bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Neoantigen Landscape of Mycosis Fungoides
Authors: Sivanand Arunima , Hennessey Dylan , Iyer Aishwarya , O’Keefe Sandra , Surmanowicz Philip , Vaid Gauravi , Xiao Zixuan , Gniadecki Robert 
Published: November 2020

BackgroundMycosis fungoides (MF) is the most common cutaneous T-cell lymphoma, for which there is no cure. Immune checkpoint inhibitors have been tried in MF but the results have been inconsistent. To gain insight into the immunogenicity of MF we characterized the neoantigen landscape of this lymphoma, focusing on the known predictors of responses to immunotherapy: the quantity, HLA-binding strength and subclonality of neoantigens.MethodsWhole exome and whole transcriptome sequences were obtained from 24 MF samples (16 plaques, 8 tumors) from 13 patients. Bioinformatic pipelines (Mutect2, OptiType, MuPeXi) were used for mutation calling, HLA typing, and neoantigen prediction. PhyloWGS was used to subdivide malignant cells into stem and clades, to which neoantigens were matched to determine their clonality.ResultsMF has a high mutational load (median 3,217 non synonymous mutations), resulting in a significant number of total neoantigens (median 1,309 per sample) and high-affinity neoantigens (median 328). In stage I disease most neoantigens were clonal but with stage progression, 75% of lesions had &gt;50% subclonal antigens and 53% lesions had CSiN scores &lt;1. There was very little overlap in neoantigens across patients or between different lesions on the same patient, indicating a high degree of heterogeneity.ConclusionsThe neoantigen landscape of MF is characterized by high neoantigen load and significant subclonality which could indicate potential challenges for immunotherapy in patients with advanced-stage disease.
CSF HIV RNA Escape in Opsoclonus-Myoclonus-Ataxia Syndrome: Case Report and Review of the Literature
Authors: Cabaraux Pierre , Poncelet Arthur , Honnorat Jérome , Demeester Remy , Cherifi Soraya , Manto Mario 
Published: November 2020

Background: Human immunodeficiency viruses (HIV) infection is associated with a broad range of neurological manifestations, including opsoclonus-myoclonus ataxia syndrome (OMAS) occurring in primary infection, immune reconstitution syndrome or in case of opportunistic co-infection.Case: We report the exceptional case of a 43-year-old female under HIV treatment for 10 years who presented initially with suspected epileptic seizure. Although the clinical picture slightly improved under anti-epileptic treatment, it was rapidly attributed to OMAS. The patient exhibited marked opsoclonus, mild dysarthria, upper limbs intermittent myoclonus, ataxia in 4 limbs, truncal ataxia, and a severe gait ataxia (SARA score: 34). The diagnostic work-up showed radiological and biological signs of central nervous system (CNS) inflammation and cerebral venous sinus thromboses. The HIV viral load was higher in cerebrospinal fluid (CSF) than in the blood (4,560 copies/ml vs. 76 copies/ml). She was treated for 5 days with pulsed corticotherapy. Dolutegravir and anticoagulation administration were initiated. Follow-ups at 2 and 4 months showed a dramatic improvement of clinical neurologic status (SARA score at 4 months: 1), reduction of CNS inflammation and revealed undetectable CSF and serum viral loads.Conclusion: This case underlines the importance of the evaluation of the CSF viral load in HIV patients developing OMAS and suggests CSF HIV RNA escape as a novel cause for OMAS.
SHP-2-Induced Activation of c-Myc Is Involved in PDGF-B-Regulated Cell Proliferation and Angiogenesis in RMECs
Authors: Ma Jun , Tang Wenyi , Gu Ruiping , Hu Fangyuan , Zhang Lei , Wu Jihong , Xu Gezhi 
Published: November 2020

Background: Aberrant neovascularization resulting from inappropriate angiogenic signaling is closely related to many diseases, such as cancer, cardiovascular disease, and proliferative retinopathy. Although some factors involved in regulating pathogenic angiogenesis have been identified, the molecular mechanisms of proliferative retinopathy remain largely unknown. In the present study, we determined the role of platelet-derived growth factor-B (PDGF-B), one of the HIF-1-responsive gene products, in cell proliferation and angiogenesis in retinal microvascular endothelial cells (RMECs) and explored its regulatory mechanism.Methods: Cell counting kit-8 (CCK-8), bromodeoxyuridine (BrdU) incorporation, tube formation, cell migration, and Western blot assays were used in our study.Results: Our results showed that PDGF-B promoted cell proliferation and angiogenesis by increasing the activity of Src homology 2 domain-containing tyrosine phosphatase 2 (SHP-2) in RMECs, which was attenuated by the inhibition of PDGF receptor (PDGFR) or SHP-2 knockdown. Moreover, activation of c-Myc was involved in the processes of PDGF-B/SHP-2-driven cell proliferation in RMECs. The promoting effects of PDGF-B/SHP-2 on c-Myc expression were mediated by the Erk pathway.Conclusion: These results indicate that PDGF-B facilitates cell proliferation and angiogenesis, at least in part, via the SHP-2/Erk/c-Myc pathway in RMECs, implying new potential treatment candidates for retinal microangiopathy.
The Joint Effect of a Combination of Components From the Fruit of Crataegus pinnatifida Bge. Var. major N.E. Br. and the Root of Salvia miltiorrhiza Bge. With Exercises on Swimming in Focal Cerebral Infraction in Rat
Authors: Ding Shilan , Wang Wei , Yin Xiaojie , Wang Lan , Gong Leilei , Liao Fulong , Liang Rixin 
Published: November 2020

Background: In our previous study, we found that the combination of a traditional Chinese medicine (TCM) and swimming could prevent atherosclerosis through a synergistic interaction. However, whether the combined application of active components from the fruit of Crataegus pinnatifida Bge. Var. major N.E. Br. and the root of Salvia miltiorrhiza Bge. (CPSM) and swimming has been effective in the prevention and treatment of focal cerebral infraction remained unclear. This work aimed to conduct detailed investigation on the joint effects of CPSM extract with swimming on focal cerebral infraction in rats and its underlying mechanisms.Method: A photochemical method of the combination of Rose Bengal (RB) injection and cold-light source irradiation was performed to establish the rat focal cerebral thrombosis model. The pathological changes of the brain were observed by a DCP-7030 laser multifunction machine, and the protein levels of von Willebrand factor (vWF), vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) were detected by Western blotting. Blood samples were collected to assay tissue plasminogen activator (t-PA), plasminogen activator inhibitor type-1 (PAI-1), endothelin-1 (ET-1), 6-keto-prostaglandin F1α (6-keto-PGF1α), and thromboxane B2 (TXB2). Finally, the gene expression of t-PA, PAI-1, and ICAM-1 in human umbilical vein endothelial cells (HUVECs) stimulated by tumor necrosis factor-α (TNF-α) was assayed via real-time (RT) quantitative PCR (qPCR).Results: The joint effects of CPSM extract and swimming demonstrated significant interactions, which including increased blood perfusion, increased serum t-PA and 6-keto-PGF1α, decreased serum PAI-1 and TXB2, decreased protein levels of vWF, VCAM-1 and ICAM-1, and decreased ICAM-1 gene expression.Conclusion: This research demonstrated that the combined therapy of CP and SM extracts with swimming could prevent focal cerebral infraction through interactions on the regulation of vascular endothelial functions and inflammatory factors. It stresses the promising effects of the drugs and shear stress of blood flow in prevention and treatment of thrombosis. The mechanism may be related to regulating the protein expression of vWF, VCAM-1, and ICAM-1, and downregulating the gene expression of ICAM-1.
A Systematic Review of the Impact of Viral Respiratory Epidemics on Mental Health: An Implication on the Coronavirus Disease 2019 Pandemic
Authors: Luo Yang , Chua Cher Rui , Xiong Zhonghui , Ho Roger C. , Ho Cyrus S. H. 
Published: November 2020

Background:The twenty-first century viral respiratory epidemics have taught us valuable lessons. Our systematic review examined the impact of these epidemics, including coronavirus disease 2019 (COVID-19), on mental health among different population groups, drawing on their insights for recommendations for the current COVID-19 pandemic.Methods:Searches were performed on PubMed, Embase, PsycINFO, Web of Science, Scopus, CINAHL, and Cochrane on April 4, 2020. Studies that had undefined mental health outcomes or did not use a validated scale for measure were excluded. Quality assessment was carried outviathe Newcastle–Ottawa Scale.Results:We included 95 studies, most of which were conducted in Hong Kong (31.6%) and China (21.4%). A total of 30 (30.9%) studies are on the general public, 41 (42.2%) on healthcare workers, and 26 (26.6%) on patients and quarantined individuals. Furthermore, 36 (37.1%) of the studies are of high quality, 48 (49.5%) are of moderate quality, and 13 (13.4%) are of low quality. The most significant mental health outcomes reported include anxiety, depression, and post-traumatic stress disorder symptoms. The subgroups identified to have a higher risk of psychiatric symptoms among the general public include females, the elderly, individuals with chronic illness, migrant workers, and students. Long-term mental health impact was reported in some healthcare workers and epidemic patients, even up to 3 years in the former. Interestingly, when compared to non-quarantined groups, quarantine was not significantly associated with worse mental health outcomes.Conclusion:Important implications for the COVID-19 pandemic were highlighted. Respiratory epidemics pose a significant psychological morbidity onto many population groups. Psychological support for vulnerable groups, including healthcare workers and patients, should be implemented to prevent them from spiraling into clinical psychiatric conditions.
Profiles of Depressive Symptoms and Anger in Men: Associations With Postpartum Family Functioning
Authors: Macdonald Jacqui A. , Greenwood Christopher J. , Francis Lauren M. , Harrison Tessa R. , Graeme Liam G. , Youssef George J. , Di Manno Laura , Skouteris Helen , Fletcher Richard , Knight Tess , Williams Joanne , Milgrom Jeannette , Olsson Craig A. 
Published: November 2020

Background: Evidence suggests that men commonly experience depression as feelings of anger; yet, research has not investigated what this means for the manifestation of depressive symptoms in the early years of fatherhood and for key indicators of family functioning.Methods: Using data from a longitudinal cohort study of men at the normative age for entering fatherhood (28–32 years), we conducted latent class analyses to identify patterns of depressive symptoms and 3 sub-types of state anger (feeling; verbal; physical). We then assessed whether class membership was associated with paternity status (n = 535). In a subsample of fathers of infants aged up to 18 months (n = 162), we prospectively assessed associations with paternal-infant bonding, co-parenting, perceived social support, paternal involvement in childcare and alcohol use up to 2 years later.Results: Five classes emerged that differentiated men by anger and depressive symptom severity and by the degree to which men endorsed the feeling of wanting to express anger physically. Compared to the reference class with minimal symptoms, fathers had a higher probability of being in either the mild or most severe symptom classes. Men in symptomatic classes were at higher risk of lower levels of social support, co-parenting problems, and paternal-infant bonds. Class membership was not associated with alcohol use or paternal involvement in childcare.Conclusions: Our results reveal patterns of co-existing symptoms of depression and anger in fathers of infants that will be relevant to men's own need for support, their family safety, partner mental health and child developmental outcomes.
Mental Health Impacts of the COVID-19 Pandemic on International University Students, Related Stressors, and Coping Strategies
Authors: Lai Agnes Yuen-kwan , Lee Letitia , Wang Man-ping , Feng Yibin , Lai Theresa Tze-kwan , Ho Lai-ming , Lam Veronica Suk-fun , Ip Mary Sau-man , Lam Tai-hing 
Published: November 2020

Background: The coronavirus disease 2019 (COVID-19) pandemic has disrupted university teaching globally. The mental health impacts on international university students have been overlooked.Aims: This study examined the differences in COVID-19-related stressors and mental health impacts between international university students studying in the UK or USA who returned to their home country or region (returnees) and those who stayed in their institution country (stayers), and identified COVID-19-related stressors and coping strategies that were predictors of mental health.Method: An online questionnaire survey was conducted from April 28 through May 12, 2020 using an exponential, non-discriminative snowball sampling strategy (registered at the National Institutes of Health: NCT04365361).Results: A total of 124 full-time international university students (36.3% male) were included: 75.8% had returned to their home country or region for reasons related to COVID-19; 77.4% were pursuing a bachelor's program, and 53.2% were in programs with practicum component. 84.7% of all students had moderate-to-high perceived stress, 12.1% had moderate-to-severe symptoms of anxiety and depression, and 17.7% had moderate-to-severe symptoms of insomnia. Compared with returnees, stayers had significantly higher stress from COVID-19-related stressors such as personal health and lack of social support (Cohen's d: 0.57–1.11), higher perceived stress [10-item Perceived Stress Scale (PSS-10)] {22.6 ± 6.2 vs. 19.1 ± 6.1, β [95% confidence interval (CI)]: 4.039 (0.816, 7.261), Cohen's d: 0.52}, and more severe insomnia symptoms [Insomnia Severity Index (ISI)] [11.8 ± 6.1 vs. 7.6 ± 5.2, β (95% CI): 3.087 (0.262, 5.912), Cohen's d: 0.45], with moderate-to-large effect sizes. Compared with males, females reported significantly higher stress from uncertainties about academic program (Cohen's d: 0.45) with a small effect size. In the total sample, stress related to academics (e.g., personal attainment, uncertainties about academic program, and changes in teaching/learning format), health (including personal health and health of family and friends), availability of reliable COVID-19-related information, and lack of social support predicted more negative mental health impacts. Resilience, positive thinking, and exercise were predictors of less severe mental health impacts.Conclusions: Stayers experienced more adverse mental health impacts than returnees. We call on educators and mental health professionals to provide appropriate support for international students, particularly the stayers, during the pandemic.
The Effect of Physical Exercise Training on Neck and Shoulder Muscle Function Among Military Helicopter Pilots and Crew: A Secondary Analysis of a Randomized Controlled Trial
Authors: Murray Mike , Lange Britt , Søgaard Karen , Sjøgaard Gisela 
Published: November 2020

Introduction: This study presents secondary outcome analyses, in terms of muscle function [i.e., maximal voluntary contraction (MVC) and rate of torque development (RTD)] from a parallel group, single blinded, randomized controlled trial introducing a physical exercise training intervention aiming to reduce neck pain among military helicopter pilots and crew-members.Methods: Participants (50 pilots, 58 crew-members) were recruited from the Royal Danish Air Force and randomized to either an exercise-training-group (ETG; n = 35) or a reference-group (REF; n = 34). Participants in ETG received 20 weeks of self-administered exercise training specifically tailored to target the neck and shoulder muscles. REF received no training. Outcome: (1) MVC was measured for cervical extension and flexion as well as shoulder elevation and abduction, (2) RTD was measured for cervical extension and flexion. Adherence to training was self-reported and categorized as regular if performed at least once a week.Results: MVC for cervical extension was significantly increased at follow-up in ETG (37.5 ± 11.2 Nm at baseline, change: 2.1 ± 8.3 Nm) compared to REF (38.1 ± 10.7 Nm at baseline, change: −2.4 ± 6.8 Nm) according to intension-to-treat analysis (p = 0.018). Likewise, RTD was significantly increased in ETG for cervical extension (149.6 ± 63.3 Nm/s at baseline, change: 14.7 ± 49.0 Nm/s) compared to REF (165.4 ± 84.7 Nm/s at baseline, change: −16.9±70.9 Nm/s) (p = 0.034). The cervical extension/flexion MVC-ratio was significantly different at follow-up (p = 0.039) between ETG (1.5 ± 0.5 at baseline, change: −0.0 ± 0.3) compared to REF (1.5 ± 0.5 at baseline, change: −0.2 ± 0.4). Per-protocol analysis of MVC, including only participants in ETG with regular training adherence (n = 10), showed a significant increase for cervical extension (33.2 ± 7.3 Nm at baseline, change: 6.0 ± 5.4 Nm) and shoulder elevation right side (143.0 ± 25.8 Nm at baseline, change: 15.8 ± 18.1 Nm).Conclusion: Physical exercise training significantly improved MVC and RTD in the upper neck extensors. Only approximately 1/3 of participants in ETG adhered to training regularly, which likely attenuated the effectiveness of the training intervention on neck and shoulder muscle function. Future studies should focus on the practical implementation of self-administered exercise training to improve adherence.
GPs’ perspectives on acne management in primary care: a qualitative interview study
Authors: Platt Duncan , Muller Ingrid , Sufraz Anicka , Little Paul , Santer Miriam 
Published: November 2020

BackgroundAcne is a common skin condition, affecting most adolescents at some point. While guidelines recommend topical treatments first-line, long courses of oral antibiotics are commonly prescribed.AimTo explore GPs’ perspectives on managing acne.Design and settingQualitative interview study with GPs in South West England.MethodGPs were invited to participate via existing email lists used by GP educators to disseminate information. Purposive sampling was used to recruit a range of participants by sex, number of years in practice, and whether their practice was rural or urban. Semi-structured telephone interviews followed an interview guide and were audiorecorded and transcribed. Data were explored using inductive thematic analysis facilitated by NVivo software (version 11).ResultsA total of 102 GPs were invited, of whom 20 participated. Analysis revealed uncertainties regarding topical treatments, particularly around available products, challenges regarding side effects, and acceptability of topical treatments. GPs generally either perceived topical treatments to be less effective than oral antibiotics or perceived pressure from patients to prescribe oral antibiotics due to patients’ views of topical treatments being ineffective. GPs described a familiarity with prescribing oral antibiotics and expressed little concern about antimicrobial stewardship in the context of acne. Some seemed unaware of guidance suggesting that antibiotic use in acne should not exceed 3 months, while others spoke about avoiding difficult conversations with patients regarding discontinuation of antibiotics.ConclusionGPs expressed uncertainty about the use of topical treatments for acne and either felt that treatments were of low effectiveness or perceived pressure from patients to prescribe oral antibiotics.
Management of non-urgent paediatric emergency department attendances by GPs: a retrospective observational study
Authors: Leigh Simon , Mehta Bimal , Dummer Lillian , Aird Harriet , McSorley Sinead , Oseyenum Venessa , Cumbers Anna , Ryan Mary , Edwardson Karl , Johnston Phil , Robinson Jude , Coenen Frans , Taylor-Robinson David , Niessen Louis W , Carrol Enitan D 
Published: November 2020

BackgroundNon-urgent emergency department (ED) attendances are common among children. Primary care management may not only be more clinically appropriate, but may also improve patient experience and be more cost-effective.AimTo determine the impact on admissions, waiting times, antibiotic prescribing, and treatment costs of integrating a GP into a paediatric ED.Design and settingRetrospective cohort study explored non-urgent ED presentations in a paediatric ED in north-west England.MethodFrom 1 October 2015 to 30 September 2017, a GP was situated in the ED from 2.00 pm until 10.00 pm, 7 days a week. All children triaged as ‘green’ using the Manchester Triage System (non-urgent) were considered to be ‘GP appropriate’. In cases of GP non-availability, children considered non-urgent were managed by ED staff. Clinical and operational outcomes, as well as the healthcare costs of children managed by GPs and ED staff across the same timeframe over a 2-year period were compared.ResultsOf 115 000 children attending the ED over the study period, a complete set of data were available for 13 099 categorised as ‘GP appropriate’; of these, 8404 (64.2%) were managed by GPs and 4695 (35.8%) by ED staff. Median duration of ED stay was 39 min (interquartile range [IQR] 16–108 min) in the GP group and 165 min (IQR 104–222 min) in the ED group (P<0.001). Children in the GP group were less likely to be admitted as inpatients (odds ratio [OR] 0.16; 95% confidence interval [CI] = 0.13 to 0.20) and less likely to wait >4 hours before being admitted or discharged (OR 0.11; 95% CI = 0.08 to 0.13), but were more likely to receive antibiotics (OR 1.42; 95% CI = 1.27 to 1.58). Treatment costs were 18.4% lower in the group managed by the GP (P<0.0001).ConclusionGiven the rising demand for children’s emergency services, GP in ED care models may improve the management of non-urgent ED presentations. However, further research that incorporates causative study designs is required.
Recurso terapêutico ocupacional para tratamento de delirium em pacientes com COVID-19
Authors: Barreto Renata Gomes , Sousa Wendy Chrystyan Medeiros de , Silva Silmara Maria Alves Fernandes da , Souza Thais Alves de , Silva Erika Carneiro da , Brito Bruno da Silva , Teodozio Gilberto Costa , Silvestre Maria Cecilia de Araújo 
Published: November 2020

Objetivo. A reabilitação cognitiva precoce e suas formas de intervenção para prevenção e tratamento do delirium é um foco relativamente novo de pesquisa. O objetivo deste artigo é apresentar uma alternativa de intervenção cognitiva para prevenção e manejo de delirium em pacientes com COVID-19 no contexto hospitalar. Método. Trata-se de um estudo descritivo definido pela elaboração de um livro como recurso terapêutico ocupacional baseado na intervenção cognitiva para prevenção e manejo de delirium dos pacientes internados em um hospital estadual de referência no tratamento do COVID-19. Resultados. O livro interativo “Você pode tudo menos desistir” utilizou estratégias de compensação que facilitam e fortalecem o processamento cognitivo, além de treinamento cognitivo de funções específicas, tais como a memória, pensamento, aspectos emocionais e consciência da própria identidade. Conclusão. Sugere-se que o livro interativo pode ser utilizado como uma estratégia não farmacológica de ntervenção, proporcionando o engajamento terapêutico durante as atividades de estimulação cognitiva para prevenção e manejo de delirium em pacientes hospitalizados com COVID-19.