tbuckley/cabot-search huggingface dataset:
Effect of CD47 Blockade on Vascular Inflammation
Authors: Kai-Uwe Jarr, Ryusuke Nakamoto, Brandon H Doan, Yoko Kojima, Irving L Weissman, Ranjana H Advani, Andrei Iagaru, Nicholas J Leeper
Journal: New England Journal of Medicine (2021)

may reduce arterial 18 F-FDG uptake and suppress vascular inflammation.These preliminary observations require confirmation in a prospective trial.
SAT0115 Efficacy of celecoxib in patients with acute shoulder pain: randomised double-blind comparison with naproxen
Authors: P Bertin, JM Behier, E Noel, JL Leroux, H Herman, I Jolchine
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> To evaluate and compare the efficacy of 14-day dosing with celecoxib 200 mg BID and naproxen 500 mg BID in patients with acute shoulder pain. <h3>Methods</h3> Patients with pain onset within the previous 14 days and pain intensity of &gt; = 40 mm on a 100-mm VAS were randomly assigned to enter one of two parallel groups of a double-blind controlled, multicenter study. The primary assessment was pain at rest. <h3>Results</h3> The primary ITT analysis was conducted in 202 randomised and treated patients, 99 in the celecoxib group and 103 in the naproxen group. Baseline characteristics were similar (47 ± 12 years of age; mean duration of acute episode, 5.6 ± 5.1 days). At 14 days, the mean (± SE) decrease in pain at rest was not statistically significantly different between the two groups. According to the limits of 95% CI of the difference between groups, celecoxib seemed to be at least as effective as naproxen. Fewer patients experienced epigastric pain with celecoxib (7 patients vs 14 with naproxen). This adverse event led to treatment discontinuation in 2 patients receiving celecoxib and 5 receiving naproxen. One patient with a history of ulcer had duodenitis (Hp positive) in the celecoxib group. <h3>Conclusion</h3> This study provides data in favour of the use of celecoxib, which is probably at least as effective as naproxen in acute shoulder pain. Observed upper GI events rates in this study of limited sample size do not permit drawing conclusions in terms of improved GI safety, which has previously been shown in larger randomised controlled trials. Sponsored by Pharmacia Corporation and Pfizer, Inc.
Intensive Care Unit Strain and Mortality Risk Among Critically Ill Patients With COVID-19—There Is No “Me” in COVID
Authors: Lewis Rubinson
Journal: JAMA Network Open (2021)

Dawn M. Bravata, MD; Anthony J. Perkins, MS; Laura J. Myers, PhD; Greg Arling, PhD; Ying Zhang, PhD; Alan J. Zillich, PharmD; Lindsey Reese, MD; Andrew Dysangco, MD; Rajiv Agarwal, MD; Jennifer Myers, MSW; Charles Austin, MDiv; Ali Sexson, MBA; Samuel J. Leonard, MS; Sharmistha Dev, MD; Salomeh Keyhani, MD, MPH
Diagnosis and referral of adults with suspected bony metastases
Authors: Samantha Downie, Elizabeth Bryden, Fergus Perks, A Hamish RW Simpson
Journal: BMJ (2021)

### What you need to know

Of the 44 million people worldwide who are living with treated cancer, 30-80% will experience bone metastases.12345 Metastatic bone disease (MBD) can lead to pain, loss of function, and pathological (low energy) fractures.67

Patients can present to any specialty, and half of those with a first recurrence present to primary care.8 Initial diagnosis can be difficult as lesions may not be visible on radiographs until 50-70% of bone has been destroyed.9 Early treatment can reduce the need for surgery and improve outcomes101112; therefore, a high degree of suspicion is essential when assessing cancer patients with new bone pain.

Despite evidence that outcomes are better when we operate to stabilise bony lesions before they break, more than half of patients are not referred for surgery until they have sustained a pathological fracture.41314

Guidelines from the British Orthopaedic Oncology Society for good practice in metastatic bone disease were published in 201512 and called for targeted guidance for oncology and primary care to ensure that patients who could benefit from surgery were referred to their …
Impaired Kv7 channel activity in the central amygdala contributes to elevated sympathetic outflow in hypertension
Authors: Zhao-Fu Sheng, Hua Zhang, PeiRu Zheng, Shanyan Chen, Zezong Gu, Jing-Jing Zhou, Jeffery G Phaup, Hui-Ming Chang, Edward T H Yeh, Hui-Lin Pan, De-Pei Li
Journal: Cardiovascular Research (2021)

Abstract Aims Elevated sympathetic outflow is associated with primary hypertension. However, the mechanisms involved in heightened sympathetic outflow in hypertension are unclear. The central amygdala (CeA) regulates autonomic components of emotions through projections to the brainstem. The neuronal Kv7 channel is a non-inactivating voltage-dependent K+ channel encoded by KCNQ2/3 genes involved in stabilizing the neuronal membrane potential and regulating neuronal excitability. In this study, we investigated if altered Kv7 channel activity in the CeA contributes to heightened sympathetic outflow in hypertension. Methods and results The mRNA and protein expression levels of Kv7.2/Kv7.3 in the CeA were significantly reduced in spontaneously hypertensive rats (SHRs) compared with Wistar–Kyoto (WKY) rats. Lowering blood pressure with coeliac ganglionectomy in SHRs did not alter Kv7.2 and Kv7.3 channel expression levels in the CeA. Fluospheres were injected into the rostral ventrolateral medulla (RVLM) to retrogradely label CeA neurons projecting to the RVLM (CeA–RVLM neurons). Kv7 channel currents recorded from CeA–RVLM neurons in brain slices were much smaller in SHRs than in WKY rats. Furthermore, the basal firing activity of CeA–RVLM neurons was significantly greater in SHRs than in WKY rats. Bath application of specific Kv7 channel blocker 10, 10-bis (4-pyridinylmethyl)-9(10H)-anthracnose (XE-991) increased the excitability of CeA–RVLM neurons in WKY rats, but not in SHRs. Microinjection of XE-991 into the CeA increased arterial blood pressure (ABP) and renal sympathetic nerve activity (RSNA), while microinjection of Kv7 channel opener QO-58 decreased ABP and RSNA, in anaesthetized WKY rats but not SHRs. Conclusions Our findings suggest that diminished Kv7 channel activity in the CeA contributes to elevated sympathetic outflow in primary hypertension. This novel information provides new mechanistic insight into the pathogenesis of neurogenic hypertension.
Evaluation of oral dextrose gel for prevention of neonatal hypoglycemia (hPOD): A multicenter, double-blind randomized controlled trial
Authors: Jane E. Harding, Joanne E. Hegarty, Caroline A. Crowther, Richard P. Edlin, Gregory D. Gamble, Jane M. Alsweiler
Journal: PLoS Medicine (2021)

Background Neonatal hypoglycemia is common and can cause brain injury. Buccal dextrose gel is effective for treatment of neonatal hypoglycemia, and when used for prevention may reduce the incidence of hypoglycemia in babies at risk, but its clinical utility remains uncertain. Methods and findings We conducted a multicenter, double-blinded, placebo-controlled randomized trial in 18 New Zealand and Australian maternity hospitals from January 2015 to May 2019. Babies at risk of neonatal hypoglycemia (maternal diabetes, late preterm, or high or low birthweight) without indications for neonatal intensive care unit (NICU) admission were randomized to 0.5 ml/kg buccal 40% dextrose or placebo gel at 1 hour of age. Primary outcome was NICU admission, with power to detect a 4% absolute reduction. Secondary outcomes included hypoglycemia, NICU admission for hypoglycemia, hyperglycemia, breastfeeding at discharge, formula feeding at 6 weeks, and maternal satisfaction. Families and clinical and study staff were unaware of treatment allocation. A total of 2,149 babies were randomized (48.7% girls). NICU admission occurred for 111/1,070 (10.4%) randomized to dextrose gel and 100/1,063 (9.4%) randomized to placebo (adjusted relative risk [aRR] 1.10; 95% CI 0.86, 1.42; p = 0.44). Babies randomized to dextrose gel were less likely to become hypoglycemic (blood glucose &lt; 2.6 mmol/l) (399/1,070, 37%, versus 448/1,063, 42%; aRR 0.88; 95% CI 0.80, 0.98; p = 0.02) although NICU admission for hypoglycemia was similar between groups (65/1,070, 6.1%, versus 48/1,063, 4.5%; aRR 1.35; 95% CI 0.94, 1.94; p = 0.10). There were no differences between groups in breastfeeding at discharge from hospital (aRR 1.00; 95% CI 0.99, 1.02; p = 0.67), receipt of formula before discharge (aRR 0.99; 95% CI 0.92, 1.08; p = 0.90), and formula feeding at 6 weeks (aRR 1.01; 95% CI 0.93, 1.10; p = 0.81), and there was no hyperglycemia. Most mothers (95%) would recommend the study to friends. No adverse effects, including 2 deaths in each group, were attributable to dextrose gel. Limitations of this study included that most participants (81%) were infants of mothers with diabetes, which may limit generalizability, and a less reliable analyzer was used in 16.5% of glucose measurements. Conclusions In this placebo-controlled randomized trial, prophylactic dextrose gel 200 mg/kg did not reduce NICU admission in babies at risk of hypoglycemia but did reduce hypoglycemia. Long-term follow-up is needed to determine the clinical utility of this strategy. Trial registration ACTRN 12614001263684 .
Abstract 15809: Large Gaps in Coverage of Effective Policies to Prevent Youth Smoking Initiation: A Systematic Analysis of 195 Countries and Territories
Authors: Marissa B Reitsma, Vin Gupta, Thomas Hsiao, Hayley Tymeson, Nicholas Arian, Austin Tapp, Emmanuela Gakidou
Journal: Circulation (2019)

Introduction: Studies from high-income countries demonstrate that youth are particularly vulnerable to addiction. Global data on youth smoking initiation are needed to effectively target policies t...
SequencErr: measuring and suppressing sequencer errors in next-generation sequencing data
Authors: Eric M. Davis, Yu Sun, Yanling Liu, Pandurang Kolekar, Ying Shao, Karol Szlachta, Heather L. Mulder, Dongren Ren, Stephen V. Rice, Zhaoming Wang, Joy Nakitandwe, Alexander M. Gout, Bridget Shaner, Salina Hall, Leslie L. Robison, Stanley Pounds, Jeffery M. Klco, John Easton, Xiaotu Ma
Journal: Genome biology (2021)

There is currently no method to precisely measure the errors that occur in the sequencing instrument/sequencer, which is critical for next-generation sequencing applications aimed at discovering the genetic makeup of heterogeneous cellular populations.We propose a novel computational method, SequencErr, to address this challenge by measuring the base correspondence between overlapping regions in forward and reverse reads. An analysis of 3777 public datasets from 75 research institutions in 18 countries revealed the sequencer error rate to be ~ 10 per million (pm) and 1.4% of sequencers and 2.7% of flow cells have error rates > 100 pm. At the flow cell level, error rates are elevated in the bottom surfaces and > 90% of HiSeq and NovaSeq flow cells have at least one outlier error-prone tile. By sequencing a common DNA library on different sequencers, we demonstrate that sequencers with high error rates have reduced overall sequencing accuracy, and removal of outlier error-prone tiles improves sequencing accuracy. We demonstrate that SequencErr can reveal novel insights relative to the popular quality control method FastQC and achieve a 10-fold lower error rate than popular error correction methods including Lighter and Musket.Our study reveals novel insights into the nature of DNA sequencing errors incurred on DNA sequencers. Our method can be used to assess, calibrate, and monitor sequencer accuracy, and to computationally suppress sequencer errors in existing datasets.
Genetic loci shared between major depression and intelligence with mixed directions of effect
Authors: Shahram Bahrami, Alexey Shadrin, Oleksandr Frei, Kevin S. O’Connell, Francesco Bettella, Florian Krull, Chun C. Fan, Jan I. Røssberg, Guy Hindley, Torill Ueland, Anders M. Dale, Srdjan Djurovic, Nils Eiel Steen, Olav B. Smeland, Ole A. Andreassen
Journal: Nature Human Behaviour (2021)
One piece of the jigsaw for the cancerrecovery strategy: Prevalence of COVID-19 in patients with cancer
Authors: C. Moss, B. Russell, M. Lei, S. Ghosh, S. Papa, R. Sullivan, M. Van Hemelrijck, A. Rigg
Journal: Clinical Cancer Research (2020)

Background: COVID-19 has forced governments to make drastic changes to the health care system  While thesemay have reduced COVID-19 morbidity/mortality, there have been unintended consequences on society and non-COVID-19 health issues  Although initial data start to inform us how to care for cancer patients during COVID-19, there is as yet no long-term follow-up  To start making informed decisions about cancer care, it is crucial tounderstand the scale of COVID-19 infection in cancer patients  Therefore, we introduced swab testing for patientsvisiting Guy's Cancer Centre  Methods: Our Centre in South-East London treats approximately 8,800 patients annually (including 4,500 newdiagnoses) and is one of the largest Comprehensive Cancer Centres in the UK at the epicenter of the UK COVID-19epidemic  The first COVID-19-positive cancer patient was reported on 29 February, 2020  Until 30 April, 2020, aCOVID-19 swab was ordered for cancer patients with symptoms necessitating hospitalization or if they werescheduled to undergo a cancer-related treatment  From 1 May, 2020, COVID-19 testing was introduced as standardof care, with about 25% of patients being swabbed daily depending upon staff and testing kit availability  Weanalyzed data from 7-15 May, 2020 for COVID-19 test results in all cancer patients at our Centre  Results: 2,647 patients attended for outpatient, chemotherapy, or radiotherapy appointments from across SouthEast London (and England)  Of these, 654 were swabbed for COVID-19 (25%)  Over 57% of patients filled out asymptom assessment, and 97% were asymptomatic  Of the patients tested, nine were positive for COVID-19(1 38%) of whom seven were asymptomatic  Based on data from the Office for National Statistics, between 28 April-10 May, 2020, 0 27% of the community population had COVID-19 (95%CI: 0 17-0 41)  However, for those working inpatient-facing health care or resident-facing social care roles, this was estimated at 1 33% (95CI%: 0 39-3 28) Nevertheless, London has been the region hardest hit by COVID-19, so the rate of 1 38% among asymptomaticcancer patients, the majority of whom will have been shielding, is likely to be more representative of the localsituation  However, this “snapshot” of prevalence is not enough for an evolving situation  Conclusion: Cancer service providers will need to understand their local cancer population prevalence and keepthis under regular review  The absolute priority is that cancer patients have the confidence to attend hospitals andbe reassured that they will be treated in a COVID-19-managed environment
Predicting the Evolution of Sexual Dimorphism in Gene Expression
Authors: David Houle, Changde Cheng
Journal: Molecular Biology and Evolution (2021)

Abstract Sexual dimorphism in gene expression is likely to be the underlying source of dimorphism in a variety of traits. Many analyses implicitly make the assumption that dimorphism only evolves when selection favors different phenotypes in the two sexes, although theory makes clear that it can also evolve as an indirect response to other kinds of selection. Furthermore, previous analyses consider the evolution of a single transcript or trait at a time, ignoring the genetic covariance with other transcripts and traits. We first show which aspects of the genetic-variance–covariance matrix, G, affect dimorphism when these assumptions about selection are relaxed. We then reanalyze gene expression data from Drosophila melanogaster with these predictions in mind. Dimorphism of gene expression for individual transcripts shows the signature of both direct selection for dimorphism and indirect responses to selection. To account for the effect of measurement error on evolutionary predictions, we estimated a G matrix for eight linear combinations of expression traits. Sex-specific genetic variances in female- and male-biased transcription, as well as one relatively unbiased combination, were quite unequal, ensuring that most forms of selection on these traits will have large effects on dimorphism. Predictions of response to selection based on the whole G matrix showed that sexually concordant and antagonistic selection are equally capable of changing sexual dimorphism. In addition, the indirect responses of dimorphism due to cross-trait covariances were quite substantial. The assumption that sexual dimorphism in transcription is an adaptation could be incorrect in many specific cases.
Regulation of p14ARF by Siva1 in <i>H. pylori</i>-infected gastric epithelial cells.
Authors: Manikandan Palrasu, Elena Zaika, El-Rifai Wael, Richard Peek, Alexander Zaika
Journal: Journal of Clinical Oncology (2021)

243 Background: Helicobacter pylori ( H. pylori) is the strongest known risk factor for gastric cancer. Bacterial degradation of tumor suppressor proteins affect the host microbe’s interactions and host cellular response, which contribute to tumorigenesis. p14ARF, a crucial tumor suppressor protein that activates p53 protein under oncogenic stress plays a major role in oncogenic stress response (OSR) regulation. However, little is known about the mechanism of ARF and OSR regulation in H. pylori-infected gastric epithelial cells. Methods: The expression of p14ARF and cytotoxin-associated gene A (CagA) were analyzed in gastric cells co-cultured with H. pylori strains isolated from high-gastric risk and low-gastric risk areas by immunoblotting. To investigate the potential role of CagA in regulation of p14ARF, we employed isogenic cagA− and cagE− H. pylori mutants in gastric epithelial cells, and C57BL/6 mice (n = 10). We also analyzed the expression of Siva1 in human individual infected with cagA-positive (n = 13) and cagA-negative (n = 13) bacteria as well as uninfected human subjects (n = 6). siRNA was used to inhibit activity of Siva1 protein. Results: In this study, H. pylori strains expressing high levels of CagA virulence factor and associated with a higher gastric cancer risk more strongly suppress p14ARF compared with low-risk strains in vivo and in vitro. We found that degradation of p14ARF induced by CagA is mediated by E3 ubiquitin ligase Siva1, which works in concert with another E3 ubiquitin ligase TRIP12. Decreased expression of Siva1 protein and consequent up-regulation of p14ARF was also found in gastric mucosa of H. pylori-infected mice and human individuals. Tumorigenic strain 7.13 was more potent in upregulation of Siva1 and downregulation of p14ARF than non-tumorigenic strain B128. Inhibition of p14ARF protein by H. pylori causes inhibition of autophagy in infected cells. Conclusions: Our results provide first evidence that carcinogenic H. pylori strains significantly alter the host tumor suppressor protein p14ARF, leading to suppression of host OSR and autophagy, which may affect host-bacteria interactions and tumorigenic alteration in the stomach.
Expression of NKG2D ligands is downregulated by β-catenin signalling and associates with HCC aggressiveness
Authors: Mathilde Cadoux, Stefano Caruso, Sandrine Pham, Angélique Gougelet, Céline Pophillat, Rozenn Riou, Robin Loesch, Sabine Colnot, Công Trung Nguyen, Julien Calderaro, Séverine Celton-Morizur, Nadia Guerra, Jessica Zucman-Rossi, Chantal Desdouets, Jean-Pierre Couty
Journal: Journal of Hepatology (2021)
Regorafenib-Avelumab Combination in Patients with Microsatellite Stable Colorectal Cancer (REGOMUNE): A Single-arm, Open-label, Phase II Trial
Authors: Sophie Cousin, Coralie Cantarel, Jean-Philippe Guegan, Carlos Gomez-Roca, Jean-Philippe Metges, Antoine Adenis, Simon Pernot, Carine Bellera, Michèle Kind, Céline Auzanneau, François Le Loarer, Isabelle Soubeyran, Alban Bessede, Antoine Italiano
Journal: Clinical Cancer Research (2021)

Abstract Purpose: Regorafenib is synergistic with immune checkpoint inhibition in colorectal cancer preclinical models. Patients and Methods: This was a single-arm, multicentric phase II trial. Regorafenib was given 3 weeks on/1 week off, 160 mg every day; avelumab 10 mg/kg i.v. was given every 2 weeks, beginning at cycle 1, day 15 until progression or unacceptable toxicity. The primary endpoint was the confirmed objective response rate under treatment, as per RECIST 1.1. The secondary endpoints included a 1-year nonprogression rate, progression-free survival (PFS), and overall survival (OS), safety and biomarkers studies performed on sequential tumor samples obtained at baseline and at cycle 2 day 1. Results: Forty-eight patients were enrolled in four centers. Forty-three were assessable for efficacy after central radiological review. Best response was stable disease for 23 patients (53.5%) and progressive disease for 17 patients (39.5%). The median PFS and OS were 3.6 months [95% confidence interval (CI), 1.8–5.4] and 10.8 months (95% CI, 5.9–NA), respectively. The most common grade 3 or 4 adverse events were palmar-plantar erythrodysesthesia syndrome (n = 14, 30%), hypertension (n = 11, 23%), and diarrhea (n = 6, 13%). High baseline infiltration by tumor-associated macrophages was significantly associated with adverse PFS (1.8 vs. 3.7 months; P = 0.002) and OS (3.7 months vs. not reached; P = 0.002). Increased tumor infiltration by CD8+ T cells at cycle 2, day 1 as compared with baseline was significantly associated with better outcome. Conclusions: The combination of regorafenib + avelumab mobilizes antitumor immunity in a subset of patients with microsatellite stable colorectal cancer. Computational pathology through quantification of immune cell infiltration may improve patient selection for further studies investigating this approach.
Abstract 17304: Stem Cell Model for Down Syndrome-Related Heart Defects
Authors: Yekaterina Galat, Irina Elcheva, Mariana Perepitchka, Philip Iannaccone, Vasil Galat
Journal: Circulation (2014)

About 60% of newborns with Down syndrome (DS) are born with heart defects. The most common heart defect is the failure of formation of the part of the heart that arises from an embryonic structure ...
Is it all right for women to drink small amounts of alcohol in pregnancy? No
Authors: Vivienne Nathanson, Nicky Jayesinghe, George Roycroft
Journal: BMJ (2007)

The National Institute for Health and Clinical Excellence draft guidance on drinking during pregnancy has added to confusion about safety. <b>Pat O9Brien</b> believes that telling women to abstain is overly paternalistic on current evidence, but <b>Vivienne Nathanson</b> and <b>colleagues</b> argue that this is the safest message
Skin-resident natural killer T cells participate in cutaneous allergic inflammation in atopic dermatitis
Authors: ZhengWang Sun, Ji Hye Kim, Seo Hyeong Kim, Hye Ran Kim, KeLun Zhang, Youdong Pan, Min Kyung Ko, Bo Mi Kim, Howard Chu, Hee Ra Lee, Hye Li Kim, Ji Hyung Kim, Xiujun Fu, Young-Min Hyun, Ki Na Yun, Jin Young Kim, Dong Won Lee, Seung Yong Song, Charles P. Lin, Rachael A. Clark, Kwang Hoon Lee, Thomas S. Kupper, Chang Ook Park
Journal: Journal of Allergy and Clinical Immunology (2021)