tbuckley/cabot-search huggingface dataset:
Hepatocyte Nuclear Factor 4‐Alpha Is Essential for the Active Epigenetic State at Enhancers in Mouse Liver
Authors: Avinash Thakur, Jasper C.H. Wong, Evan Y. Wang, Jeremy Lotto, Donghwan Kim, Jung‐Chien Cheng, Matthew Mingay, Rebecca Cullum, Vaishali Moudgil, Nafeel Ahmed, Shu‐Huei Tsai, Wei Wei, Colum P. Walsh, Tabea Stephan, Misha Bilenky, Bettina M. Fuglerud, Mohammad M. Karimi, Frank J. Gonzalez, Martin Hirst, Pamela A. Hoodless
Journal: Hepatology (2019)

Cell‐fate determination is influenced by interactions between master transcription factors (TFs) and cis‐regulatory elements. Hepatocyte nuclear factor 4 alpha (HNF4A), a liver‐enriched TF, acts as a master controller in specification of hepatic progenitor cells by regulating a network of TFs to control onset of hepatocyte cell fate. Using analysis of genome‐wide histone modifications, DNA methylation, and hydroxymethylation in mouse hepatocytes, we show that HNF4A occupies active enhancers in hepatocytes and is essential for active histone and DNA signatures, especially acetylation of lysine 27 of histone 3 (H3K27ac) and 5‐hydroxymethylcytosine (5hmC). In mice lacking HNF4A protein in hepatocytes, we observed a decrease in both H3K27ac and hydroxymethylation at regions bound by HNF4A. Mechanistically, HNF4A‐associated hydroxymethylation (5hmC) requires its interaction with ten‐eleven translocation methylcytosine dioxygenase 3 (TET3), a protein responsible for oxidation from 5mC to 5hmC. Furthermore, HNF4A regulates TET3 expression in liver by directly binding to an enhancer region. Conclusion : In conclusion, we identified that HNF4A is required for the active epigenetic state at enhancers that amplifies transcription of genes in hepatocytes.
Treatment-Related Complications of Systemic Therapy and Radiotherapy
Authors: Vikram Jairam, Victor Lee, Henry S. Park, Charles R. Thomas, Edward R. Melnick, Cary P. Gross, Carolyn J. Presley, Kerin B. Adelson, James B. Yu
Journal: JAMA Oncology (2019)

Systemic therapy and radiotherapy can be associated with acute complications that may require emergent care. However, there are limited data characterizing complications and the financial burden of cancer therapy that are treated in emergency departments (EDs) in the United States.To estimate the incidence of treatment-related complications of systemic therapy or radiotherapy, examine factors associated with inpatient admission, and investigate the overall financial burden.A retrospective analysis of the Healthcare Cost and Utilization Project Nationwide Emergency Department Sample was performed. Between January 2006 and December 2015, there was a weighted total of 1.3 billion ED visits; of these, 1.5 million were related to a complication of systemic therapy or radiotherapy for cancer. Data analysis was conducted from February 22 to December 23, 2018. External cause of injury codes, Clinical Classifications Software, International Classification of Diseases, Ninth Revision, Clinical Modification, and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10), Clinical Modification codes were used to identify patients with complications of systemic therapy or radiotherapy.Patterns in treatment-related complications, patient- and hospital-related factors associated with inpatient admission, and median and total charges for treatment-related complications were the main outcomes.Of the 1.5 million ED visits included in the analysis, 53.2% of patients were female and mean age was 63.3 years. Treatment-related ED visits increased by a rate of 10.8% per year compared with 2.0% for overall ED visits. Among ED visits, 90.9% resulted in inpatient admission to the hospital and 4.9% resulted in death during hospitalization. Neutropenia (136 167 [8.9%]), sepsis (128 171 [8.4%]), and anemia (117 557 [7.7%]) were both the most common and costliest (neutropenia: $5.52 billion; sepsis: $11.21 billion; and anemia: $6.78 billion) complications diagnosed on presentation to EDs; sepsis (odds ratio [OR], 21.00; 95% CI, 14.61-30.20), pneumonia (OR, 9.73; 95% CI, 8.08-11.73), and acute kidney injury (OR, 9.60; 95% CI, 7.77-11.85) were associated with inpatient admission. Costs related to the top 10 most common complications totaled $38 billion and comprised 48% of the total financial burden of the study cohort.Emergency department visits for complications of systemic therapy or radiotherapy increased at a 5.5-fold higher rate over 10 years compared with overall ED visits. Neutropenia, sepsis, and anemia appear to be the most common complications; sepsis, pneumonia, and acute kidney injury appear to be associated with the highest rates of inpatient admission. These complications suggest that significant charges are incurred on ED visits.
GPs must pass on patients’ advance treatment decisions to hospitals, says judge
Authors: Clare Dyer
Journal: BMJ (2019)

A High Court judge has told GPs that if they have in their files an advance decision on treatment made by a patient before losing capacity, they must pass it on to any hospital treating the patient.1

Mr Justice Hayden gave the warning when ruling that a patient in a persistent vegetative state who had been kept alive for three years, despite an advance decision refusing all treatment, should have treatment withdrawn and be allowed to die.

He said that GPs were under “an onerous burden” to ensure, wherever possible, that an advance decision placed in their records was passed on to clinicians in hospital. “A copy of the decision should be made available and placed within the hospital records with the objective that the …
Disruption of MAGI2-RapGEF2-Rap1 signaling contributes to podocyte dysfunction in congenital nephrotic syndrome caused by mutations in MAGI2
Authors: Bingbing Zhu, Aili Cao, Jianhua Li, James Young, Jenny Wong, Shazia Ashraf, Agnieszka Bierzynska, Madhav C. Menon, Steven Hou, Charles Sawyers, Kirk N. Campbell, Moin A. Saleem, John C. He, Friedhelm Hildebrandt, Vivette D. D’Agati, Wen Peng, Lewis Kaufman
Journal: Kidney International (2019)
Metformin Reduces Tumor Burden and Splenomegaly in JAK2V617F Murine Models
Authors: João Agostinho Machado-Neto, Renata Scopim Ribeiro, Juan Luiz Coelho-Silva, Christopher A. Eide, Bruna Alves Fenerich, Jaqueline Cristina Fernandes, Ana Paula Nunes Rodrigues Alves, Priscila S Scheucher, Cristina E. Tognon, Lorena Lobo Figueiredo-Pontes, Brian J. Druker, Eduardo Magalhães Rego, Fabiola Traina
Journal: Blood (2017)
Most men on top BMA committee don’t think lack of diversity is a problem
Authors: Melanie Newman
Journal: BMJ (2019)

A survey of members of the BMA’s UK General Practitioners Committee found that most male members did not believe that the committee needed to reflect the diversity of the doctors it represents.

The survey also found that most women on the 83 member GPC said that they were aware of “gender specific negative behaviours” among their committee colleagues, whereas less than a fifth of male respondents were aware of such behaviour.

The research, which was finalised in March 2019 and whose findings have not been made public to the wider BMA membership, was leaked to The BMJ in the wake of accusations of misogynistic and discriminatory behaviour among GPC members.1 …
角质形成细胞中的 HG 和 KdPT 的影响
Authors: P. Gkogkolou, M. Sarna, T. Sarna, R. Paus, T.A. Luger, M. Böhm
Journal: British Journal of Dermatology (2019)

糖尿病是一种常见病,影响全世界数百万人。它表现为血液和身体内的葡萄糖浓度增高。慢性足部溃疡是糖尿病最严重的并发症之一,影响高达 10% 的糖尿病患者。这类溃疡依然难以治疗,导致医疗保健系统成本高昂和患者中的死亡率增高。这项来自德国的研究旨在了解高血糖对表皮角质形成细胞的影响,这种细胞是皮肤最外层的细胞,也是伤口愈合的关键细胞。此外,该研究还调查了一种称为 KdPT 的小分子能否使角质形成细胞免于葡萄糖引发应激和毒性的伤害。作者们在有或无 KdPT 的情况下,通过细胞培养物模型和来自健康受试者的皮肤活检标本调查了角质形成细胞在高糖条件下的各种功能。高糖可减少角质形成细胞的细胞增殖和活力(意味着导致细胞数量减少和健康细胞数量减少)以及迁移(细胞运动)。它还改变了细胞大小和弹性。除了上述发现,还观察到对细胞具有毒性的活性氧簇数量增加和细胞内应激。但是,KdPT 缓解了高血糖的部分负面影响。作者们的这些发现强调了 KdPT 的一种新作用,即,可能被用于开发针对糖尿病皮肤溃疡的新疗法。
Opportunities and challenges for transcriptome-wide association studies
Authors: Michael Wainberg, Nasa Sinnott-Armstrong, Nicholas Mancuso, Alvaro N. Barbeira, David A. Knowles, David Golan, Raili Ermel, Arno Ruusalepp, Thomas Quertermous, Ke Hao, Johan L. M. Björkegren, Hae Kyung Im, Bogdan Pasaniuc, Manuel A. Rivas, Anshul Kundaje
Journal: Nature Genetics (2019)
Safety, Diagnostic Accuracy, and Effects of Endoscopic Ultrasound Fine-Needle Aspiration on Detection of Extravascular Migratory Metastases
Authors: Tarun Rustagi, Ferga C. Gleeson, Suresh T. Chari, Heidi D. Lehrke, Naoki Takahashi, Thomas M. Malikowski, Barham K. Abu Dayyeh, Vinay Chandrasekhara, Prasad G. Iyer, Michael L. Kendrick, Randall K. Pearson, Bret T. Petersen, Elizabeth Rajan, Rory L. Smoot, Andrew C. Storm, Mark D. Topazian, Mark J. Truty, Santhi S. Vege, Kenneth K. Wang, Michael J. Levy
Journal: Clinical Gastroenterology and Hepatology (2019)
Haptic Telerobotic Cardiovascular Intervention: A Review of Approaches, Methods, and Future Perspectives
Authors: Amir Hooshiar, Siamak Najarian, Javad Dargahi
Journal: IEEE Reviews in Biomedical Engineering (2019)

Cardiac diseases are recognized as the leading cause of mortality, hospitalization, and medical prescription globally. The gold standard for the treatment of coronary artery stenosis is the percutaneous cardiac intervention that is performed under live X-ray imaging. Substantial clinical evidence shows that the surgeon and staff are prone to serious health problems due to X-ray exposure and occupational hazards. Telerobotic vascular intervention systems with a master-slave architecture reduced the X-ray exposure and enhanced the clinical outcomes; however, the loss of haptic feedback during surgery has been the main limitation of such systems. This paper is a review of the state of the art for haptic telerobotic cardiovascular interventions. A survey on the literature published between 2000 and 2019 was performed. Results of the survey were screened based on their relevance to this paper. Also, the leading research disciplines were identified based on the results of the survey. Furthermore, different approaches for sensor-based and model-based haptic telerobotic cardiovascular intervention, haptic rendering and actuation, and the pertinent methods were critically reviewed and compared. In the end, the current limitations of the state of the art, unexplored research areas as well as the future perspective of the research on this technology were laid out.
Environmental Chemicals and Autism: A Scoping Review of the Human and Animal Research
Authors: Katherine E. Pelch, Ashley L. Bolden, Carol F. Kwiatkowski
Journal: Environmental Health Perspectives (2019)

Background: Estimates of autism prevalence have increased dramatically over the past two decades. Evidence suggests environmental factors may contribute to the etiology of the disorder. Objectives: This scoping review aimed to identify and categorize primary research and reviews on the association between prenatal and early postnatal exposure to environmental chemicals and the development of autism in epidemiological studies and rodent models of autism. Methods: PubMed was searched through 8 February 2018. Included studies assessed exposure to environmental chemicals prior to 2 months of age in humans or 14 d in rodents. Rodent studies were considered relevant if they included at least one measurement of reciprocal social communicative behavior or repetitive and stereotyped behavior. Study details are presented in interactive displays using Tableau Public. Results: The search returned 21,603 unique studies, of which 54 epidemiological studies, 46 experimental rodent studies, and 50 reviews were deemed relevant, covering 152 chemical exposures. The most frequently studied exposures in humans were particulate matter (n=14), mercury (n=14), nonspecific air pollution (n=10), and lead (n=10). In rodent studies, the most frequently studied exposures were chlorpyrifos (n=9), mercury (n=6), and lead (n=4). Discussion: Although research is growing rapidly, wide variability exists in study design and conduct, exposures investigated, and outcomes assessed. Conclusions focus on recommendations to guide development of best practices in epidemiology and toxicology, including greater harmonization across these fields of research to more quickly and efficiently identify chemicals of concern. In particular, we recommend chlorpyrifos, lead, and polychlorinated biphenyls (PCBs) be systematically reviewed in order to assess their relationship with the development of autism. There is a pressing need to move forward quickly and efficiently to understand environmental influences on autism in order to answer current regulatory questions and inform treatment and prevention efforts. https://doi.org/10.1289/EHP4386
Medical Aspects of Operation Desert Storm
Authors: Allen L Richards, Kenneth C Hyams, Bruce R Merrell, Gregory A Dasch
Journal: New England Journal of Medicine (1991)

Abstract : In the Special Report by Gasser et al. concerning the threat of infectious diseases associated with Americans returning from the Persian Gulf (March 21 issue), a number of febrile systemic illnesses were considered. Early in Operations Desert Shield and Desert Storm, the U.S. Navy Forward Laboratory was established at a U.S. Marine Corps surgical support facility in Saudi Arabia as a theater wide reference laboratory. No evidence of incident cases of sandfly fever, Congo Crimean hemorrhagic fever, Rift Valley fever, Sindbis, Hantaan, dengue fever, typhus, or Q fever was found in military troops stationed in Saudi Arabia. However, one presumptive case of West Nile fever was diagnosed in a soldier with a four-day, self limited clinical course of acute fever, debility, and arthralgia, which resulted in hospitalization. Both during the acute phase and during convalescence, the patient's serum was positive for IgM antibody against West Nile fever virus, but it did not react with the other arboviruses tested, including dengue. During the acute phase, the serum titers of IgM and IgG were 3200 and 4800, respectively. The IgG titer had doubled in the serum during convalescence, six weeks later.
Abstract 16108: Adverse Left Ventricular Remodelling Patterns Predict Response to Cardiac Resynchronization Therapy
Authors: Gerardo Gonzalez, David Warriner, Tom Jackson, Eva Sammut, Ernesto Zacur, David Rodney Hose, Reza Razavi, Nicolas P Smith, Pablo Lamata
Journal: Circulation (2015)

Introduction: The anatomy of the left ventricle (LV) remodels in heart failure. In this work we test the hypothesis that pre-implant LV shape can predict response to cardiac resynchronization therapy (CRT). Methods: The anatomy of the LV of 50 subjects selected for CRT was acquired and manually segmented from magnetic resonance imaging acquired using a steady-state free-precision 3D sequence. A computational atlas was built from 3D meshes that were fitted to the resulting segmentations, and was used to obtain atlas-based shape metrics from the cohort. Segmentation and 3D meshing was repeated in 19 cases to test the reproducibility of the new metrics. Results: The five most significant shape metrics were found to be reproducible. Response to CRT, defined as a reduction of a 10% in the end diastolic volume, was predicted by a linear combination of 2 atlas modes (AUC of 0.693, best operating point with sensitivity of 84% and specificity of 56%, as evaluated by a leave-1-out cross-validation test). The figure illustrates the overlay of the extreme geometry of responder (velvet) and non-responder (orange) shapes computed from the statistical shape model (the small red sphere is located at the septal wall): the adverse LV remodelling shows a shorter septal wall and angled basal plane. Conclusions: Pre-implant LV shape, described through novel atlas-based metrics, is a potential new criterion for CRT patient selection.
Sex Differences in Nonalcoholic Fatty Liver Disease: State of the Art and Identification of Research Gaps
Authors: Amedeo Lonardo, Fabio Nascimbeni, Stefano Ballestri, DeLisa Fairweather, Sanda Win, Tin A. Than, Manal F. Abdelmalek, Ayako Suzuki
Journal: Hepatology (2019)

Despite tremendous research advancements in nonalcoholic fatty liver disease (NAFLD), our understanding of sex differences in NAFLD remains insufficient. This review summarizes the current knowledge on sex differences in NAFLD, identifies gaps, and discusses important considerations for future research. The prevalence and severity of NAFLD are higher in men than in women during the reproductive age. However, after menopause, NAFLD occurs at a higher rate in women, suggesting that estrogen is protective. Sex differences also exist for the major risk factors of NAFLD. In general, animal models of NAFLD recapitulate the sex differences observed in patients, with more severe steatosis and steatohepatitis, more proinflammatory/profibrotic cytokines, and a higher incidence of hepatic tumors in male than female subjects. Based on computer modeling, female and male livers are metabolically distinct with unique regulators modulating sex-specific metabolic outcomes. Analysis of the literature reveals that most published clinical and epidemiological studies fail to examine sex differences appropriately. Considering the paucity of data on sex differences and the knowledge that regulators of pathways relevant to current therapeutic targets for NAFLD differ by sex, clinical trials should be designed to test drug efficacy and safety according to sex, age, reproductive stage (i.e., menopause), and synthetic hormone use. Conclusion: Sex differences do exist in the prevalence, risk factors, fibrosis, and clinical outcomes of NAFLD, suggesting that, while not yet incorporated, sex will probably be considered in future practice guidelines; adequate consideration of sex differences, sex hormones/menopausal status, age, and other reproductive information in clinical investigation and gene association studies of NAFLD are needed to fill current gaps and implement precision medicine for patients with NAFLD.
Association of Health Status With Receipt of Supplemental Security Income Among Individuals With Severe Disabilities and Very Low Income and Assets
Authors: Rajan A. Sonik, Susan L. Parish, Monika Mitra
Journal: JAMA Internal Medicine (2019)

Supplemental Security Income (SSI) is a cash-transfer program for individuals with severe disabilities and very low incomes and assets.Material hardships such as food insecurity are particularly problematic to the health status of individuals with disabilities. 1 These hardships have been shown to increase sharply immediately before people first receive benefits from social welfare programs and then to decrease moderately after benefits start. 2 However, whether these material hardship fluctuations are associated with changes in the health status of SSI recipients is unknown.To investigate this possibility, we examined health patterns among recipients before and after initial SSI receipt.Methods | We analyzed data from the first 12 waves of the 2008 panel of the Survey of Income and Program Participation.Waves occurred every 4 months, starting in September 2008.Self-reported health status 3 was recorded during wave 6 in June 2010.Supplemental Security Income receipt was recorded in every wave.Data analysis was performed from August 1, 2018, to October 21, 2018.The institutional review board of Brandeis University, Waltham, Massachusetts, determined that the present study was exempt from review given that all data were deidentified.Eleven groups of adults (n = 498) 18 years or older whose SSI receipt began during the study period were identified from these data.The groups were composed of individuals whose continuous SSI receipt each began in one of waves 2 through 12. Comparing SSI initiation dates with when health status was recorded in wave 6 allowed us to map each of these groups onto a timeline ranging from 24 months before initial SSI receipt to 16 months after initial SSI receipt (Table and eAppendix in the Supplement).Using this timeline, we estimated an interrupted time series (ITS) model in which the percentage of each group reporting a positive health status (excellent, very good, or good vs fair or poor) 3 was the dependent variable.The ITS model assessed the pre-SSI trend in health status, as well as changes in this trend after SSI receipt.Stata, version 15.0 (StataCorp) was used to conduct the ITS analysis.The following sociodemographic characteristics were used as covariates: non-Hispanic white race/ethnicity, female, age, high school degree, and married.However, for parsimony, we only included covariates that improved model fit (sex and age in this case).
A new protocol using a light‐emitting fabric for PDT of AK
Authors: C. Vicentini, A.S. Vignion‐Dewalle, E. Thecua, F. Lecomte, C. Maire, P. Deleporte, H. Béhal, D. Kerob, A. Duhamel, S. Mordon, L. Mortier
Journal: British Journal of Dermatology (2019)

Actinic keratoses (AKs) are areas of sun‐damaged skin found mainly on sun‐exposed parts of the body, particularly the backs of the hands and forearms, the face and ears, and the scalp in balding men. They are usually harmless although they can be unsightly or inconvenient, and there is a very small risk of some actinic keratoses progressing to a form of skin cancer called squamous cell carcinoma. There are several possible treatments, including photodynamic therapy (PDT), in which a special light activates a cream called a photosensitiser, which has been applied to the affected area of skin. This treatment kills the abnormal cells in the skin. The photosensitisers approved in Europe for PDT of AKs require either activation by red light three hours after application of the photosensitiser (referred to as C‐PDT) or activation by daylight within 30 minutes following application of the photosensitiser (referred to as D‐PDT). The major drawback of C‐PDT is pain during treatment, whereas D‐PDT is nearly pain‐free due to the short time between photosensitiser application and daylight activation. Unfortunately, D‐PDT requires favourable weather conditions. The authors of this study, who belong to the ONCO‐THAI research unit based in France, therefore tested a way to activate the photosensitiser 30 minutes after application, by red light using a flexible, light‐emitting, fabric‐based device (hereinafter referred to as FLEXI‐PDT). This study aimed to assess whether FLEXI‐PDT is at least as effective as C‐PDT in destroying AK. The authors were also interested in whether pain scores differ between FLEXI‐PDT and C‐PDT. For these purposes, 35 patients with AKs on the scalp were treated with FLEXI‐PDT on one side of the scalp and with C‐PDT on the other side. Patients rated their pain during FLEXI‐PDT and during C‐PDT separately. The response of each AK (complete or incomplete disappearance) was assessed by a dermatologist at three months after treatment. From the analyses of the data collected, the authors showed that FLEXI‐PDT, which can be performed in all weather conditions, is at least as effective as and less painful than C‐PDT in destroying AK.
Abstract 16586: Effects of Postoperative ACE Inhibitors on Patients undergoing Cardiac Surgery
Authors: Zugui Zhang, Qian Ding, Hong Liu, Linong Yao, Mark Berguson, Jordan Goldhammer, Rohinton Morris, Jian-Zhong Sun
Journal: Circulation (2017)

Background: Both experimental studies and clinical trials have shown that angiotensin-converting enzyme inhibitors (ACEi) hold promise as protective agents for cardiac surgery patients. However, th...
Asrij/OCIAD1 suppresses CSN5-mediated p53 degradation and maintains mouse hematopoietic stem cell quiescence
Authors: Saloni Sinha, Tirath Raj Dwivedi, Roja Yengkhom, Venkata Anudeep Bheemsetty, Takaya Abe, Hiroshi Kiyonari, K. VijayRaghavan, Maneesha S. Inamdar
Journal: Blood (2019)