Background There is a paucity of real-world outcome data comparing clopidogrel, prasugrel and ticagrelor in primary percutaneous coronary intervention (PPCI) for ST-segment elevation myocardial infarction (STEMI). We sought to assess the association of choice of oral P2Y12-receptor inhibitor with clinical
In utero exposure to antibiotics and risk of congenital malformations: A population-based study.
Antibiotics are commonly prescribed during pregnancy. While the safety of most penicillins are well established, some controversy and uncertainty are associated with the use of other commonly prescribed antibiotics.
Mutagenesis-based protein structure determination
Nature Genetics, Published online: 28 June 2019; doi:10.1038/s41588-019-0461-4 Genetics has played a key role in understanding the relationship between the DNA sequence encoding a protein and the protein’s three-dimensional structure. Two new studies present similar analytical approaches to predict three-dimensional
Author Correction: The role of sex in the genomics of human complex traits
Nature Reviews Genetics, Published online: 28 June 2019; doi:10.1038/s41576-019-0148-9 Author Correction: The role of sex in the genomics of human complex traits
Factors influencing long-term heart failure mortality in patients with obstructive hypertrophic cardiomyopathy in Western Sweden: probable dose-related protection from beta-blocker therapy
Objective In order to avoid effects of referral bias, we assessed risk factors for disease-related mortality in a geographical cohort of patients with hypertrophic obstructive cardiomyopathy (HOCM), and any therapy effect on survival. Methods Diagnostic databases in 10 hospitals in
Case 20-2019: A 52-Year-Old Woman with Fever and Rash after Heart Transplantation
Presentation of Case. Dr. Taylor A. Lebeis: A 52-year-old woman who had undergone orthotopic heart transplantation because of dilated cardiomyopathy was admitted to this hospital with painful red lesions on the left arm and leg. Eight years before this admission,
Nonnarcotic Methods of Pain Management
Pain is “an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or [is] described in terms of such damage” when there is no physical derangement. The function of pain is to protect the body by making
Prophylaxis Pharmacotherapy to Prevent the Onset of Post-Traumatic Brain Injury Depression: A Systematic Review
Journal of Neurotrauma, Volume 36, Issue 13, Page 2053-2064, July 1, 2019.
Heatstroke
Heatstroke is the most hazardous condition in a spectrum of illnesses progressing from heat exhaustion to heatstroke, in which a shared finding is hyperthermia (i.e. the rise in core body temperature when heat accumulation overrides heat dissipation during exercise or
Doctors’ pensions: no trust in this government
Mahase reports that doctors will be able to halve pension contributions to ease tax burden.1 I won’t hold my breath. A consultation will start at the end of June. Meanwhile, many doctors are worried…
Google’s lung cancer AI: a promising tool that needs further validation
Nature Reviews Clinical Oncology, Published online: 27 June 2019; doi:10.1038/s41571-019-0248-7 Researchers from Google AI have presented results obtained using a deep learning model for the detection of lung cancer in screening CT images. The authors report a level of performance
RAC1P29S Induces a Mesenchymal Phenotypic Switch via Serum Response Factor to Promote Melanoma Development and Therapy Resistance
RAC1P29S is a common mutation in human cutaneous melanoma. Lionarons et al. show that RAC1P29S induces a melanocytic to mesenchymal switch via an SRF/MRTF-mediated gene expression program, cooperates with BRAF in melanomagenesis, and drives BRAF inhibitor resistance, which is reversed by
Clinical and Genomic Risk to Guide the Use of Adjuvant Therapy for Breast Cancer
Clinicopathological features, including tumor size, histologic grade, and the presence of axillary lymph-node metastases, provide prognostic information about disease recurrence in women who have localized breast cancer after surgery, but these features have not been shown to be predictive of…
Case 18-2019: A 24-Year-Old Woman with a Pelvic Mass
Presentation of Case. Dr. Alexander Melamed: A 24-year-old woman was seen in the emergency department of this hospital because of a pelvic mass. The patient had been well until 4 weeks before this presentation, when she began to notice an
Routine screening of pregnant women for Zika virus in the setting of local transmission – Miami-Dade County, Florida, 2016–2017
Clinical and Genomic Risk to Guide the Use of Adjuvant Therapy for Breast Cancer
Clinicopathological features, including tumor size, histologic grade, and the presence of axillary lymph-node metastases, provide prognostic information about disease recurrence in women who have localized breast cancer after surgery, but these features have not been shown to be predictive of…
Five-Year Follow-up after Face Transplantation
To the Editor: Facial vascularized composite allograft transplantation holds the promise of restoring form and function to patients with severe facial disfigurement for whom other satisfactory treatment options are lacking. We previously reported the transplantation of full facial vascularized…
Transmitral inflow wave and progression from paroxysmal to permanent atrial fibrillation in Asian people
Objective Paroxysmal atrial fibrillation could progress to permanent atrial fibrillation. Whether the transmitral inflow waves could be used to predict progression from paroxysmal atrial fibrillation to permanent atrial fibrillation is unknown. Therefore, we investigated the association between the transmitral inflow
Procedural Volume and Outcomes for Transcatheter Aortic-Valve Replacement
Transcatheter aortic-valve replacement (TAVR) was approved in 2011 in the United States. As a condition of reimbursement, the Centers for Medicare and Medicaid Services (CMS) requires TAVR programs to perform a minimum of 20 TAVR procedures per year or 40
Nintedanib for Systemic Sclerosis–Associated Interstitial Lung Disease
Systemic sclerosis is a rare and heterogeneous autoimmune disease characterized by immune dysregulation, microvascular damage, and organ fibrosis. Interstitial lung disease (ILD) is a common manifestation of systemic sclerosis that tends to occur early in the course of disease; the
Nonbacterial Thrombotic Endocarditis
Figure 1.
A Breakdown in Metabolic Reprogramming Causes Microglia Dysfunction in Alzheimer’s Disease
Baik et al. report that amyloid-β acutely triggers microglial activation and metabolic reprogramming from OXPHOS to glycolysis. However, chronic exposure to amyloid-β induces overall metabolic defects in microglia in a model of Alzheimer’s disease. Treatment with IFN-γ restores glycolytic metabolism and
Pathogenesis and Diagnosis of Growth Hormone Deficiency in Adults
In a landmark 1962 review of growth hormone, Raben wrote, “Pituitary growth hormone is distinctive in causing growth of almost all tissues and in increasing size without advancing maturation….” Written in an era of hormone bioassays, before the introduction of
Colovesical Fistula
Figure 1.
Serious-Illness Care 2.0 — Meeting the Needs of Patients with Heart Failure
Heart failure is the most common cause of hospitalizations among elderly Americans, and despite much medical and scientific progress, it remains a source of substantial suffering, expense, and caregiver burden. Palliative care can improve quality of life, symptoms, and functioning
Heatstroke
Heatstroke is the most hazardous condition in a spectrum of illnesses progressing from heat exhaustion to heatstroke, in which a shared finding is hyperthermia (i.e. the rise in core body temperature when heat accumulation overrides heat dissipation during exercise or
Lack of Glycemic Legacy Effects in the Veterans Affairs Diabetes Trial
In randomized trials, intensive glycemic control has not resulted in lower risks of major cardiovascular events or death than standard glycemic control among patients with type 1 or type 2 diabetes during intervention periods. However, extended follow-up in some of
Intensive Glucose Control in Patients with Type 2 Diabetes — 15-Year Follow-up
Observational cohort studies have shown increasing risks of both macrovascular and microvascular events with increasing average blood glucose levels. Trials involving patients with type 1 diabetes and patients with new-onset type 2 diabetes showed that improving glucose control reduced the…
Randomized Trial of Verubecestat for Prodromal Alzheimer’s Disease
The amyloid hypothesis of Alzheimer’s disease proposes that accumulation of amyloid-beta (Aβ) in the brain triggers the spread of tau-related neurofibrillary tangles, neuroinflammation, and neuronal degeneration. Aβ is produced when amyloid precursor protein (APP) is cleaved sequentially by β-site…
The Upcoming U.S. Health Care Cost Debate — The Public’s Views
U.S. health care costs — and not merely prescription-drug prices — have risen to the top of the national agenda. More than two thirds (69%) of the U.S. public has said that reducing these costs should be a top priority
Case 20-2019: A 52-Year-Old Woman with Fever and Rash after Heart Transplantation
Presentation of Case. Dr. Taylor A. Lebeis: A 52-year-old woman who had undergone orthotopic heart transplantation because of dilated cardiomyopathy was admitted to this hospital with painful red lesions on the left arm and leg. Eight years before this admission,
Comparison of Dual Therapies for Lowering Blood Pressure in Black Africans
Increased blood pressure is the largest single contributor to the global burden of disease, leading to 10.4 million deaths in 2017. Extensive data from randomized trials have shown that lowering blood pressure reduces cardiovascular morbidity and mortality. Results from such
Non-Canonical Wnt-Signaling through Ryk Regulates the Generation of Somatostatin- and Parvalbumin-Expressing Cortical Interneurons
Non-canonical Wnt signaling through the Ryk receptor establishes regional subdomains within the MGE along the rostral-caudal axis. These subdomains are defined by graded Ryk signaling, which regulates the proportions of parvalbumin and somatostatin cortical interneurons produced during development.
Early Sedation with Dexmedetomidine in Critically Ill Patients
Sedation is a component of the care of critically ill patients who are undergoing mechanical ventilation, but the appropriate choice of a primary sedative agent remains uncertain. Propofol and midazolam, which act mainly through pathways mediated by γ-aminobutyric acid, are
Reanalysis of Clinical Exome Sequencing Data
To the Editor: The rapid accrual of knowledge in genomic medicine has prompted the reanalysis of existing data. We clinically reanalyzed data from two patient series that had undergone diagnostic proband-only exome sequencing. The exome sequences of the first series
BACH1 Orchestrates Lung Cancer Metastasis
Two studies in this issue position the stabilization of the transcription factor BACH1 as a critical node in the metastasis of lung cancer and propose two new therapeutic approaches for this leading cause of cancer-related deaths (Lignitto et al., 2019; Wiel
[Editorial] Refugee health is a crisis of our own making
Another World Refugee Day has passed, and the number of displaced people around the world is at its highest ever. The wellbeing of those fleeing their homes because of persecution, poverty, and war to seek a better life elsewhere, although
Five-Year Follow-up after Face Transplantation
To the Editor: Facial vascularized composite allograft transplantation holds the promise of restoring form and function to patients with severe facial disfigurement for whom other satisfactory treatment options are lacking. We previously reported the transplantation of full facial vascularized…
Five-Year Follow-up after Face Transplantation
To the Editor: Facial vascularized composite allograft transplantation holds the promise of restoring form and function to patients with severe facial disfigurement for whom other satisfactory treatment options are lacking. We previously reported the transplantation of full facial vascularized…
Early Sedation with Dexmedetomidine in Critically Ill Patients
Sedation is a component of the care of critically ill patients who are undergoing mechanical ventilation, but the appropriate choice of a primary sedative agent remains uncertain. Propofol and midazolam, which act mainly through pathways mediated by γ-aminobutyric acid, are
Nintedanib for Systemic Sclerosis–Associated Interstitial Lung Disease
Systemic sclerosis is a rare and heterogeneous autoimmune disease characterized by immune dysregulation, microvascular damage, and organ fibrosis. Interstitial lung disease (ILD) is a common manifestation of systemic sclerosis that tends to occur early in the course of disease; the
Invasive strep A outbreak in Essex leaves 12 people dead
A dozen people have died in Essex after an outbreak of invasive group A streptococcal (iGAS) disease.1NHS Mid Essex Clinical Commissioning Group (CCG) has reported 32 cases of iGAS to date in the…
Knowledge and global health: reducing the burden of non-communicable diseases using physical activity
In this BASRaT guided issue of BJSM, we look at how we can support healthy lifestyles for our patients, athletes and also to improve public health (figure 1). In its global action plan on physical activity (PA; 2018–2030) the WHO
Assessing the interactions between radiotherapy and antitumour immunity
Nature Reviews Clinical Oncology, Published online: 26 June 2019; doi:10.1038/s41571-019-0238-9 Despite their promise, immunotherapy–radiotherapy combinations could be limited by the patient-specific nature of radiation-induced immune responses. This Review discusses methods of assessing the immune response to radiotherapy and approaches to
Anatomy, Histology, and Nerve Density of Clitoris and Associated Structures: Clinical Applications to Vulvar Surgery
Precise understanding of structures comprising female external genitalia is essential in obstetric and gynecologic practice.
Increased baseline ECG R-R dispersion predicts improvement in systolic function after atrial fibrillation ablation
Background Atrial fibrillation (AF) is associated with left ventricular (LV) systolic dysfunction which may improve after AF ablation. We hypothesised that increased ventricular irregularity, as measured by R-R dispersion on the baseline ECG, would predict improvement in the left ventricular
[Editorial] HIV epidemics in Pakistan
The Lancet Infectious Diseases has received several letters from concerned health professionals in Pakistan about HIV epidemics that appear to have stemmed from unsanitary and unregulated medical practice, usually in isolated, rural towns. In March, 2019, Braira Wahid reported an
Thrombospondin-1 Mediates Axon Regeneration in Retinal Ganglion Cells
Here, Bray et al. used a variety of transgenic mice to demonstrate high survival and regenerative ability of one neuronal type in the retina and show several factors within these neurons, including thrombospondin-1 and syndecan-1 that confer high regenerative capacity.
Rising homelessness is public health emergency, say doctors
Doctors have expressed serious concern at increases in homelessness in the UK and the consequent harm to health, urging governments to fund better access to healthcare for homeless people.The BMA’s…
Correction: 23 Long term lead survival in adult congenital heart disease patients: a retrospective analysis using clinical correspondence data mining
Stokes A, Brigante O, Rohan K, et al 23 Long term lead survival in adult congenital heart disease patients: a retrospective analysis using clinical correspondence data mining. Heart 2018;104:A22–3. doi: 10.1136/heartjnl-2018-BCS.23. In this article the author Ozhin Brigante should have been listed as
BRAF+MEKi and ICI triplets show promise in melanoma
Nature Reviews Clinical Oncology, Published online: 25 June 2019; doi:10.1038/s41571-019-0247-8 BRAF+MEKi and ICI triplets show promise in melanoma
[Editorial] A painful path to transparency
The management of pain, particularly chronic pain, has been an ongoing challenge for many disciplines, particularly as the ongoing opioid crisis continues to be a major public health issue. With its ties with the pharmaceutical industry highlighted by a US
Author Correction: Multi-trait analysis of genome-wide association summary statistics using MTAG
Nature Genetics, Published online: 25 June 2019; doi:10.1038/s41588-019-0469-9 Author Correction: Multi-trait analysis of genome-wide association summary statistics using MTAG
A map of human individuality
Nature Reviews Genetics, Published online: 25 June 2019; doi:10.1038/s41576-019-0149-8 A study in Genome Biology reports an unbiased screen for human genomic regions at which interindividual variation in DNA methylation is consistent across cell types and tissues, providing new targets for
Evolution of the human pelvis and obstructed labor: New explanations of an old obstetrical dilemma
Without cesarean delivery, obstructed labor due to a disproportion of the fetus and the maternal birth canal can result in maternal and fetal injuries or even death. The precise frequency of obstructed labor is difficult to estimate because of the
Orbitofrontal Circuits Control Multiple Reinforcement-Learning Processes
The orbitofrontal cortex (OFC) plays a critical role in guiding decisions in dynamic environments. Groman et al. use a directionally specific viral ablation approach to demonstrate that OFC circuits encode separable reinforcement-learning processes that guide decisions.
Lupus Survival Disparities
Despite advances in treatment for systemic lupus erythematosus (SLE) that have significantly increased the disease’s 5-year survival rate, serious racial disparities in outcomes persist, according to a CDC report.
[Editorial] Efforts to tackle air pollution should focus on accountability
World Environment Day, held on June 5, 2019, emphasised that health-care providers identify improvements in air quality as a public health priority. However, is the same focus seen among other groups, such as industry, governments, and individuals? Efforts by stakeholders,
Ebola: Epidemic in DRC is one of world’s “most complex health emergencies”
bmj;365/jun25_20/l4405/FAF1faReutersFamily members and healthcare workers gather for the funeral of a baby killed by Ebola in Beni, a town in the North Kivu province of the Democratic Republic of the…
Genomics of disease risk in globally diverse populations
Nature Reviews Genetics, Published online: 24 June 2019; doi:10.1038/s41576-019-0144-0 Global genomic diversity can provide new opportunities for discovery and translation into therapies, as well as a better understanding of population disease risks. This Review considers the value of examining diverse
Defining Genetic Variation in Widely Used Congenic and Backcrossed Mouse Models Reveals Varied Regulation of Genes Important for Immune Responses
Congenic and backcrossed mouse models retain genetic content from their original parent strains, but this genetic variable often remains unknown. Chisolm et al. present alternative processing strategies for next-generation sequencing datasets to define genetic variation and find substantial differences in SJL
Deep Sequencing of Somatosensory Neurons Reveals Molecular Determinants of Intrinsic Physiological Properties
Zheng et al. defined distinct intrinsic physiological properties and transcriptome profiles of eight somatosensory neuron subtypes and further revealed subtype-specific contributions of differentially expressed potassium channels to the intrinsic membrane properties in these sensory neurons.
Dexrazoxane preferentially mitigates doxorubicin cardiotoxicity in female children with sarcoma
Objective We sought to determine how sex and dexrazoxane therapy influence cardiac remodelling in children with sarcoma receiving high-dose doxorubicin. Methods In a retrospective cohort of 85 children with sarcoma receiving high-dose doxorubicin, echocardiography measures prior to, early after (within
Cardioprotective medication adherence among patients with coronary heart disease in China: a systematic review
In China, poor cardioprotective medication adherence is a key reason for the high mortality rate of coronary heart disease (CHD). The aims of this systematic review are to (1) describe and synthesise factors that influence medication adherence among Chinese people
JMG in 2019: looking forward, looking back
The Journal of Medical Genetics (JMG) is now in its 55th year of publication. In that time, both medical genetics and scientific publishing have changed almost beyond recognition. In 1964, it would have seemed inconceivable that when there was a
Fighting loneliness with architecture, agencies, and activities
Make no mistake: loneliness is a killer.12 In our systematic review, depression was the most strongly evidenced consequence for mental health, but many other disorders could contribute to the higher…
Can Statins be Protagonists in Our Approach to Cancer Treatment?
No abstract available
First Stage of Labor Progression in Women with Large-for-Gestational Age Infants
Women with suspected large-for-gestational age (LGA) fetuses have higher rates of dysfunctional labor and labor arrest diagnoses, and consequently higher rates of cesarean deliveries. Identifying factors that significantly affect labor progression of women with LGA infants may better inform expected
The influence of frailty under direct oral anticoagulant use in patients with atrial fibrillation
Background Frailty is a prognostic factor in patients with atrial fibrillation (AF). However, there is no report on the associations between frailty and clinical adverse events in patients with AF taking direct oral anticoagulants (DOAC). The factors related to the
IL-6-PAD4 axis in the earliest phase of arthritis in knock-in gp130F759 mice, a model for rheumatoid arthritis
Objective Animal models for human diseases are especially valuable for clarifying molecular mechanisms before or around the onset. As a model for rheumatoid arthritis (RA), we utilise knock-in mice gp130F759. They have a Y759F mutation in gp130, a common receptor
Frequency of spontaneous resolution of vasa previa with advancing gestational age
Vasa previa is a serious obstetric complication that can result in fetal hemorrhage and demise upon spontaneous labor. Suggested management for vasa previa is elective hospitalization and caesarean delivery prior to spontaneous labor. There is little reported evidence of the
Echocardiographic subtypes of heart failure in consecutive hospitalised patients with dyspnoea
Heart failure with preserved ejection fraction (HFpEF) involves half of hospitalised patients with heart failure (HF), but estimates vary due to unclear diagnostic criteria. We performed a prospective observational study of hospitalised patients admitted with dyspnoea. The aim was to
Severe adverse events following benzathine penicillin G injection for rheumatic heart disease prophylaxis: cardiac compromise more likely than anaphylaxis
Objective Secondary prophylaxis through long-term antibiotic administration is essential to prevent the progression of acute rheumatic fever to rheumatic heart disease (RHD). Benzathine penicillin G (BPG) has been shown to be the most efficacious antibiotic for this purpose; however, adverse
Refining the management of acute coronary and aortic syndromes
Social media addiction: technological deȷa vu
Zendle and Bowden-Jones are correct about the methodological shortcomings of research that aims to understand the effects of social media.12 But these observations also apply to related research that…
Highlights from this issue
Prevalence and causes of vision loss in North Africa and Middle East in 2015: Magnitude, temporal trends, and projections (see page 863) The age-standardised prevalence of vision impairment for all ages and genders decreased from 1990 to 2015 in NAME.
Single-Cell Transcriptomic Analyses of Cell Fate Transitions during Human Cardiac Reprogramming
Zhou et al. performed single-cell RNA sequencing to unravel molecular features of human cardiac reprogramming. They identified a “decision” point where cells either reprogram or regress to initial fate. Further, progression of reprogramming was quantitatively assessed by their developed “cell fate
Two-dose versus single-dose methotrexate for treatment of ectopic pregnancy
Single-Cell RNA Sequencing of the T Helper Cell Response to House Dust Mites Defines a Distinct Gene Expression Signature in Airway Th2 Cells
Th2 cells play a pathogenic role in allergies such as asthma, yet a clear picture of their transcriptional profile in this setting is lacking. Tibbitt, Stark, et al. elucidate a distinct gene expression signature in Th2 cells responding to house dust
Correction: Clinical and cost-effectiveness of the Ross procedure versus conventional aortic valve replacement in young adults
Effects of heat stroke on surface ECG: a study on clinical outcomes
Aims Classic heat stroke is associated with high in-hospital mortality and morbidity. The relation between the ECG findings in heat stroke and the clinical outcomes of these patients has not been studied. The aim of this study was to describe
Ultra-Processed Food and Obesity: The Pitfalls of Extrapolation from Short Studies
In the short term, eating behavior and body weight may be influenced by many behavioral, psychological, and environmental factors, such as room temperature, social interactions, food appearance, portion size, and more. However, research demonstrates that biology exerts dominant control over
The Autism-Associated Gene Scn2a Contributes to Dendritic Excitability and Synaptic Function in the Prefrontal Cortex
Haploinsufficiency in the gene SCN2A, which encodes the sodium channel NaV1.2, has strong autism association. Spratt et al. show that Scn2a contributes to dendritic excitability in mature neocortical pyramidal cells, where its loss impairs excitatory synaptic function and plasticity.
Glia Accumulate Evidence that Actions Are Futile and Suppress Unsuccessful Behavior
Whole-brain imaging in virtual-reality-immersed zebrafish reveals that failed swim attempts are detected by noradrenergic neurons, which drive glial cells that accumulate calcium until they trigger the suppression of further futile attempts.
[Editorial] Stonewall: 50 years of fighting for their lives
A single image survives of the early morning hours of June 28, 1969. The grainy black and white photograph is a juxtaposition: a macramé vest, eyes wide, the sheen of sweat on young faces, the officers’ crisp uniforms, the glint
[Editorial] Seeing the whole picture of postpartum depression
This past May, the American Psychiatric Association (APA) convened for its annual meeting, with the theme “Disrupt, Include, Engage & Innovate”. During the 4-day event, no fewer than 28 sessions were dedicated to collaborative care models for mental health, making
Satisfaction with hospital care falls as pressure mounts on NHS, finds CQC
Satisfaction among hospital patients in England has stalled or fallen across many key indicators, show the results of a survey by the Care Quality Commission.The healthcare sector regulator’s annual…
Emerging patterns in clonal haematopoiesis
Clonal haematopoiesis (CH) is defined by the presence of acquired mutations and/or cytogenetic abnormalities in haematopoietic cells. By definition, these premalignant clones do not meet criteria for haematopoietic neoplasms listed in the Revised Fourth Edition of the WHO classification. CH
Randomized comparison of a reduced-visit prenatal care model enhanced with remote monitoring
Standard prenatal care, consisting of 12 – 14 visits per pregnancy, is expensive and resource intensive, with limited evidence supporting the structure, rhythm, or components of care. Some studies suggest a reduced-frequency prenatal care model is as safe as the
The Intestine Harbors Functionally Distinct Homeostatic Tissue-Resident and Inflammatory Th17 Cells
The distinctions between inflammatory Th17 cells elicited by pathogens and tissue-resident homeostatic Th17 cells elicited by commensals are unclear. Omenetti et al. show that tissue-resident Th17 cells, in contrast to pathogen-elicited Th17 cells, exhibit little plasticity towards inflammatory cytokines, show muted
NHS chief admits that bed closures need to be reversed
The NHS will need to increase the number of acute hospital beds over the next five years to meet the growing needs of the population, the head of NHS England has said.In his keynote speech to the NHS…
Highlights from this issue
Global health: tuberculosisDiagnosis Though the WHO endorsed gold standard for diagnosing tuberculosis in all age groups is positive microbiology, this is notoriously difficult to achieve in children. If all else fails and the infrastructure allows, bronchoscopy is an option, but
Highlights from this issue
Automated FiO2 adjustment In an issue bursting with great content the Editor’s choice this month is closed-loop automated FiO2 control. The potential for this technology to improve clinical outcomes of high-risk preterm infants is obvious and most manufacturers are working
New daratumumab quadruplets and triplets for newly diagnosed MM
Nature Reviews Clinical Oncology, Published online: 18 June 2019; doi:10.1038/s41571-019-0244-y New daratumumab quadruplets and triplets for newly diagnosed MM
Reproductive Services for Women at High Risk for Maternal Mortality Workshop
[Editorial] Celebrating uniqueness in endocrinology and sport
The first modern Olympic Games, held in Athens, Greece, in 1896, featured no female athletes. The games’ founder, Pierre de Coubertin, felt their participation would not be appropriate: “No matter how toughened a sportswoman may be, her organism is not
Unusual Physiological Properties of Smooth Monostratified Ganglion Cell Types in Primate Retina
Rhoades et al. find the smooth monostratified retinal ganglion cells in the primate retina have unusual receptive fields consisting of multiple hotspots. This differs from classic center-surround receptive field models and suggests a role in nonlinear visual computation.
Vaccine Reduces Pneumonia in Kenya
Introduction of the 10-valent pneumococcal conjugate vaccine (PCV10) resulted in sharply reduced pneumonia cases in Kenya, according to a report from an international team of researchers.
US suicide rates in young people are highest since 2000
Suicide rates among young people in the US have increased to their highest since 2000, new figures show.1Researchers from Harvard Medical School analysed data from the Centers for Disease Control and…
Tinkering in the garage — tuning CARs for safety
Nature Reviews Clinical Oncology, Published online: 17 June 2019; doi:10.1038/s41571-019-0240-2 The adoptive transfer of T cells expressing a chimeric antigen receptor (CAR) is an effective therapy for patients with relapsed or refractory CD19+ B cell malignancies, but can cause life-threatening
Recessive gene disruptions in autism spectrum disorder
Nature Genetics, Published online: 17 June 2019; doi:10.1038/s41588-019-0433-8 Analysis of whole-exome sequencing data from 2,343 individuals with autism spectrum disorder compared to 5,852 unaffected individuals demonstrates an excess of biallelic, autosomal mutations for both loss-of-function and damaging missense variants.
A trip down memory lane
Nature Reviews Genetics, Published online: 17 June 2019; doi:10.1038/s41576-019-0147-x Reporting in Cell, two groups now show that parental responses to the environment are passed to their offspring by small RNAs.
High-Frequency Activation of Nucleus Accumbens D1-MSNs Drives Excitatory Potentiation on D2-MSNs
Reward outcomes depend on the stimulation protocol used to activate nucleus accumbens medium spiny neuron (MSN) subtypes. In this issue of Neuron, Francis et al. demonstrate rebalanced MSN subtype excitation driven by high-frequency stimulation and substance P release.
Doctors alleging sexism at BMA welcome appointment of QC to lead review
A leading employment lawyer who specialises in discrimination has been appointed to lead an independent review of sexism in the BMA, which will begin this month and publish recommendations later this…
Cancer treatment and survivorship statistics, 2019
Abstract The number of cancer survivors continues to increase in the United States because of the growth and aging of the population as well as advances in early detection and treatment. To assist the public health community in better serving
Pharmacokinetics of Vaginal Progesterone in Pregnancy
Characterization of pharmacokinetics (PK) is lacking for vaginal progesterone in pregnancy. Dosing of vaginal progesterone for preterm birth prevention has been empirical. Due to pregnancy-related changes in vaginal and uterine blood flow, hepatic metabolism, renal clearance, and endogenously elevated serum
Creating headspace for integrated youth mental health care
The Fetal Origins of Mental Illness
The impact of infections and inflammation during pregnancy on the developing fetal brain remains incompletely defined with important clinical and research gaps. Though the classic infectious TORCH pathogens [i.e. Toxoplasma gondii, rubella virus, cytomegalovirus (CMV), herpes simplex virus] are known
Center for Thrombosis and Hemostasis MainzFostering and integrating interdisciplinary academic research and patient care for a decade now
James Fraser Taylor
bmj;365/jun14_10/l4227/FAF1faHaving experienced six years of general practice in Aberdeen, James Fraser Taylkor (“Jim”) took up a career in industrial medicine. He was to become chief medical officer…
Sport and exercise medicine: bringing you up to date
Welcome to the 2019 British Association of Sport & Exercise Medicine (BASEM) issue of the British Journal of Sports Medicine. Bringing this issue together has been an enjoyable experience allowing us as editors to peruse topics in the spotlight for
Heartbeat: impact of suboptimal response to primary prevention statin therapy
A key element in primary prevention of cardiovascular disease (CVD) is the use of statin therapy to lower low-density lipoprotein cholesterol (LDL-C) levels in people at increased risk of CVD with many guidelines recommending a fixed statin dose for each
Screening for and management of comorbidities after a nurse-led program: results of a 3-year longitudinal study in 769 established rheumatoid arthritis patients
Background/purpose Cardiovascular (CV) risk, cancer, infections and osteoporosis should be screened for in rheumatoid arthritis (RA). The objective was to assess 3-year effects of a nurse visit for comorbidity counselling. Methods This was an open long-term (3 years) extension of
Induction chemotherapy improves efficacy
Nature Reviews Clinical Oncology, Published online: 13 June 2019; doi:10.1038/s41571-019-0242-0 Induction chemotherapy improves efficacy
Antibody Conditioning Enables MHC-Mismatched Hematopoietic Stem Cell Transplants and Organ Graft Tolerance
Treatment of hematological disorders via donor cell transplantation requires harsh and non-specific conditioning protocols. George et al. report an antibody-based conditioning protocol for HSC engraftment that does not require chemotherapy or irradiation and allows robust hematopoietic reconstitution even with fully mismatched
Author Correction: Genome sequencing and population genomic analyses provide insights into the adaptive landscape of silver birch
Nature Genetics, Published online: 13 June 2019; doi:10.1038/s41588-019-0442-7 Author Correction: Genome sequencing and population genomic analyses provide insights into the adaptive landscape of silver birch
The HVEM-BTLA Axis Restrains T Cell Help to Germinal Center B Cells and Functions as a Cell-Extrinsic Suppressor in Lymphomagenesis
HVEM is one of the most frequently mutated surface proteins in germinal-center-derived B cell lymphomas. Mintz et al. find that T cell help is restrained by the interaction between HVEM on B cells and BTLA on T follicular helper cells. Loss of
Cardiovascular outcomes of early versus delayed coronary intervention in low to intermediate-risk patients with STEMI in Thailand: a randomised trial
Background The benefit of an early coronary intervention after streptokinase (SK) therapy in low to intermediate-risk patients with ST-elevation myocardial infarction (STEMI) still remains uncertain. The current study aimed to evaluate the cardiovascular outcomes of early versus delayed coronary intervention
Transient Receptor Potential V Channels Are Essential for Glucose Sensing by Aldolase and AMPK
Falling levels of glucose, and consequentially fructose-1,6-bisphosphate (FBP), are sensed by glycolytic enzyme aldolase. Li et al. demonstrate that FBP-unoccupied aldolase binds to and inhibits ER-localized TRPV channels, with the decreased calcium at the ER-lysosome contact enabling the channel proteins to
A Discrete Dorsal Raphe to Basal Amygdala 5-HT Circuit Calibrates Aversive Memory
Sengupta and Holmes use in vivo imaging, optogenetic, electrophysiological, and histological approaches to investigate the circuit-specific role of the DRN→BA 5-HT pathway in fear learning. They show this pathway is uniquely positioned, functionally and anatomically, to shape fear memory.
Fc Characteristics Mediate Selective Placental Transfer of IgG in HIV-Infected Women
The impaired transfer of maternal IgG from HIV-infected mothers to their infants is associated with altered binding to Fc receptors FcγRIIa and FcγRIIIa as well as glycan modifications in the Fc region.
[Editorial] The devastating impact of Trump’s global gag rule
About 56 million abortions are done annually, and almost half (25 million) are unsafe, of which 97% occur in developing countries. An estimated 8% of all maternal deaths are due to abortion, leaving a massive unmet global need for access
Alan Stevens: diagnostic histopathologist and author of prizewinning textbooks
bmj;365/jun13_15/l4172/FAF1faPhoto credit: James LoweAlan Stevens (called “Steve” by his friends and colleagues) was born in Chesterfield to Ivy (a milliner) and Herman (an accountant). He soon shone…
Case-control investigation of occupational lead exposure and kidney cancer
Objectives Lead is a suspected carcinogen that has been inconsistently associated with kidney cancer. To clarify this relationship, we conducted an analysis of occupational lead exposure within a population-based study of kidney cancer using detailed exposure assessment methods. Methods Study
Correction: Comparison of fingolimod, dimethyl fumarate and teriflunomide for multiple sclerosis
Kalincik T, Kubala Havrdova E, Horakova D, et al. Comparison of fingolimod, dimethyl fumarate and teriflunomide for multiple sclerosis. J Neurol Neurosurg Psychiatry 2019;90:458–68. Under heading Fingolimod vs teriflunomide: “(HR 0.77, 95% CI 0.63 to 0.95, p=0.03; figure 3C)” should
Highlights from this issue
In recent months the Triumvirate have indulged their guilty pleasures of musicals and sitcoms. This month they get serious – the theme is “works of art”. Tracey Emin’s Bed “My Bed”, by young British artist Tracey Emin was first exhibited
The changing therapeutic landscape of head and neck cancer
Nature Reviews Clinical Oncology, Published online: 12 June 2019; doi:10.1038/s41571-019-0227-z The authors of this Review discuss treatments currently available for patients with head and neck squamous cell carcinomas (focusing in those of the oral cavity, oropharynx, hypopharynx and larynx). Advances
Vasa Previa: A multicenter retrospective cohort study
To describe the characteristics and outcomes of patients with antenatal diagnosis of vasa previa and evaluate the predictive factors of resolution in a contemporary large multicenter dataset
A VTA GABAergic Neural Circuit Mediates Visually Evoked Innate Defensive Responses
Zhou et al. identified a neural circuit related to VTAGABA+ neurons that mediates visually evoked innate defensive responses, involving the SCGlut+- VTAGABA+-CeA pathway.
[Editorial] A focus on patient outcomes in cervical myelopathy
Cervical myelopathy, also known as cervical spondylotic myelopathy, is a common spinal cord disorder. The disease can reduce quality of life similarly to diabetes or cancer, but data on its prevalence and incidence are scarce. Myelopathy is a progressive condition
NHS negligence pay-out to boy with brain damage could reach {pound}26m
The NHS has agreed to a clinical negligence pay-out that could total £26m (€29.2m; $33m) for failings at the birth of a boy who will “forever remain a child.”That total, one of the highest NHS…
To DAPSA or not to DAPSA? That is not the question
In a recent publication in the Annals of the Rheumatic Diseases, van Mens et al have provided an analysis of different criteria for assessment of remission and low disease activity (LDA) in psoriatic arthritis (PsA).1 We would like to congratulate the
Glucocorticoid withdrawal in systemic lupus erythematosus: are remission and low disease activity reliable starting points for stopping treatment? A real-life experience
Objectives To evaluate the proportion of patients who have successfully withdrawn glucocorticoids (GCs) in a longitudinal cohort of patients with systemic lupus erythematosus (SLE) over a period of 6 years; to evaluate patient characteristics during GC withdrawal in relation to
A Subset of Skin Macrophages Contributes to the Surveillance and Regeneration of Local Nerves
Macrophages perform a wide variety of functions in mammalian tissues. Kolter and colleagues provide a map of dermal macrophages in mouse skin and identify a subset of embryonic macrophages that populates sensory nerve fibers. These self-maintaining macrophages actively patrol axons
Somatic genetic rescue in Mendelian haematopoietic diseases
Nature Reviews Genetics, Published online: 11 June 2019; doi:10.1038/s41576-019-0139-x Somatic genetic rescue (SGR) occurs when an acquired somatic mutation counteracts the effects of a germline mutation at a cellular level. The increasing number of SGR events reported for Mendelian haematopoietic
Cerebellar Contribution to Preparatory Activity in Motor Neocortex
Chabrol et al. show that the cerebellum is directly involved in maintaining preparatory activity in the premotor neocortex during learned, goal-directed behavior. Their results suggest the cerebellum provides a learned timing signal required for motor preparation in the neocortex.
Acute Flaccid Myelitis Cluster
A cluster of 6 cases of acute flaccid myelitis paralysis (AFM) in children was reported in Minnesota in the fall of 2018, according to a CDC report. It was the largest cluster reported in the state to date and part
Ohio doctor is charged with 25 counts of murder over patients’ deaths
An intensive care physician in Columbus, Ohio, has been charged with 25 counts of murder, accused of prescribing lethal doses of fentanyl to critically ill patients in his care.William Husel, 43,…
Should we offer elective induction of labor to nulliparous women at 39 weeks?
Mutation of a histidine-rich calcium-binding-protein gene in wheat confers resistance to Fusarium head blight
Nature Genetics, Published online: 10 June 2019; doi:10.1038/s41588-019-0426-7 Genetic mapping and functional studies show that mutation of a histidine-rich calcium-binding-protein gene at the Fhb1 locus confers resistance to Fusarium head blight in wheat. Notably, transgenic plants expressing the R allele
Paraventricular Thalamus Projection Neurons Integrate Cortical and Hypothalamic Signals for Cue-Reward Processing
The paraventricular nucleus of the thalamus is a substrate underlying reward seeking. Otis, Zhu, et al. demonstrate that projection-defined thalamic neurons are controlled by dissociable response features in cortical and hypothalamic inputs during reward processing.
Comprehensive Integration of Single-Cell Data
A computational approach to integrate diverse modalities associated with single-cell sequencing datasets can be used to better understand cellular identity and function.
Our choices
Many scientific journals these days have taken to designating a particularly intriguing, important or extremely well done paper that appears in that month’s issue. At the EMJ, we actually have several such papers, and I was thinking that perhaps our
Sixty seconds on . . . prostate cancer screening
Uh oh, there’s that “S” word again . . .Screening is often a controversial topic within medicine, and a new £5bn (€5.6bn; $6.3bn) trial offering magnetic resonance imaging (MRI) scans to test…
Highlights from this issue
Click here to listen to the Podcast
Care of adolescents and young adults with cancer in Asia: results of an ESMO/SIOPE/SIOP Asia survey
Background Adolescents and young adults (AYAs) with cancer require dedicated management encompassing both adult and paediatric cancer services. Following a European survey, the European Society for Medical Oncology, the European Society for Paediatric Oncology and the Asian continental branch of
Cystoscopy at the time of benign hysterectomy: A decision analysis
Nitric oxide discovery Nobel Prize winnersRobert F. Furchgott, Louis J. Ignarro, and Ferid Murad shared the Noble Prize in 1998 for their discoveries concerning nitric oxide as a signalling molecule in the cardiovascular system
Stem cell treatment: FDA court victory opens way to regulation in US
Companies that offer treatments in the US that are based on mesenchymal stem cells derived from human fat are likely to face effective regulation by the Food and Drug Administration for the first…
John Lennard-Jones 1927-2019: physician and gastroenterologist
Professor John Lennard-Jones, affectionately known by his colleagues as ‘LJ’, was an exceptional man; a caring and astute physician, a gentle but inspirational teacher and a prodigious clinical researcher. His clinical judgements were always well considered and invariably correct. He
Harnessing Hematopoietic Stem Cell Low Intracellular Calcium Improves Their Maintenance In Vitro
Maintenance of blood stem cells in vitro remains challenging. Snoeck and colleagues show that blood stem cells are endowed with low intracellular calcium and that culture in low-calcium media enhances their maintenance, among others, through stabilization of TET enzymes, which are
Genetic correlations of polygenic disease traits: from theory to practice
Nature Reviews Genetics, Published online: 06 June 2019; doi:10.1038/s41576-019-0137-z In this Review, van Rheenen et al. outline how improved methodologies have enabled genetic correlations to be estimated for almost any trait pair. Genetic correlations can improve our understanding of the
Sleep Regulation by Neurotensinergic Neurons in a Thalamo-Amygdala Circuit
Using a three-step approach for systematic screening, Ma et al. identified GABAergic neurons in CeA and glutamatergic neurons in the posterior thalamus that promote NREM sleep. Each population uses both the NTS peptide and a classical neurotransmitter to promote sleep.
A Small Molecule Targeting Mutagenic Translesion Synthesis Improves Chemotherapy
A small molecule specifically targeting the mutagenic branch of translesion synthesis binds a nearly featureless surface of REV1 to induce dimerization and block recruitment of POL ζ.
[Editorial] ICD-11
The International Classification of Diseases (ICD) is a health statistics coding tool that aims to describe an entity that is challenging to quantify and even more problematic to standardise—the human condition. The history of ICD dates back to 16th century
[Editorial] The lost boys
The gravity of gender inequality seems to have, at last, reached all sectors of society. A watershed on dangerously permissive attitudes to sexual assaults, outrage at gender-oriented discrimination, and a refusal to accept socially constructed gender roles are aired daily
Abortion: US “global gag rule” is killing women and girls, says report
A US government policy that blocks federal funding for non-governmental organisations that provide or support abortion is killing women, a new report says, because they are being excluded from a…
Exercise-based cardiac rehabilitation for stable angina: systematic review and meta-analysis
Objective A systematic review was undertaken to assess the effects of exercise-based cardiac rehabilitation (CR) for patients with stable angina. Methods Databases (Cochrane Central Register of Controlled Trials, MEDLINE, Embase and CINAHL) were searched up to October 2017, without language
Finger necrosis with eosinophilia and symmetrical occlusion of the peripheral artery
Case presentation A 59-year-old man with hypertension, dyslipidemia and a current smoking history had presented with bilateral painful finger ulcers (figure 1A). The patient was referred to our hospital for the diagnosis and treatment. On his arrival, his fingers showed
GP who stole {pound}25 000 after receiving unexpectedly large tax bill is spared ȷail
A GP who stole £25 000 after receiving an unexpected £90 000 tax bill and then falsified accounts to cover his tracks has been spared jail because strong mitigating circumstances persuaded the judge…
Analysis of the risk of ovarian torsion in 49 consecutive pediatric patients treated at a single institution
Purpose An early diagnosis of ovarian torsion is sometimes difficult due to variable clinical symptoms and non-specific imaging findings. We retrospectively reviewed patients with pediatric ovarian masses manifesting torsion. Methods Fifty-eight ovarian masses (55 episodes) in 49 non-neonatal patients treated
Multimodality imaging in carcinoid heart disease
Neuroendocrine neoplasms arise from the gastrointestinal tract and can lead to carcinoid syndrome. Carcinoid heart disease affects more than half of these patients and is the initial presentation of carcinoid syndrome in up to 20 % of patients. Carcinoid heart
Maternal drug-related death and suicide are leading causes of post-partum death in California
Reducing maternal mortality is a priority in the U.S. and worldwide. Drug-related deaths and suicide may account for a substantial and growing portion of maternal deaths, yet information on the incidence of and sociodemographic variation in these deaths is scarce.
Inflammasome Regulates Hematopoiesis through Cleavage of the Master Erythroid Transcription Factor GATA1
Chronic inflammatory diseases are associated to altered hematopoiesis that could result in neutrophilia and anemia. In this issue of Immunity, Tyrkalska et al. (2019) provide evidence of an evolutionarily conserved mechanism by which inflammasome regulates the erythroid/myeloid decision in HSC, which
Non-vitamin K antagonist oral anticoagulants in adults with a Fontan circulation: are they safe
Background In Fontan patients with atrial arrhythmias (AA), non-vitamin K antagonist oral anticoagulants(NOACs) have a class III recommendation according to the Pediatric & Congenital Electrophysiology Society (PACES)/Heart Rhythm Society (HRS) guideline in 2014, due to lack of data on outcomes
Spontaneous and Stimulus-Evoked Respiratory Rate Elevation Corresponds to Development of Allodynia in Spinal Cord–Injured Rats
Journal of Neurotrauma, Volume 36, Issue 12, Page 1909-1922, June 15, 2019.
Regional Heterogeneity in Gene Expression, Regulation, and Coherence in the Frontal Cortex and Hippocampus across Development and Schizophrenia
Collado-Torres et al. describe the BrainSeq Phase II gene expression resource encompassing two brain regions from 551 genotyped individuals spanning the entire human lifespan (286 with schizophrenia). This resource can answer region-specific questions about development and schizophrenia and its genetic risk.
JAMA
Lung cancer: audit shows improvement in surgery survival
Significantly more patients are undergoing surgery for lung cancer, and survival rates are improving, shows a new report that analysed progress over the past 35 years.1The report by the Society for…
Tumour-associated neutrophils in patients with cancer
Nature Reviews Clinical Oncology, Published online: 03 June 2019; doi:10.1038/s41571-019-0222-4 Neutrophils accumulate in the circulation of patients with cancer, and the neutrophil-to-lymphocyte ratio is a widely used biomarker. However, the effects of neutrophils on tumour development and progression, and the
Publisher Correction: Molecular and functional variation in iPSC-derived sensory neurons
Nature Genetics, Published online: 03 June 2019; doi:10.1038/s41588-019-0445-4 Publisher Correction: Molecular and functional variation in iPSC-derived sensory neurons
Chromatin-associated RNAs as facilitators of functional genomic interactions
Nature Reviews Genetics, Published online: 03 June 2019; doi:10.1038/s41576-019-0135-1 Enabled by genome-wide profiling approaches, there is growing appreciation for the prevalence and functional importance of various types of chromatin-associated RNAs. As Li and Fu describe in this Review, these RNAs
[Editorial] Global alcohol targets unlikely to be met
Global targets for the reduction of harmful use of alcohol are unlikely to be met, according to a modelling study published in The Lancet. Global per-head consumption increased from 5·9 L in 1990 to 6·5 L in 2017, with the
A Systematic Review of Closed Head Injury Models of Mild Traumatic Brain Injury in Mice and Rats
Journal of Neurotrauma, Volume 36, Issue 11, Page 1683-1706, June 2019.
Accurate Estimation of Neural Population Dynamics without Spike Sorting
Trautmann et al. ask whether spike sorting is necessary for investigation at the level of neural populations. They show that combining multiple neurons on each electrode introduces only minor distortions in estimates of neural population state.
Global Burden of Diseases, Injuries, and Risk Factors in Child and Adolescent Health, 1990 to 2017
This analysis of the Global Disease Burden data estimates mortality and morbidity in children and adolescents from 1990 to 2017 by age and sex in 195 countries and territories worldwide.
E-cigarettes: Indian government research council recommends “complete prohibition”
The Indian Council of Medical Research, part of the government’s department of health, has recommended a complete prohibition on e-cigarettes, citing their highly addictive and harmful ingredients…
Bempegaldesleukin Stimulates Immune Response [News in Brief]
In two clinical trials, the CD122-preferential IL2 pathway agonist bempegaldesleukin increased proliferation and activation of tumor-infiltrating lymphocytes in patients with solid tumors. Despite the lack of response to the agent as a monotherapy in the first-in-human trial, patients with metastatic
Screw osteosynthesis of transverse fracture of the patella in children
Objective Patella fractures in children are rare, with an incidence of less than 1% of all pediatric fractures. Literature describes different surgical techniques and outcomes, but there is not a specified superior technique for children. The aim of this study
Placental Bed Research: 1. The Placental Bed. From Spiral Arteries Remodeling to the Great Obstetrical Syndromes
The term ‘placental bed’ was coined to describe the maternal-fetal interface, i.e. the area where the placenta attaches itself to the uterus. Appropriate vascularization of this area is of vital importance for the development of the fetus; this is why
The UK National Amyloidosis CentreThe National Amyloidosis Centre at the Royal Free Hospital and University College London is the world’s largest amyloidosis centre with almost 1500 patient referrals annually
The National Amyloidosis Centre (NAC) is a wholly integrated clinic and research facility located in the Royal Free Hospital and University College London (UCL). The NAC has been at the cutting edge of research and treatment into all aspects of
Illuminating G-Protein-Coupling Selectivity of GPCRs
A large-scale functional interaction study reveals how GPCRs engage with subsets of G(alpha) proteins and outlines characteristic predictive of these associations.
From the EACR–ESMO liquid biopsy meeting
Nature Reviews Clinical Oncology, Published online: 31 May 2019; doi:10.1038/s41571-019-0237-x From the EACR–ESMO liquid biopsy meeting
Expanding the single-cell genomics toolkit
Nature Genetics, Published online: 31 May 2019; doi:10.1038/s41588-019-0429-4 Epigenetic heterogeneity underlies the diversity of cell states found in health and disease. A new study presents a method for profiling of histone modifications in single cells and applies it to identify
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