tbuckley/cabot-search huggingface dataset:
Covid 19: How to feel safe working on the front line—your legal and ethical questions answered
Authors: Clare Dyer
Journal: BMJ (2021)

Covid 19: How to feel safe working on the front line-your legal and ethical questions answeredThe pandemic has presented doctors with legal and ethical challenges around how to treat patients in overstretched health services.Clare Dyer examines some of the key questions Clare DyerIf resources such as critical care are insufficient, who decides which patients need to be prioritised, and how will the decision be taken?Many NHS trusts will have guidelines or protocols to help doctors decide.Guidance is also available from the BMA's ethics committee, 1 the National Institute for Health and Care Excellence, 2 and the Royal College of Physicians. 3 The basic principle is to use the resources available to try to ensure the greatest medical benefit for the greatest number of patients.Admission to intensive care or access to advanced life support may depend on whether the patient has responded to treatment within a certain time frame.Decisions should not be based purely on the patient's age or any disability or medical condition.But where age, disability, or medical condition means that the patient is significantly less likely to survive the treatment, this becomes a relevant factor, says the BMA guidance. Could I face misconduct charges from the General Medical Council over my treatment decisions?The GMC's guidance says that, in launching any investigation, it will take account of the difficult
Social strain, distress, and gender dysphoria among transgender women and Hijra in Vadodara, India
Authors: Amrita Arvind, Apurvakumar Pandya, Lekha Amin, Mansi Aggarwal, Dhriti Agrawal, Krishma Tiwari, Saumya Singh, Merina Nemkul, Pankhuri Agarwal
Journal: International Journal of Transgender Health (2021)

Background: There is immense diversity among transgender people in India with respect to ethnicity, sub-culture, and gender expression. Aim: This study examines psychological distress, gender dysphoria, transgender congruence, and social strain among transgender women, and explores their reflections on self and community using a mixed-method approach. Method: Gender dysphoria, psychological distress, and transgender congruence were assessed with standardized scales while the participants' reflections were captured using semi-structured interviews. A total of 20 transgender women and Hijras were included in the study using convenience sampling. Data was analyzed using quantitative and qualitative techniques. Results: A positive correlation was found between psychological distress and social strain, but no correlation was found between psychological distress and gender dysphoria. Half of the participants fell into the range of gender dysphoria, five of them underwent gender affirming surgery, while two could not undergo the surgery and the rest did not express any discomfort with their gender. While all participants experienced psychological distress due to psycho-socio-cultural stressors, Hijra reported additional stressors related to the Hijra tradition. Discussion: Findings reveal that the psychological distress experienced by transgender women and Hijra had a significant, positive relationship with social strain rather than gender dysphoria. Participants reported various psycho-socio-cultural factors causing psychological distress, which impacted their lives more negatively than gender identity conflicts. These findings support the recent advances by the World Health Organization in ICD-11 to extract transgender conditions from the Mental and Behavioral Disorders category. Limitations of the study are elucidated by authors and the need for a culturally relevant and nonbinary gender dysphoria scale, and implications are discussed.
AB1266 JOINTS STILL PLEADING FOR ATTENTION
Authors: P. Arora, L. H. Lee
Journal: Annals of the Rheumatic Diseases (2020)

Background: Despite the prevalence of musculoskeletal diseases in an increasingly elderly patient population, musculoskeletal (MSK) examination remains frequently overlooked and poorly completed in medical clerking. Indeed, studies over the years have emphatically demonstrated the widespread omission of MSK examination. (1,2) Objectives: The aim of this study was to evaluate the documentation of MSK examination in medical clerking on the acute medical take. Furthermore, we sought to assess doctors’ perception of MSK examination and to evaluate the effect of GALS teaching. Methods: Medical clerkings of 50 patients in the medical assessment unit (MAU) were reviewed on a single day irrespective of the pathology. Case notes were assessed for presenting complaints and documentation of clinical examination findings. Results of the baseline study along with GALS examination techniques were presented at the departmental meeting. Case notes review was subsequently repeated with the same sample size. Results: Baseline study showed that MSK exam was recorded in only 10% of patients despite 20% of patients presenting with fall/collapse. In contrast, 100% of medical clerkings had respiratory examination, 94% had cardiovascular examination while 94% had abdominal examination documented. Although confidence in performing MSK examination was not felt to be a problem, perceived time constraints was a major barrier. Repeat study with another 50 set of clerkings demonstrated a significant improvement, with 22% of clerkings having MSK examination recorded. However, the quality of documentation of MSK examination remained sketchy. Conclusion: Our study reaffirms the fact that MSK examination remains broadly neglected despite the high proportion of patients admitted with fall or collapse. Although the completion of MSK examination improved following GALS screen teaching, the quality of clinical examination documentation remained inadequate. Evidently, the indifference towards MSK examination warrants prompt attention and action by medical educators and rheumatologists. References: [1]Kwok F, Lee L, Gupta A. THU0598 Can you hear the joints crying? musculoskeletal examination in junior doctors’ medical admission clerkings. Annals of the Rheumatic Diseases 2017; 76: 432. [2]Lillicrap MS, Byrne E, Speed CA. Musculoskeletal assessment of general medical in-patients--joints still crying out for attention. Rheumatology (Oxford). 2003 Aug;42(8):951-954. Disclosure of Interests: None declared
Repetitive aeroallergen challenges elucidate maladaptive epithelial and inflammatory traits that underpin allergic airway diseases
Authors: Alisha M. Smith, Nathan Harper, Justin A. Meunier, Anne P. Branum, Fabio Jimenez, Lavanya Pandranki, Andrew Carrillo, Charles S. Dela Cruz, Marcos I. Restrepo, Diego J. Maselli, Cynthia G. Rather, Anna H. Heisser, Daniel A. Ramirez, Weijing He, Robert A. Clark, Charles P. Andrews, Scott E. Evans, Jacqueline A. Pugh, Nu Zhang, Grace C. Lee, Alvaro G. Moreira, Leopoldo N. Segal, Robert M. Ramirez, Robert L. Jacobs, Muthu Saravanan Manoharan, Jason F. Okulicz, Sunil K. Ahuja
Journal: Journal of Allergy and Clinical Immunology (2021)

Signifying the 2-compartments/1-disease paradigm, allergic rhinoconjunctivitis (ARC) and asthma (AA) are prevalent, comorbid conditions triggered by environmental factors (eg, house dust mites [HDMs]). However, despite the ubiquity of triggers, progression to severe ARC/AA is infrequent, suggesting either resilience or adaptation.We sought to determine whether ARC/AA severity relates to maladaptive responses to disease triggers.Adults with HDM-associated ARC were challenged repetitively with HDMs in an aeroallergen challenge chamber. Mechanistic traits associated with disease severity were identified.HDM challenges evoked maladaptive (persistently higher ARC symptoms), adaptive (progressive symptom reduction), and resilient (resistance to symptom induction) phenotypes. Symptom severity in the natural environment was an imprecise correlate of the phenotypes. Nasal airway traits, defined by low inflammation-effectual epithelial integrity, moderate inflammation-effectual epithelial integrity, and higher inflammation-ineffectual epithelial integrity, were hallmarks of the resilient, adaptive, and maladaptive evoked phenotypes, respectively. Highlighting a crosstalk mechanism, peripheral blood inflammatory tone calibrated these traits: ineffectual epithelial integrity associated with CD8+ T cells, whereas airway inflammation associated with both CD8+ T cells and eosinophils. Hallmark peripheral blood maladaptive traits were increased natural killer and CD8+ T cells, lower CD4+ mucosal-associated invariant T cells, and deficiencies along the TLR-IRF-IFN antiviral pathway. Maladaptive traits tracking HDM-associated ARC also contributed to AA risk and severity models.Repetitive challenges with HDMs revealed that maladaptation to disease triggers may underpin ARC/AA disease severity. A combinatorial therapeutic approach may involve reversal of loss-of-beneficial-function traits (ineffectual epithelial integrity, TLR-IRF-IFN deficiencies), mitigation of gain-of-adverse-function traits (inflammation), and blocking of a detrimental crosstalk between the peripheral blood and airway compartments.
An update on the roles of immune system-derived microRNAs in cardiovascular diseases
Authors: Luke B Roberts, Puja Kapoor, Jane K Howard, Ajay M Shah, Graham M Lord
Journal: Cardiovascular Research (2021)

Cardiovascular diseases (CVD) are a leading cause of human death worldwide. Over the past two decades, the emerging field of cardioimmunology has demonstrated how cells of the immune system play vital roles in the pathogenesis of CVD. MicroRNAs (miRNAs) are critical regulators of cellular identity and function. Cell-intrinsic, as well as cell-extrinsic, roles of immune and inflammatory cell-derived miRNAs have been, and continue to be, extensively studied. Several 'immuno-miRNAs' appear to be specifically expressed or demonstrate greatly enriched expression within leucocytes. Identification of miRNAs as critical regulators of immune system signalling pathways has posed the question of whether and how targeting these molecules therapeutically, may afford opportunities for disease treatment and/or management. As the field of cardioimmunology rapidly continues to advance, this review discusses findings from recent human and murine studies which contribute to our understanding of how leucocytes of innate and adaptive immunity are regulated-and may also regulate other cell types, via the actions of the miRNAs they express, in the context of CVD. Finally, we focus on available information regarding miRNA regulation of regulatory T cells and argue that targeted manipulation of miRNA regulated pathways in these cells may hold therapeutic promise for the treatment of CVD and associated risk factors.
Final results of the ACTS-CC 02 trial: A randomized phase III trial of S-1/oxaliplatin (SOX) versus UFT/leucovorin as adjuvant chemotherapy for high-risk stage III colon cancer.
Authors: Naohiro Tomita, Shin Sasaki, Tetsuya Kusumoto, Jun Watanabe, Yoshiyuki Sakamoto, Kazuhiro Yoshida, Atsuyuki Maeda, Jin Teshima, Mitsuru Yokota, Chihiro Tanaka, Junichiro Yamauchi, Hiroyuki Uetake, Michio Itabashi, Keiichi Takahashi, Hideo Baba, Kenjiro Kotake, Narikazu Boku, Keisuke Aiba, Satoshi Morita, Kenichi Sugihara
Journal: Journal of Clinical Oncology (2021)

59 Background: As previously reported (Sunami E, et al. Clin Colorectal Cancer. 2020), the ACTS-CC 02 trial demonstrated that S-1 and oxaliplatin (SOX) was not superior to UFT/leucovorin (LV) in terms of disease-free survival (DFS) as adjuvant chemotherapy for high-risk stage III colon cancer (any T, N2, or positive nodes around the origin of the feeding arteries). We now report the final overall survival (OS) after a median follow-up of more than 6 years. Methods: A total of 966 patients with high-risk stage III colon cancer were randomly assigned to receive either UFT/LV (300–600 mg/day of UFT according to body surface area [BSA] and 75 mg/day of LV on days 1-28, every 35 days, 5 courses) or SOX (100 mg/m 2 of oxaliplatin on day 1 and 80–120 mg/day of S-1 according to BSA on days 1-14, every 21 days, 8 courses). The primary endpoint was DFS. Patients’ data were updated in February 2020. Results: The subjects of this final efficacy analysis were 955 patients (478 in the UFT/LV group and 477 in the SOX group). Totally, Stage IIIA/IIIB/IIIC were 1.3%/50.2%/48.6% and T1/2/3/4 were 1.5%/4.0%/61.8%/32.7%. With median follow-up time of 74.3 months, the 5-year OS rate was 78.3% in the UFT/LV group and 79.1% in the SOX group (HR: 0.97; 95% CI: 0.76-1.24; p = 0.8175). The 5-year DFS rate was 55.2% in the UFT/LV group and 58.1% in the SOX group (HR: 0.92; 95% CI: 0.76-1.11; p = 0.3973). In an exploratory analysis, the 5-year OS rate in patients with T4 disease was 65.2% and 70.8% in the UFT/LV group and SOX group, respectively (HR: 0.81; 95% CI: 0.56-1.17), and the 5-year DFS rate was 45.4% and 50.5% (HR: 0.87; 95% CI: 0.65-1.19), respectively. Notably, in patients with T4N2b disease, the 5-year OS rate was 51.0% and 64.1% in the UFT/LV group and SOX group, (HR: 0.72; 95% CI: 0.40-1.31) and the 5-year DFS rate was 31.1% and 37.2% (HR: 0.87; 95% CI: 0.50-1.31), respectively. Conclusions: In Japanese patients with high-risk stage III colon cancer, the 5-year OS rate was similar in the UFT/LV group and SOX group. However, the oxaliplatin-based regimen was suggested to be more effective for DFS and OS in patients with advanced disease, such as T4N2b. Clinical trial information: JapicCTI-101073.
NRG Oncology NRG-GI007 trial-in-progress: Phase I study of OBP-301 (Telomelysin) and definitive chemoradiation (CRT) for patients with locally advanced esophageal and gastroesophageal adenocarcinoma who are not candidates for surgery.
Authors: Geoffrey Yuyat Ku, Kathryn A. Winter, Terence Marques Williams, Prasad S. Adusumilli, Makoto Nishimura, Adam Yock, David H. Ilson, Theodore S. Hong
Journal: Journal of Clinical Oncology (2021)

TPS262 Background: Definitive CRT is a standard-of-care for patients with medically inoperable esophageal cancer (EC, NEJM 326:1593). The NRG/RTOG 0436 study of cisplatin/paclitaxel and RT (+/- cetuximab) as definitive therapy showed that about ½ of patients have locally persistent disease (JAMA Oncol 3:1520). OBP-301 is a conditionally-restricted, replication-competent adenovirus derived from human adenovirus type 5 (Ad-5) that adds a human Telomerase Reverse Transcriptase (hTERT) gene promoter; it replicates only in tumor cells to cause lysis. It may enhance RT and may cause immunogenic cell death. A phase I study with RT in Japanese patients with inoperable EC showed tolerability and activity. Methods: In NRG-GI007, OBP-301 is added to weekly carboplatin/paclitaxel and RT to 50.4 Gy (1.8 Gy/fx ×28 fx) for patients with medically inoperable esophageal or gastroesophageal junction (GEJ) adenocarcinoma. Patients receive intratumoral OBP-301 1×10 12 virus particles (vp)/ml via endoscopy (EGD) 3 days prior to CRT, then at days 12 and 26 of CRT, for a total of 3 doses. Restaging with PET and EGD occur 6-8 weeks later. Blood and tumor tissue are collected for immune- and viral-based correlative assays. Patients must be assessed to be medically inoperable and have ECOG performance status &lt;1. The primary endpoint is safety, and clinical complete response (cCR) rate is a secondary endpoint. Initially, 6 patients are enrolled. If protocol-defined dose-limiting toxicity (DLT) occurs in &lt;1 of 6 patients, the dose will be deemed to be safe and 9 more will be enrolled to further assess safety and obtain a preliminary assessment of cCR rate. If &gt;2 of 6 patients have DLT, the dose of OBP-301 is reduced to 1×10 11 vp/ml and another 6 patients will be treated. If &lt;1 of 6 patients has a DLT at the lower dose, that dose will be deemed to be safe and 9 more will be enrolled. If &gt;2 of 6 patients have DLT, then neither dose level will have met the safety rule and the trial will be ended. This trial opened to accrual on June 29, 2020. Clinicaltrials.gov NCT04391049. Funding: This project was supported by grants U10CA180868 (NRG Oncology Operations), U10CA180822 (NRG Oncology SDMC), U24CA180803 (IROC), from the National Cancer Institute (NCI) and Oncolys BioPharma. Clinical trial information: NCT04391049.
“It’s like my kid came back overnight”: Experiences of trans and non-binary young people and their families seeking, finding and engaging with clinical care in England
Authors: Anna Carlile, Ethan Butteriss, Annie Pullen Sansfaçon
Journal: International Journal of Transgender Health (2021)

Trans and non-binary children and young people in England, UK struggle to gain access to affirming clinical care, despite the international research evidence pointing toward this best practice approach. Concurrently, they are subject to constant discussion in the UK national media and politics, where many negative assumptions are made about their needs, experiences and clinical provision. Their journey to seek appropriate care has not yet been documented.We trace the experiences of trans and non-binary children and youth and their families in their decision to seek, searches for and experiences with affirmative and non-affirmative clinical input for help with their gender.27 dyadic, semi-structured interviews were undertaken with trans and non-binary children and young people and their parents from 13 families.The process of seeking support via National Health Service clinical routes in England, UK is beset with lengthy waiting lists, issues with geographical inaccessibility, a lack of relevant clinical knowledge, and a failure to recognize the value of family expertise. Family doctors provide contraceptive hormones in lieu of proper access to puberty blocking or gender affirming hormones, and most families resort to private care they can ill afford.Training in gender identity and gender dysphoria is recommended for both family doctors, and children's mental health services. Gender identity development services could be decentralized, with local hubs offering more accessible support.
Artificial intelligence in GI endoscopy: stumbling blocks, gold standards and the role of endoscopy societies
Authors: Rüdiger Schmitz, Rene Werner, Alessandro Repici, Raf Bisschops, Alexander Meining, Michael Zornow, Helmut Messmann, Cesare Hassan, Prateek Sharma, Thomas Rösch
Journal: Gut (2021)

Recent developments in artificial intelligence and machine learning have led to novel and promising applications in gastrointestinal endoscopy and beyond.Endoscopic AI has already become a topic of intensive research and marketing, and a recent review in this journal is a timely and thorough guide that defines terminology and outlines best practices for the development and assessment of AI systems.Our commentary highlights selected aspects of AI research and elaborates upon potential roles that the GI scientific community and professional societies may play in ensuring that the preclinical achievements translate into clinical reality.We believe that: Databases of diagnostic AI software need to be made transparent as should the conditions of the testing scenarios.Clinical expertise is required from the early phases of system development and testing.Medicolegal implications need to be clarified as AI gets increasingly involved in medical decision making.Finally, through the establishment of a continuously updated and curated, dedicated database for AI system evaluation ("rolling gold standard"), the GI societies could actively advance and frame this everchanging field.
Author Correction: Multimodel preclinical platform predicts clinical response of melanoma to immunotherapy
Authors: Eva Pérez-Guijarro, Howard H. Yang, Romina E. Araya, Rajaa El Meskini, Helen T. Michael, Suman Kumar Vodnala, Kerrie L. Marie, Cari Smith, Sung Chin, Khiem C. Lam, Andres Thorkelsson, Anthony J. Iacovelli, Alan Kulaga, Anyen Fon, Aleksandra M. Michalowski, Willy Hugo, Roger S. Lo, Nicholas P. Restifo, Shyam K. Sharan, Terry Van Dyke, Romina S. Goldszmid, Zoe Weaver Ohler, Maxwell P. Lee, Chi-Ping Day, Glenn Merlino
Journal: Nature Medicine (2021)
STARD1 promotes NASH-driven HCC by sustaining the generation of bile acids through the alternative mitochondrial pathway
Authors: Laura Conde de la Rosa, Carmen Garcia-Ruiz, Carmen Vallejo, Anna Baulies, Susana Nuñez, Maria J. Monte, Jose J.G. Marin, Lucia Baila-Rueda, Ana Cenarro, Fernando Civeira, Josep Fuster, Juan C. Garcia-Valdecasas, Joana Ferrer, Michael Karin, Vicent Ribas, Jose C. Fernandez-Checa
Journal: Journal of Hepatology (2021)
Reply to Watchorn <i>et al.</i>: Asthma Exacerbations in Individuals on Glucagon-like Peptide-1 Receptor Agonists for Type 2 Diabetes
Authors: Dinah Foer, Patrick E. Beeler, Jing Cui, Elizabeth W. Karlson, David W. Bates, Katherine N. Cahill
Journal: American Journal of Respiratory and Critical Care Medicine (2021)
Equal, Not Really
Authors: None Anonymous
Journal: JAMA (1985)

How can it be that at the age of 35, being an accomplished, respected physician, a happily married woman for 11 years, and a mother of two beautiful children, I feel melancholy, inadequate, and guilt ridden? Ever since I can remember, my goals have been similar to those of most men. I have enjoyed competitive, physically demanding sports and achieved multiple varsity letters in high school. Excellence in general academics, and in particular science, was more important to me than even to my brother. The resultant conflicts of being a competitive and feminine woman in our society have been numerous. Nevertheless, I have always managed. In my 20s I was able to ride the early waves of "women's liberation." But now, at 35, the waves have crashed into the shore and eroded the sand. My 6 1/2-year-old gentle, vulnerable, and sensitive son has developed a "mild-to-moderate stutter." Stutter, stammer, and
Biodegradable Nanoparticles: Tumor Targeted Delivery of an Anti‐Cancer Therapeutic: An In Vitro and In Vivo Evaluation (Adv. Healthcare Mater. 2/2021)
Authors: You Jung Kang, Claire K. Holley, Mohammad Reza Abidian, Achuthamangalam B. Madhankumar, James Connor, Sheereen Majd
Journal: Advanced Healthcare Materials (2021)

This cover art represents a new anti-cancer nanoformulation that targets the brain glioma tumors, offering a potential treatment for these aggressive tumors. In article number 2001261 by Sheereen Majd and co-workers, biodegradable nanoparticles that carry a potent anti-tumor chelator are decorated with targeting molecules to address and kill glioma tumor cells selectively while sparing the healthy cells.