tbuckley/cabot-search huggingface dataset:
Abstract 134: Increased Ca2+ Influx Through Cav1.2 in Vascular Smooth Muscle Cells Causes Hypertension Due to Impairment of Acetylcholine-dependent Vascular Relaxation
Authors: xiaoying Zhang, Zhongjian Cheng, Xiaojie Ai, Mingxin Tang, Xiang Hua, Steven R Houser, Manuel F Navedo, Luis F Santana, Hong Wang, Xiongwen Chen
Journal: Circulation Research (2016)

Calcium channel plays an important role in smooth muscle contraction and relaxation and L-type calcium channel (Cav1.2) antagonist is widely used for treating hypertension. However, whether increasing Ca2+ influx into smooth muscle cells results in hypertension (through increasing smooth muscle cell contractility) or hypotension (through activating BKCa channels) is unclear. Aiming to answer this question, we established a transgenic (TG) mouse model with smooth muscle cell specific (SM22-α promoter driven) overexpression of a splicing variant of Cavβ2 subunit, Cavβ2a, tagged with GFP. Methods and Results: Immunostaining showed that Cavβ2a-GFP expressed in smooth muscle cells specifically and L-type Ca2+ current in smooth muscle cells from the 4 th branch of mesenteric arteries of transgenic mice was significantly increased (5.1±0.7pA/pF in TG, n=12 vs. 2.2±0.5pA/pF in control, n=10). Telemetric blood pressure measurement showed that 24h-averaged systolic pressure was significantly increased (135.2±9.8mmHg, n=25) compared to that of that of control c57bl/6 mice (110.2±7.8mmHg, n=16). The diastolic pressure was also significantly elevated in TG mice than in control mice. Maximum contractility of the 4 th branch mesenteric arteries measured with 40mM KCl was not different between control and TG groups. Sodium nitroprusside relaxed the phenylephrine-precontracted mesenteric artery in the same dose-dependent manner However, acetylcholine induced mesenteric artery relaxation was signficantly impaired in TG mesenteric arteries. Conclusions: Increasing Ca2+ influx through the L-type Ca2+ channel in smooth muscle cells causing hypertension via impairment of acetylcholine-dependent relaxation.
Association of Plaque Composition and Vessel Remodeling in Atherosclerotic Renal Artery Stenosis
Authors: Tetsuro Kataoka, Verghese Mathew, Ronen Rubinshtein, Charanjit S. Rihal, Ryan Lennon, Lilach O. Lerman, Amir Lerman
Journal: JACC. Cardiovascular imaging (2009)
IDH-Mutant Brain Tumors Hit the Achilles’ Heel of Macrophages with R-2-Hydroxyglutarate
Authors: Xanthe A.M.H. van Dierendonck, Kyra E. de Goede, Jan Van den Bossche
Journal: Trends in cancer (2021)

Isocitrate dehydrogenase (IDH) mutations produce high levels of the 'oncometabolite' R-2-hydroxyglutarate (R-2-HG) and play a key role in the initiation and progression of glioma tumors in the brain. A recent study in Nature Cancer by Friedrich et al. describes how IDH-mutant-derived R-2-HG elicits an immunosuppressive phenotype in glioma-associated macrophages. As such, the authors uncovered a new vulnerability that can be exploited for therapy.
A lump in the hand
Authors: Lydia Robb, Tim Buick, Philippa A Rust
Journal: BMJ (2021)

A man in his late 40s presented to his general practitioner with a history of skin changes and two lumps in his left hand, which had been present for several years. He thought the symptoms were from repeated trauma after carrying heavy buckets as part of his job. The nodular lumps had recently increased in size. In the months before referral, the patient began to experience a severe burning sensation in the nodules in his hand, which interrupted his sleep.

Examination of the hand revealed an area of skin tethering with a palpable thickening deep to it in the palm over the hypothenar eminence (fig 1, fig 2). Two small erythematous lumps were found, one proximal to the main lesion at the wrist crease and another on the ulnar border of the hypothenar eminence. In addition, the patient had numbness over the ulnar border of the hand, little finger, and half of the ring finger, and weakness in the intrinsic muscles of the hand (palmar and dorsal interossei). He …
Determining the effect size of aerobic exercise training on the standard lipid profile in sedentary adults with three or more metabolic syndrome factors: a systematic review and meta-analysis of randomised controlled trials
Authors: Gina Wood, Emily Taylor, Vanessa Ng, Anna Murrell, Aditya Patil, Tom van der Touw, Ronald Sigal, Mitch Wolden, Neil Smart
Journal: British Journal of Sports Medicine (2021)

Objectives To estimate the change in the standard lipid profile (SLP) of adults diagnosed with ≥3 metabolic syndrome (MetS) factors following aerobic exercise training (AET); and to investigate whether study/intervention covariates are associated with this change. Design Systematic review with univariate meta-analysis and meta-regression. Data sources English language searches of online databases from inception until July 2020. Eligibility criteria (1) Published randomised controlled human trials with study population ≥10 per group; (2) sedentary adults with ≥3 MetS factors but otherwise free of chronic disease, not pregnant/lactating; (3) AET-only intervention with duration ≥12 weeks; and (4) reporting pre–post intervention SLP outcomes. Results Various univariate meta-analyses pooled 48 data sets of 2990 participants. Aerobic exercise training significantly ( P &lt;.001) improved all lipids (mmol/L mean difference ranges, 95% CIs): total cholesterol, –0.19 (–0.26 to –0.12) to –0.29 (−0.36 to –0.21); triglycerides, −0.17 (–0.19 to –0.14) to –0.18 (−0.24 to –0.13); high-density lipoprotein-cholesterol (HDL-C), 0.05 (0.03 to 0.07) to 0.10 (0.05 to 0.15); and low-density lipoprotein-cholesterol (LDL-C), –0.12 (–0.16 to –0.9) to –0.20 (−0.25 to –0.14). Meta-regression showed that intensity may explain change in triglycerides and volume may explain change in HDL-C and LDL-C. Conclusion Aerobic exercise training positively changes the SLP of sedentary and otherwise healthy adults with ≥3 MetS factors. Adjusting AET intervention training variables may increase the effects of AET on triglycerides and HDL-C. PROSPERO registration number CRD42020151925.
Commensal microbiota regulates skin barrier function and repair via signaling through the aryl hydrocarbon receptor
Authors: Aayushi Uberoi, Casey Bartow-McKenney, Qi Zheng, Laurice Flowers, Amy Campbell, Simon A.B. Knight, Neal Chan, Monica Wei, Victoria Lovins, Julia Bugayev, Joseph Horwinski, Charles Bradley, Jason Meyer, Debra Crumrine, Carrie Hayes Sutter, Peter Elias, Elizabeth Mauldin, Thomas R. Sutter, Elizabeth A. Grice
Journal: Cell Host & Microbe (2021)
Health Equity and Medicaid Transformation — Operationalizing President Biden’s Agenda
Authors: Sara Rosenbaum
Journal: New England Journal of Medicine (2021)

Interview with Prof. Sara Rosenbaum on policy and operational challenges related to advancing the Medicaid program. (23:29)Download President Biden has made reforms intended to “protect and strengthen Medicaid” a centerpiece of his health policy agenda. Given Medicaid’s size and complexity, the administration faces myriad policy and operational challenges.
Site-specific antibody-drug conjugates with variable drug-to-antibody-ratios for AML therapy
Authors: Zhefu Dai, Xiao-Nan Zhang, Qinqin Cheng, Fan Fei, Tianling Hou, Jiawei Li, Alireza Abdolvahabi, Junji Watanabe, Hua Pei, Goar Smbatyan, Jianming Xie, Heinz-Josef Lenz, Stan G. Louie, Yong Zhang
Journal: Journal of Controlled Release (2021)
Effectiveness of BNT162b2 and ChAdOx1 nCoV-19 COVID-19 vaccination at preventing hospitalisations in people aged at least 80 years: a test-negative, case-control study
Authors: Catherine Hyams, Robin Marlow, Zandile Maseko, Jade King, Lana Ward, Kazminder Fox, Robyn Heath, Anabella Tuner, Zsolt Friedrich, Leigh Morrison, Gabriella Ruffino, Rupert Antico, David Adegbite, Zsuzsa Szasz-Benczur, Maria Garcia Gonzalez, Jennifer Oliver, Leon Danon, Adam Finn
Journal: The Lancet Infectious Diseases (2021)
An evidence that SARS-Cov-2/COVID-19 spike protein (SP) damages hematopoietic stem/progenitor cells in the mechanism of pyroptosis in Nlrp3 inflammasome-dependent manner
Authors: Magdalena Kucia, Janina Ratajczak, Kamila Bujko, Mateusz Adamiak, Andrzej Ciechanowicz, Vira Chumak, Katarzyna Brzezniakiewicz-Janus, Mariusz Z. Ratajczak
Journal: Leukemia (2021)
Steroid use in elderly critically ill COVID-19 patients
Authors: Christian Jung, Bernhard Wernly, Jesper Fjølner, Raphael Romano Bruno, David Dudzinski, Antonio Artigas, Bernardo Bollen Pinto, Joerg C. Schefold, Georg Wolff, Malte Kelm, Michael Beil, Sviri Sigal, Peter Vernon van Heerden, Wojciech Szczeklik, Miroslaw Czuczwar, Muhammed Elhadi, Michael Joannidis, Sandra Oeyen, Tilemachos Zafeiridis, Brian Marsh, Finn H. Andersen, Rui Moreno, Maurizio Cecconi, Susannah Leaver, Ariane Boumendil, Dylan W. De Lange, Bertrand Guidet, Hans Flaatten
Journal: European Respiratory Journal (2021)

<b>This secondary analysis of the COVIP study shows a higher 30-day mortality in critically ill elderly COVID-19 patients who received steroids as part of their treatment @cjungMD</b>https://bit.ly/3xdyEur
Intratumoral follicular regulatory T cells curtail anti-PD-1 treatment efficacy
Authors: Simon Eschweiler, James Clarke, Ciro Ramírez-Suástegui, Bharat Panwar, Ariel Madrigal, Serena J. Chee, Ioannis Karydis, Edwin Woo, Aiman Alzetani, Somaia Elsheikh, C. J. Hanley, G. J. Thomas, Peter S. Friedmann, Tilman Sanchez-Elsner, Ferhat Ay, Christian H. Ottensmeier, Pandurangan Vijayanand
Journal: Nature Immunology (2021)
Abstract 96: Simvastatin Prevents TGF-β1-induced SMAD2/3 Phosphorylation Involved in Ventricular Fibrosis: Role of Protein Phosphatases
Authors: Farhan Rizvi, Ramail Siddiqui, Alessandra DeFranco, Alisher Holmuhamedov, Hao Xu, Larisa Emelyanova, Gracious Ross, Yang Shi, Ekhson Holmuhamedov, A. Jamil Tajik, Arshad Jahangir
Journal: Circulation Research (2016)

Background: Ventricular fibrosis leads to progressive cardiac dysfunction and heart failure (HF). Statins are reported to reduce cardiac fibrosis through the cholesterol-independent pathway, but mechanisms remain elusive. We hypothesize simvastatin reduced TGF-β1-induced ventricular fibrosis through activation of SMAD protein phosphatase Mg 2+ /Mn 2+ -1A (PPM1A), -2A (PP2A). Methods: In the absence and presence of TGF-β1 (5ng) with or without simvastatin (1μM), the rate of fibroblast proliferation (doubling time), myofibroblast differentiation (ICC), α-SMA mRNA (RT-PCR) and protein expression (Western blot) and the release of collagen synthesis markers, pro-collagen type I C-terminal peptide (PICP) and pro-collagen type III N-terminal peptide (PIIINP), in the media (ELISA) were determined along with protein interaction between SMAD2/3 and PPM1A or PP2A (Co-IP) and SMAD2/3 phosphorylation (Western blot). Results: Simvastatin reduced the effect of TGF-β1 on hVF proliferation by 47% (50000 to 26500), p&lt;0.01; myofibroblast differentiated population from 48% (avg 48/100) to 11% (avg 11/100), p&lt;0.01; expression of α-SMA mRNA by 76%, p&lt;0.01; and protein by 60%, p&lt;0.05. Simvastatin also decreased release of PICP by 66%, p&lt;0.01, and PIIINP by 83%, p&lt;0.01, into the media. Time-dependent increases in SMAD2/3 phosphorylation were reduced by simvastatin through activation of protein phosphatases PPM1A and PP2A by interacting with SMAD2/3. Conclusion: Involvement of PPM1A and PP2A in the anti-fibrotic effect of simvastatin reveals novel signaling mediators that may be selectively targeted for prevention of myocardial injury-induced ventricular fibrosis and HF.
CMOS Time-to-Digital Converters for Biomedical Imaging Applications
Authors: Ryan Scott, Wei Jiang, M. Jamal Deen
Journal: IEEE Reviews in Biomedical Engineering (2021)

Time-to-digital converters (TDCs) are high-performance mixed-signal circuits capable of timestamping events with sub-gate delay resolution. As a result of their high-performance, in recent years TDCs were integrated in complementary metal-oxide-semiconductor (CMOS) technology with highly sensitive photodetectors known as single-photon avalanche diodes (SPADs), to form digital silicon photomultipliers (dSiPMs) and SPAD imagers. Time-resolved SPAD-based sensors are capable of detecting the absorption of a single photon and timestamping it with picosecond resolution. As such, SPAD-based sensors are very useful in the field of biomedical imaging, using time-of-flight (ToF) information to produce data that can be used to reconstruct high-quality biological images. Additionally, the capability of integration in standard CMOS technologies, allows SPAD-based sensors to provide high-performance, while maintaining low cost. In this paper, we present an overview of fundamental TDC principles, and an analysis of state-of-the-art TDCs. Furthermore, the integration of TDCs into dSiPMs and SPAD imagers will be discussed, with an analysis of the current results of TDCs in different biomedical imaging applications. Finally, several important research challenges for TDCs in biomedical imaging applications are presented.
Osteogenesis and angiogenesis of a bulk metallic glass for biomedical implants
Authors: K. Sun, R. Fu, X.W. Liu, L.M. Xu, G. Wang, S.Y. Chen, Q.J. Zhai, S. Pauly
Journal: Bioactive Materials (2021)

Implantation is an essential issue in orthopedic surgery. Bulk metallic glasses (BMGs), as a kind of novel materials, attract lots of attentions in biological field owing to their comprehensive excellent properties. Here, we show that a Zr
The Psychosocial Assessment of Patients Discharged from Accident and Emergency Departments after Deliberate Self-Poisoning
Authors: J Ebbage, C Farr, D V Skinner, P D White
Journal: Journal of the Royal Society of Medicine (1994)

One-third of accident and emergency (A &amp; E) patients who deliberately take an overdose are not admitted to hospital, and this proportion is increasing. We conducted an audit of 300 case records of such patients from two different district health authorities in London. We found that only 4% of patients were assessed in the manner recommended by the Department of Health and 10% had no psychosocial assessment whatsoever. We recommend specific training, an assessment form, regular audit, and communication with the general practitioner.
Reconceptualizing ‘Psychiatric Futility’: Could Harm Reduction, Palliative Psychiatry and Assisted Dying Constitute a Three-Component Spectrum of Appropriate Practices?
Authors: Jeffrey Kirby
Journal: The American Journal of Bioethics (2021)

Bianchi, Stanley, and Sutander (2021) argue in an insightful, cogent manner for the consideration of harm reduction as an ethically-defensible, non-paternal management approach for capable persons ...
Nail involvement in psoriatic arthritis patients is an independent risk factor for carotid plaque
Authors: Iris Jazmin Colunga-Pedraza, Dionicio Angel Galarza-Delgado, Jose Ramon Azpiri-Lopez, Alejandra Berenice Rodriguez-Romero, Natalia Guajardo-Jauregui, Jesus Alberto Cardenas-de la Garza, Salvador Lugo-Perez, Alejandro Meza-Garza, Julieta Loya-Acosta, Andrea Cecilia Garza-Acosta
Journal: Annals of the Rheumatic Diseases (2021)

Psoriatic arthritis (PsA) is a chronic, inflammatory and immune-mediated disease that affects up to 30% of psoriasis (PsO) patients.1 Nail involvement affects 80% of PsA patients and 30%–50% of PsO patients. Nail PsO has been associated with worse quality of life, higher score on the PsO Area Severity Index, early disease onset, arthritis, depression and anxiety.2 Patients with PsO and PsA have a higher risk of cardiovascular atherosclerotic morbidity and mortality than the general population. Nail PsO and cardiovascular disease have been seldom studied. Nail involvement in PsO patients has been associated to a higher prevalence of metabolic syndrome, higher risk of heart failure and higher cardiovascular risk overall.3 4 If PsA patients with nail PsO also have a higher cardiovascular risk is unknown. We aimed to determine if nail involvement in PsA patients is associated with a higher prevalence of subclinical atherosclerosis by carotid ultrasound.

We performed a cross-sectional, observational and comparative study that included a total of 64 PsA patients consecutively recruited from …
Abstract 469: Gene Expression Profiling Reveals Genes and Pathways Involved in the Cardiac Protection of Valosin-containing Protein in the Heart
Authors: Shaunrick Stoll, Xin Chen, Charles Wang, Hongyu Qiu
Journal: Circulation Research (2016)

Aims: Valosin-containing protein (VCP) participates in signaling pathways essential for cell homeostasis in multiple tissues, yet its role in mammalian heart remains largely unknown. Our recent studies showed that overexpression of VCP protects cardiomyocytes from stress- induced cell death in both in vitro and in vivo , however, it is unknown which target genes and pathways are regulated by VCP through which the heart may be protected from stress-induced injury. Here we provided the first in vivo evidence of the VCP-regulated target genes by microarray gene expression profiling in a transgenic mouse model. Methods and results: We generated a transgenic (TG) mouse that over-expressed 3.5 fold VCP specifically in the heart. Total RNA extracted from the heart tissues from both adult VCP TG and their litter-matched wild type (WT) mice (N=4/group) was assayed by using Affymetrix Mouse Genome 430 2.0 Array, which interrogates over 39,000 transcripts. Differentially expressed genes (DEGs) were defined by p-value ≤ 0.05 and FC (fold change) ≥ 1.5, and totally 581 DEGs were identified between VCP TG and WT. Applying a more stringent criteria (FDR ≤ 0.05 and FC ≥ 1.5), we identified 21 upregulated and 28 downregulated genes in VCP TG mouse hearts compared to WT. Among the top DEGs, there is a significant up-regulation in the genes regulating the stress response and oxidation in VCP TG versus WT, such as a kinase interacting protein by 2.6 folds which is a key regulator of cardiac stress; glutathione peroxidase 1 by 2.2 folds which is an antioxidant enzyme and anti-apoptotic mediators: protein kinase C delta by 2.3 folds and B-cell lymphoma 2 by 2.7 folds. VCP TG mice also exhibits an upregulation in the genes involved in cellular structure and contractility, e.g., alpha 1 actin by 3.3 folds, myosin light chain 9 by 8.2 folds and Tropomyosin 2 by 4.5 folds which is a gene regulating the binding of myosin and actin. Other DEGs include the upregulated-genes regulating cellular amino acid metabolism such as pterin-4 alpha-carbinolamine dehydratase by 9.7folds, phosphatidic acid phosphatase 2c by 3.4 folds and sortilin 1 by 2.4 folds. Conclusion: Significant difference of gene regulation exists between VCP TG and WT in the heart, which may be the mechanism of VCP-mediated cardiac protection.
Punctate Anetoderma After Colony-Stimulating Factor 1 Receptor and Programmed Cell Death 1 Blockade With Irradiation
Authors: Julia Dai, Yuanyuan Zha, Corey C. Foster, Jason J. Luke, Steven J. Chmura, Mark D. Hoffman
Journal: JAMA Dermatology (2021)

results are limited by the cross-sectional nature of this study, which prevents determination of causation, as well as by the study's location at specialized itch clinics, where disease manifestations may tend to be more severe.However, we hope that these findings encourage clinicians to learn more about these understudied yet bothersome and debilitating conditions, 4 as well as future research to improve management and treatment of neuropathic pruritus.
CPX-351 versus 7+3 cytarabine and daunorubicin chemotherapy in older adults with newly diagnosed high-risk or secondary acute myeloid leukaemia: 5-year results of a randomised, open-label, multicentre, phase 3 trial
Authors: Jeffrey E Lancet, Geoffrey L Uy, Laura F Newell, Tara L Lin, Ellen K Ritchie, Robert K Stuart, Stephen A Strickland, Donna Hogge, Scott R Solomon, Dale L Bixby, Jonathan E Kolitz, Gary J Schiller, Matthew J Wieduwilt, Daniel H Ryan, Stefan Faderl, Jorge E Cortes
Journal: The Lancet Haematology (2021)
SRC-1トランスクリプトームの全体的な特性評価により,内分泌腺耐性乳癌のER非依存性メディエーターとしてのADAM22が特定される
Authors: Mccartan Damian, C Bolger Jarlath, Fagan Ailis, Byrne Christopher, Hao Yuan, Qin Li, Mcllroy Marie, XU Jianming, D Hill Arnold, Gaora Peadar O, S Young Leonie
Journal: Cancer Research (2012)
Consultants will consider industrial action if government’s 1% pay rise offer is not improved
Authors: Matthew Limb
Journal: BMJ (2021)

Senior doctors will be consulted on taking industrial action if the government’s 1% pay rise offer is not improved, though they have vowed not to leave patients “unsupported.”

The BMA said on Friday 2 July that an overtime ban by consultants was a possibility to protect consultants’ pay, which had fallen by nearly 30% over the past decade.

“For the government to be suggesting a below-inflation pay award of 1% when inflation’s been projected at 4% is absolutely shocking,” Vishal Sharma, deputy chair of the BMA’s UK Consultants Committee, told the BBC Today programme. “It’s really left consultants angry and feeling underappreciated.”

Sharma said data …
Erectile function in men with type 2 diabetes treated with dulaglutide: an exploratory analysis of the REWIND placebo-controlled randomised trial
Authors: Harpreet S Bajaj, Hertzel C Gerstein, Purnima Rao-Melacini, Jan Basile, Helen Colhoun, Ignacio Conget, William C Cushman, Gilles R Dagenais, Edward Franek, Markolf Hanefeld, Matyas Keltai, Mark Lakshmanan, Fernando Lanas, Lawrence A Leiter, Patricio Lopez-Jaramillo, Valdis Pirags, Nana Pogosova, Jeffrey Probstfield, Peter Raubenheimer, Lars Ryden, Jonathan E Shaw, Wayne H-H Sheu, Denis Xavier
Journal: The Lancet Diabetes & Endocrinology (2021)