that the first infection could already be a cancer risk, and this fits with earlier work that showed an increase in the incidence of Hodgkin’s lymphoma in people who underwent an episode of infectious mononucleosis.”

EBV-infected cell (green/red)

among uninfected cells (blue)

Image courtesy of

Benjamin Chaigne-Delalande

New research published in Nature Communications appears to explain how Epstein-Barr virus (EBV) reprograms cells into cancer cells.

Investigators said they discovered a mechanism by which EBV particles induce chromosomal instability without establishing a chronic infection, thereby conferring a risk for the development of tumors that do not necessarily carry the viral genome.

“The contribution of the viral infection to cancer development in patients with a weakened immune system is well understood,” said study author Henri-Jacques Delecluse, MD, PhD, of the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) in Heidelberg.

“But in the majority of cases, it remains unclear how an EBV infection leads to cancer development.”

With their research, Dr Delecluse and his colleagues found that BNRF1, a protein component of EBV, promotes the development of cancer. They said BNRF1 induces centrosome amplification, which is associated with chromosomal instability.

When a dividing cell comes in contact with EBV, BNRF1 frequently prompts the formation of an excessive number of centrosomes. As a result, chromosomes are no longer divided equally and accurately between daughter cells—a known cancer risk factor.

In contrast, when the investigators studied EBV deficient of BNRF1, they found the virus did not interfere with chromosome distribution to daughter cells.

The team noted that EBV normally remains silent in a few infected cells, but, occasionally, it reactivates to produce viral offspring that infects nearby cells. As a consequence, these cells come in close contact with BNRF1, thus increasing their risk of transforming into cancer cells.

“The novelty of our work is that we have uncovered a component of the viral particle as a cancer driver,” Dr Delecluse said. “All human-tumors viruses that have been studied so far cause cancer in a completely different manner.”

“Usually, the genetic material of the viruses needs to be permanently present in the infected cell, thus causing the activation of one or several viral genes that cause cancer development. However, these gene products are not present in the infectious particle itself.”

Dr Delecluse and his colleagues therefore suspect that EBV could cause cancers other than those that have already been linked to EBV. Certain cancers might not have been linked to the virus because they do not carry the viral genetic material.

“We must push forward with the development of a vaccine against EBV infection,” Dr Delecluse said. “This would be the most direct strategy to prevent an infection with the virus.”

“Our latest results show that the first infection could already be a cancer risk, and this fits with earlier work that showed an increase in the incidence of Hodgkin’s lymphoma in people who underwent an episode of infectious mononucleosis.”

EBV-infected cell (green/red)

among uninfected cells (blue)

Image courtesy of

Benjamin Chaigne-Delalande

New research published in Nature Communications appears to explain how Epstein-Barr virus (EBV) reprograms cells into cancer cells.

Investigators said they discovered a mechanism by which EBV particles induce chromosomal instability without establishing a chronic infection, thereby conferring a risk for the development of tumors that do not necessarily carry the viral genome.

“The contribution of the viral infection to cancer development in patients with a weakened immune system is well understood,” said study author Henri-Jacques Delecluse, MD, PhD, of the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) in Heidelberg.

“But in the majority of cases, it remains unclear how an EBV infection leads to cancer development.”

With their research, Dr Delecluse and his colleagues found that BNRF1, a protein component of EBV, promotes the development of cancer. They said BNRF1 induces centrosome amplification, which is associated with chromosomal instability.

When a dividing cell comes in contact with EBV, BNRF1 frequently prompts the formation of an excessive number of centrosomes. As a result, chromosomes are no longer divided equally and accurately between daughter cells—a known cancer risk factor.

In contrast, when the investigators studied EBV deficient of BNRF1, they found the virus did not interfere with chromosome distribution to daughter cells.

The team noted that EBV normally remains silent in a few infected cells, but, occasionally, it reactivates to produce viral offspring that infects nearby cells. As a consequence, these cells come in close contact with BNRF1, thus increasing their risk of transforming into cancer cells.

“The novelty of our work is that we have uncovered a component of the viral particle as a cancer driver,” Dr Delecluse said. “All human-tumors viruses that have been studied so far cause cancer in a completely different manner.”

“Usually, the genetic material of the viruses needs to be permanently present in the infected cell, thus causing the activation of one or several viral genes that cause cancer development. However, these gene products are not present in the infectious particle itself.”

Dr Delecluse and his colleagues therefore suspect that EBV could cause cancers other than those that have already been linked to EBV. Certain cancers might not have been linked to the virus because they do not carry the viral genetic material.

“We must push forward with the development of a vaccine against EBV infection,” Dr Delecluse said. “This would be the most direct strategy to prevent an infection with the virus.”

“Our latest results show that the first infection could already be a cancer risk, and this fits with earlier work that showed an increase in the incidence of Hodgkin’s lymphoma in people who underwent an episode of infectious mononucleosis.”

Lab mouse

Granulocyte colony-stimulating factor (G-CSF) could prevent infertility in male cancer patients, according to preclinical research published in Reproductive Biology and Endocrinology.

Researchers said they found that G-CSF protects spermatogenesis after alkylating chemotherapy by stimulating the proliferation of surviving spermatogonia.

The team also found evidence to suggest that G-CSF may be useful as a fertility-restoring treatment.

The researchers have been pursuing initiatives to restore fertility in men who have lost their ability to have children as a result of cancer treatments they received as children.

While working on methods to restart sperm production, the team discovered a link between G-CSF and the absence of normal damage to reproductive ability.

“We were using G-CSF to prevent infections in our research experiments,” said study author Brian Hermann, PhD, of The University of Texas at San Antonio.

“It turned out that the drug also had the unexpected impact of guarding against male infertility.”

To test the fertility-related impact of G-CSF, the researchers treated male mice with G-CSF before and/or after treatment with busulfan.

The team then evaluated effects on spermatogenesis in these mice and control mice that only received busulfan.

G-CSF had a protective effect on spermatogenesis that was stable for at least 19 weeks after chemotherapy.

And mice treated with G-CSF for 4 days after busulfan showed modestly enhanced spermatogenic recovery compared to controls.

The researchers said these results suggest G-CSF promotes spermatogonial proliferation, leading to enhanced spermatogenic regeneration from surviving spermatogonial stem cells.

Lab mouse

Granulocyte colony-stimulating factor (G-CSF) could prevent infertility in male cancer patients, according to preclinical research published in Reproductive Biology and Endocrinology.

Researchers said they found that G-CSF protects spermatogenesis after alkylating chemotherapy by stimulating the proliferation of surviving spermatogonia.

The team also found evidence to suggest that G-CSF may be useful as a fertility-restoring treatment.

The researchers have been pursuing initiatives to restore fertility in men who have lost their ability to have children as a result of cancer treatments they received as children.

While working on methods to restart sperm production, the team discovered a link between G-CSF and the absence of normal damage to reproductive ability.

“We were using G-CSF to prevent infections in our research experiments,” said study author Brian Hermann, PhD, of The University of Texas at San Antonio.

“It turned out that the drug also had the unexpected impact of guarding against male infertility.”

To test the fertility-related impact of G-CSF, the researchers treated male mice with G-CSF before and/or after treatment with busulfan.

The team then evaluated effects on spermatogenesis in these mice and control mice that only received busulfan.

G-CSF had a protective effect on spermatogenesis that was stable for at least 19 weeks after chemotherapy.

And mice treated with G-CSF for 4 days after busulfan showed modestly enhanced spermatogenic recovery compared to controls.

The researchers said these results suggest G-CSF promotes spermatogonial proliferation, leading to enhanced spermatogenic regeneration from surviving spermatogonial stem cells.

Lab mouse

Granulocyte colony-stimulating factor (G-CSF) could prevent infertility in male cancer patients, according to preclinical research published in Reproductive Biology and Endocrinology.

Researchers said they found that G-CSF protects spermatogenesis after alkylating chemotherapy by stimulating the proliferation of surviving spermatogonia.

The team also found evidence to suggest that G-CSF may be useful as a fertility-restoring treatment.

The researchers have been pursuing initiatives to restore fertility in men who have lost their ability to have children as a result of cancer treatments they received as children.

While working on methods to restart sperm production, the team discovered a link between G-CSF and the absence of normal damage to reproductive ability.

“We were using G-CSF to prevent infections in our research experiments,” said study author Brian Hermann, PhD, of The University of Texas at San Antonio.

“It turned out that the drug also had the unexpected impact of guarding against male infertility.”

To test the fertility-related impact of G-CSF, the researchers treated male mice with G-CSF before and/or after treatment with busulfan.

The team then evaluated effects on spermatogenesis in these mice and control mice that only received busulfan.

G-CSF had a protective effect on spermatogenesis that was stable for at least 19 weeks after chemotherapy.

And mice treated with G-CSF for 4 days after busulfan showed modestly enhanced spermatogenic recovery compared to controls.

The researchers said these results suggest G-CSF promotes spermatogonial proliferation, leading to enhanced spermatogenic regeneration from surviving spermatogonial stem cells.

Irish setter, a breed of dog

that can develop hemophilia B

A plant-made therapy has demonstrated safety and efficacy in dogs with hemophilia B, according to research published in Molecular Therapy.

Previously, researchers found they could produce freeze-dried lettuce cells expressing human coagulation factor IX (FIX) fused with cholera toxin B subunit (CTB).

These cells were able to prevent inhibitor formation and allergic reactions to intravenous FIX therapy in mice with hemophilia B.

With the current study, the researchers showed that lettuce cells expressing CTB-FIX were safe and could prevent anaphylaxis and inhibitor formation in dogs receiving intravenous FIX to treat hemophilia B.

“The results were quite dramatic,” said study author Henry Daniell, PhD, of the University of Pennsylvania in Philadelphia.

“We corrected blood clotting time in each of the dogs and were able to suppress antibody formation as well. All signs point to this material being ready for the clinic.”

This study made use of Dr Daniell’s patented plant-based drug-production platform, in which genetic modifications enable the growth of plants that have specified human proteins in their leaves.

The researchers grew lettuce that had been modified to produce a fusion protein of human FIX and CTB. CTB helps the fused protein cross the intestinal lining as the lettuce cells are digested by gut microbes, while the plant cell walls protect FIX from digestion.

The researchers said they were able to achieve commercial-scale production of CTB-FIX fusions expressed in lettuce chloroplasts by growing the plants in a hydroponic facility.

The team first tested their product in 2 dogs with hemophilia B. Twice a week for 10 months, the dogs consumed the freeze-dried lettuce material, which was spiked with bacon flavor and sprinkled on their food.

Observing no negative effects of the treatment, the researchers went on to a more robust study, including 4 dogs that were fed the lettuce material and 4 that served as controls.

The 4 dogs in the experimental group were fed the lettuce material for 4 weeks. At that point, they also began receiving weekly injections of FIX, which continued for 8 weeks. The control dogs only received the FIX injections.

All 4 dogs in the control group developed significant levels of antibodies against FIX, and 2 had visible anaphylactic reactions that required the administration of antihistamine.

In contrast, 3 of the 4 dogs in the experimental group had only minimal levels of one type of antibody, IgG2, and no detectable levels of IgG1 or IgE.

The fourth dog in the experimental group had only a partial response to the lettuce cells expressing CTB-FIX. The researchers believe this was due to a pre-existing antibody to human FIX.

Overall, levels of IgG2 were 32 times lower in the experimental group than in the controls.

In addition, the dogs showed no negative side effects from ingesting the lettuce material, and blood samples taken throughout the experiment revealed no signs of toxicity.

“Looking at the dogs that were fed the lettuce material, you can see it’s quite effective,” Dr Daniell said. “They either developed no antibodies to factor IX, or their antibodies went up just a little bit and then came down.”

The next steps for the researchers include additional toxicology and pharmacokinetics studies before applying for an investigational new drug application with the US Food and Drug Administration, a step they hope to take before the end of the year.

Irish setter, a breed of dog

that can develop hemophilia B

A plant-made therapy has demonstrated safety and efficacy in dogs with hemophilia B, according to research published in Molecular Therapy.

Previously, researchers found they could produce freeze-dried lettuce cells expressing human coagulation factor IX (FIX) fused with cholera toxin B subunit (CTB).

These cells were able to prevent inhibitor formation and allergic reactions to intravenous FIX therapy in mice with hemophilia B.

With the current study, the researchers showed that lettuce cells expressing CTB-FIX were safe and could prevent anaphylaxis and inhibitor formation in dogs receiving intravenous FIX to treat hemophilia B.

“The results were quite dramatic,” said study author Henry Daniell, PhD, of the University of Pennsylvania in Philadelphia.

“We corrected blood clotting time in each of the dogs and were able to suppress antibody formation as well. All signs point to this material being ready for the clinic.”

This study made use of Dr Daniell’s patented plant-based drug-production platform, in which genetic modifications enable the growth of plants that have specified human proteins in their leaves.

The researchers grew lettuce that had been modified to produce a fusion protein of human FIX and CTB. CTB helps the fused protein cross the intestinal lining as the lettuce cells are digested by gut microbes, while the plant cell walls protect FIX from digestion.

The researchers said they were able to achieve commercial-scale production of CTB-FIX fusions expressed in lettuce chloroplasts by growing the plants in a hydroponic facility.

The team first tested their product in 2 dogs with hemophilia B. Twice a week for 10 months, the dogs consumed the freeze-dried lettuce material, which was spiked with bacon flavor and sprinkled on their food.

Observing no negative effects of the treatment, the researchers went on to a more robust study, including 4 dogs that were fed the lettuce material and 4 that served as controls.

The 4 dogs in the experimental group were fed the lettuce material for 4 weeks. At that point, they also began receiving weekly injections of FIX, which continued for 8 weeks. The control dogs only received the FIX injections.

All 4 dogs in the control group developed significant levels of antibodies against FIX, and 2 had visible anaphylactic reactions that required the administration of antihistamine.

In contrast, 3 of the 4 dogs in the experimental group had only minimal levels of one type of antibody, IgG2, and no detectable levels of IgG1 or IgE.

The fourth dog in the experimental group had only a partial response to the lettuce cells expressing CTB-FIX. The researchers believe this was due to a pre-existing antibody to human FIX.

Overall, levels of IgG2 were 32 times lower in the experimental group than in the controls.

In addition, the dogs showed no negative side effects from ingesting the lettuce material, and blood samples taken throughout the experiment revealed no signs of toxicity.

“Looking at the dogs that were fed the lettuce material, you can see it’s quite effective,” Dr Daniell said. “They either developed no antibodies to factor IX, or their antibodies went up just a little bit and then came down.”

The next steps for the researchers include additional toxicology and pharmacokinetics studies before applying for an investigational new drug application with the US Food and Drug Administration, a step they hope to take before the end of the year.

Irish setter, a breed of dog

that can develop hemophilia B

A plant-made therapy has demonstrated safety and efficacy in dogs with hemophilia B, according to research published in Molecular Therapy.

Previously, researchers found they could produce freeze-dried lettuce cells expressing human coagulation factor IX (FIX) fused with cholera toxin B subunit (CTB).

These cells were able to prevent inhibitor formation and allergic reactions to intravenous FIX therapy in mice with hemophilia B.

With the current study, the researchers showed that lettuce cells expressing CTB-FIX were safe and could prevent anaphylaxis and inhibitor formation in dogs receiving intravenous FIX to treat hemophilia B.

“The results were quite dramatic,” said study author Henry Daniell, PhD, of the University of Pennsylvania in Philadelphia.

“We corrected blood clotting time in each of the dogs and were able to suppress antibody formation as well. All signs point to this material being ready for the clinic.”

This study made use of Dr Daniell’s patented plant-based drug-production platform, in which genetic modifications enable the growth of plants that have specified human proteins in their leaves.

The researchers grew lettuce that had been modified to produce a fusion protein of human FIX and CTB. CTB helps the fused protein cross the intestinal lining as the lettuce cells are digested by gut microbes, while the plant cell walls protect FIX from digestion.

The researchers said they were able to achieve commercial-scale production of CTB-FIX fusions expressed in lettuce chloroplasts by growing the plants in a hydroponic facility.

The team first tested their product in 2 dogs with hemophilia B. Twice a week for 10 months, the dogs consumed the freeze-dried lettuce material, which was spiked with bacon flavor and sprinkled on their food.

Observing no negative effects of the treatment, the researchers went on to a more robust study, including 4 dogs that were fed the lettuce material and 4 that served as controls.

The 4 dogs in the experimental group were fed the lettuce material for 4 weeks. At that point, they also began receiving weekly injections of FIX, which continued for 8 weeks. The control dogs only received the FIX injections.

All 4 dogs in the control group developed significant levels of antibodies against FIX, and 2 had visible anaphylactic reactions that required the administration of antihistamine.

In contrast, 3 of the 4 dogs in the experimental group had only minimal levels of one type of antibody, IgG2, and no detectable levels of IgG1 or IgE.

The fourth dog in the experimental group had only a partial response to the lettuce cells expressing CTB-FIX. The researchers believe this was due to a pre-existing antibody to human FIX.

Overall, levels of IgG2 were 32 times lower in the experimental group than in the controls.

In addition, the dogs showed no negative side effects from ingesting the lettuce material, and blood samples taken throughout the experiment revealed no signs of toxicity.

“Looking at the dogs that were fed the lettuce material, you can see it’s quite effective,” Dr Daniell said. “They either developed no antibodies to factor IX, or their antibodies went up just a little bit and then came down.”

The next steps for the researchers include additional toxicology and pharmacokinetics studies before applying for an investigational new drug application with the US Food and Drug Administration, a step they hope to take before the end of the year.

DNA helix
Image by Spencer Phillips

Researchers have developed an online “knowledgebase” called CIViC, an open access resource for collecting and interpreting information from scientific publications on cancer genetics.

“CIViC” stands for Clinical Interpretations of Variants in Cancer, and the researchers liken it to a Wikipedia of cancer genetics.

Anyone can create an account and contribute information. That information is then curated by editors and moderators who are considered experts in the field.

The researchers described the resource in Nature Genetics.

“It’s relatively easy now to sequence the DNA of tumors—to gather the raw information—but there’s a big interpretation problem,” said study author Obi L. Griffith, PhD, of Washington University School of Medicine in St Louis, Missouri.

“What do these hundreds or thousands of mutations mean for this patient? There are a lot of studies being done to answer these questions. But oncologists trying to interpret the raw data are faced with an overwhelming task of plumbing the literature, reading papers, trying to understand what the latest studies tell them about these mutations and how they may or may not be important.”

The CIViC knowledgebase is an attempt to solve this problem. The researchers said this is one of many efforts to collect and interpret such information, but, to their knowledge, CIViC is the only one that is entirely open access. Anyone is free to contribute and use the content as well as the source code.

“We are committed to keeping this resource open and available to anyone who wants to contribute or make use of the information,” said Malachi Griffith, PhD, of Washington University School of Medicine.

“We would like it to be a community exercise and public resource. The information is in the public domain. There are no restrictions on its use, academic or commercial.”

Though anyone can submit a new piece of information or suggest edits to existing data, at least 2 independent contributors must agree that the new information should be incorporated, and 1 of those users must be an “expert editor.”

Expert editors are not permitted to approve their own submissions. Information on the CIViC website provides details about how new users may be promoted to expert editors and administrators.

To date, the site has seen over 17,500 users from academic institutions, governmental organizations, and commercial entities around the world.

Since CIViC’s launch, 59 users have volunteered their time to contribute their knowledge to CIViC, including descriptions of the clinical relevance of 732 mutations from 285 genes for 203 types of cancer, all gleaned from reviewing 1090 scientific and medical publications.

Despite the fact that there are many groups attempting to collect and interpret genomic variants in cancer, the researchers said the sheer volume of information has resulted in relatively little overlap in data gathered so far.

“While we believe this is the only such open access knowledgebase, there are other large research centers with similar resources,” Malachi Griffith said. “We did an analysis to compare the big ones.”

“Even though we all have access to the same published literature, if you look at the overlap of the information mined by each of these resources, it’s remarkably small. We’re all approaching the same problem, and, just by chance—and probably because of the amount of information out there—we haven’t duplicated our efforts very much yet.”

Obi and Malachi Griffith said finding a way to combine these resources is the primary goal of an international group they are helping lead called the Variant Interpretation for Cancer Consortium, which is a part of the Global Alliance for Genomics and Health (GA4GH).

“We’re just scratching the surface of the potential this holds for precision medicine,” Obi Griffith said. “There’s a lot of work to do.”

DNA helix
Image by Spencer Phillips

Researchers have developed an online “knowledgebase” called CIViC, an open access resource for collecting and interpreting information from scientific publications on cancer genetics.

“CIViC” stands for Clinical Interpretations of Variants in Cancer, and the researchers liken it to a Wikipedia of cancer genetics.

Anyone can create an account and contribute information. That information is then curated by editors and moderators who are considered experts in the field.

The researchers described the resource in Nature Genetics.

“It’s relatively easy now to sequence the DNA of tumors—to gather the raw information—but there’s a big interpretation problem,” said study author Obi L. Griffith, PhD, of Washington University School of Medicine in St Louis, Missouri.

“What do these hundreds or thousands of mutations mean for this patient? There are a lot of studies being done to answer these questions. But oncologists trying to interpret the raw data are faced with an overwhelming task of plumbing the literature, reading papers, trying to understand what the latest studies tell them about these mutations and how they may or may not be important.”

The CIViC knowledgebase is an attempt to solve this problem. The researchers said this is one of many efforts to collect and interpret such information, but, to their knowledge, CIViC is the only one that is entirely open access. Anyone is free to contribute and use the content as well as the source code.

“We are committed to keeping this resource open and available to anyone who wants to contribute or make use of the information,” said Malachi Griffith, PhD, of Washington University School of Medicine.

“We would like it to be a community exercise and public resource. The information is in the public domain. There are no restrictions on its use, academic or commercial.”

Though anyone can submit a new piece of information or suggest edits to existing data, at least 2 independent contributors must agree that the new information should be incorporated, and 1 of those users must be an “expert editor.”

Expert editors are not permitted to approve their own submissions. Information on the CIViC website provides details about how new users may be promoted to expert editors and administrators.

To date, the site has seen over 17,500 users from academic institutions, governmental organizations, and commercial entities around the world.

Since CIViC’s launch, 59 users have volunteered their time to contribute their knowledge to CIViC, including descriptions of the clinical relevance of 732 mutations from 285 genes for 203 types of cancer, all gleaned from reviewing 1090 scientific and medical publications.

Despite the fact that there are many groups attempting to collect and interpret genomic variants in cancer, the researchers said the sheer volume of information has resulted in relatively little overlap in data gathered so far.

“While we believe this is the only such open access knowledgebase, there are other large research centers with similar resources,” Malachi Griffith said. “We did an analysis to compare the big ones.”

“Even though we all have access to the same published literature, if you look at the overlap of the information mined by each of these resources, it’s remarkably small. We’re all approaching the same problem, and, just by chance—and probably because of the amount of information out there—we haven’t duplicated our efforts very much yet.”

Obi and Malachi Griffith said finding a way to combine these resources is the primary goal of an international group they are helping lead called the Variant Interpretation for Cancer Consortium, which is a part of the Global Alliance for Genomics and Health (GA4GH).

“We’re just scratching the surface of the potential this holds for precision medicine,” Obi Griffith said. “There’s a lot of work to do.”

DNA helix
Image by Spencer Phillips

Researchers have developed an online “knowledgebase” called CIViC, an open access resource for collecting and interpreting information from scientific publications on cancer genetics.

“CIViC” stands for Clinical Interpretations of Variants in Cancer, and the researchers liken it to a Wikipedia of cancer genetics.

Anyone can create an account and contribute information. That information is then curated by editors and moderators who are considered experts in the field.

The researchers described the resource in Nature Genetics.

“It’s relatively easy now to sequence the DNA of tumors—to gather the raw information—but there’s a big interpretation problem,” said study author Obi L. Griffith, PhD, of Washington University School of Medicine in St Louis, Missouri.

“What do these hundreds or thousands of mutations mean for this patient? There are a lot of studies being done to answer these questions. But oncologists trying to interpret the raw data are faced with an overwhelming task of plumbing the literature, reading papers, trying to understand what the latest studies tell them about these mutations and how they may or may not be important.”

The CIViC knowledgebase is an attempt to solve this problem. The researchers said this is one of many efforts to collect and interpret such information, but, to their knowledge, CIViC is the only one that is entirely open access. Anyone is free to contribute and use the content as well as the source code.

“We are committed to keeping this resource open and available to anyone who wants to contribute or make use of the information,” said Malachi Griffith, PhD, of Washington University School of Medicine.

“We would like it to be a community exercise and public resource. The information is in the public domain. There are no restrictions on its use, academic or commercial.”

Though anyone can submit a new piece of information or suggest edits to existing data, at least 2 independent contributors must agree that the new information should be incorporated, and 1 of those users must be an “expert editor.”

Expert editors are not permitted to approve their own submissions. Information on the CIViC website provides details about how new users may be promoted to expert editors and administrators.

To date, the site has seen over 17,500 users from academic institutions, governmental organizations, and commercial entities around the world.

Since CIViC’s launch, 59 users have volunteered their time to contribute their knowledge to CIViC, including descriptions of the clinical relevance of 732 mutations from 285 genes for 203 types of cancer, all gleaned from reviewing 1090 scientific and medical publications.

Despite the fact that there are many groups attempting to collect and interpret genomic variants in cancer, the researchers said the sheer volume of information has resulted in relatively little overlap in data gathered so far.

“While we believe this is the only such open access knowledgebase, there are other large research centers with similar resources,” Malachi Griffith said. “We did an analysis to compare the big ones.”

“Even though we all have access to the same published literature, if you look at the overlap of the information mined by each of these resources, it’s remarkably small. We’re all approaching the same problem, and, just by chance—and probably because of the amount of information out there—we haven’t duplicated our efforts very much yet.”

Obi and Malachi Griffith said finding a way to combine these resources is the primary goal of an international group they are helping lead called the Variant Interpretation for Cancer Consortium, which is a part of the Global Alliance for Genomics and Health (GA4GH).

“We’re just scratching the surface of the potential this holds for precision medicine,” Obi Griffith said. “There’s a lot of work to do.”

AML cells

CRISPR-based genetic screens have revealed essential genes—those required for cellular proliferation and survival—in 14 acute myeloid leukemia (AML) cell lines, according to investigators.

By combining this information with the existing genomic information on these cell lines, the investigators believe they have identified vulnerabilities that could potentially be exploited with new therapies.

The group described their research in Cell.

A major aspect of their study focused on the genes and protein pathways connected to the Ras oncogene, which is the most commonly mutated oncogene in human cancers and plays a role in AML.

“For the most part, the mutant Ras protein itself has been considered to be ‘undruggable,’” said study author Tim Wang, a doctoral student at the Massachusetts Institute of Technology in Cambridge.

“An alternative approach has been to find other genes that Ras-mutant cancers rely on with the hope that one of them may be druggable. Unfortunately, such ‘Ras-synthetic-lethal’ genes have been difficult to identify.”

Using CRISPR-based screens, the investigators were able to gauge the impact of individually knocking out each of the 18,000 protein-coding genes in the human genome.

“This process rapidly enabled us to identify the short list of genes that were selectively required in only the Ras-mutant cells,” explained study author David Sabatini, MD, PhD, of the Massachusetts Institute of Technology.

He and his colleagues found that the enzymes catalyzing the latter steps of the Ras processing pathway, Rce1 and Icmt, displayed synthetic lethality with oncogenic Ras, which suggests they might be therapeutic targets in AML and other cancers driven by oncogenic Ras.

The investigators also said their findings provide further support for the central role of MAPK signaling in Ras-driven cancers, suggest PREX1 and the Rac pathway are critical regulators of MAPK pathway activation, and indicate that c-Raf could be a therapeutic target in cancers driven by oncogenic Ras.

In addition to defining the Ras-specific gene essentiality network, the investigators said they were able to determine the function of previously unstudied genes.

The team started by focusing on genes that were essential in some of the AML cell lines but dispensable for others. For each of these genes, the investigators sifted through their data to find others that showed a matching pattern of essentiality, with the idea that all of them had similar functions.

Indeed, this analysis revealed gene groups that were already known to act together and uncovered novel associations between genes that were not known to be related or had been previously unstudied.

“What’s particularly exciting about this work is that we have just begun to scratch the surface with our method,” Wang concluded. “By applying it broadly, we could reveal a huge amount of information about the functional organization of human genes and their roles in many diseases.”

AML cells

CRISPR-based genetic screens have revealed essential genes—those required for cellular proliferation and survival—in 14 acute myeloid leukemia (AML) cell lines, according to investigators.

By combining this information with the existing genomic information on these cell lines, the investigators believe they have identified vulnerabilities that could potentially be exploited with new therapies.

The group described their research in Cell.

A major aspect of their study focused on the genes and protein pathways connected to the Ras oncogene, which is the most commonly mutated oncogene in human cancers and plays a role in AML.

“For the most part, the mutant Ras protein itself has been considered to be ‘undruggable,’” said study author Tim Wang, a doctoral student at the Massachusetts Institute of Technology in Cambridge.

“An alternative approach has been to find other genes that Ras-mutant cancers rely on with the hope that one of them may be druggable. Unfortunately, such ‘Ras-synthetic-lethal’ genes have been difficult to identify.”

Using CRISPR-based screens, the investigators were able to gauge the impact of individually knocking out each of the 18,000 protein-coding genes in the human genome.

“This process rapidly enabled us to identify the short list of genes that were selectively required in only the Ras-mutant cells,” explained study author David Sabatini, MD, PhD, of the Massachusetts Institute of Technology.

He and his colleagues found that the enzymes catalyzing the latter steps of the Ras processing pathway, Rce1 and Icmt, displayed synthetic lethality with oncogenic Ras, which suggests they might be therapeutic targets in AML and other cancers driven by oncogenic Ras.

The investigators also said their findings provide further support for the central role of MAPK signaling in Ras-driven cancers, suggest PREX1 and the Rac pathway are critical regulators of MAPK pathway activation, and indicate that c-Raf could be a therapeutic target in cancers driven by oncogenic Ras.

In addition to defining the Ras-specific gene essentiality network, the investigators said they were able to determine the function of previously unstudied genes.

The team started by focusing on genes that were essential in some of the AML cell lines but dispensable for others. For each of these genes, the investigators sifted through their data to find others that showed a matching pattern of essentiality, with the idea that all of them had similar functions.

Indeed, this analysis revealed gene groups that were already known to act together and uncovered novel associations between genes that were not known to be related or had been previously unstudied.

“What’s particularly exciting about this work is that we have just begun to scratch the surface with our method,” Wang concluded. “By applying it broadly, we could reveal a huge amount of information about the functional organization of human genes and their roles in many diseases.”

AML cells

CRISPR-based genetic screens have revealed essential genes—those required for cellular proliferation and survival—in 14 acute myeloid leukemia (AML) cell lines, according to investigators.

By combining this information with the existing genomic information on these cell lines, the investigators believe they have identified vulnerabilities that could potentially be exploited with new therapies.

The group described their research in Cell.

A major aspect of their study focused on the genes and protein pathways connected to the Ras oncogene, which is the most commonly mutated oncogene in human cancers and plays a role in AML.

“For the most part, the mutant Ras protein itself has been considered to be ‘undruggable,’” said study author Tim Wang, a doctoral student at the Massachusetts Institute of Technology in Cambridge.

“An alternative approach has been to find other genes that Ras-mutant cancers rely on with the hope that one of them may be druggable. Unfortunately, such ‘Ras-synthetic-lethal’ genes have been difficult to identify.”

Using CRISPR-based screens, the investigators were able to gauge the impact of individually knocking out each of the 18,000 protein-coding genes in the human genome.

“This process rapidly enabled us to identify the short list of genes that were selectively required in only the Ras-mutant cells,” explained study author David Sabatini, MD, PhD, of the Massachusetts Institute of Technology.

He and his colleagues found that the enzymes catalyzing the latter steps of the Ras processing pathway, Rce1 and Icmt, displayed synthetic lethality with oncogenic Ras, which suggests they might be therapeutic targets in AML and other cancers driven by oncogenic Ras.

The investigators also said their findings provide further support for the central role of MAPK signaling in Ras-driven cancers, suggest PREX1 and the Rac pathway are critical regulators of MAPK pathway activation, and indicate that c-Raf could be a therapeutic target in cancers driven by oncogenic Ras.

In addition to defining the Ras-specific gene essentiality network, the investigators said they were able to determine the function of previously unstudied genes.

The team started by focusing on genes that were essential in some of the AML cell lines but dispensable for others. For each of these genes, the investigators sifted through their data to find others that showed a matching pattern of essentiality, with the idea that all of them had similar functions.

Indeed, this analysis revealed gene groups that were already known to act together and uncovered novel associations between genes that were not known to be related or had been previously unstudied.

“What’s particularly exciting about this work is that we have just begun to scratch the surface with our method,” Wang concluded. “By applying it broadly, we could reveal a huge amount of information about the functional organization of human genes and their roles in many diseases.”