tbuckley/cabot-search huggingface dataset:
Randomized Clinical Trials and COVID-19
Authors: Howard Bauchner, Phil B. Fontanarosa
Journal: JAMA (2020)

Despite the millions of cases and hundreds of thousands of deaths that have occurred in this devastating coronavirus disease 2019 (COVID-19) pandemic, no peer-reviewed studies of specific therapies proven to be effective in reducing mortality have been published and a vaccine is many months to years away.To date, more than 1000 studies addressing various aspects of COVID-19 are registered on ClinicalTrials.gov,including more than 600 interventional studies and randomized clinical trials (RCTs). 1 During the next few weeks and months, the results of numerous RCTs involving therapies for COVID-19 will be reported.Indeed, preliminary results from some studies have already been reported in social media and the popular press.How will clinicians, the public, and politicians understand the results of these much-anticipated and critically needed clinical trials?First, the interventions in some of these trials are being evaluated in various ways.For instance, some studies do not have a control group, whereas others lack true "controls" such as trials that compare different dosages of the same drugs.This will limit the inferences that can be drawn, likely necessitating further research to define the true benefit of a specific treatment.In addition, in some trials, the investigational agents are administered in combination with multiple other therapies given at various time points in the disease process.Without rigorous design and attention to trial protocols for study drug administration, there will be challenges disentangling the true effect of the intervention.Second, many ongoing trials were designed prior to emerging information that is providing a better understanding of the disease process.It has become clear that some critically ill patients with COVID-19 have substantially different manifestations, including profound hypoxia, extensive inflammatory activation, or evidence of coagulopathy.Accordingly, there may be significant heterogeneity of treatment effects based on the timing or constellation of disease manifestations.It is possible that an antiviral agent or other agents, such as those directed against inflammatory markers (ie, certain cytokines), could be helpful for critically ill patients who do not have overwhelming inflammation but would not be effective for patients in whom the inflammatory cascade is markedly activated.Given that the size of many ongoing trials is limited, few investigations will be appropriately powered to conduct meaningful secondary and subgroup analyses.Most additional analyses should likely be considered exploratory.Third, the outcomes for many of these trials involve time to symptom resolution, improvement of laboratory or radiographic abnormalities, or reduction in the use of mechanical
Genetic alteration, RNA expression, and DNA methylation profiling of coronavirus disease 2019 (COVID-19) receptor ACE2 in malignancies: a pan-cancer analysis
Authors: Peiwei Chai, Jie Yu, Shengfang Ge, Renbing Jia, Xianqun Fan
Journal: Journal of Hematology & Oncology (2020)

Abstract The novel coronavirus (2019-nCoV) is an emerging causative agent that was first described in late December 2019 and causes a severe respiratory infection in humans. Notably, many of affected patients of COVID-19 were people with malignancies. Moreover, cancer has been identified as an individual risk factor for COVID-19. In addition, the expression of angiotensin converting enzyme 2 (ACE2), the receptor of COVID-19, were aberrantly expressed in many tumors. However, a systematic analysis of ACE2 aberration remained to be elucidated in human cancers. Here, we analyzed genetic alteration, RNA expression, and DNA methylation of ACE2 across over 30 tumors. Notably, overexpression of ACE2 have been observed in including colon adenocarcinoma (COAD), kidney renal papillary cell carcinoma (KIRP), pancreatic adenocarcinoma (PAAD), rectum adenocarcinoma (READ), stomach adenocarcinoma (STAD), and lung adenocarcinoma (LUAD). In addition, hypo DNA methylation of ACE2 has also been identified in most of these ACE2 highly expressed tumors. Conclusively, our study for the first time curated both genetic and epigenetic variations of ACE2 in human malignancies. Notably, because our study is a bioinformatics assay, further functional and clinical validation is warranted.
Psychological Treatment of Eating Disorders
Authors: G. Terence Wilson
Journal: Annual Review of Clinical Psychology (2005)

Manual-based cognitive behavior therapy (CBT) is presently the most effective treatment of bulimia nervosa. Its efficacy is limited, however. Different strategies for improving upon current manual-based CBT are discussed, including combining CBT with antidepressant medication, integrating CBT with alternative psychological therapies, and expanding the scope and flexibility of manual-based CBT. CBT is underutilized in clinical practice. Dissemination of evidence-based treatment is a priority. Research on anorexia nervosa is minimal. Effective treatments have yet to be developed, although the Maudsley method of family therapy has shown the most promise in the treatment of adolescents. The most commonly seen eating disorders in clinical practice are those classified as "eating disorder not otherwise specified." With the exception of binge eating disorder (BED), however, they have been neglected by researchers. Several psychological therapies have been shown to be effective in treating BED. Controversy exists over whether treatment-specific effects have been identified. Whereas treatments have proved effective in eliminating binge eating and associated eating disorder psychopathology, achieving clinically significant weight loss remains a challenge.
PET in Lung Cancer and Mediastinal Malignancies
Authors: Florian C. Gaertner
Journal: Clinical Nuclear Medicine (2020)

FDG PET/CT plays a major role in the clinical management of lung cancer. Its main uses are staging of non-small cell lung cancer (NSCLC) and characterization of solitary pulmonary nodules (SPM). Furthermore, it can be employed for staging of small cell lung cancer (SCLC) and for recurrence detection. Other thoracic malignancies accessible to FDG PET/CT are malignant pleural effusion, pleural mesothelioma, and thymic epithelial tumors (TETs). This chapter gives an overview of the diagnostic work-up of patients with these malignancies with special focus on the clinical significance of FDG PET/CT in relation to other imaging modalities such as diagnostic CT and MRI and its significance to guide clinical algorithms.
Selective Progesterone Receptor Modulators—Mechanisms and Therapeutic Utility
Authors: Md Soriful Islam, Sadia Afrin, Sara Isabel Jones, James Segars
Journal: Endocrine Reviews (2020)

Selective progesterone receptor modulators (SPRMs) are a new class of compounds developed to target the progesterone receptor (PR) with a mix of agonist and antagonist properties. These compounds have been introduced for the treatment of several gynecological conditions based on the critical role of progesterone in reproduction and reproductive tissues. In patients with uterine fibroids, mifepristone and ulipristal acetate have consistently demonstrated efficacy, and vilaprisan is currently under investigation, while studies of asoprisnil and telapristone were halted for safety concerns. Mifepristone demonstrated utility for the management of endometriosis, while data are limited regarding the efficacy of asoprisnil, ulipristal acetate, telapristone, and vilaprisan for this condition. Currently, none of the SPRMs have shown therapeutic success in treating endometrial cancer. Multiple SPRMs have been assessed for efficacy in treating PR-positive recurrent breast cancer, with in vivo studies suggesting a benefit of mifepristone, and multiple in vitro models suggesting the efficacy of ulipristal acetate and telapristone. Mifepristone, ulipristal acetate, vilaprisan, and asoprisnil effectively treated heavy menstrual bleeding (HBM) in patients with uterine fibroids, but limited data exist regarding the efficacy of SPRMs for HMB outside this context. A notable class effect of SPRMs are benign, PR modulator-associated endometrial changes (PAECs) due to the actions of the compounds on the endometrium. Both mifepristone and ulipristal acetate are effective for emergency contraception, and mifepristone was approved by the US Food and Drug Administration (FDA) in 2012 for the treatment of Cushing's syndrome due to its additional antiglucocorticoid effect. Based on current evidence, SPRMs show considerable promise for treatment of several gynecologic conditions.
Tyrosine phosphatase Shp2 regulates p115RhoGEF/Rho-dependent dendritic cell migration
Authors: Yun Xu, Yun Zhang, Yanyan Yang, Yanqi Liu, Qiaoying Tian, Pan Liu, Zhifan Ding, Hongqiang Cheng, Xue Zhang, Yuehai Ke
Journal: Cellular and Molecular Immunology (2020)
Association of Brain Cancer With Risk of Suicide
Authors: Anas M. Saad, Abdelmagid M. Elmatboly, Mohamed M. Gad, Muneer J. Al-Husseini, Khalid A. Jazieh, Muayad A. Alzuabi, Ahmad Samir Alfaar
Journal: JAMA Network Open (2020)

This cohort study examines outcomes of patients with brain cancer to provide demographic details on the increase in suicide rate after brain cancer diagnosis.
Eccentric calf muscle exercise produces a greater acute reduction in Achilles tendon
Authors: Nicole Grigg, Scott Wearing, James Smeathers
Journal: British Journal of Sports Medicine (2009)

Objective: To investigate the acute effects of isolated eccentric and concentric calf muscle exercise on Achilles tendon sagittal thickness. ---------- Design: Within-subject, counterbalanced, mixed design. ---------- Setting: Institutional. ---------- Participants: 11 healthy, recreationally active male adults. ---------- Interventions: Participants performed an exercise protocol, which involved isolated eccentric loading of the Achilles tendon of a single limb and isolated concentric loading of the contralateral, both with the addition of 20% bodyweight. ---------- Main outcome measurements: Sagittal sonograms were acquired prior to, immediately following and 3, 6, 12 and 24 h after exercise. Tendon thickness was measured 2 cm proximal to the superior aspect of the calcaneus. ---------- Results: Both loading conditions resulted in an immediate decrease in normalised Achilles tendon thickness. Eccentric loading induced a significantly greater decrease than concentric loading despite a similar impulse (−0.21 vs −0.05, p<0.05). Post-exercise, eccentrically loaded tendons recovered exponentially, with a recovery time constant of 2.5 h. The same exponential function did not adequately model changes in tendon thickness resulting from concentric loading. Even so, recovery pathways subsequent to the 3 h time point were comparable. Regardless of the exercise protocol, full tendon thickness recovery was not observed until 24 h. ---------- Conclusions: Eccentric loading invokes a greater reduction in Achilles tendon thickness immediately after exercise but appears to recover fully in a similar time frame to concentric loading.
High risk of thrombosis in patients with severe SARS-CoV-2 infection: a multicenter prospective cohort study
Authors: Julie Helms, Charles Tacquard, François Severac, Ian Leonard-Lorant, Mickaël Ohana, Xavier Delabranche, Hamid Merdji, Raphaël Clere-Jehl, Malika Schenck, Florence Fagot Gandet, Samira Fafi-Kremer, Vincent Castelain, Francis Schneider, Lélia Grunebaum, Eduardo Anglés-Cano, Laurent Sattler, Paul-Michel Mertes, Ferhat Meziani
Journal: Intensive Care Medicine (2020)
Coronavirus disease (COVID-19) – impact on vaccine preventable diseases
Authors: Daniel Hungerford, Nigel A Cunliffe
Journal: Eurosurveillance (2020)

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Selection following Gene Duplication Shapes Recent Genome Evolution in the Pea Aphid Acyrthosiphon pisum
Authors: Rosa Fernández, Marina Marcet-Houben, Fabrice Legeai, Gautier Richard, Stéphanie Robin, Valentin Wucher, Cinta Pegueroles, Toni Gabaldón, Denis Tagu
Journal: Molecular Biology and Evolution (2020)

Ecology of insects is as wide as their diversity, which reflects their high capacity of adaptation in most of the environments of our planet. Aphids, with over 4,000 species, have developed a series of adaptations including a high phenotypic plasticity and the ability to feed on the phloem sap of plants, which is enriched in sugars derived from photosynthesis. Recent analyses of aphid genomes have indicated a high level of shared ancestral gene duplications that might represent a basis for genetic innovation and broad adaptations. In addition, there are a large number of recent, species-specific gene duplications whose role in adaptation remains poorly understood. Here, we tested whether duplicates specific to the pea aphid Acyrthosiphon pisum are related to genomic innovation by combining comparative genomics, transcriptomics, and chromatin accessibility analyses. Consistent with large levels of neofunctionalization, we found that most of the recent pairs of gene duplicates evolved asymmetrically, showing divergent patterns of positive selection and gene expression. Genes under selection involved a plethora of biological functions, suggesting that neofunctionalization and tissue specificity, among other evolutionary mechanisms, have orchestrated the evolution of recent paralogs in the pea aphid and may have facilitated host-symbiont cooperation. Our comprehensive phylogenomics analysis allowed us to tackle the history of duplicated genes to pave the road toward understanding the role of gene duplication in ecological adaptation.
Association between DNA repair polymorphisms and survival in pancreatic cancer patients treated with combination chemotherapy.
Authors: P. Pacetti, E. Giovannetti, M. Reni, A. Mambrini, M. Ghidini, L. Gleon, N. Funel, S. Cereda, G. Peters, M. Cantore
Journal: Journal of Clinical Oncology (2010)

4098 Background: One major cause of the poor outcome of pancreatic adenocarcinoma (PDAC) is its chemoresistant nature. A phase III trial of cisplatin-epirubicin-5-fluorouracil-gemcitabine regimen reported a 1-year survival rate of 38.5%, which was significantly better than gemcitabine single-agent (Reni et al., Lancet 2005). Similar data were observed with the substitution of 5FU with capecitabine (PEXG), as well as the use of docetaxel (PDXG) or cisplatin-epirubicin intraarterial infusion (ECGemCap). A pharmacogenetic approach is warranted to maximize risk-benefit ratio of these regimens. Therefore this study was aimed at evaluating the association of polymorphisms in genes involved in activity/resistance to drugs of selected polychemotherapeutic regimens, with overall survival (OS) of PDAC patients. Methods: We studied with Taqman PCR assays 10 polymorphisms of 7 genes (ERCC1, XPD, XRCC1, CYP1B1, ABCB1, CDA, and RRM1) in genomic DNA from blood of 123 stage III-IV PDAC patients treated upfront with PEXG (n = 57), PDXG (n = 33) and ECGemCap (n = 33), from 2005 to 2009. Associations of clinical parameters (age, sex, performance status (PS), stage, CA19.9) and genotypes with OS were evaluated by Log-rank test and Cox proportional regression models. Results: Median OS was 407 days (95%CI 336-478), patients with stage IV tumors (n = 70) and PS£80 (n = 35) had significantly shorter OS. Three polymorphisms of DNA repair genes (XPD Asp312Asn, XPD Lys751Gln, ERCC1 C118T) were associated with OS in univariate analysis. XPD Lys751Gln and PS remained significant predictors for OS in multivariate analysis. In particular, patients harboring the XPD Gln751Gln genotype (n = 17) had a worse prognosis, with 262 days (95%CI 203-423) of median OS versus 446 days (95%CI 346-546) of Lys751Lys+Lys751Gln patients (HR = 8, p = 0.001). This association was observed also in the subgroups of epirubicin (n = 90) and docetaxel (n = 33) treated patients. Conclusions: XPD Lys751Gln polymorphism can be a new possible predictive marker of OS in advanced PDAC patients treated with gemcitabine/cisplatin-based polychemotherapeutic regimens, and offer a potential new tool for treatment optimization. No significant financial relationships to disclose.
Train and deploy a community level public health workforce to combat covid-19
Authors: Paul Redgrave, Joan Miller, Jack Czauderna, Tom Heller, Mike Tomson, Bing Jones, Jeremy Wight
Journal: BMJ (2020)

We strongly support Pollock and colleagues’ views.1 We do not understand why the government did not follow World Health Organization guidelines regarding basic infection control practice2 on contact tracing in the early days of the pandemic. We welcome the plan to train 18 000 contact tracers but, in the government’s current proposal, the public are in danger of being seen as …
PTH-026 Improvement of an ERCP service in practice
Authors: Wendy Dowdles
Journal: Endoscopy (2018)

<h3>Introduction</h3> The NHS Tayside ERCP service performs around 450 procedures per annum, serving a population of 5 50 000. A review of our service identified that whilst responsive for emergency inpatient (IP) procedures we had a nine week wait for an elective out-patient (OP) procedures. We wish to describe the review and redesign of our service. <h3>Method</h3> The patient pathway was mapped with key stakeholders and areas of variation were identified. A test of change was undertaken over 7 weeks to promote a more consistent approach as below: A&amp;C processes: A single point of booking for ERCP out–patients was created. Lists were adapted to support IP and OP demand. The ERCP referral form was updated. Patient flow: Lists were distributed evenly throughout the week having been previously weighted at the start of the week. Defined ERCP beds were secured in our Clinical Investigations Unit (CIU) rather than clinical wards. Patients from external hospitals are also now booked into CIU. Same day discharge: A 24 hour Stay Core Data Set was implemented and included criteria for Nurse Led Discharge and a Discharge Checklist enabling same day discharge of out–patients. Patient information: The ERCP Patient Information Booklet was updated supporting postal consent. All outpatients have a full medical clerk–in pre–procedure supported by a Physician's Associate. An Endoscopy RN visits in–patients the day before their procedure. Out patients were given a patient satisfaction questionnaire. <h3>Results</h3> Waiting times: The wait for both IP and OP ERCP has reduced from 9 weeks to zero weeks. All patients are now booked 'real–time'. Savings/efficiencies: 34 patients were booked into CIU. 21 were discharged home the same day. No patients were booked to come into hospital the day before the procedure. This resulted in a total saving of 40 overnight stays. Patient experience: Patient Satisfaction Questionnaires were returned from 14 patients booked into CIU. Feedback was mainly positive. There have been no serious complications. 3 patients had mild pain post procedure but this did not prevent same day discharge. Procedural Change: Patients no longer telephone pre admission to enquire about bed availability, patient admission time has changed from 8 am to 10 am for patients on the pm list, OPs receive an ERCP report and reports are sent to GP. Impact and other services: Streamlining of the patient pathway has supported appropriate use of acute in–patient beds and avoided/reduced cancellations. Impact on staff: It has encouraged disciplines to work together with exceptional staff engagement. <h3>Conclusion</h3> An overview of an established service identified inefficiencies at several points which were rectified. The cumulative effect of these changes has transformed the patient journey and released resource in other areas.
A novel postal-based approach to diagnosing obstructive sleep apnoea in a high risk population
Authors: Benjamin Prudon, Joan Hughes, John Stradling, Sophie West
Journal: European Respiratory Journal (2014)

Over 50% of patients with Diabetic Macular Oedema (DMO) have Obstructive Sleep Apnoea (OSA), but the majority remain undiagnosed. Guidelines approve domiciliary sleep studies to assess OSA in high-risk patients, but availability of standard approaches remains limited. We used a 4-channel device (ApneaLink (AL), ResMed, UK) to establish a remote postal-based diagnostic service for patients with DMO; we describe our experience.  Patients with DMO from English Ophthalmology centres were given written invitations to participate. Patients returned a free-post reply slip to us, and were then phoned to explain practicalities of the study. The AL was posted with pictorial and written instructions with a support telephone number, and an ESS questionnaire. Following a single night study, the AL was returned by a freepost service.  Responses were received from 448 patients; 287 males (64%), mean age 64 (SD 10.4) years. ALs were issued to 423; 350 completed studies, 37 were unable to use the ALs, and 36 are in progress. Fifty-three patients required repeat studies (23 short duration, 11 poor quality, 19 recording failure), with 5 requiring a 2nd repeat. Additionally, 35 studies failed to capture either airflow or oximetry. Age or gender of those unable to complete studies was not significantly different compared to those who could. During 906 postal events with the national post service, 10 ALs were lost. Completed studies revealed: 4%ODI   We have demonstrated that a remote postal-based diagnostic service for populations with a high risk of OSA can be successfully performed. This novel approach avoiding clinic attendance may be useful in clinical practice.
A randomised trial of high-flow nasal cannula in infants with moderate bronchiolitis
Authors: Philippe Durand, Tamazoust Guiddir, Christèle Kyheng, Florence Blanc, Olivier Vignaud, Ralph Epaud, Frédéric Dugelay, Isabelle Breant, Isabelle Badier, Vanessa Degas-Bussière, Florence Phan, Valérie Soussan-Banini, Agnès Lehnert, Célestin Mbamba, Catherine Barrey, Cédric Tahiri, Marion Decobert, Marie Saunier-Pernaudet, Irina Craiu, Mélanie Taveira, Vincent Gajdos
Journal: European Respiratory Journal (2020)

Background The objective was to determine whether high-flow nasal cannula (HFNC), a promising respiratory support in infant bronchiolitis, could reduce the proportion of treatment failure requiring escalation of care. Methods In this randomised controlled trial, we assigned infants aged &lt;6 months who had moderate bronchiolitis to receive either HFNC at 3 L·kg −1 ·min −1 or standard oxygen therapy. Crossover was not allowed. The primary outcome was the proportion of patients in treatment failure requiring escalation of care (mostly noninvasive ventilation) within 7 days following randomisation. Secondary outcomes included rates of transfer to the paediatric intensive care unit (PICU), oxygen, number of artificial nutritional support-free days and adverse events. Results The analyses included 268 patients among the 2621 infants assessed for inclusion during two consecutive seasons in 17 French paediatric emergency departments. The percentage of infants in treatment failure was 14% (19 out of 133) in the study group, compared to 20% (27 out of 135) in the control group (OR 0.66, 95% CI 0.35–1.26; p=0.21). HFNC did not reduce the risk of admission to PICU (21 (15%) out of 133 in the study group versus 26 (19%) out of 135 in the control group) (OR 0.78, 95% CI 0.41–1.41; p=0.45). The main reason for treatment failure was the worsening of modified Wood clinical asthma score (m-WCAS). Short-term assessment of respiratory status showed a significant difference for m-WCAS and respiratory rate in favour of HFNC. Three pneumothoraces were reported in the study group. Conclusions In patients with moderate bronchiolitis, there was no evidence of lower rate of escalating respiratory support among those receiving HFNC therapy.
Anti-CD3 Preconditioning Separates GVL from GVHD Via Modulating Host Dendritic and Donor T Cell Migration in TBI-Conditioned Recipients
Authors: Nainong Li, Ying Chen, Wei He, Tangsheng Yi, Dongchang Zhao, Chunyan Zhang, Chia-Lei Lin, Stephen Forman, Defu Zeng
Journal: Blood (2008)