bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of COVID-19 pandemic on medical students: a scoping review protocol
Authors: Sanjaya Ardo , Edwin Christian , Supantini Dedeh 
Published: August 2022

IntroductionThe COVID-19 pandemic has spread globally and has been reported in every known country. The effects can be felt in universities and schools, shifting their learning to online platforms. However, medical schools bear the burden of protecting students and ensuring the continuation of the education process. The rapid transition to online learning, coupled with the lack of preparation from the educational system, leads to stresses that affect students’ academic performance, mental health and social life. Nevertheless, no review tried to synthesise the complete picture of the pandemic’s effects. Therefore, this scoping review aims to identify and explore the available literature on the effects or impacts of the pandemic on medical students without limiting it to specific dimensions.MethodsThis review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews and the Joanna Briggs Institute manual for evidence synthesis. We examine articles reporting data from any country. However, only articles written in English will be included. For studies to be included, they must report any form of impact on medical students, qualitatively or quantitatively. Furthermore, the impact must occur within the context of the COVID-19 pandemic. Searches will be done on Medline, EMBASE, ERIC, the Cochrane Library, CINAHL and PsycInfo. After data extraction, we will narratively synthesise the data and explore the types of impacts COVID-19 has on medical students.Ethics and disseminationNo formal ethical approval is required. The scoping review will be published in peer-reviewed journals and as conference presentations and summaries, wherever appropriate.
Heterogeneous impact of the COVID-19 pandemic on lung, colorectal and breast cancer incidence in Hungary: results from time series and panel data models
Authors: Elek Peter , Csanádi Marcell , Fadgyas-Freyler Petra , Gervai Nóra , Oross-Bécsi Rita , Szécsényi-Nagy Balázs , Tatár Manna , Váradi Balázs , Zemplényi Antal 
Published: August 2022

ObjectiveDuring the COVID-19 pandemic, health system resources were reallocated to provide care for patients with COVID-19, limiting access for others. Patients themselves also constrained their visits to healthcare providers. In this study, we analysed the heterogeneous effects of the pandemic on the new diagnoses of lung, colorectal and breast cancer in Hungary.DesignTime series and panel models of quarterly administrative data, disaggregated by gender, age group and district of residence.ParticipantsData for the whole population of Hungary between the first quarter of 2017 and the second quarter of 2021.Main outcome measuresNumber of patients newly diagnosed with lung, colorectal and breast cancer, defined as those who were hospitalised with the appropriate primary International Classification of Diseases Tenth Revision diagnosis code but had not had hospital encounters with such a code within the previous 5 years.ResultsThe incidence of lung, colorectal and breast cancer decreased by 14.4% (95% CI 10.8% to 17.8%), 19.9% (95% CI 12.2% to 26.9%) and 15.5% (95% CI 2.5% to 27.0%), respectively, during the examined period of the pandemic, with different time patterns across cancer types. The incidence decreased more among people at least 65 years old than among the younger (p<0.05 for lung cancer and p<0.1 for colorectal cancer). At the district level, both the previously negative income gap in lung cancer incidence and the previously positive income gap in breast cancer incidence significantly narrowed during the pandemic (p<0.05).ConclusionsThe decline in new cancer diagnoses, caused by a combination of supply-side and demand-side factors, suggests that some cancer cases have remained hidden. It calls for action by policy makers to engage individuals with high risk of cancer more in accessing healthcare services, to diagnose the disease early and to prepare for effective management of patient pathways from diagnosis to survival or end-of-life care.
Protein kinase inhibitor ceritinib blocks ectonucleotidase CD39 – a promising target for cancer immunotherapy
Authors: Schäkel Laura , Mirza Salahuddin , Winzer Riekje , Lopez Vittoria , Idris Riham , Al-Hroub Haneen , Pelletier Julie , Sévigny Jean , Tolosa Eva , Müller Christa E 
Published: August 2022

BackgroundAn important mechanism, by which cancer cells achieve immune escape, is the release of extracellular adenosine into their microenvironment. Adenosine activates adenosine A2Aand A2Breceptors on immune cells constituting one of the strongest immunosuppressive mediators. In addition, extracellular adenosine promotes angiogenesis, tumor cell proliferation, and metastasis. Cancer cells upregulate ectonucleotidases, most importantly CD39 and CD73, which catalyze the hydrolysis of extracellular ATP to AMP (CD39) and further to adenosine (CD73). Inhibition of CD39 is thus expected to be an effective strategy for the (immuno)therapy of cancer. However, suitable small molecule inhibitors for CD39 are not available. Our aim was to identify drug-like CD39 inhibitors and evaluate them in vitro.MethodsWe pursued a repurposing approach by screening a self-compiled collection of approved, mostly ATP-competitive protein kinase inhibitors, on human CD39. The best hit compound was further characterized and evaluated in various orthogonal assays and enzyme preparations, and on human immune and cancer cells.ResultsThe tyrosine kinase inhibitor ceritinib, a potent anticancer drug used for the treatment of anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer, was found to strongly inhibit CD39 showing selectivity versus other ectonucleotidases. The drug displays a non-competitive, allosteric mechanism of CD39 inhibition exhibiting potency in the low micromolar range, which is independent of substrate (ATP) concentration. We could show that ceritinib inhibits ATP dephosphorylation in peripheral blood mononuclear cells in a dose-dependent manner, resulting in a significant increase in ATP concentrations and preventing adenosine formation from ATP. Importantly, ceritinib (1–10 µM) substantially inhibited ATP hydrolysis in triple negative breast cancer and melanoma cells with high native expression of CD39.ConclusionsCD39 inhibition might contribute to the effects of the powerful anticancer drug ceritinib. Ceritinib is a novel CD39 inhibitor with high metabolic stability and optimized physicochemical properties; according to our knowledge, it is the first brain-permeant CD39 inhibitor. Our discovery will provide the basis (i) to develop more potent and balanced dual CD39/ALK inhibitors, and (ii) to optimize the ceritinib scaffold towards interaction with CD39 to obtain potent and selective drug-like CD39 inhibitors for future in vivo studies.
Single-cell analysis reveals clonally expanded tumor-associated CD57+CD8 T cells are enriched in the periphery of patients with metastatic urothelial cancer responding to PD-L1 blockade
Authors: Fehlings Michael , Kim Leesun , Guan Xiangnan , Yuen Kobe , Tafazzol Alireza , Sanjabi Shomyseh , Zill Oliver A , Rishipathak Deepali , Wallace Andrew , Nardin Alessandra , Ma Siming , Milojkovic Ana , Newell Evan W , Mariathasan Sanjeev , Yadav Mahesh 
Published: August 2022

BackgroundA growing body of evidence suggests that T-cell responses against neoantigens are critical regulators of response to immune checkpoint blockade. We previously showed that circulating neoantigen-specific CD8 T cells in patients with lung cancer responding to anti-Programmed death-ligand 1 (PD-L1) (atezolizumab) exhibit a unique phenotype with high expression of CD57, CD244, and KLRG1. Here, we extended our analysis on neoantigen-specific CD8 T cells to patients with metastatic urothelial cancer (mUC) and further profiled total CD8 T cells to identify blood-based predictive biomarkers of response to atezolizumab.MethodsWe identified tumor neoantigens from 20 patients with mUC and profiled their peripheral CD8 T cells using highly multiplexed combinatorial tetramer staining. Another set of patients with mUC treated with atezolizumab (n=30) or chemotherapy (n=40) were selected to profile peripheral CD8 T cells by mass cytometry. Using single-cell transcriptional analysis (single-cell RNA sequencing (scRNA-seq)), together with CITE-seq (cellular indexing of transcriptomes and epitopes by sequencing) and paired T-cell receptor (TCR) sequencing, we further characterized peripheral CD8 T cells in a subset of patients (n=16).ResultsHigh frequency of CD57 was observed in neoantigen-specific CD8 T cells in patients with mUC responding to atezolizumab. Extending these findings to bulk CD8 T cells, we found higher frequency of CD57 expressing CD8 T cells before treatment in patients responding to atezolizumab (n=20, p<0.01) but not to chemotherapy. These findings were corroborated in a validation cohort (n=30, p<0.01) and notably were independent of known biomarkers of response. scRNA-seq analysis identified a clonally expanded cluster enriched within CD57+CD8 T cells in responding patients characterized by higher expression of genes associated with activation, cytotoxicity, and tissue-resident memory markers. Furthermore, compared with CD57−CD8 T cells, TCRs of CD57+CD8 T cells showed increased overlap with the TCR repertoire of tumor-infiltrating T cells.ConclusionsCollectively, we show high frequencies of CD57 among neoantigen-specific and bulk CD8 T cells in patients responding to atezolizumab. The TCR repertoire overlap between peripheral CD57+CD8 T cells and tumor-infiltrating lymphocytes suggest that accumulation of peripheral CD57+CD8 T cells is reflective of an ongoing antitumor T-cell response. Our findings provide evidence and rationale for using circulating CD8 T cells expressing CD57 as a readily accessible blood-based biomarker for selecting patients with mUC for atezolizumab therapy.
Preclinical Characterization of Relatlimab, a Human LAG-3–Blocking Antibody, Alone or in Combination with Nivolumab
Authors: Thudium Kent , Selby Mark , Zorn Julie A. , Rak Gregory , Wang Xi-Tao , Bunch Roderick Todd , Hogan Jason M. , Strop Pavel , Korman Alan J. 
Published: August 2022

Abstract

Novel therapeutic approaches combining immune-checkpoint inhibitors are needed to improve clinical outcomes for patients with cancer. Lymphocyte-activation gene 3 (LAG-3) is an immune-checkpoint molecule that inhibits T-cell activity and antitumor immune responses, acting through an independent mechanism from that of programmed death-1 (PD-1) and cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4). Here, we describe the development and preclinical characterization of relatlimab, a human antibody that binds to human LAG-3 with high affinity and specificity to block the interaction of LAG-3 with the ligands MHC II and fibrinogen-like protein-1, and to reverse LAG-3–mediated inhibition of T-cell function in vitro. Consistent with previous reports, in mouse models, the combined blockade of LAG-3 and PD-1 with surrogate antibodies resulted in enhanced antitumor activity greater than the individual blockade of either receptor. In toxicity studies in cynomolgus monkeys, relatlimab was generally well tolerated when combined with nivolumab. These results are consistent with findings from the RELATIVITY-047 phase II/III trial showing that relatlimab combined with nivolumab is a well-tolerated regimen that demonstrates superior progression-free survival compared with nivolumab monotherapy in patients with unresectable or metastatic melanoma.
Dialogismo e heterodiscurso na divulgação científica brasileira e francesa: uma análise dialógico-comparativa
Authors: Cavalcante Filho Urbano 
Published: August 2022

Neste trabalho, propomos uma análise dialógico-comparativa da presença do heterodiscurso na divulgação científica (DC), com o objetivo de verificar como se manifestam as diferentes formas da presença do outro no fio discursivo da DC. Para tanto, discutimos dois importantes conceitos da teoria bakhtiniana, o dialogismo e o heterodiscurso, e apresentamos a concepção de DC que pauta o estudo, enquanto relação dialógico-semântica entre esferas, destacando o papel do divulgador enquanto regente das vozes que povoam a DC. O corpus constitui-se de enunciados materializados em duas revistas de divulgação científica: Ciência Hoje e La Recherche, produções brasileira e francesa, respectivamente. As reflexões apresentadas apontam para a existência de várias formas de presença de outros no discurso da DC (a exemplo da forma dissimulada, construção híbrida, motivação pseudo-objetiva, palavra autoritária e sob a forma de gêneros intercalados), formas também observadas por Bakhtin no seu estudo sobre o heterodiscurso no romance.
Stimmung, de Karlheinz Stockhausen: improvisação, notação musical, experiências e interações estéticas e mediações culturais nas maneiras de fazer música sob a influência do oriente e das múltiplas culturas a partir da segunda metade do século XX
Authors: Carvalho Diogo Rebel e 
Published: August 2022

A partir da segunda metade do século XX, o declínio da representação do som através da notação tradicional, principalmente no continente europeu, é potencializado pelo florescer da multiplicidade cultural e das linguagens e estéticas oriundas, sobretudo, do oriente. O presente artigo visa examinar os processos de criação da obra Stimmung, de Karlheinz Stockhausen —reconhecidamente a primeira obra vocal do ocidente baseada, inteiramente, na produção de harmônicos vocais —, onde, a partir de uma única altura, numa obra com cerca de 75 minutos de duração, o compositor trabalha com sonoridades que remetem à tradição dos ritos e cerimônias exóticas ao interagir com elementos sonoros e textuais oriundos de diversos agentes culturais.
Appropriate Imaging for Geriatric Trauma
Authors: Pearcy Christopher , Grossman Verner Heather M. , Figueroa Brian A. , Burris Jennifer , Truitt Michael S. , Karpisek Andrew 
Published: August 2022

Background Trauma is the leading cause of preventable death in the United States. Early detection of life-threatening injuries leads to improved survival. Computed tomography (CT) scanning has become the modality of choice for early detection of injuries in the stable patient. Some studies have associated selective imaging (Selective-CT) with equivalent outcomes compared to whole body imaging (Pan-CT) with lower costs and radiation exposure. Within the geriatric population, however, the utility of Pan-CT remains controversial. Therefore, the aim of this study was to determine if a difference exists between Selective-CT and Pan-CT imaging in the geriatric trauma patient. Methods A retrospective analysis of Level 3 (G60) trauma activations presenting to our urban Level I trauma center between June 2016 and June 2019 was performed. Pan-CT was defined by ICD-10 codes indicating a head, cervical spine, chest, abdomen, and pelvis CT series. Patients with missing images and those who were transferred from other institutions were excluded. Logistic regression controlling for age, gender, injury type, severity, and Glasgow Coma Score was performed. Results A total of 1014 patients met inclusion criteria. Of these, 30.9% underwent Pan-CT (n = 314), 48.9% had Selective-CT (n = 497), and 20.2% received no CT imaging (n = 203). After logistic regression, no clinically significant variations in emergency department length of stay (LOS), hospital LOS, ICU LOS, ventilator days, discharge disposition, missed injury rate, or mortality rate were observed between imaging strategies. Conclusions Pan-CT provides no clinically significant advantage over Selective-CT in the geriatric trauma patient.
The Spectrum of Brittle Diabetes
Authors: Gill G V 
Published: August 2022

A group of 42 severely brittle insulin dependent diabetic patients were studied, and compared with a similar number of ‘stable’ diabetic patients. Brittle diabetics were predominantly female (86% v 45%, P<0.01), were of younger age (mean±SD 27.9±12.8 years v 40.1±13.6 years, P<0.001), and of shorter duration of diabetes (13.7±9.4 years v 19.6±11.2 years, P<0.01). Control as measured by glycosylated haemoglobin (HbA1) was poorer (13.7±3.1% v 10.1±1.5%, P <0.001), and daily insulin dose higher (98±81 u v 47±14 u, P <0.001). There was no difference in diabetic complication rates, but psychosocial disturbances (74% v 17%) and factitious instability (40% v 2%) were highly significantly more common amongst brittle patients. Examination of patterns of admission revealed most brittle diabetics to have hyperglycaemic problems (70%), mainly due to recurrent ketoacidosis (52%). Recurrent hypoglycaemia accounted for 12% of the group, and only 5/42 patients (12%) had mixed forms of instability. Brittle diabetes is thus characterized by young age and female sex, and usually manifests itself as recurrent ketoacidosis or other forms of hyperglycaemic instability. Psychosocial problems and factitious metabolic decompensation are common.
Endotracheal Intubation Skills of Medical Students
Authors: O'Flaherty D , Adams A P 
Published: August 2022

The ability and confidence of clinical medical students to insert endotracheal tubes correctly and quickly and to recognize oesophageal misplacement was evaluated. Ten (33%) of the medical students intubated the trachea correctly at their first attempt but 14 (47%) incorrectly identified the position of the endotracheal tube. However, recognition improved by their second and third attempts (70% and 80% respectively). Ninety-three percent of students intubated correctly on their third attempt. Although medical students can obtain better results at correct tube placement with repeated attempts under optimum conditions — A practice effect — And do better at recognizing correct tube placement there is still a persistent failure to recognize endotracheal tube misplacement, ie oesophageal intubation. It is the ability to recognize oesophageal intubation promptly that is a life-saving skill. This essential skill should be taught during the introductory anaesthesia programme through the use of clinical patients.
Emotional Distress in Doctors: Sources, Effects and Help Sought
Authors: King M B , Cockcroft A , Gooch C 
Published: August 2022

All doctors in a London Teaching Hospital were sent a self-administered, anonymous questionnaire, to study past episodes of emotional distress. We enquired about frequency of past and current emotional distress, sources of distress, effects on work and home life, type of help sought and perceived outcome of that help. Of 320 doctors, 210 (66%) responded. One hundred and forty-one (68%) reported previous episodes of moderate or severe emotional distress. Logistic regression revealed that distress was significantly more common in younger doctors and in women. Many respondents reported work problems as causing their distress and work was frequently adversely affected by episodes of distress. Professional help was rarely sought; non-professional help was from family and friends. Current emotional distress was related to a history of past distress, especially among the most junior doctors. We conclude that past emotional distress is reported by most doctors, with work pressures an important contributing factor. Doctors do not appear to use available sources of professional help. Our findings confirm that doctors have difficulty disclosing psychological problems. Specific programmes aimed at prevention and management of distress in doctors need to be initiated and evaluated.
An Evaluation of the Royal Air Force Helicopter Search and Rescue Services in Britain with Reference to Royal Air Force Valley 1980–1989
Authors: Liskiewicz W J 
Published: August 2022

The Royal Air Force (RAF) operates a helicopter Search and Rescue (SAR) service in the United Kingdom and territorial waters; it also provides a similar service in several locations abroad. A 10-year retrospective study of the SAR helicopter service operating from the RAF base at Valley on the island of Anglesey in North Wales is presented, with national SAR statistics over a similar period provided for comparison. Analysis of records kept by SAR aircrew at RAF Valley shows that their assistance had been requested on 1490 occasions during the 10-year period studied; most of these requests were the result of incidents involving holidaymakers, particularly in the mountains or along the coast. The results illustrate the versatility and life-saving potential of a highly-skilled and motivated service able to work in adverse weather and dangerous locations. In the light of current debate, the value of aeromedical evacuation of seriously ill patients using helicopters is discussed.
Management of Drug Misusers in Police Custody
Authors: Stark Margaret M 
Published: August 2022

Police surgeons are increasingly being asked by the police to assess whether drug misusers held in police custody are fit to be detained and fit for interview. There has been little published on how they manage these questions, furthermore the management appears to vary in different parts of the country. This study sets out to determine the attitudes and practise of police surgeons to the management of drug misusers in police custody. A questionnaire was sent to the full members of the Association of Police Surgeons of Great Britain (APSGB) in March 1993. It was found that police surgeons are very aware of the increasing drug problem, indeed 76% reported that they were seeing an increasing number of drug misusers. However, they exhibit significantly negative attitudes to drug misusers and there is no common practice for prescribing controlled drugs. Fifty-two per cent said that on average they notified no drug misusers each month. Seventy-six per cent of respondents said they had received a hepatitis B immunization. The majority of respondents called for more training on drug problems. Therefore, there is an urgent need for specific guidelines for police surgeons on the management of drug misusers in police custody to address the arbitrary nature of the current practice.
Are dietary pattern associated with alexithymia in Saudi adults?
Authors: Metwally Reham Shawky , Abdullah Ahmed Amr , AlAmmar Welayah A , Sebastian Tunny 
Published: August 2022

Background Alexithymia is characterized by difficulties in describing feelings and physical sensations. Few studies have shown that there is a relation between alexithymia and dietary habits. Objectives To determine the prevalence of alexithymia and its association with dietary patterns among a sample of communities in the Eastern Region of the Kingdom of Saudi Arabia. Materials and Methods A cross-sectional study was conducted using a sample of 247 participants, were selected using convenience sampling. A well-organized and valid online questionnaire was administered, which covered variables related to socio-demographic data, anthropometric measurements, dietary patterns, and the Toronto Alexithymia Scale (TAS). Results The prevalence of Alexithymia was found as 39.3%. Moreover, among the alexithymia and possible alexithymia groups, the majority eat pasta 1–4 times per week (70% and 67% respectively). Alexithemic participants eat fewer vegetables and fruits 46%), while the remaining eat more (70%), p = .001. Only 34% of the cases eat breakfast regularly (p = .005). Furthermore, the cases drink soft drinks and juices at meals more than controls in this study (p = .025). Conclusion The present study provides further experimental evidence which supports existing literature that indicating the strong association between alexithymia and unhealthy dietary patterns. Also, Alexithymia prevalence in our study is (39.3%) ; because of the cultural impact of the Saudi environment due to the fact that the face of Saudi women is not revealed, and because the face is one of the main sources of expression of feelings, which makes females unable to express or read feelings well.