tbuckley/cabot-search huggingface dataset:
Environmentally-induced <i>mdig</i> contributes to the severity of COVID-19 through fostering expression of SARS-CoV-2 receptor NRPs and glycan metabolism
Authors: Qian Zhang, Priya Wadgaonkar, Liping Xu, Chitra Thakur, Yao Fu, Zhuoyue Bi, Yiran Qiu, Bandar Almutairy, Wenxuan Zhang, Paul Stemmer, Fei Chen
Journal: Theranostics (2021)

The novel β-coronavirus, SARS-CoV-2, the causative agent of coronavirus disease 2019 , has infected more than 177 million people and resulted in 3.84 million death worldwide.Recent epidemiological studies suggested that some environmental factors, such as air pollution, might be the important contributors to the mortality of COVID-19.However, how environmental exposure enhances the severity of COVID-19 remains to be fully understood.In the present report, we provided evidence showing that mdig, a previously reported environmentally-induced oncogene that antagonizes repressive trimethylation of histone proteins, is an important regulator for SARS-CoV-2 receptors neuropilin-1 (NRP1) and NRP2, cathepsins, glycan metabolism and inflammation, key determinants for viral infection and cytokine storm of the patients.Depletion of mdig in bronchial epithelial cells by CRISPR-Cas-9 gene editing resulted in a decreased expression of NRP1, NRP2, cathepsins, and genes involved in protein glycosylation and inflammation, largely due to a substantial enrichment of lysine 9 and/or lysine 27 trimethylation of histone H3 (H3K9me3/H3K27me3) on these genes as determined by ChIP-seq.Meanwhile, we also validated that environmental factor arsenic is able to induce mdig, NRP1 and NRP2, and genetic disruption of mdig lowered expression of NRP1 and NRP2.Furthermore, mdig may coordinate with the Neanderthal variants linked to an elevated mortality of COVID-19.These data, thus, suggest that mdig is a key mediator for the severity of COVID-19 in response to environmental exposure and targeting mdig may be the one of the effective strategies in ameliorating the symptom and reducing the mortality of COVID-19.
トランスジェニックマウスの腎髄質における、モル浸透圧濃度の急激な変化に応じたイヌベタインGABA輸送体遺伝子の5’フランキング領域による転写活性化
Authors: Kaneko T, Takenaka M, Itoh T, Yoshimura Y, Okabe M, Moriyama T, Yamauchi A, Kwon M, Handler J, Imai E
Journal: Journal of the American Society of Nephrology (1996)
Abstract 13984: Left Atrial Strain and Stiffness in Patients With Atrial Fibrillation Pre- And Post-Cardioversion: A Speckle Echocardiographic Study
Authors: Amir Shaikh, Fnu Abhishek, Jeffrey Hill, Umar Khan, Dionyssios Robotis, Gerard Aurigemma, David McManus
Journal: Circulation (2011)

Introduction: Currently, the influence of underlying heart rhythm on left atrial (LA) strain measures is not well established. The purpose of this prospective investigation was to (a) study left at...
Assessment of the Financial Health of Rural Hospitals After Implementation of the Georgia Rural Hospital Tax Credit Program
Authors: Bettye A. Apenteng, Samuel T. Opoku, Charles Owens, Emmanuel Akowuah, Linda Kimsey, Angie Peden
Journal: JAMA Network Open (2021)

In 2016, Georgia implemented the Rural Hospital Tax Credit Program, which allows taxpayers to receive a tax credit for contributions to qualifying rural hospitals in the state. Empirical evidence of the program's association with the viability of the state's rural hospitals is needed.To examine the association of the tax credit program with the financial health of participating rural hospitals.This longitudinal cross-sectional study used hospital financial data from the Centers for Medicare & Medicaid Services for 2015 to 2019. A difference-in-differences analytic approach was used to examine the association of the tax credit program with rural hospital financial health. Study participants included Georgia rural hospitals eligible to participate in the program. Comparison hospitals were selected from the southern states of Alabama, Florida, Mississippi, North Carolina, South Carolina, and Tennessee.Hospital participation in the Georgia Rural Hospital Tax Credit Program.The primary outcome of the study was financial health measured with total margin, days cash on hand, debt-asset ratio, and average age of plant as well as a Financial Strength Index (FSI), which combined the previous measures to assess overall financial strength.The analytical sample included a balanced panel of 136 hospitals, with 47 Georgia Rural Hospital Tax Credit Program participants (18 [38%] critical access hospitals; 5 [11%] system affiliated; mean [SD] bed count, 60 [47]; mean [SD] Medicare inpatient mix, 52% [16]) and 89 comparison hospitals (43 [48%] critical access hospitals; 24 [27%] system affiliated; mean [SD] bed count, 52 [41]; mean [SD] Medicare inpatient mix, 67% [18]). Two years after implementation, program participation was associated with a 23% increased probability of good or excellent financial health (b = 0.23; 95% CI, 0.10-0.37; P < .001) and a 6.7-point increase in total margin (b = 6.67; 95% CI, 3.61-9.73; P < .001).These early findings suggest that the Georgia Rural Hospital Tax Credit Program is associated with improvements in hospital financial health; however, additional studies are needed to assess the program's long-term impact on the financial sustainability of Georgia's rural hospitals.
Drowning prevention: turning the tide on a leading killer
Authors: David R Meddings, Justin-Paul Scarr, Kelly Larson, James Vaughan, Etienne G Krug
Journal: The Lancet Public Health (2021)

Drowning is a leading killer, particularly of children and young adults, yet has been greatly neglected. Despite accounting for a higher number of deaths than many other substantial public health issues, drowning has not benefitted from the targeted attention it requires, which is particularly tragic because low cost and effective drowning prevention interventions exist. Therefore, the recent UN General Assembly's adoption of a resolution on global drowning prevention is a historic first, and offers an exciting opportunity by providing a comprehensive framework and a practical roadmap that a range of actors and sectors, including governments, can follow to address the challenge of drowning prevention.
Haploidentical Hematopoietic Cell Transplantation Followed By Donor Natural Killer Cell Infusion and Sirolimus Maintenance Can Successfully Treat Patients with High-Risk Ewing Sarcoma
Authors: Monica Thakar, Meghen Browning, Parameswaran Hari, John Charlson, Amy Newman, Brent R. Logan, Nathan Schloemer, Michael Kelly, Bryon Johnson, Subramaniam Malarkannan, Carolyn A. Keever-Taylor
Journal: Blood (2017)
MO27-6 Clinical significance of urinary cell-free DNA in urothelial cancer
Authors: Kazutoshi Fujita, Yujiro Hayahi, Taigo Kato, Koji Hatano, Atsunari Kawashima, Takeshi Ujike, Motohide Uemura, Takafumi Minami, Masahiro Nozawa, Kazuhiro Nose, Kazuhiro Yoshimura, George Netto, Hirotsugu Uemura, Norio Nonomura
Journal: Annals of Oncology (2021)
Abstract O.50: Favorable Outcome Of Patients With Kawasaki Disease Treated With Unified Protocol With Cyclosporine A As The Third Line Therapy
Authors: Hiromichi Hamada, Takafumi Honda, Kumi Yasukawa, Takuya Matsui, Masaru Terai
Journal: Circulation (2015)

Background: Cyclosporin A (CsA), which potently suppresses inflammatory cytokines by negative regulation of nuclear factor of activated T cells pathway, may be a promising option for the treatment of Kawasaki disease (KD), especially in patients resistant to intravenous immunoglobulin (IVIG). We treat KD patients with the unified protocol using CsA after 2nd IVIG. Here we report 6 years-outcome of this treatment. Patients and Methods: From 2008 to 2014, 441 patients were treated. At the persistence or recurrence of fever at the end of the 2nd IVIG (2 g/kg for 24 hours), patients were treated with CsA (4-5mg/kg/day) through oral administration except for infants younger than 4 months old. If patients failed to become afebrile after CsA treatment, they received 3rd IVIG. All patients received aspirin 50mg/kg/day at febrile stage. Results: 419 patients became afebrile after 1st or 2nd IVIG. At this point, 2 patients had mild CALs (max 4.7 mm, 2.5mm in 2month-old infant). Among the other 22 patients (5.0%) who failed to become afebrile, one infant aged 1 month-old received 3rd IVIG. Among a total of 21 patients treated with CsA, 10 patients responded promptly to be afebrile within 5 days. The other 11 patients failed to become afebrile and received 3rd IVIG. Eight out of the 11 patients became afebrile after 3rd IVIG. Three patients developed mild CALs (max 3.1mm, 3.7mm, 5.5mm). There were no serious adverse effects in CsA treatment. A total number of patients with CAL was 5 (1.1%). The maximum CAL diameter was 5.5 mm. Conclusions: The outcome of KD patients treated with CsA and 3rd IVIG as a third line therapy is safe and favorable. CsA could be a candidate drug of the first line therapy.
P48-2 A case of MYH9-ROS1 fusion gene-positive pulmonary adenocarcinoma who responded to entrectinib
Authors: Takeshi Tsuda, Atsushi Muto, Mami Shimizu, Takahiro Hirai, Yasuaki Masaki, Hirokazu Taniguchi, Shin Ishizawa
Journal: Annals of Oncology (2021)
Abstract 14078: Mammalian UNC-51-Like Kinase (ULK)-1 Plays a Crucial Role in Mediating Autophagy Under Stress Conditions in the Heart
Authors: Yasuhiro Maejima, Peiyong Zhai, Mondira Kundu, Junichi Sadoshima
Journal: Circulation (2011)

Autophagy plays an important role in mediating protein quality control (QC) in cells. Inhibition of autophagy below physiological levels induces protein aggregation and cellular dysfunction. On the...
Inequalities in incident and prevalent multimorbidity in England, 2004–19: a population-based, descriptive study
Authors: Anna Head, Kate Fleming, Chris Kypridemos, Pieta Schofield, Jonathan Pearson-Stuttard, Martin O'Flaherty
Journal: The Lancet Healthy Longevity (2021)

The increasing burden of multimorbidity and its socioeconomic gradient poses unique challenges to the provision and structure of health care. We aimed to describe inequalities and trends over time in multimorbidity prevalence, incidence, and case fatality among adults of all ages in England using primary care electronic health records.We used a random sample of 991 243 individuals from the Clinical Practice Research Datalink Aurum database registered at participating general practices within England between Jan 1, 2004, and Dec 31, 2019, linked to the 2015 English Index of Multiple Deprivation (IMD). We used the following two outcome measures: basic multimorbidity, comprising two or more chronic conditions; and complex multimorbidity, comprising at least three chronic conditions affecting at least three body systems. We calculated crude, age-standardised, and age-sex-standardised annual incidence, prevalence, and case fatality rates, along with median age of onset for both multimorbidity types. We calculated absolute and relative inequalities for each outcome.In 2004, 30·8% of our study population had basic multimorbidity and 15·1% had complex multimorbidity. This increased to 52·8% and 32·7%, respectively, in 2019. Although the overall incidence of basic multimorbidity remained stable over the 16-year study period, the incidence among people of working age and the incidence of complex multimorbidity increased gradually. Socioeconomic deprivation was associated with an increased incidence of both multimorbidity types in working-age adults. The median age at onset of complex multimorbidity was 7 years younger for the most deprived quintile of the IMD compared with the least deprived quintile.The burden of multimorbidity in England has increased substantially over the past 16 years with persistent inequalities, which are worse in working-age adults and for complex multimorbidity. Prevention efforts to reduce the onset and slow the progression of multimorbidity are essential to reduce the increasing impact on patients and health systems alike.University of Liverpool and UK National Institute for Health Research School for Public Health Research.
Survival outcomes in older men with non-metastatic castration-resistant prostate cancer treated with androgen receptor inhibitors: a US Food and Drug Administration pooled analysis of patient-level data from three randomised trials
Authors: Jaleh Fallah, Lijun Zhang, Anup Amatya, Yutao Gong, Bellinda King-Kallimanis, Vishal Bhatnagar, Chana Weinstock, Daniel L Suzman, Sundeep Agrawal, Elaine Chang, Mitchell S Anscher, Dow-Chung Chi, James X Xu, Jamie R Brewer, Michael H Brave, Mehrnoosh Hadadi, Marc R Theoret, Paul G Kluetz, Kirsten B Goldberg, Amna Ibrahim, Shenghui Tang, Richard Pazdur, Julia A Beaver, Laleh Amiri-Kordestani, Harpreet Singh
Journal: The Lancet Oncology (2021)
Hypoxia-inducible factors individually facilitate inflammatory myeloid metabolism and inefficient cardiac repair
Authors: Matthew DeBerge, Connor Lantz, Shirley Dehn, David P. Sullivan, Anja M. van der Laan, Hans W.M. Niessen, Margaret E. Flanagan, Daniel J. Brat, Matthew J. Feinstein, Sunjay Kaushal, Lisa D. Wilsbacher, Edward B. Thorp
Journal: The Journal of Experimental Medicine (2021)

Hypoxia-inducible factors (HIFs) are activated in parenchymal cells in response to low oxygen and as such have been proposed as therapeutic targets during hypoxic insult, including myocardial infarction (MI). HIFs are also activated within macrophages, which orchestrate the tissue repair response. Although isoform-specific therapeutics are in development for cardiac ischemic injury, surprisingly, the unique role of myeloid HIFs, and particularly HIF-2α, is unknown. Using a murine model of myocardial infarction and mice with conditional genetic loss and gain of function, we uncovered unique proinflammatory roles for myeloid cell expression of HIF-1α and HIF-2α during MI. We found that HIF-2α suppressed anti-inflammatory macrophage mitochondrial metabolism, while HIF-1α promoted cleavage of cardioprotective MerTK through glycolytic reprogramming of macrophages. Unexpectedly, combinatorial loss of both myeloid HIF-1α and HIF-2α was catastrophic and led to macrophage necroptosis, impaired fibrogenesis, and cardiac rupture. These findings support a strategy for selective inhibition of macrophage HIF isoforms and promotion of anti-inflammatory mitochondrial metabolism during ischemic tissue repair.
Salidroside Activates the AMP‐Activated Protein Kinase Pathway to Suppress Nonalcoholic Steatohepatitis in Mice
Authors: Manli Hu, Dingran Zhang, Hongyang Xu, Yan Zhang, Hongjie Shi, Xiaoli Huang, Xinhui Wang, Yan Wu, Zhili Qi
Journal: Hepatology (2021)

Background and Aims NASH is becoming a leading cause of liver cirrhosis and HCC. Salidroside (p-hydroxyphenethyl-β-D-glucoside; SAL) has various biological and pharmacological activities, including anti-inflammatory, -oxidant, and -cancer activities. However, the therapeutic effect and underlying molecular mechanism of SAL in NASH remain to be further clarified. Methods and Results In this study, we found that SAL alleviated lipid accumulation and inflammatory response in primary hepatocytes after palmitic acid/oleic acid (PO) stimulation. In addition, SAL effectively prevented high-fat/high-cholesterol (HFHC)-diet–induced NASH progression by regulating glucose metabolism dysregulation, insulin resistance, lipid accumulation, inflammation, and fibrosis. Mechanistically, integrated RNA-sequencing and bioinformatic analysis showed that SAL promoted AMPK-signaling pathway activation in vitro and in vivo, and this finding was further verified by determining the phosphorylation levels of AMPK. Furthermore, the protective effects of SAL on lipid accumulation and inflammation in hepatocytes and livers induced by PO or HFHC stimulation were blocked by AMPK interruption. Conclusions Our studies demonstrate that SAL protects against metabolic-stress–induced NASH progression through activation of AMPK signaling, indicating that SAL could be a potential drug component for NASH therapy.
P28-6 IL-6, IL-8, and VEGF secreted by PC9 and PC9-MET cells may impair the function of NK cells
Authors: Md Mohiuddin, Hideharu Kimura, Takashi Sone, Hiroki Matsuoka, Keigo Saeki, Nanao Terada, Kazuo Kasahara
Journal: Annals of Oncology (2021)
Covid-19: Two thirds in India carry antibodies, while research suggests country’s death toll is 10 times official figure
Authors: Owen Dyer
Journal: BMJ (2021)

Covid-19: Two thirds in India carry antibodies, while research suggests country's death toll is 10 times official figure 2 WHO-AIIMS seroprevalence survey outcome "positive"; larger nationwide sample size needed for comprehensive results: Guleria.Times of India 2021 Jun 18. https://timesofindia.indiatimes.com/
Jeffrey Michael Dolphin
Authors: Mandy Beinder, Sue Fray, Nick Dolphin
Journal: BMJ (2021)

Jeffrey Michael Dolphin (“Jeff”) Dolphin was senior consultant surgeon at Walsall and District General hospitals. He was born to Raymond and Joyce Dolphin. He grew up in Harborne, Birmingham, and was educated at King Edwards Five Ways and King Edwards High School, Edgbaston. His father was a research scientist and was keen for Jeff to study metallurgy. However, influenced by his future wife, Peggy, whose ambition was to go into nursing, Jeff chose to study chemistry, physics, and biology in what was called the “medical sixth.”

After qualifying he undertook his house officer posts at the Queen Elizabeth Hospital in Birmingham. He then took a short service commission …
Using Artificial Intelligence to Make Use of Electronic Health Records Less Painful—Fighting Fire With Fire
Authors: Richard J. Baron
Journal: JAMA Network Open (2021)

Ethan Andrew Chi; Gordon Chi; Cheuk To Tsui, BS; Yan Jiang, MD; Karolin Jarr, MD; Chiraag V. Kulkarni, MD; Michael Zhang, MD; Jin Long, PhD; Andrew Y. Ng, PhD; Pranav Rajpurkar, PhD; Sidhartha R. Sinha, MD
MO22-6 Second-line systemic therapy in patients with recurrent or metastatic adenoid cystic carcinoma
Authors: Shigenori Kadowaki, Taiko Nakazawa, Takatsugu Ogata, Yuki Matsubara, Kazuki Nozawa, Kyoko Kato, Yukiya Narita, Kazunori Honda, Toshiki Masuishi, Hideaki Bando, Masashi Ando, Nobuhiro Hanai, Kei Muro
Journal: Annals of Oncology (2021)
First Efficacy Results From the Turandot Phase III Trial Comparing Two Bevacizumab (BEV)-Containing Regimens as First-Line Therapy for HER2-Negative Metastatic Breast Cancer (MBC)
Authors: C. Zielinski, I. Lang, M. Inbar, Z. Kahan, R. Greil, S. Beslija, S.M. Stemmer, B. Kaufman, Z. Zvirbule, G. Steger, B. Melichar, T. Pienkowski, D. Sirbu, L. Petruzelka, A. Eniu, B. Nisenbaum, M. Dank, R. Anghel, D. Messinger, T. Brodowicz
Journal: Annals of Oncology (2012)
Response by Lee et al to Letter Regarding Article, “Effect of Empagliflozin on Left Ventricular Volumes in Patients With Type 2 Diabetes, or Prediabetes, and Heart Failure With Reduced Ejection Fraction (SUGAR-DM-HF)”
Authors: Matthew M.Y. Lee, John J.V. McMurray, Pardeep S. Jhund, Mark C. Petrie, Naveed Sattar
Journal: Circulation (2021)
Frailty and Clinical Outcomes of Direct Oral Anticoagulants Versus Warfarin in Older Adults With Atrial Fibrillation
Authors: Dae Hyun Kim, Ajinkya Pawar, Joshua J. Gagne, Lily G. Bessette, Hemin Lee, Robert J. Glynn, Sebastian Schneeweiss
Journal: Annals of Internal Medicine (2021)

Background: The role of differing levels of frailty in the choice of oral anticoagulants for older adults with atrial fibrillation (AF) is unclear. Objective: To examine the outcomes of direct oral anticoagulants (DOACs) versus warfarin by frailty levels. Design: 1:1 propensity score–matched analysis of Medicare data, 2010 to 2017. Setting: Community. Patients: Medicare beneficiaries with AF who initiated use of dabigatran, rivaroxaban, apixaban, or warfarin. Measurements: Composite end point of death, ischemic stroke, or major bleeding by frailty levels, defined by a claims-based frailty index. Results: In the dabigatran–warfarin cohort (n = 158 730; median follow-up, 72 days), the event rate per 1000 person-years was 63.5 for dabigatran initiators and 65.6 for warfarin initiators (hazard ratio [HR], 0.98 [95% CI, 0.92 to 1.05]; rate difference [RD], −2.2 [CI, −6.5 to 2.1]). For nonfrail, prefrail, and frail persons, HRs were 0.81 (CI, 0.68 to 0.97), 0.98 (CI, 0.90 to 1.08), and 1.09 (CI, 0.96 to 1.23), respectively. In the rivaroxaban–warfarin cohort (n = 275 944; median follow-up, 82 days), the event rate per 1000 person-years was 77.8 for rivaroxaban initiators and 83.7 for warfarin initiators (HR, 0.98 [CI, 0.94 to 1.02]; RD, −5.9 [CI, −9.4 to −2.4]). For nonfrail, prefrail, and frail persons, HRs were 0.88 (CI, 0.77 to 0.99), 1.04 (CI, 0.98 to 1.10), and 0.96 (CI, 0.89 to 1.04), respectively. In the apixaban–warfarin cohort (n = 218 738; median follow-up, 84 days), the event rate per 1000 person-years was 60.1 for apixaban initiators and 92.3 for warfarin initiators (HR, 0.68 [CI, 0.65 to 0.72]; RD, −32.2 [CI, −36.1 to −28.3]). For nonfrail, prefrail, and frail persons, HRs were 0.61 (CI, 0.52 to 0.71), 0.66 (CI, 0.61 to 0.70), and 0.73 (CI, 0.67 to 0.80), respectively. Limitations: Residual confounding and lack of clinical frailty assessment. Conclusion: For older adults with AF, apixaban was associated with lower rates of adverse events across all frailty levels. Dabigatran and rivaroxaban were associated with lower event rates only among nonfrail patients. Primary Funding Source: National Institute on Aging.
A urine extracellular vesicle circRNA classifier for detection of high-grade prostate cancer in patients with prostate-specific antigen 2–10 ng/mL at initial biopsy
Authors: Ya-Di He, Wen Tao, Tao He, Bang-Yu Wang, Xiu-Mei Tang, Liang-Ming Zhang, Zhen-Quan Wu, Wei-Ming Deng, Ling-Xiao Zhang, Chun-Kui Shao, Jing Zhou, Li-Min Rong, Xin Gao, Liao-Yuan Li
Journal: Molecular Cancer (2021)

Abstract The aim of this study was to identify a urine extracellular vesicle circular RNA (circRNA) classifier that could detect high-grade prostate cancer (PCa) of Grade Group (GG) 2 or greater. For this purpose, we used RNA sequencing to identify candidate circRNAs from urinary extracellular vesicles from 11 patients with high-grade PCa and 11 case-matched patients with benign prostatic hyperplasia. Using ddPCR in a training cohort (n = 263), we built a urine extracellular vesicle circRNA classifier (Ccirc, containing circPDLIM5, circSCAF8 , circPLXDC2 , circSCAMP1 , and circCCNT2 ), which was evaluated in two independent cohorts (n = 497, n = 505). Ccirc showed higher accuracy than two standard of care risk calculators (RCs) (PCPT-RC 2.0 and ERSPC-RC) in both the training cohort and the validation cohorts. In all three cohorts, this novel urine extracellular vesicle circRNA classifier plus RCs was statistically more predictive than RCs alone for predicting ≥ GG2 PCa. This assay, which does not require precollection digital rectal examination nor special handling, is repeatable, noninvasive, and can be easily implemented as part of the basic clinical workflow.
Abstract 14529: Higher Activation of the Ventromedial Prefrontal Cortex During Mental Stress Predicts Major Cardiovascular Disease Events in Patients With Coronary Artery Disease
Authors: Kasra Moazzami, Matthew T Wittbrodt, Bruno B Lima, Jonathon A Nye, Puja K Mehta, Arshed A Quyyumi, J Douglas Bremner, Amit J Shah, Viola Vaccarino
Journal: Circulation (2019)

Introduction: Psychological stress is a risk factor for major adverse cardiovascular events (MACE) in patients with coronary artery disease (CAD). Certain brain regions that control both emotional ...
Telomere Length Is Significantly Reduced in Patients with Aplastic Anemia and Is Not Influenced By Gender and Severity
Authors: Eunice Sindhuvi Edison, Aruna Barade, Anu Korula, Nisham Pn, Anup Joseph Devasia, Kavitha M Lakshmi, Kulkarni Uday Prakash, Aby Abraham, Alok Srivastava, Vikram Mathews, Biju George
Journal: Blood (2017)