tbuckley/cabot-search huggingface dataset:
The curious case of the Danish mask study
Authors: Kamran Abbasi
Journal: BMJ (2020)

DANMASK-19, the first trial of mask use during covid-19, was "negative."Masks didn't work.We knew this before the trial was published because we were told so on social media.The authors were reported by the media to be struggling to find a major journal for their trial. 1Journals weren't proving brave enough to publish the study, said the authors, and they didn't make a preprint available.When the mythical trial was finally published last week in the Annals of Internal Medicine we didn't need to read it.We already knew its damning verdict on mask wearing.
182P Lenvatinib (LEN) plus anti-PD-1 antibodies vs LEN alone for advanced hepatocellular carcinoma (HCC): A real-world study
Authors: Q. Li, M. Chen, M. Cao, G. Yuan, X. Hu, W. Dai, M. Zang, X. Cheng, J. Huang, J. Hou, J. Chen
Journal: Annals of Oncology (2020)
The ACC professional life survey: career decisions of women and men in cardiology: A report of the Committee on Women in Cardiology 11Address for reprints: American College of Cardiology, 9111 Old Georgetown Road, Bethesda, Maryland 20814. Attention: Educational Services Department (800-257-4740).
Authors: MarianC Limacher, CarolA Zaher, MaryN Walsh, WendyJ Wolf, PamelaS Douglas, JaniceB Schwartz, JanetS Wright, DavidP Bodycombe
Journal: Journal of the American College of Cardiology (1998)
68TiP KEYLYNK-009: A phase II/III, open-label, randomized study of pembrolizumab (pembro) + olaparib (ola) vs pembro + chemotherapy after induction with first-line (1L) pembro + chemo in patients (pts) with locally recurrent inoperable or metastatic TNBC
Authors: S. Saji, A. Llombart Cussac, F. Andre, M.E. Robson, N. Harbeck, P. Schmid, D.W. Cescon, J.S. Ahn, R. Nanda, L. Fan, J.A. Mejia, V. Karantza, A. Bardia, H.S. Rugo
Journal: Annals of Oncology (2020)
394P Apatinib plus etoposide capsules as third-line or further-line treatment for extensive stage small cell lung cancer patients: A multicenter, single arm, phase II clinical trial
Authors: Z. He, C. Xu, G. Chen, J. Wang, X. Zhang, P. Wang, T. Ma, Y. Zhang, C. Tian, Y. Chen, M. Zou, Y. Han, L. Wang, S. Ma, H. Chen, Y. Wu, X. Wu, S. Yang, Y. Gao, Q. Wang
Journal: Annals of Oncology (2020)
Abstract 15087: Canagliflozin, a SGLT2 Inhibitor Improves Skeletal Muscle Function in High-Fat Diet-Fed Obesity Mice
Authors: Tomohiro Komatsu, Satomi Abe, Shihoko Nakashima, Eri Soneda, Yasuki Higaki, Yoshinari Uehara
Journal: Circulation (2019)

Introduction: Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been demonstrated to prevent heart failure and cardiovascular death in patients with type 2 diabetes and cardiovascular disease....
Retraction: Antitumor Effects of a Novel Phenylbutyrate-based Histone Deacetylase Inhibitor, (<i>S</i>)-HDAC-42, in Prostate Cancer
Authors: Samuel K. Kulp, Chang-Shi Chen, Da-Sheng Wang, Ching-Yu Chen, Ching-Shih Chen
Journal: Clinical Cancer Research (2019)
162P Evaluation of neutrophil/lymphocyte ratio (NLR) in monitoring anastomotic leakage after radical total gastrectomy for gastric cancer
Authors: R-H. Tu, Z-K. Wang, J-P. Lin, J-X. Lin, C-H. Zheng, P. Li, J-W. Xie, J-B. Wang, J. Lu, Q-Y. Chen, L-L. Cao, M. Lin, Z-N. Huang, J-L. Lin, H-L. Zheng, C. Huang
Journal: Annals of Oncology (2020)
Abstract PO-040: The role of mTOR in epigenetic regulation in cancer
Authors: HaEun Kim, David Papadopoli, Ivan Topisirovic
Journal: Cancer Research (2020)

Abstract Changes in gene expression, including those caused by epigenetic dysregulation, represent a hallmark of cancer. The mechanistic/mammalian Target of Rapamycin (mTOR) is a serine/threonine kinase that coordinates nutrient availability to the regulation of cell growth and metabolism, which is frequently perturbed in cancer. mTOR exists in two structurally and functionally divergent complexes, mTOR complex 1 and 2 (mTORC1 and 2). mTORC1 regulates many metabolic pathways, including the serine-glycine-one carbon network (SGOC), a pathway modulating the production of S-adenosyl methionine (SAM) and α-ketoglutarate (α-KG). The latter two metabolites constitute essential co-substrates of histone methyltransferases and demethylases, respectively. However, how mTOR signaling controls epigenetic dynamics remains largely unknown. To address this important gap in knowledge, we treated two breast cancer cell lines (MCF7 and T47D) with allosteric (rapamycin) and active-site (INK128) mTOR inhibitors to study how mTOR may influence global histone methylation. We found that mTOR inhibitors significantly increased histone 3 lysine 9 tri-methylation (H3K9me3) and histone 3 lysine 27 tri-methylation (H3K27me3) but not histone 3 lysine 4 tri-methylation (H3K4me3) suggesting this effect was selective. Metabolomic tools were employed to decipher changes of epigenetic metabolites α-KG, SAM, S-Adenosyl homocysteine (SAH), methionine, and serine upon mTOR inhibition. These findings provide bases for my future work which will focus on establishing the role of alterations in mTOR signaling on epigenetic programs which drive tumorigenesis. A better understanding of this network may help identify new therapeutic targets to improve current cancer treatments. Citation Format: HaEun Kim, David Papadopoli, Ivan Topisirovic. The role of mTOR in epigenetic regulation in cancer [abstract]. In: Abstracts: AACR Special Virtual Conference on Epigenetics and Metabolism; October 15-16, 2020; 2020 Oct 15-16. Philadelphia (PA): AACR; Cancer Res 2020;80(23 Suppl):Abstract nr PO-040.
Outcomes of therapy with venetoclax combined with a hypomethylating agent in favorable‐risk acute myeloid leukemia
Authors: Shukaib Arslan, Jianying Zhang, Prajwal Dhakal, Jenna Moran, Nuthana Naidoo, Jennifer Lombardi, Vinod Pullarkat, Anthony S. Stein, Guido Marcucci, George Yaghmour, Vijaya R. Bhatt, Amir T. Fathi, Ibrahim Aldoss
Journal: American Journal of Hematology (2020)

towards better response in patients with less severe mutations (non-β0/β0).Together, these observations suggest that NTDT patients may be considered in future studies with interventions targeting the underlying genetic abnormality, especially when the risk-benefit ratio is low.
Abstract 11838: Cardiac Tissue Factor Regulates Inflammation and Hypertrophy in Mouse Model of Type 1 Diabetes Mellitus
Authors: Anamika Singh, Cibi M Dasan, Reddemma Sandireddy, Nicole Tee, Nigel Mackman, Manvendra Singh
Journal: Circulation (2019)

Introduction: Diabetes mellitus (DM) is on the rise and cardiovascular diseases cause highest mortality in DM. Patients with DM have increased risk of heart failure (HF). Diabetes has higher preval...
Risk Factors for Morbidity and Mortality Following Hospitalization for Pericarditis
Authors: Flora L. Sigvardt, Morten L. Hansen, Søren L. Kristensen, Finn Gustafsson, Muzhda Ghanizada, Morten Schou, Lars Køber, Christian Torp-Pedersen, Gunnar H. Gislason, Christian Madelaire
Journal: Journal of the American College of Cardiology (2020)
Thrombocytopenia and thrombosis in hospitalized patients with COVID-19
Authors: Heng Mei, Lili Luo, Yu Hu
Journal: Journal of Hematology & Oncology (2020)

Abstract As our understanding on coronavirus disease 2019 (COVID-19) deepens, it is increasingly recognized that COVID-19 is more than a respiratory condition. Thrombocytopenia and thromboembolic complications are a composite factor associated with critical COVID-19 and increased mortality. Immune-inflammation-mediated destruction, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection per se and increased consumption are proposed to be responsible for thrombocytopenia. Multiple concomitant conditions or results caused by SARS-CoV-2 infection are high risk factors for thrombosis. Recently, platelet activation and platelet-mediated immune inflammation induced by SARS-CoV-2 infection were also found to be the contributors to the thrombosis in COVID-19 patients. In addition to thrombus scoring system, D-dimer is an excellent indicator for monitoring thrombosis. COVID-19 patients with high risk for thrombosis should be subjected to early thromboprophylaxis, and prolonged activated partial-thromboplastin time should not be a barrier to the use of anticoagulation therapies in the control of thrombosis in COVID-19 patients.
Abstract IA14: Increasing viral mimicry with vitamin C
Authors: Peter A. Jones
Journal: Cancer Research (2020)

Abstract Responses of MDS patients to DNA methylation inhibitors (DNMTis) is due in part to the induction of expression of transposable elements, particularly endogenous retroviruses (ERVs). Induction of these transcripts leads to an innate immune response which may be responsible for the clinical efficacy of the drugs and we have called this “viral mimicry”. We investigated whether physiological concentrations of vitamin C given simultaneously with treatment with DNMTis would increase the expression of ERVs. The rationale being that the TET enzymes require vitamin C for their maximum activities, and we hypothesized that the induction of 5-hydroxymethylcytosine would stimulate the expression of these retroviruses. Experiments in culture showed that addition of vitamin C, strongly increases the expression of ERVs and increases the formation of 5-hydroxymethylcytosine during treatment. This is important since culture medium is mostly not supplemented with vitamin C. In more recent patient trials we have shown that responses to DNMTis may indeed be partially due to the induction of ERVs. Because we and others have shown that many patients in hematology clinics are severely vitamin C deficient, we are now exploring whether restoration of vitamin C levels to normal may potentiate the activities of the DNMTis. Preliminary data shows that oral administration of vitamin C increases the expression of ERVs and also the quantity of 5-hydroxymethylcytosine in the DNA of circulating cells. We have now designed a prospective clinical trial to test these hypothesis and preliminary data will be presented. Citation Format: Peter A. Jones. Increasing viral mimicry with vitamin C [abstract]. In: Abstracts: AACR Special Virtual Conference on Epigenetics and Metabolism; October 15-16, 2020; 2020 Oct 15-16. Philadelphia (PA): AACR; Cancer Res 2020;80(23 Suppl):Abstract nr IA14.
Diagnostic application of sound speed correction for endoscopic ultrasound-guided tissue acquisition of pancreatic mass
Authors: Wei-Qing Chen, Xu Tian
Journal: Endoscopy (2020)

Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is a preferred option for acquiring samples from a solid pancreatic lesion [1] [2]. However, inadequate samples will cause a false-negative diagnosis [3]. It is thus imperative to acquire adequate tissue specimens to improve the accuracy of histological examination [4].
Combining Nivolumab and Ipilimumab with Infliximab or Certolizumab in Patients with Advanced Melanoma: First Results of a Phase Ib Clinical Trial
Authors: Anne Montfort, Thomas Filleron, Mathieu Virazels, Carine Dufau, Jean Milhès, Cécile Pagès, Pascale Olivier, Maha Ayyoub, Muriel Mounier, Amélie Lusque, Stéphanie Brayer, Jean-Pierre Delord, Nathalie Andrieu-Abadie, Thierry Levade, Céline Colacios, Bruno Ségui, Nicolas Meyer
Journal: Clinical Cancer Research (2020)

TNF blockers can be used to manage gastrointestinal inflammatory side effects following nivolumab and/or ipilimumab treatment in patients with advanced melanoma. Our preclinical data showed that anti-TNF could promote the efficacy of immune checkpoint inhibitors.TICIMEL (NTC03293784) is an open-label, two-arm phase Ib clinical trial. Fourteen patients with advanced and/or metastatic melanoma (stage IIIc/IV) were enrolled. Patients were treated with nivolumab (1 mg/kg) and ipilimumab (3 mg/kg) combined to infliximab (5 mg/kg, N = 6) or certolizumab (400/200 mg, N = 8). The primary endpoint was safety and the secondary endpoint was antitumor activity. Adverse events (AEs) were graded according to the NCI Common Terminology Criteria for Adverse Events and response was assessed following RECIST 1.1.Only one dose-limiting toxicity was observed in the infliximab cohort. The two different combinations were found to be safe. We observed lower treatment-related AEs with infliximab as compared with certolizumab. In the certolizumab cohort, one patient was not evaluable for response. In this cohort, four of eight patients exhibited hepatobiliary disorders and seven of seven evaluable patients achieved objective response including four complete responses (CRs) and three partial responses (PRs). In the infliximab cohort, we observed one CR, two PRs, and three progressive diseases. Signs of activation and maturation of systemic T-cell responses were seen in patients from both cohorts.Our results show that both combinations are safe in human and provide clinical and biological activities. The high response rate in the certolizumab-treated patient cohort deserves further investigations.
Plant Exosome-like Nanovesicles: Emerging Therapeutics and Drug Delivery Nanoplatforms
Authors: Haseeb Anwar Dad, Ting-Wei Gu, Ao-Qing Zhu, Lu-Qi Huang, Li-Hua Peng
Journal: Molecular Therapy (2020)

Plant exosome-like nanovesicles, being innately replete with bioactive lipids, proteins, RNA, and other pharmacologically active molecules, offer unique morphological and compositional characteristics as natural nanocarriers. Furthermore, their compelling physicochemical traits underpin their modulative role in physiological processes, all of which have fostered the concept that these nanovesicles may be highly proficient in the development of next-generation biotherapeutic and drug delivery nanoplatforms to meet the ever-stringent demands of current clinical challenges. This review systemically deals with various facets of plant exosome-like nanovesicles ranging from their origin and isolation to identification of morphological composition, biological functions, and cargo-loading mechanisms. Efforts are made to encompass their biotherapeutic roles by elucidating their immunological modulating, anti-tumor, regenerative, and anti-inflammatory roles. We also shed light on re-engineering these nanovesicles into robust, innocuous, and non-immunogenic nanovectors for drug delivery through multiple stringent biological hindrances to various targeted organs such as intestine and brain. Finally, recent advances centered around plant exosome-like nanovesicles along with new insights into transdermal, transmembrane and targeting mechanisms of these vesicles are also elucidated. We expect that the continuing development of plant exosome-like nanovesicle-based therapeutic and delivery nanoplatforms will promote their clinical applications.
How to optimise duration of antibiotic treatment in patients with sepsis?
Authors: TP Hellyer, T Mantle, R McMullan, P Dark
Journal: BMJ (2020)

### What you need to know

Sepsis occurs when the body’s response to infection is imbalanced. It can result in life threatening organ dysfunction.1 About 49 million patients had sepsis worldwide in 2017 and 11 million people died of the condition.2 Among those hospitalised with sepsis, 17% die in hospital and a further 15% die within a year of hospital discharge.34

Antibiotics represent the cornerstone of treatment. The Surviving Sepsis Campaign (SSC) consensus guidelines recommend treatment for 7 to 10 days, but this is a weak recommendation.5 Use of antibiotics risks the emergence of antimicrobial resistance and antibiotic-associated infections, such as Clostridiodes difficile . Patients may suffer from toxic effects of the drugs.6 Balancing the need to treat severe infections effectively against the risks of overuse of antibiotics is central to the principle of antibiotic stewardship. For severe covid-19, antibiotic stewardship remains important for critically ill patients with pneumonitis and sepsis who are commonly treated with broad spectrum antibiotics.7 Antibiotic overuse in sepsis results in substantial risk of acquiring difficult-to-treat infections, with further risk of sepsis and poor patient outcomes.5

The optimum duration of antibiotic treatment for patients with sepsis is uncertain. A biomarker-guided approach—for example, using serial measurements of procalcitonin to determine optimal duration of antibiotics—has been studied. Trials …
Impact of 9-Minute Withdrawal Time on the Adenoma Detection Rate: A Multicenter Randomized Controlled Trial
Authors: Shengbing Zhao, Xia Yang, Shuling Wang, Qianqian Meng, Rundong Wang, Lumin Bo, Xin Chang, Peng Pan, Tian Xia, Fan Yang, Jun Yao, Jinghua Zheng, Jianqiu Sheng, Xiaojun Zhao, Shan Tang, Yali Wang, Yiping Wang, Aixia Gong, Weigang Chen, Jianwei Shen, Xian Zhu, Shaofeng Wang, Caiwen Yan, Youlin Yang, Yangbei Zhu, Rui-Jun Ma, Rong Wang, Yingcai Ma, Zhaoshen Li, Yu Bai
Journal: Clinical Gastroenterology and Hepatology (2020)
Regional binding of tau and amyloid PET tracers in Down syndrome autopsy brain tissue
Authors: L. Lemoine, A. Ledreux, E. J. Mufson, S. E. Perez, G. Simic, E. Doran, I. Lott, S. Carroll, K. Bharani, S. Thomas, A. Gilmore, E. D. Hamlett, A. Nordberg, A. C. Granholm
Journal: Molecular Neurodegeneration (2020)

Abstract Introduction Tau pathology is a major age-related event in Down syndrome with Alzheimer’s disease (DS-AD). Although recently, several different Tau PET tracers have been developed as biomarkers for AD, these tracers showed different binding properties in Alzheimer disease and other non-AD tauopathies. They have not been yet investigated in tissue obtained postmortem for DS-AD cases. Here, we evaluated the binding characteristics of two Tau PET tracers ( 3 H-MK6240 and 3 H-THK5117) and one amyloid ( 3 H-PIB) ligand in the medial frontal gyrus (MFG) and hippocampus (HIPP) in tissue from adults with DS-AD and DS cases with mild cognitive impairment (MCI) compared to sporadic AD. Methods Tau and amyloid autoradiography were performed on paraffin-embedded sections. To confirm respective ligand targets, adjacent sections were immunoreacted for phospho-Tau (AT8) and stained for amyloid staining using Amylo-Glo. Results The two Tau tracers showed a significant correlation with each other and with AT8, suggesting that both tracers were binding to Tau deposits. 3 H-MK6240 Tau binding correlated with AT8 immunostaining but to a lesser degree than the 3 H-THK5117 tracer, suggesting differences in binding sites between the two Tau tracers. 3 H-THK5117, 3 H-MK6240 and 3 H-PIB displayed dense laminar binding in the HIPP and MFG in adult DS brains. A regional difference in Tau binding between adult DS and AD was observed suggesting differential regional Tau deposition in adult DS compared to AD, with higher THK binding density in the MFG in adult with DS compared to AD. No significant correlation was found between 3 H-PIB and Amylo-Glo staining in adult DS brains suggesting that the amyloid PIB tracer binds to additional sites. Conclusions This study provides new insights into the regional binding distribution of a first-generation and a second-generation Tau tracer in limbic and neocortical regions in adults with DS, as well as regional differences in Tau binding in adult with DS vs. those with AD. These findings provide new information about the binding properties of two Tau radiotracers for the detection of Tau pathology in adults with DS in vivo and provide valuable data regarding Tau vs. amyloid binding in adult DS compared to AD.
Cost-effectiveness of Screening for Osteoporosis in Older Men With a History of Falls
Authors: Kouta Ito
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Falls and osteoporosis share the potential clinical end point of fractures among older patients. To date, few fall prevention guidelines incorporate screening for osteoporosis to reduce fall-related fractures. <h3>Objective</h3> To assess the cost-effectiveness of screening for osteoporosis using dual-energy x-ray absorptiometry (DXA) followed by osteoporosis treatment in older men with a history of falls. <h3>Design, Setting, and Participants</h3> In this economic evaluation, a Markov model was developed to simulate the incidence of major osteoporotic fractures in a hypothetical cohort of community-dwelling men aged 65 years who had fallen at least once in the past year. Data sources included literature published from January 1, 1946, to July 31, 2020. The model adopted a societal perspective, a lifetime horizon, a 1-year cycle length, and a discount rate of 3% per year for both health benefits and costs. The analysis was designed and conducted from October 1, 2019, to September 30, 2020. <h3>Interventions</h3> Screening with DXA followed by treatment for men diagnosed with osteoporosis compared with usual care. <h3>Main Outcomes and Measures</h3> Incremental cost-effectiveness ratio (ICER), measured by cost per quality-adjusted life-year (QALY) gained. <h3>Results</h3> Among the hypothetical cohort of men aged 65 years, the screening strategy had an ICER of $33 169/QALY gained and was preferred over usual care at the willingness-to-pay threshold of $100 000/QALY gained. The number needed to screen to prevent 1 hip fracture was 1876; to prevent 1 major osteoporotic fracture, 746. The screening strategy would become more effective and less costly than usual care for men 77 years and older. The ICER for the screening strategy did not substantially change across a wide range of assumptions tested in all other deterministic sensitivity analyses. At a willingness-to-pay threshold of $50 000/QALY gained, screening was cost-effective in 56.0% of simulations; at $100 000/QALY gained, 90.8% of simulations; and at $200 000/QALY gained, 99.6% of simulations. <h3>Conclusions and Relevance</h3> These findings suggest that for older men who have fallen at least once in the past year, screening with DXA followed by treatment for those diagnosed with osteoporosis is a cost-effective use of resources. Fall history could be a useful cue to trigger assessment for osteoporosis in men.