tbuckley/cabot-search huggingface dataset:
Treatment Recommendations for Patients With Multivessel Coronary Artery Disease—There Is No “I” in Heart Team, But Is the Heart Team Better Than the I?
Authors: James C. Blankenship, Nestor Mercado
Journal: JAMA Network Open (2020)

Michael B. Tsang, MD, MSc; J. D. Schwalm, MD, MSc; Sumeet Gandhi, MD, MD; Matthew G. Sibbald, MD, PhD; Amiram Gafni, PhD; Mathew Mercuri, PhD; Omid Salehian, MD, MSc; Andre Lamy, MD, MHSc; Dan Pericak, MMath; Sanjit Jolly, MD, MSc; Tej Sheth, MD; Craig Ainsworth, MD; James Velianou, MD; Nicholas Valettas, MD, MASc; Shamir Mehta, MD, MSc; Natalia Pinilla, MD, MSc; Bobby Yanagawa, MD, PhD; Li Zhang, MD; Victor Chu, MD; Dominic Parry, MBChb, MRSC, MMedSC; Richard Whitlock, MD, PhD; Adel Dyub, MD; Irene Cybulsky, MD; Lloyd Semelhago, MD; Kostas Ioannou, MD; Adnan Hameed, MD; Douglas Wright, MD; Amin Mulji, MD; Saeed Darvish-Kazem, MD; Nandini Gupta, MD; Ahmed Alshatti, MD; Madhu K. Natarajan, MD, MSc
Making the most of shielding: covid-19 is exposing the unpaid carers in NHS workforce
Authors: Raka Maitra
Journal: BMJ (2020)

<h3>Objective</h3> To investigate the relationship between personality traits and <i>Catechol O-methyltransferase (COMT)</i> rs4680 genotypewith concussion history in rugby players. <h3>Design</h3> Case-control study. <h3>Setting</h3> High school, amateur, and professional rugby teams in South Africa. <h3>Participants</h3> Participants were excluded if they reported a previous brain-related medical condition or a non rugby-related concussion, or were not of European ancestry. Three hundred and one participants were included in the study. Based on self-reported concussion history (30 suspected concussion cases were excluded), participants were grouped into the control (non-concussed, n=140) or case group (one or more diagnosed concussions, n=131). <h3>Assessment of risk factors</h3> Participants completed a concussion history questionnaire, Cloninger’s Tridimensional Personality Questionnaire (TPQ) and all DNA samples were genotyped for <i>COMT</i> rs4680. Logistic regression, co-varying for age, was used to determine differences in genotype frequencies. A one-way analysis of variance was used to compare TPQ dimension (novelty seeking, harm avoidance, and reward dependence) scores. <h3>Outcome measures</h3> <i>COMT</i> rs4680 genotype frequencies and TPQ scores. <h3>Main results</h3> The <i>COMT</i> rs4680 VV genotype was overrepresented in the controlgroup when all participants were combined (p=0.030, OR: 1.89, 95% CI: 1.05 – 3.45; control: 31%, cases: 18%) and whenonly school participants were analysed (p=0.009, OR: 3.23, 95% CI: 1.27 – 8.33; control:37%, cases:15%). Furthermore, the schoolcontrol group had higher harm avoidance scores compared to cases (p=0.004), andthe VV genotype was associated with increased harm avoidance subscale 1 scores (p=0.023). <h3>Conclusions</h3> This study provides preliminary indication that personality traits, and associated genetic variants, can influence concussion in rugby. <h3>Competing interests</h3> None.
Lipoprotein(a) and Family History Predict Cardiovascular Disease Risk
Authors: Anurag Mehta, Salim S. Virani, Colby R. Ayers, Wensheng Sun, Ron C. Hoogeveen, Anand Rohatgi, Jarett D. Berry, Parag H. Joshi, Christie M. Ballantyne, Amit Khera
Journal: Journal of the American College of Cardiology (2020)
The load of dyspnoea on brain and legs
Authors: Andreas von Leupoldt, Núria Farre
Journal: European Respiratory Journal (2020)

<b>Cognitive impairments are common in patients with dyspnoea, associated with additional adverse health effects, but remain under-recognised and under-treated. Acute dyspnoea can worsen cognitive and locomotor performance, potentiating patient burden.</b>https://bit.ly/3biHnAN
A phase 2, double-blinded, placebo-controlled trial of toll-like receptor 7/8/9 antagonist, IMO-8400, in dermatomyositis
Authors: Yoo Jung Kim, Elena Schiopu, Katalin Dankó, Tahseen Mozaffar, Srinivas Chunduru, Kirstin Lees, Namita A. Goyal, Jeffrey Sarazin, David F. Fiorentino, Kavita Y. Sarin
Journal: Journal of the American Academy of Dermatology (2020)
Tobacco and tobacco branding in films most popular in the UK from 2009 to 2017
Authors: Alexander Barker, Jo Cranwell, Iona Fitzpatrick, Kathy Whittamore, Khaldoon Alfayad, Amira Haridy, Rachael Murray, John Britton
Journal: Thorax (2020)

Exposure to tobacco content in films is a cause of smoking uptake in young people. In an earlier study, we reported that tobacco content occurred in 70% of UK box office films popular between 1989 and 2008. We now report an analysis of tobacco content in a sample of the top grossing UK box office films between 2009 and 2017, and of population exposure resulting from audience exposure to the 2017 films.Occurrence of tobacco intervals (actual tobacco use, implied use, appearance of smoking paraphernalia or branding) was measured by 5 min interval coding in the 15 most commercially successful films in the UK in each year from 2009 to 2017. A nationally representative survey was used to estimate population exposure to the top 15 films from 2017.We coded 3248 intervals from the 135 films. Tobacco content appeared in 245 intervals (8%, 95% CI 7% to 9%) across 56 (41%, 95% CI 33% to 49%) films. Tobacco content occurred in films in all BBFC age ratings, and 36 (64%, 95% CI 51% to 77%) of films containing tobacco imagery were classified as suitable for viewing by people aged under 15 years. Although less prevalent than in our earlier study, there was no evidence of a secular decline in tobacco content during this study period. The top 15 films from 2017 delivered approximately 21.6 (95% CI 21.06-22.14) million tobacco impressions to young people aged 10-18 years in the UK.Tobacco content continues to appear in UK Box Office films and is widely seen by young people, representing a major driver of smoking uptake.
The chromosome-level wintersweet (Chimonanthus praecox) genome provides insights into floral scent biosynthesis and flowering in winter
Authors: Junzhong Shang, Jingpu Tian, Huihui Cheng, Qiaomu Yan, Lai Li, Abbas Jamal, Zhongping Xu, Lin Xiang, Christopher A. Saski, Shuangxia Jin, Kaige Zhao, Xiuqun Liu, Longqing Chen
Journal: Genome biology (2020)

Wintersweet (Chimonanthus praecox), an important ornamental plant, has evolved unique fragrant aroma and winter-flowering properties, which are critical for its successful sexual reproduction. However, the molecular mechanisms underlying these traits are largely unknown in this species. In addition, wintersweet is also a typical representative species of the magnoliids, where the phylogenetic position of which relative to eudicots and monocots has not been conclusively resolved.Here, we present a chromosome-level wintersweet genome assembly with a total size of 695.36 Mb and a draft genome assembly of Calycanthus chinensis. Phylogenetic analyses of 17 representative angiosperm genomes suggest that Magnoliids and eudicots are sister to monocots. Whole-genome duplication signatures reveal two major duplication events in the evolutionary history of the wintersweet genome, with an ancient one shared by Laurales, and a more recent one shared by the Calycantaceae. Whole-genome duplication and tandem duplication events have significant impacts on copy numbers of genes related to terpene and benzenoid/phenylpropanoid (the main floral scent volatiles) biosynthesis, which may contribute to the characteristic aroma formation. An integrative analysis combining cytology with genomic and transcriptomic data reveals biological characteristics of wintersweet, such as floral transition in spring, floral organ specification, low temperature-mediated floral bud break, early blooming in winter, and strong cold tolerance.These findings provide insights into the evolutionary history of wintersweet and the relationships among the Magnoliids, monocots, and eudicots; the molecular basis underlying floral scent biosynthesis; and winter flowering, and highlight the utility of multi-omics data in deciphering important ornamental traits in wintersweet.
Emergence of mcr-1, mcr-3 and mcr-8 in clinical Klebsiella pneumoniae isolates in Taiwan
Authors: Feng-Jui Chen, Tsai-Ling Lauderdale, Wei-Cheng Huang, Yih-Ru Shiau, Hui-Ying Wang, Shu-Chen Kuo
Journal: Clinical Microbiology and Infection (2020)
Targeting Tumor‐Associated Antigens in Hepatocellular Carcinoma for Immunotherapy: Past Pitfalls and Future Strategies
Authors: Ligong Lu, Jun Jiang, Meixiao Zhan, Hui Zhang, Qian‐Ting Wang, Sheng‐Nan Sun, Xiao‐Kai Guo, Hua Yin, Yadong Wei, Shi‐You Li, Jun O. Liu, Yong Li, You‐Wen He
Journal: Hepatology (2020)

Lu, Ligong; Jiang, Jun; Zhan, Meixiao; Zhang, Hui; Wang, Qian‐Ting; Sun, Sheng‐Nan; Guo, Xiao‐Kai; Yin, Hua; Wei, Yadong; Li, Shi‐You; Liu, Jun O.; Li, Yong; He, You‐Wen Author Information
High-Flow Nasal Cannula in Critically III Patients with Severe COVID-19
Authors: Alexandre Demoule, Antoine Vieillard Baron, Michael Darmon, Alexandra Beurton, Guillaume Géri, Guillaume Voiriot, Thibault Dupont, Lara Zafrani, Lola Girodias, Vincent Labbé, Martin Dres, Muriel Fartoukh, Elie Azoulay
Journal: American Journal of Respiratory and Critical Care Medicine (2020)
Evaluating a New Cancer Screening Blood Test: Unintended Consequences and the Need for Clarity in Policy Making
Authors: David F Ransohoff
Journal: JNCI Journal of the National Cancer Institute (2020)

A blood test for cancer screening has been the "holy grail" ever since the carcino-embryonic antigen blood test in the 1960s was claimed to have nearly 100% sensitivity and specificity-but turned out not to (1)-for colorectal cancer (CRC).Nonadherence with CRC screening recommendations, now approximately 40%, might be reduced if a blood test were available to persons unwilling to have current tests that may be unpleasant (colonoscopy and its preparation) or distasteful (stool collection).The process of screening test approval and adoption involves policy-making decisions by leading professional institutions.The US Food and Drug Administration (FDA) in 2016 approved the methylated SEPT9 DNA plasma assay, mSEPT9, also known as Epi proColonV R (Epigenomics AG, Berlin, Germany), after they initially decided not to approve it in 2014.Currently, the Centers for Medicare and Medicaid Services (CMS) are considering a National Coverage Determination regarding payment (2).Ultimately, the test will be considered in practice recommendations by the US Preventive Services Task Force (USPSTF) and others.In this issue of the Journal, researchers use a costeffectiveness analysis (CEA) to compare 4 innovative CRCscreening strategies.They conclude that "for people who are unwilling to be screened with fecal immunochemical testing (FIT) or colonoscopy, annual screening with the mSEPT9 is the test of choice given its cost-effectiveness profile compared with CTC (computed tomographic colonography), PillCam (capsule endoscopy) and mtSDNA (multitarget stool DNA, comprised of FIT and stool DNA, also known as Cologuard V R [Exact Sciences Corporation, Madison, WI])" (3).Modeling analyses, often used by CMS and USPSTF, are designed to simulate a randomized controlled clinical trial (RCT) that quantitatively assesses outcomes-that is, harms and benefits of screening such as CRC mortality reduction-to compare new testing strategies with others like FIT and colonoscopy that are supported by evidence from RCTs and are considered to be cost-effective.Modeling typically incorporates a new test's performance features, particularly sensitivity and
13 Medications that affect the lower oesophageal sphincter and risk of oesophageal cancer: a nested case-control study
Authors: A Spence, J Busby, P Murchie, H Coleman, B Johnston, L Murray, L Iversen, A Lee, C Cardwell
Journal: Gut (2017)

Background  Excessive relaxation of the lower oesophageal sphincter results in increased gastro-oesophageal acid reflux, a risk factor for oesophageal cancer.  Aim  We aimed to investigate the risk of oesophageal cancer in patients prescribed medications known to relax of the lower oesophageal sphincter.  Method  Using the Scottish Primary Care Clinical Informatics Unit (PCCIU) database, a nested case-control study of Scottish patients diagnosed with oesophageal cancer between 1999 and 2011 was performed. Medication use was determined from GP prescription records. Conditional logistic regression was used to calculate OR and 95% CI for oesophageal cancer risk in patients prescribed benzodiazepines, calcium channel blockers, nitrates, respiratory sympathomimetics or xanthine medications.  Results  A total of 1979 oesophageal cancer patients were matched to 9543 controls. There was a significantly increased risk of oesophageal cancer in patients prescribed respiratory sympathomimetics (adjusted OR 1.27, 95% CI 1.08–1.48) but no dose-response association was observed. No significant increased oesophageal cancer risks were seen for users of other medications that relax the lower oesophageal sphincter (adjusted OR for benzodiazepines 0.94, 95% CI 0.79–1.11; calcium channel blockers 1.05, 95% CI 0.92–1.20; nitrates 1.09, 95% CI 0.92–1.29; or xanthines 1.44, 95% CI 0.91–2.28).  Conclusions  Respiratory sympathomimetic medication use was associated with an increased risk of oesophageal cancer. Oesophageal cancer risk was not significantly increased for users of other medications known as relaxants of the lower oesophageal sphincter. Further, the observed association may not be causal because there was no dose response relationship, and possible confounding due to asthma symptoms.
Krabbe disease successfully treated via monotherapy of intrathecal gene therapy
Authors: Allison M. Bradbury, Jessica H. Bagel, Duc Nguyen, Erik A. Lykken, Jill Pesayco Salvador, Xuntian Jiang, Gary P. Swain, Charles A. Assenmacher, Ian J. Hendricks, Keiko Miyadera, Rebecka S. Hess, Arielle Ostrager, Patricia ODonnell, Mark S. Sands, Daniel S. Ory, G. Diane Shelton, Ernesto R. Bongarzone, Steven J. Gray, Charles H. Vite
Journal: Journal of Clinical Investigation (2020)

Globoid cell leukodystrophy (GLD; Krabbe disease) is a progressive, incurable neurodegenerative disease caused by deficient activity of the hydrolytic enzyme galactosylceramidase (GALC). The ensuing cytotoxic accumulation of psychosine results in diffuse central and peripheral nervous system (CNS, PNS) demyelination. Presymptomatic hematopoietic stem cell transplantation (HSCT) is the only treatment for infantile-onset GLD; however, clinical outcomes of HSCT recipients often remain poor, and procedure-related morbidity is high. There are no effective therapies for symptomatic patients. Herein, we demonstrate in the naturally occurring canine model of GLD that presymptomatic monotherapy with intrathecal AAV9 encoding canine GALC administered into the cisterna magna increased GALC enzyme activity, normalized psychosine concentration, improved myelination, and attenuated inflammation in both the CNS and PNS. Moreover, AAV-mediated therapy successfully prevented clinical neurological dysfunction, allowing treated dogs to live beyond 2.5 years of age, more than 7 times longer than untreated dogs. Furthermore, we found that a 5-fold lower dose resulted in an attenuated form of disease, indicating that sufficient dosing is critical. Finally, postsymptomatic therapy with high-dose AAV9 also significantly extended lifespan, signifying a treatment option for patients for whom HSCT is not applicable. If translatable to patients, these findings would improve the outcomes of patients treated either pre- or postsymptomatically.
Preadmission Diabetes-Specific Risk Factors for Mortality in Hospitalized Patients With Diabetes and Coronavirus Disease 2019
Authors: Shivani Agarwal, Clyde Schechter, Will Southern, Jill P. Crandall, Yaron Tomer
Journal: Diabetes Care (2020)

To examine whether HbA1c, outpatient diabetes treatment regimen, demographics, and clinical characteristics are associated with mortality in hospitalized patients with diabetes and coronavirus disease 2019 (COVID-19).This was a retrospective cohort analysis of patients with diabetes hospitalized with confirmed COVID-19 infection from 11 March to 7 May 2020 at a large academic medical center in New York City. Multivariate modeling was used to assess the independent association of HbA1c levels and outpatient diabetes treatment regimen with mortality, in addition to independent effects of demographic and clinical characteristics.We included 1,126 hospitalized patients with diabetes and COVID-19 for analysis, among whom mean age was 68 years, 50% were male, 75% were Black, mean BMI was 30 kg/m2, 98% had type 2 diabetes, mean HbA1c was 7.5%, and 33.1% died. HbA1c levels were not associated with mortality in unadjusted or adjusted analyses, but an outpatient regimen with any insulin treatment was strongly predictive. Additionally, age, sex, and BMI interacted such that in all age categories, mortality was higher with increasing BMI in males compared with females.In this large U.S. cohort of hospitalized patients with diabetes and COVID-19, insulin treatment, as a possible proxy for diabetes duration, and obesity rather than long-term glycemic control were predictive of mortality. Further investigation of underlying mechanisms of mortality and inpatient glycemic control is needed.
Letter to the Editor: COVID‐19–Related Liver Injury: The Interpretation for Aspartate Aminotransferase Needs to Be Cautious
Authors: Xiu‐He Lv, Jin‐Lin Yang, Kai Deng
Journal: Hepatology (2020)

Potential conflict of interest: Nothing to report. TO THE EDITOR: We read with great interest the article by Bloom et al.(1) Although the results of their study are interesting and important, we do have some concerns. First, the authors believed that elevated levels of liver injury markers, particularly aspartate aminotransferase (AST), may reflect true hepatic injury in COVID‐19. However, it should be noted that AST is usually considered a less specific marker for liver injury than alanine aminotransferase (ALT).(2) In a recent study involving severe COVID‐19 cases, the level of AST was discovered to be elevated first, followed by ALT,(3) suggesting that changes in AST level may be attributed to other confounders. In fact, AST has two isoforms that cannot be distinguished in a regular liver function test, and the cytosolic isoenzyme is produced by other tissues, such as kidney, cardiac, and skeletal muscle, rather than liver. Furthermore, more obese people were included in the current study, and higher baseline AST levels may also be a factor leading to bias. Therefore, misinterpretation of AST data may lead to an overestimation of the incidence of liver injury in patients with COVID‐19. Second, the authors stated that elevated AST level may be associated with disease severity. In fact, COVID‐19‐related liver function abnormalities have been reported to be mostly mild in many studies, and liver failure has not been reported.(4) Although the relationship between AST and disease severity cannot be denied, this association may not result in serious consequences for the liver. On the other hand, the association between liver injury markers and clinical outcomes of COVID‐19 may be further confounded by the use of medications such as antibiotics and antiviral drugs during hospitalization. Thus, the actual incidence of liver injury and its contribution to the development of severe illness remain unclear. The association of AST level with disease severity probably involves the development of multiple organ dysfunction.(5) In conclusion, the role of abnormal AST level in COVID‐19 needs to be interpreted cautiously.
Treatment approaches and outcomes associated with the use of abobotulinumtoxinA for the treatment of hyperhidrosis: A systematic review
Authors: Hassan Galadari, Ibrahim Galadari, Riekie Smit, Inna Prygova, Alessio Redaelli
Journal: Journal of the American Academy of Dermatology (2020)

Botulinum neurotoxin type A has been used for the treatment of hyperhidrosis.To perform a systematic review of the literature to identify evidence on the treatment approaches and outcomes associated with abobotulinumtoxinA (aboBoNT-A) treatment of hyperhidrosis.EMBASE, MEDLINE, and the Cochrane Library were searched for relevant observational studies, randomized controlled trials, and nonrandomized controlled trials. There were no date or country restrictions. Bibliographies of review articles and recent congress proceedings (2017-2019) were also searched. Articles were screened using predefined eligibility criteria and relevant data were extracted.Of 191 unique articles identified, 23 were considered relevant (3 observational studies, 10 nonrandomized controlled trials, and 10 randomized controlled trials). These articles provided data on axillary (13), palmar (7), and forehead (1) hyperhidrosis, compensatory hyperhidrosis of the back (1), Frey syndrome (1), and diabetic gustatory sweating (1). All studies reported that aboBoNT-A reduced sweating and no serious adverse events were observed. Patient satisfaction was high and improvements to quality of life were observed after aboBoNT-A treatment.Variability in the injection technique when data were compared across studies.This study describes a range of treatment approaches and demonstrates positive outcomes of aboBoNT-A treatment for multiple types of hyperhidrosis.
Letter to the Editor: Statins and COVID‐19: Efficacy Still to Be Proven
Authors: Lucy Meunier, Magdalena Meszaros, Georges‐Philippe Pageaux
Journal: Hepatology (2020)

Potential conflict of interest: Nothing to report. TO THE EDITOR: We read with interest the article by Bloom et al.(1) reporting liver biochemistry–associated trends, etiologies, and outcomes in 60 patients with COVID‐19. The authors reported that 69% of the patients had abnormal liver function tests (LFTs) on admission and 93% during their hospital stay, with an aspartate aminotransferase (AST) predominance. These results are similar to our own experience of 234 patients admitted with COVID‐19 according to World Health Organization diagnostic guidelines.(2) In our study, 149 (63.7%) patients were male (mean age [SD], 67 [±14] years), 9 (3.8%) had chronic liver disease, and 64 (27.4%) had diabetes. On admission, 66.6% of patients had abnormal LFTs, with an AST predominance. Median AST on admission was also significantly higher than median alanine aminotransferase (ALT) (45 vs. 37 IU/L; P < 0.005). On admission, AST was correlated with ALT (r = 0.7; P < 0.005), confirming true hepatic, but not severe, COVID‐19‐related liver injury.(2) Statins were proposed for their capacity to modulate immune response as in the retrospective study by Zhang et al., in which patients with statins had better survival and lower biologic inflammatory parameters compared to patients without statins.(3) In our cohort, only 42 (18%) patients were on statins before admission, compared with 40% in Bloom et al.'s study. Likewise, AST levels were not significantly different between patients who were and were not prescribed statins before admission. Among 114 patients with severe disease on admission, 26 (23%) were taking statins. Statin prescription before admission did not affect COVID‐19 severity (P = 0.06). We agree with Bloom et al. that statin‐related drug‐induced liver injury is uncommon but that caution should be taken when prescribing remdesivir with statins, because remdesivir interaction clinical trials have not been conducted.(4) Furthermore, remdesivir and statins are both cytochrome P450 3A4 (CYP3A4) substrates, which could favor adverse effects with concurrent administration and explain why more patients needed to stop statins in the remdesivir trial. Many unanswered questions remain concerning the interactions between severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and the liver, the role of the proinflammatory state favoring cytokine release,(4) and the impact of ischemia, hepatotoxic drugs, and viral load on COVID‐19 severity.(5)