Snapshot of Science for June 2022

Welcome to our Snapshot of Science for June 2022.

Here's a quick look at some recent publications, press releases and stories about the Mass General Research Institute community.

In this issue we highlight:

32 new studies published in high-impact journals, along with 26 summaries submitted by the research teams
9 new research-related press releases from the Mass General Public Affairs office
7 posts from the Mass General Research Institute blog

Publications

Motor Cortex Replays Learned Sequences During Sleep
Learned Motor Patterns Are Replayed in Human Motor Cortex During Sleep
Rubin DB, Hosman T, Kelemen JN, Kapitonava A, Willett FR [et al.], Cash SS
Published in Journal of Neuroscience on 19-May | *Summary available | Press Release

Association Between Physician Fatigue and Patient Outcomes
Assessment of Perioperative Outcomes Among Surgeons Who Operated the Night Before
Sun EC, Mello MM, Vaughn MT, Kheterpal S, Hawn MT, Dimick JB, Jena AB
Published in JAMA Internal Medicine on 23-May

Improving the Quality of Artificial Hearing
Magnetic Stimulation Allows Focal Activation of the Mouse Cochlea
Lee JI, Seist R, McInturff S, Lee DJ, Brown MC, Stankovic KM, Fried S
Published in eLife on 24-May | *Summary available

Isolating Neuronal Stem Cells From Schwann Cells
Schwann Cells in the Subcutaneous Adipose Tissue Have Neurogenic Potential and Can Be Used for Regenerative Therapies
Stavely R, Hotta R, Picard N, Rahman AA, Pan W [et al.], Goldstein AM
Published in Science Translational Medicine on 25-May | *Summary available

Multiple Proteins May Be Targeted to Reduce Fibrosis
Nanchangmycin Regulates FYN, PTK2, and MAPK1/3 to Control the Fibrotic Activity of Human Hepatic Stellate Cells
Li W, Chen JY, Sun C, Sparks RP, Pantano L [et al.], Mullen AC
Published in eLife on 26-May | *Summary available

A Neurophysiological and Computational Framework for Invasive Brain Signal Decoding
Electrocorticography Is Superior to Subthalamic Local Field Potentials for Movement Decoding in Parkinson's Disease
Merk T, Peterson V, Lipski WJ, Blankertz B, Turner RS [et al.], Neumann WJ
Published in eLife on 27-May

A Model for Protecting and Analyzing Opioid Policies
Modeling the Evolution of the U.S. Opioid Crisis for National Policy Development
Lim TY, Stringfellow EJ, Stafford CA, DiGennaro C, Homer JB [et al.], Jalali MS
Published in PNAS on 31-May | *Summary available | Press Release

Accurate Differentiation of Urate and Non-Urate Kidney Stones
Comparison of Four Dual-Energy CT Scanner Technologies for Determining Renal Stone Composition: A Phantom Approach
Pourvaziri A, Parakh A, Cao J, Locascio J, Eisner B, Sahani D, Kambadakone A
Published in Radiology on 31-May | *Summary available

Black Children Less Likely Than White Children to Receive Diagnostic Imaging in EDs
Analysis of Racial and Ethnic Diversity of Population Served and Imaging Used in U.S. Children's Hospital Emergency Departments
Samuels-Kalow ME, De Souza HG, Neuman MI, Alpern E, Marin JR [et al.], Goyal MK
Published in JAMA Network Open on 1-Jun | *Summary available

Medicaid Expansion Alone May Be Insufficient to Improve CV Health for Low Income Adults
Health Care Access and Management of Cardiovascular Risk Factors Among Working-Age Adults With Low Income by State Medicaid Expansion Status
Oseran AS, Sun T, Wadhera RK
Published in JAMA Cardiology on 1-Jun | *Summary available

Changes in Florescence Lifetime Differentiate Cancer Cells and Healthy Tissue
First Clinical Results of Fluorescence Lifetime-enhanced Tumor Imaging Using Receptor-targeted Fluorescent Probes
Pal R, Hom ME, van den Berg NS, Lwin TM, Lee YJ [et al.], Kumar ATN
Published in Clinical Cancer Research on 1-Jun | *Summary available

Imaging Living Cells and Tissues in their Many-Colored Complexity
Spatiotemporal Multiplexed Immunofluorescence Imaging of Living Cells and Tissues With Bioorthogonal Cycling of Fluorescent Probes
Ko J, Wilkovitsch M, Oh J, Kohler RH, Bolli E, [et al.], Carlson JCT
Published in Nature Biotechnology on 2-Jun | *Summary available

Spatial Organization of DNA, RNA and Proteins
Condensates Induced by Transcription Inhibition Localize Active Chromatin to Nucleoli
Yasuhara T, Xing YH, Bauer NC, Lee L, Dong R [et al.], Zou L
Published in Molecular Cell on 2-Jun

A Prominent Immune Cell Type Suppresses Breast Cancer Development
CD4+ T Helper 2 Cells Suppress Breast Cancer by Inducing Terminal Differentiation
Boieri M, Malishkevich A, Guennoun R, Marchese E, Kroon S [et al.], Demehri S
Published in Journal of Experimental Medicine on 3-Jun | *Summary available | Press Release

Correcting a Splicing Defect in Familial Dysautonomia
Selective Retinal Ganglion Cell Loss and Optic Neuropathy in a Humanized Mouse Model of Familial Dysautonomia
Chekuri A, Logan EM, Krauson AJ, Salani M, Ackerman S [et al.], Morini E
Published in Human Molecular Genetics on 4-Jun | *Summary available

How Immune Cells Sense pH to Regulate Inflammatory Circuits and Tissue Homeostasis
pH Sensing Controls Tissue Inflammation by Modulating Cellular Metabolism and Endo-lysosomal Function of Immune Cells
Chen X, Jaiswal A, Costliow Z, Herbst P, Creasey EA [et al.], Xavier RJ
Published in Nature Immunology on 6-Jun | *Summary available

A New Treatment Strategy for NF2 Disease
Intratumoral Injection of Schwannoma With Attenuated Salmonella Typhimurium Induces Antitumor Immunity and Controls Tumor Growth
Ahmed SG, Oliva G, Shao M, Wang X, Mekalanos JJ, Brenner GJ
Published in PNAS on 8-Jun | *Summary available

Neurodevelopmental Effects of SARS-CoV-2 Exposure In Utero
Neurodevelopmental Outcomes at 1 Year in Infants of Mothers Who Tested Positive for SARS-CoV-2 During Pregnancy
Edlow AG, Castro VM, Shook LL, Kaimal AJ, Perlis RH
Published in JAMA Network Open on 9-Jun | *Summary available

Smoking Cessation Treatment Intervention Cost-effective
Cost-effectiveness of Implementing Smoking Cessation Interventions for Patients With Cancer
Levy DE, Regan S, Perez GK, Muzikansky A, Friedman ER [et al.], Park ER
Published in JAMA Network Open on 9-Jun | *Summary available

Looking to Electronic Health Records to Learn More About Long COVID
Post-Acute Sequelae of SARS-CoV-2 Infection: A Descriptive Clinical Study
Gutierrez-Martinez L, Karten J, Kritzer MD, Josephy-Hernandez S, Kim D [et al.], Chemali Z
Published in Journal of Neuropsychiatry and Clinical Neurosciences on 10-Jun | Press Release

Fentanyl May Cause Autism-like Behavior in Young Mice
Fentanyl Induces Autism-like Behaviours in Mice by Hypermethylation of the Glutamate Receptor Gene Grin2b
Sheng Z, Liu Q, Cheng C, Li M, Barash J [et al.], Xie Z
Published in British Journal of Anaesthesia on 11-Jun | *Summary available | Press Release

Large Scale Cardiac Phenotyping of Right Heart Structure and Function
Genetic Analysis of Right Heart Structure and Function in 40,000 People
Pirruccello JP, Di Achille P, Nauffal V, Nekoui M, Friedman SF [et al.], Ellinor PT
Published in Nature Genetics on 13-Jun | *Summary available

Brain-related Symptoms Were Common in People Previously Hospitalized for COVID-19 and Other Issues
Case-control Study of Neuropsychiatric Symptoms in Electronic Health Records Following COVID-19 Hospitalization in 2 Academic Health Systems
Castro VM, Rosand J, Giacino JT, McCoy TH, Perlis RH
Published in Molecular Psychiatry on 15-Jun | *Summary available

Predicting Outcomes for Patients With Smoldering Multiple Myeloma
Genetic Subtypes of Smoldering Multiple Myeloma Are Associated With Distinct Pathogenic Phenotypes and Clinical Outcomes
Bustoros M, Anand S, Sklavenitis-Pistofidis R, Redd R, Boyle EM [et al.], Ghobrial IM
Published in Nature Communications on 15-Jun | *Summary available

How Aphasia Patients Compensate for Challenges With Language
A Syntax-Lexicon Trade-Off in Language Production
Rezaii N, Mahowald K, Ryskin R, Dickerson B, Gibson E
Published in PNAS on 16-Jun | *Summary available

The Activation of the Viral-like Repeatome in Ovarian Cancer
Satellite Repeat RNA Expression in Epithelial Ovarian Cancer Associates With a Tumor Immunosuppressive Phenotype
Porter RL, Sun S, Flores MN, Berzolla E, You E [et al.], Ting DT
Published in The Journal of Clinical Investigation on 16-Jun | *Summary available

Liso-Cel as a Second-Line Treatment for Early Relapsed or Refractory LBCL
Lisocabtagene Maraleucel Versus Standard of Care With Salvage Chemotherapy Followed by Autologous Stem Cell Transplantation As Second-line Treatment in Patients With Relapsed or Refractory Large B-cell Lymphoma (TRANSFORM): Results From an Interim Analysis of an Open-label, Randomised, Phase 3 Trial
Kamdar M, Solomon SR, Arnason J, Johnston PB, Glass B [et al.], Abramson JS; TRANSFORM Investigators
Published in Lancet on 18-Jun | *Summary available

A Deep Learning Model of Human Psychology
Optimizing Future Well-Being With Artificial Intelligence: Self-organizing Maps (SOMs) for the Identification of Islands of Emotional Stability
Galkin F, Kochetov K, Keller M, Zhavoronkov A, Etcoff N
Published in Aging on 20-Jun | Press Release

DNA Mimicry by a Protein Regulates Cell Signaling Critical in Development and Cancer
Cytoskeletal Regulation of a Transcription Factor by DNA Mimicry Via Coiled-Coil Interaction
Haque F, Freniere C, Ye Q, Mani N, Wilson-Kubalek EM [et al.], Subramanian R
Published in Nature Cell Biology on 20-Jun | *Summary available

Medication Associated With Lower Risk of Breakthrough SARS-CoV-2 Infection
Tixagevimab/Cilgavimab Pre-exposure Prophylaxis Is Associated With Lower Breakthrough Infection Risk in Vaccinated Solid Organ Transplant Recipients During the Omicron Wave
Al Jurdi A, Morena L, Cote M, Bethea E, Azzi J, Riella LV
Published in American Journal of Transplantation on 21-Jun

Publication Summaries

Simple, Cost Effective Sensor-integrated Wound Dressings
Quantitative Luminescence Photography of a Swellable Hydrogel Dressing With a Traffic-Light Response to Oxygen
Marks HL, Cook K, Roussakis E, Cascales JP, Korunes-Miller JT, Grinstaff MW, Evans CL
Published in Advanced Healthcare Materials on 18-May

We have developed a color-changing hydrogel wound dressing featuring a red-to-green 'traffic light' response to oxygen. Using simple macroscopic photography, the concentration of oxygen was quantified by monitoring the hue of the hydrogel’s luminescence, while the brightness of a secondary green dye could be used to account for changes in pH. The 'traffic light' response is maintained despite high autofluorescence from skin—allowing visualization with any standard camera and thereby providing clinician friendly naked-eye feedback.

(Summary submitted by Haley L. Marks, PhD, Department of Dermatology)

Cardiopulmonary Symptoms in Athletes After COVID-19
Diagnostic Evaluation and Cardiopulmonary Exercise Test Findings in Young Athletes With Persistent Symptoms Following COVID-19
Moulson N, Gustus SK, Scirica C, Petek BJ, Vanatta C [et al.], Wasfy MM
Published in British Journal of Sports Medicine on 18-May

COVID-19 may cause symptoms that linger after the initial infection has resolved, so called “long COVID.” Young healthy athletes are relatively protected from serious consequences of COVID-19, but still may have lingering symptoms. When these symptoms consist of chest pain, shortness of breath, or reduced ability to exercise, this prompts concern for a dangerous cardiac consequence of COVID-19 known as myocarditis (heart muscle inflammation). We evaluated a series of athlete patients and found none of them had myocarditis as a cause for their lingering exercise symptoms after COVID-19. On exercise testing, we found many had abnormal lung parameters suggestive of asthma, which can be common after viral infections, and some had lower than expected fitness or big swings in their heart rate and blood pressure. We followed these athlete patients over several months. Most of them felt improved over time, and with this their fitness improved, some had normalization of their lung function, and their heart rates with exercise were lower. Our results suggest most “long COVID” exercise symptoms in athletes are not due to dangerous cardiac causes. More work is needed to evaluate COVID-19’s impact on the lungs and the regulation of heart rate during exercise as causes for lingering exercise symptoms.

(Summary submitted by Meagan M. Wasfy, MD, MPH, Division of Cardiology, Department of Medicine)

We demonstrated the direct replay of learned neural sequences during sleep in human motor cortex. A research participant enrolled in the BrainGate clinical trial spent multiple afternoons playing a video game using an intracortical brain computer interface. After each research session, the investigators then recorded the neural activity in motor cortex as he slept. By projecting that neural activity through the same decoding algorithm used to play the game while awake, they found that his motor cortex continued to play (and often “win”) the game all night as he slept. These findings provide insight into the brain’s activity during sleep— one of the great mysteries of neuroscience— and support the hypothesis of sleep’s role in learning and consolidation of memory.

(Summary submitted by Daniel B. Rubin, MD, PhD, Division of Neurocritical Care, Department of Neurology)

Cochlear implants (CIs) enable speech recognition for those with severe hearing loss, but performance is limited in noisy environments, and most users cannot appreciate music. Suboptimal performance arises because existing devices typically create only ~10 independent spectral channels, much less than that utilized by the healthy cochlea. Here, we show that a novel stimulation modality, magnetic stimulation from microcoils, creates narrow channels, i.e., much narrower than those created by the electrodes used in existing CIs. This offers a way to increase the number of independent channels and therefore opens new and exciting possibilities for improving the quality of artificial hearing.

(Summary submitted by Jae-Ik Lee, PhD, Department of Neurosurgery)

The use of stem cells to repair the enteric nervous system has shown promising results in models of neurointestinal disease. While autologous neuronal stem cells (NSCs) would be ideal since they avoid the need for immunosuppression and obviate the risks associated with induced pluripotent stem cells (iPS), they have not been an easily accessible source. In this study we report the isolation of NSCs from a population of Schwann cells in nerve bundles from human and rodent subcutaneous adipose tissue (SAT). These SAT-NSCs differentiate into neurons and glia after transplantation to the gastrointestinal tract, where they ameliorate functional deficits in mouse models of gastroparesis and Hirschsprung disease, offering evidence for their potential as a therapeutic tool to treat enteric neuropathies.

(Summary submitted by Allan M. Goldstein, MD and Rhian G. Stavely, PhD, Department of Surgery, Mass General for Children)

Multiple Proteins That Could Be Targeted to Reduce Fibrosis
Nanchangmycin Regulates FYN, PTK2, and MAPK1/3 to Control the Fibrotic Activity of Human Hepatic Stellate Cells
Li W, Chen JY, Sun C, Sparks RP, Pantano L [et al.], Mullen AC
Published in eLife on 26-May

Chronic injury of the liver from causes such as infections, obesity, and alcohol leads to liver fibrosis, and the progression of fibrosis is a major cause of liver failure. Hepatic stellate cells are the main cell type responsible for producing liver fibrosis, and we performed a screen of over 15,000 different conditions to identify drugs that cause hepatic stellate cells to revert to less fibrotic activity with the goal of understanding the processes in these cells that promote fibrosis. Through this work, we identified multiple proteins that could be targeted to inhibit the activity of hepatic stellate cells to reduce fibrosis.

(Summary submitted by Alan C. Mullen, MD, PhD, Division of Gastroenterology, Department of Medicine)

We developed a data-driven simulation model designed to help policymakers to better understand and address the nation’s rampant opioid crisis. We report that our model, known as SOURCE (Simulation of Opioid Use, Response, Consequences, and Effects), presents the most detailed model to date of the crisis by capturing how the interconnections between stages of prescription and illicit opioid use, from initiation and addiction treatment to relapse and overdose mortality, have evolved over time. SOURCE uses national data on opioid use from 1999 to 2020 to track stages of use and misuse of opioids, including use initiation, treatment, relapse and death by overdose. Using SOURCE, we are examining potential strategies to address the opioid crisis as part of an ongoing modeling effort, while continuing to refine the model to reflect the still-evolving nature of the crisis.

(Summary submitted by Mohammad S. Jalali, PhD, Data and Systems Science in Public Health, Department of Radiology)

High Accuracy Differentiation of Urate and Non-Urate Kidney Stones
Comparison of Four Dual-Energy CT Scanner Technologies for Determining Renal Stone Composition: A Phantom Approach
Pourvaziri A, Parakh A, Cao J, Locascio J, Eisner B, Sahani D, Kambadakone A
Published in Radiology on 31-May

Urinary stone composition, a key factor in determining management strategies, is routinely evaluated with conventional CT, which has limited accuracy. Dual-energy CT (DECT), an innovative CT technology, enables superior determination of material composition, but there is limited data on comparison of its performance across scanners from different vendors. We performed a multivendor comparison of the diagnostic performance of different DECT technologies in differentiating different types of stones in a phantom model with standard dose and low dose techniques. We found that the performance of dual-energy CT varied according to scanner parameters and DECT technique, but helped differentiate urate and non-urate stones with high accuracy. Low dose scans with radiation dose reduction of 45%-81% did not substantially impact the diagnostic performance. Further studies in large patient cohorts are needed to corroborate our findings in in vivo settings.

(Summary submitted by Avinash Kambadakone Ramesh, MD, Department of Radiology)

Previous studies have shown that Black children were less likely than white children to receive diagnostic imaging in emergency departments (EDs). We conducted a cross-sectional analysis of 38 EDs from the Pediatric Health Information System database to examine the association between hospital characteristics and imaging disparities. Our data show differences in imaging rates by race and ethnicity across children’s hospitals and suggest that hospitals with a higher percentage of non-white pediatric patients have larger differences in imaging between non-Hispanic Black and white patients. Additionally, these data do not support the hypothesis that racial and ethnic differences in imaging are caused by underlying variation in hospital propensity to image, emphasizing the need for additional work to develop interventions to improve the equity and appropriateness of imaging in pediatric emergency medicine.

(Summary submitted by Margaret E. Samuels-Kalow, MD, Department of Emergency Medicine, Mass General for Children)

This study used publicly available survey data to examine health care access and cardiovascular risk factor management among a weighted population of 28 million low-income, working age (18-64 years) adults. Based on this analysis, adults living in one of the 12 states that did not expand Medicaid as part of the Affordable Care Act (ACA) had nearly double the rate of uninsurance and worse access to care compared with their peers from Medicaid expansion states; however, that did not translate into worse cardiovascular risk factor management. Nevertheless, within non-expansion states, uninsured adults were less likely to receive monitoring for cholesterol or diabetes and treatment for hypertension and hyperlipidemia compared to those with insurance. These findings suggest that while we do need to address the major gaps in health insurance coverage that exist in Medicaid nonexpansion states. We also need to recognize that Medicaid expansion alone may be insufficient to improve cardiovascular health for all adults with low income.

(Summary submitted by Andrew S. Oseran, MD, Department of Medicine)

A major need in cancer surgery is for techniques that can help surgeons accurately identify tumors in the surgical bed, thereby ensuring no tumor is left behind while preserving healthy tissue. Fluorescence imaging is being tested to improve tumor visibility during surgery using injected fluorescent dyes that preferentially target tumors. However, non-specific uptake of dye in normal tissue has been a major problem that reduces tumor visibility, hindering clinical applicability. This paper demonstrates using clinical studies that by exploiting changes in fluorescence lifetime between cancer cells and healthy tissue, it is possible to identify tumors with an accuracy of more than 98%.

(Summary submitted by Anand T.N. Kumar, PhD, Martinos Center, Department of Radiology)

The microscopic molecular machinery of living systems is hard to watch as it works. We can observe live cells/tissues by labeling a key molecule or two with distinct fluorescent colors—akin to taking photographs of a brilliant garden in black and white. Other existing technologies can map biomolecules in superb detail (i.e., seeing the garden in color), but not in specimens that remain alive/intact, which has thus remained a key goal. Our team introduces scission-accelerated fluorophore exchange (SAFE): new biocompatible chemical tools for imaging living cells and tissues in their many-colored complexity across space and time.

(Summary submitted by Jonathan Carlson, MD, PhD, Division of Hematology/Oncology, Department of Medicine, Mass General Cancer Center, Center for Systems Biology)

The field of cancer immunology has mainly focused on the ability of the immune cells to kill cancer cells. We provide evidence that a prominent immune cell type called CD4+ T cells can suppress breast cancer development by forcing the breast cancer cells to differentiate into tissue resembling fibrocystic breast structures. CD4+ T helper 2 cells, that are commonly associated with eczema and asthma, can force breast cancer cells to return to their original programming of making a breast gland with no potential for growth or metastasis. Once the CD4+ T helper 2 cells are stimulated to infiltrate breast cancer, they release immune factors that directly reprogram the tumor cells into low-grade, fibrocystic-like structures. We have discovered a similar novel immune response against pancreatic and lung cancers. We believe this work will lead to novel treatment strategies to prevent cancer development and recurrence.

(Summary submitted by Shawn Demehri, MD, PhD, Department of Dermatology, Cutaneous Biology Research Center, Mass General Cancer Center)

Familial dysautonomia (FD) is a rare neurodegenerative disease caused by a mutation in the gene encoding for the Elongator complex protein 1 (ELP1). This mutation leads to a reduction of ELP1, mainly in the nervous system. Due to the crucial function of ELP1 in neuronal development and survival, FD patients exhibit many neurological symptoms, including retinal degeneration, and often become legally blind in their thirties. In this study, we have comprehensively characterized the eyes of an accurate mouse model to better understand the progression of retinal degeneration in FD. We found that loss of vision is due to the depletion of a specific population of neurons called “retinal ganglion cells,” and showed that it is possible to correct the disease molecular defect in the mouse retina using the novel compound BPN-15477.

(Summary submitted by Elisabetta Morini, PhD, Department of Neurology, Center for Genomic Medicine)

Increased acidity in body tissue occurs during inflammation and tumorigenesis, but how cellular sensing of pH level contributes to health and disease is not well understood. We used inflammatory bowel disease (IBD) as a paradigm to examine the role of pH sensing in inflamed tissue. Genome-wide association studies identified a mutation in the pH sensor GPR65 (specifically, GPR65 I231L) as a risk factor in IBD. By generating a mouse model, we revealed that GPR65 I231L promotes inflammation by altering metabolic and immune processes in T cells and dendritic cells. Our study illuminates mechanisms by which immune cells sense pH to regulate inflammatory circuits and tissue homeostasis in vivo.

(Summary submitted by Theresa Reimels, PhD, Center for Computational and Integrative Biology)

Neurofibromatosis type 2 (NF2) is a rare genetic disorder affecting children that is associated with the development of non-cancerous tumors that develop throughout the body causing severe pain, neurologic deficits, and death. Surgical resection and radiotherapy are the standards of care for NF2 tumors but have major limitations. The lack of highly effective and safe treatment options for NF2 represents a major unmet medical need. We have demonstrated that a direct injection of tumors with a genetically modified strain of the bacteria Salmonella typhimurium controls NF2 tumor growth. This strategy represents an immunotherapy that targets uninjected distal tumors and prevents development of new tumors. Our results support the evaluation of S. typhimurium as a treatment for NF2 disease.

(Summary submitted by Gary J. Brenner, MD, PhD, Pain Management Center, Department of Anesthesia, Critical Care and Pain Medicine)

In a collaboration between the Edlow and Perlis labs, we used electronic health records to look at outcomes for children of mothers who did, or did not, test positive for COVID-19 during pregnancy. Babies of COVID-19-positive mothers were more likely to be born preterm, as other studies had also suggested. In addition, over the first year of life, these children were slightly more likely to be diagnosed with delayed motor or speech milestones. We stressed that these differences were small and may well go away with longer-term follow-up. But this study suggests the importance of continued follow-up studies to understand whether COVID-19 exposure may have effects on brain development.

(Summary submitted by Roy Perlis, MD, Center for Quantitative Health, Center for Genomic Medicine, Department of Psychiatry)

Our research team previously established the effectiveness of a novel telehealth-based intervention model to promote smoking cessation among patients being treated for cancer. Smoking cessation treatment is a key part of quality cancer care, but cost is a prevalent barrier to implementing smoking cessation interventions in cancer care settings. In this paper, we evaluated the cost of implementing our smoking cessation intervention model and determined that it could be quite cost-effective or even cost saving—depending on how the model is staffed and what infrastructure is already in place.

(Summary submitted by Douglas E. Levy, PhD, Mongan Institute for Health Policy, Department of Medicine)

Fentanyl, a mu-opioid receptor agonist, is one of the most-commonly-used analgesics. The present study shows that fentanyl may cause autism-like behavior in young mice by reducing the amounts of N-methyl-D-aspartate receptor in the anterior cingulate cortex of the mice brain. Fentanyl decreased the expression of Grin2b, the gene encoding the N-methyl-D-aspartate receptor, in the anterior cingulate cortex of mice. However, the outcome of the animal study is not an indication to avoid fentanyl in clinical anesthesia. The present study would promote further research, including clinical investigations, to determine the potential neurobehavioral influence of opioids on brain development.

(Summary submitted by Zhongcong Xie, MD, PhD, Department of Anesthesia, Critical Care and Pain Medicine)

The right side of the heart pumps deoxygenated blood to the lungs, while the left side pumps oxygen-rich blood to the body. Some of the genes associated with rare diseases of the right heart differ from those that affect the left heart, raising the question of whether the same is true for common genetic variants (which are much more common and affect many more people, but have weaker effects). To tackle this question, we developed deep learning models to measure the right atrium, right ventricle, and pulmonary artery from cardiovascular magnetic resonance images in up to 40,000 UK Biobank participants. We found that, while most of the genetic determinants of right heart function were also shared with the left heart, many genetic variants had right heart-specific associations. When aggregated into polygenic scores, these variants helped to predict heart muscle dysfunction (cardiomyopathy) and pulmonary hypertension. These findings answered basic questions in cardiac genetics, identified targets for cardiomyopathy therapies, and demonstrated proof of principle that common genetic variation in right heart structures can play a role in identifying people at elevated risk for disease.

(Summary submitted by James Pirruccello, MD, Division of Cardiology, Cardiovascular Research Center, Department of Medicine)

Brain-related Symptoms Common in People Previously Hospitalized for COVID-19 and Other Issues
Case-control Study of Neuropsychiatric Symptoms in Electronic Health Records Following COVID-19 Hospitalization in 2 Academic Health Systems
Castro VM, Rosand J, Giacino JT, McCoy TH, Perlis RH
Published in Molecular Psychiatry on 15-Jun

While long COVID is increasingly recognized as a public health concern, there are still major gaps in our understanding of this syndrome—particularly as it relates to brain-related symptoms. Most prior studies have relied on diagnoses recording in electronic health records, or on patient surveys. In this study, we used a method called natural language processing to examine symptoms recorded in the health record, not just diagnoses. We found that brain-related symptoms were common in people previously hospitalized for COVID-19. But such symptoms were also common in people hospitalized for other reasons. The work provides a reminder that recovery from any major illness may be slow, and COVID-19 is no exception.

(Summary submitted by Roy Perlis, MD, Center for Quantitative Health, Center for Genomic Medicine, Department of Psychiatry)

Predicting Clinical Outcomes for Patients With Smoldering Multiple Myeloma
Genetic Subtypes of Smoldering Multiple Myeloma Are Associated With Distinct Pathogenic Phenotypes and Clinical Outcomes
Bustoros M, Anand S, Sklavenitis-Pistofidis R, Redd R, Boyle EM [et al.], Ghobrial IM
Published in Nature Communications on 15-Jun

Smoldering multiple myeloma (SMM) is a precursor condition in which some patients go on to develop full-blown active multiple myeloma (MM), while others never progress beyond SMM. Genomic analysis of bone marrow cells from a cohort of 214 SMM patients uncovered genetic alterations that, when separated into clusters of samples with similar patterns of alterations, identified six distinct genetic-based subtypes of SMM. Of clinical interest, each subtype associated with a different risk profile of progression to active MM (e.g., high or low risk), indicating the potential value of these subtypes in better predicting the clinical outcome of SMM patients.

(Summary submitted by Mendy Miller, PhD, Broad Institute of MIT and Harvard)

How Aphasia Patients Compensate for Challenges With Language
A Syntax-Lexicon Trade-Off in Language Production
Rezaii N, Mahowald K, Ryskin R, Dickerson B, Gibson E
Published in PNAS on 16-Jun

In the process of language production, speakers choose both words and syntactic structures. Collaborative research between Mass General and MIT has shown that speakers maintain a balance between the complexity of words and syntactic structures: a sentence that contains complex words is more likely to have simpler structures whereas a syntactically complex sentence contains simpler words. This work further shows how this syntax-lexicon trade-off may assist patients with primary progressive aphasia to better communicate. Patients who have difficulty producing complex syntax might choose more informative words while patients with word finding difficulties may choose more complex syntax to make their meaning clear.

(Summary submitted by Neguine Rezaii, MD, Department of Neurology)

Whole transcriptome analysis of a variety of epithelial cancers demonstrates the diverse and abundant expression of non-coding repeat RNAs that have features that are similar to viruses. Focusing on a panel of ovarian cancer cell line models, we find that satellite repeat RNAs have a distinct profile that is linked with an immunologically cold and invasive phenotype, which is associated with worsened outcomes. Using satellite specific anti-sense RNA technology, we can reverse this phenotype and offers a therapeutic avenue to target this viral-like cancer program.

(Summary submitted by David T. Ting, MD, Division of Hematology/Oncology, Department of Medicine, Mass General Cancer Center)

Diffuse large B-cell lymphoma is the most common subtype of non-Hodgkin lymphoma in the United States and worldwide. While approximately two-thirds of patients will be cured with first line chemotherapy, the remaining one-third will have relapsed or refractory disease and for whom the prognosis is poor using conventional therapies. The standard second line treatment for relapsed and refractory patients for decades has been intensive chemotherapy and stem cell transplantation, though this approach can be expected to cure less than one-quarter of patients in the modern era. We therefore evaluated the CAR T-cell product lisocabtagene maraleucel (liso-cel) versus standard chemotherapy and transplant as second line therapy, particularly in patients whose lymphoma progressed within 1 year of frontline chemotherapy for whom outcomes with chemotherapy and transplant are particularly poor. Liso-cel is generated by taking a patient’s own T-lymphocytes, genetically engineering them to attack the lymphoma, and infusing them back into the patient to fight their disease. Our study found liso-cel to be substantially superior to standard second-line chemotherapy with significant improvements in complete response rate, event-free survival, and progression-free survival. Liso-cel was very well tolerated and was also associated with improvement in quality of life compared to the standard of care arm. These data support the use of liso-cel as a standard second line treatment in diffuse large B-cell lymphomas and are expected to result in FDA approval of liso-cel for this indication later this year.

(Summary submitted by Jeremy S. Abramson, MD, Division of Hematology/Oncology, Department of Medicine, Mass General Cancer Center)

Cell-to-cell communication switches need to be precisely turned “off” and “on” for proper embryonic development. In an essential animal developmental pathway, called hedgehog (Hh) signaling, the final step is the entry of the transcription factor Gli (glioma associated oncogene) into the nucleus where it acts to unleash a cascade of protein production. We discover that a key pathway regulator Kif7 masquerades as DNA outside the nucleus and limits Gli nuclear entry. This strategy can be exploited to potentially “switch off” Hh signaling in cancers, where Gli is erroneously activated.

(Summary submitted by Farah Haque, PhD, Department of Molecular Biology)

Press Releases

New Data-driven Model Could Provide a Powerful Policy Planning Tool to Combat the Nation’s Opioid Crisis
Featuring Mohammad S. Jalali, PhD

Model tracks the opioid crisis over 21 years to better understand its evolving nature and guide the country’s policy response.

Novel Immunotherapy Mechanism Suppresses Breast Cancer Development
Featuring Shawn Demehri, MD, PhD

CD4+ T helper 2 cells force breast cancer cells to revert to benign breast gland cells.

The Interferon Gamma Receptor Pathway Is Necessary for CAR T-cell Mediated Killing in Solid Tumors
Featuring Marcela Maus, MD, PhD

Novel CRISPR screen revealed loss of genes in the interferon gamma receptor signaling pathway.

Opioid Analgesic Fentanyl May Cause Autism-like Behavior in Young Mice
Featuring Zhongcong Xie, MD, PhD

Research also provides new mechanistic insights into how this fentanyl-induced autism-like behavior occurs. However, there is no current evidence that fentanyl is associated with a similar effect in humans.

The Lasting Symptoms Among COVID-19 Long Haulers
Featuring Ingrid Bassett, MD, MPH, and Zeina El-Chemali, MD, MPH

Brain fog and neuropsychological effects vary in duration and cause.

Personalized Maps Created Through Artificial Intelligence May Guide Individuals to Improved Well-Being
Featuring Nancy Etcoff, PhD

Maps can be followed and tracked within a self-help app or during therapy sessions.

New Study Offers the First Evidence of Replay During Sleep in the Human Motor Cortex, Which Governs Voluntary Movement
Featuring Daniel Rubin, MD, PhD

First evidence of ‘replay’ during sleep in human motor cortex, which may play a role in how we learn and form long-term memories.

Smoking Cessation Through a Healthcare System Model Is Shown More Effective Than Telephone ‘Quitlines’ in the Short Term
Featuring Nancy Rigotti, MD

A Mass General-led study suggests that managing smoking cessation like other chronic diseases through an integrated health system approach could produce sustained results.

Which COVID-19 Vaccine Type and Timing Are Best During Pregnancy?
Featuring Andrea Edlow, MD, MSc

Study examines maternal immune responses and antibody transfer from mother to fetus for different vaccines across pregnancy trimesters.

Blog Posts

Making the Case for Adding the Kidney Emoji as an Educational Tool for Healthcare
Featuring Shuhan He, MD

Health advocates hope to gain approval for an anatomically correct kidney emoji that could be used to improve patient-provider communication.

Humans of MGRI: Emily Makowski

Emily Makowski, MS, is the communication specialist at the Ragon Institute of MGH, MIT and Harvard, which focuses on immunology and infectious disease research.

Conversations on Mental Health: Jodi Gilman, PhD & The Center for Addiction Medicine

Mass General researchers are testing how medical marijuana usage impacts mental health outcomes.

MOMi Study Seeks to Increase Inclusion of Pregnant and Lactating Women in Research
Featuring Andrea Edlow, MD, MSc

A new team research effort seeks to shed light on how mothers pass immunity to their babies during pregnancy and lactation.

Mass General Research Awards and Honors: Spring/Summer 2022

We are very excited to celebrate our researchers and the awards and honors they are given!

Congratulations to the 2022 Class of the Bridging Academia and Industry Training Program
Featuring JiaDe (Jeff) Yu, MD, Sarina Elmariah, MD, PhD, Kohei Hasegawa, MD, MPH, PhD, and Daniel Irimia, MD, PhD

The unique training course seeks to create a new culture of collaboration among researchers in academia and industry.

Part of the Solution: What It’s Like to Participate in a Clinical Research Study (Gluten Challenge) on Celiac Disease

What happens to a celiac disease patient if or when they are temporarily re-exposed to gluten? A Mass General research participant tells her story.

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Snapshot of Science for June 2022