bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characteristics, barriers, and career intentions of a national cohort of LGBTQ+ MD/PhD and DO/PhD trainees
Authors: Marr Mollie C. , Heffron Anna S. , Kwan Jennifer M. 
Published: April 2022

AbstractBackgroundLesbian, gay, bisexual, transgender, queer, non-binary, intersex, and/or asexual (LGBTQ+) individuals continue to suffer worse health outcomes compared to the general population. Data on LGBTQ+ individuals in medicine, particularly in medical training, remain sparse. National studies of LGBTQ+ students in MD/PhD and DO/PhD training programs have not been reported.MethodsTrainees pursuing MD, DO, MD/PhD, and DO/PhD degrees at 32 nationally representative institutions completed a 70-item survey about their future career and anticipated challenges using an online survey tool from September 2012 to December 2014. There were 4,433 respondents to the survey. Of those, 2,837 completed the gender identity questions and 2,849 completed the sexual orientation questions. Completion of these questions was required for inclusion. Survey results were analyzed to examine differences between LGBTQ+ and non-LGBTQ+ medical and dual degree trainees.ResultsLGBTQ+ students were underrepresented among MD/PhD and DO/PhD trainees (8.70%) compared to the US population, though their representation was higher than among MD and DO trainees (5.20%). LGBTQ+ dual degree trainees endorsed the greatest interest in pursuing careers involving academic medicine, with varying career focuses including research, clinical duties, education, and advocacy. LGBTQ+ dual degree trainees prioritized opportunities in patient care, work-life balance, and research as the most important factors for their career selection. Importantly, a higher percentage of LGBTQ+ dual degree trainees (15.50%) identified sexual harassment as a past barrier to career advancement compared to their non-LGBTQ+ peers (8.27%). LGBTQ+ dual degree trainees were more likely to report having a mentor who advocated for them.ConclusionsLGBTQ+ physician scientist trainees remain under-represented and under-studied. It is vital that medical institutions devote more time and resources towards identifying and addressing the unique needs of this group in training. Training programs should be aware of the current and prior challenges faced by their LGBTQ+ dual degree trainees, work to overcome the unique barriers they face, highlight the strengths and unique perspectives they bring, and foster their professional growth and goals during and beyond their training.
The introduction of advanced practice physiotherapy within Dutch primary care is a quest for possibilities, added value, and mutual trust: a qualitative study amongst advanced practice physiotherapists and general practitioners
Authors: Pellekooren Sylvia , Donker Marianne , Reijnders Eddy , Boutalab Lamyae , Ostelo Raymond , van Tulder Maurits , Pool-Goudzwaard Annelies 
Published: April 2022

Abstract
Background
Despite the increased deployment and added value of Advanced Practitioner Physiotherapy (APP) in musculoskeletal care internationally, APP is not yet widely accepted within Dutch primary care. This may be due to specific constraints in the implementation of APP within the Dutch healthcare system. This study aimed to explore the experiences and perceptions of Advanced Practitioner Physiotherapists (APPs) and General Practitioners (GPs) with respect to implementing APP within Dutch primary care.

Methods
This explorative and interpretive qualitative study included 12 APPs and 3 GPs who were in various stages of implementing an APP care model. Semi-structured interviews were conducted between January and March 2021. The topic list was based on existing literature, the personal input of researchers, and the Constellation Approach framework. Data were analysed using a thematic inductive approach.

Results
Four main themes emerged from the data; 1) Both GPs’ trust in APP and a clear added value of APP are critical for starting implementation, 2) APPs need continuous support from GPs, 3) APPs believe that their position needs strengthening, and 4) Implementation of the APP model creates tension over ownership. These four themes highlight the perceived difficulties in gaining trust, lack of clarity over the added value of APP, ambiguity over APPs’ professional profile and positioning, a need on behalf of GPs to maintain authority, lack of reimbursement structure, and the struggle APPs face to strike a balance with current care.

Conclusion
This study demonstrates that implementing an APP model of care is challenging, in part, because the deployment of APP does not sufficiently align with the core values of GPs, while GPs appear reluctant to hand over control of elements of patient care to APPs. APPs do not appear to have ownership over the implementation, given their strong dependence on the practice, values and needs of GPs.

Trial registration
Ethical approval was obtained from the Medical Ethics Committee of VU University Medical Centre in Amsterdam; reference number 2020.17 . All participants were asked to provide written informed consent prior to participating in the study.
Mutations of PI3K-AKT-mTOR pathway as predictors for immune cell infiltration and immunotherapy efficacy in dMMR/MSI-H gastric adenocarcinoma
Authors: Wang Zhenghang , Wang Xinyu , Xu Yu , Li Jian , Zhang Xiaotian , Peng Zhi , Hu Yajie , Zhao Xinya , Dong Kun , Zhang Bei , Gao Chan , Zhao Xiaochen , Chen Hui , Cai Jinping , Bai Yuezong , Sun Yu , Shen Lin 
Published: April 2022

Abstract
Background
A significant subset of mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) gastric adenocarcinomas (GAC) are resistant to immune checkpoint inhibitors (ICIs), yet the underlying mechanism remains largely unknown. We sought to investigate the genomic correlates of the density of tumor-infiltrating immune cells (DTICs) and primary resistance to ICI treatment.

Methods
Four independent cohorts of MSI-H GAC were included: (i) the surgery cohort (n = 175) with genomic and DTIC data, (ii) the 3DMed cohort (n = 32) with genomic and PD-L1 data, (iii) the Cancer Genome Atlas (TCGA) cohort (n = 73) with genomic, transcriptomic, and survival data, and (iv) the ICI treatment cohort (n = 36) with pre-treatment genomic profile and ICI efficacy data.

Results
In the dMMR/MSI-H GAC, the number of mutated genes in the PI3K-AKT-mTOR pathway (NMP) was positively correlated with tumor mutational burden (P < 0.001) and sensitivity to PI3K-AKT-mTOR inhibitors and negatively correlated with CD3+ (P < 0.001), CD4+ (P = 0.065), CD8+ (P = 0.004), and FOXP3+ cells (P = 0.033) in the central-tumor rather than invasive-margin area, and the transcription of immune-related genes. Compared to the NMP-low (NMP = 0/1) patients, the NMP-high (NMP ≥ 2) patients exhibited a poorer objective response rate (29.4% vs. 85.7%, P < 0.001), progression-free survival (HR = 3.40, P = 0.019), and overall survival (HR = 3.59, P = 0.048) upon ICI treatment.

Conclusions
Higher NMP was identified as a potential predictor of lower DTICs and primary resistance to ICIs in the dMMR/MSI-H GAC. Our results highlight the possibility of using mutational data to estimate DTICs and administering the PI3K-AKT-mTOR inhibitor as an immunotherapeutic adjuvant in NMP-high subpopulation to overcome the resistance to ICIs.
Deep learning for spirometry quality assurance with spirometric indices and curves
Authors: Wang Yimin , Li Yicong , Chen Wenya , Zhang Changzheng , Liang Lijuan , Huang Ruibo , Liang Jianling , Tu Dandan , Gao Yi , Zheng Jinping , Zhong Nanshan 
Published: April 2022

Abstract
Background
Spirometry quality assurance is a challenging task across levels of healthcare tiers, especially in primary care. Deep learning may serve as a support tool for enhancing spirometry quality. We aimed to develop a high accuracy and sensitive deep learning-based model aiming at assisting high-quality spirometry assurance.

Methods
Spirometry PDF files retrieved from one hospital between October 2017 and October 2020 were labeled according to ATS/ERS 2019 criteria and divided into training and internal test sets. Additional files from three hospitals were used for external testing. A deep learning-based model was constructed and assessed to determine acceptability, usability, and quality rating for FEV1 and FVC. System warning messages and patient instructions were also generated for general practitioners (GPs).

Results
A total of 16,502 files were labeled. Of these, 4592 curves were assigned to the internal test set, the remaining constituted the training set. In the internal test set, the model generated 95.1%, 92.4%, and 94.3% accuracy for FEV1 acceptability, usability, and rating. The accuracy for FVC acceptability, usability, and rating were 93.6%, 94.3%, and 92.2%. With the assistance of the model, the performance of GPs in terms of monthly percentages of good quality (A, B, or C grades) tests for FEV1 and FVC was higher by ~ 21% and ~ 36%, respectively.

Conclusion
The proposed model assisted GPs in spirometry quality assurance, resulting in enhancing the performance of GPs in quality control of spirometry.
Engineering a suite of E. coli strains for enhanced expression of bacterial polysaccharides and glycoconjugate vaccines
Authors: Kay Emily J. , Mauri Marta , Willcocks Sam J. , Scott Timothy A. , Cuccui Jon , Wren Brendan W. 
Published: April 2022

AbstractBackgroundGlycoengineering, in the biotechnology workhorse bacterium,Escherichia coli, is a rapidly evolving field, particularly for the production of glycoconjugate vaccine candidates (bioconjugation). Efficient production of glycoconjugates requires the coordinated expression within the bacterial cell of three components: a carrier protein, a glycan antigen and a coupling enzyme, in a timely fashion. Thus, the choice of a suitableE. colihost cell is of paramount importance. Microbial chassis engineering has long been used to improve yields of chemicals and biopolymers, but its application to vaccine production is sparse.ResultsIn this study we have engineered a family of 11E. colistrains by the removal and/or addition of components rationally selected for enhanced expression ofStreptococcus pneumoniaecapsular polysaccharides with the scope of increasing yield of pneumococcal conjugate vaccines. Importantly, all strains express a detoxified version of endotoxin, a concerning contaminant of therapeutics produced in bacterial cells. The genomic background of each strain was altered using CRISPR in an iterative fashion to generate strains without antibiotic markers or scar sequences.ConclusionsAmongst the 11 modified strains generated in this study,E. coliFalcon, Peregrine and Sparrowhawk all showed increased production ofS. pneumoniaeserotype 4 capsule. Eagle (a strain without enterobacterial common antigen, containing a GalNAc epimerase and PglB expressed from the chromosome) and Sparrowhawk (a strain without enterobacterial common antigen, O-antigen ligase and chain length determinant, containing a GalNAc epimerase and chain length regulators fromStreptococcus pneumoniae) respectively produced an AcrA-SP4 conjugate with 4 × and 14 × more glycan than that produced in the base strain, W3110. Beyond their application to the production of pneumococcal vaccine candidates, the bank of 11 new strains will be an invaluable resource for the glycoengineering community.
The KIDSCREEN-27 scale: translation and validation study of the Slovenian version
Authors: Budler Leona Cilar , Pajnkihar Majda , Ravens-Sieberer Ulrike , Barr Owen , Stiglic Gregor 
Published: April 2022

Abstract
Background
There are many methods available for measuring social support and quality of life (QoL) of adolescents, of these, the KIDSCREEN tools are most widely used. Thus, we aimed to translate and validate the KIDSCREEN-27 scale for the usage among adolescents aged between 10 and 19 years old in Slovenia.

Methods
A cross-sectional study was conducted among 2852 adolescents in primary and secondary school from November 2019 to January 2020 in Slovenia. 6-steps method of validation was used to test psychometric properties of the KIDSCREEN-27 scale. We checked descriptive statistics, performed a Mokken scale analysis, parametric item response theory, factor analysis, classical test theory and total (sub)scale scores.

Results
All five subscales of the KIDSCREEN-27 formed a unidimensional scale with good homogeneity and reliability. The confirmatory factor analysis showed poor fit in user model versus baseline model metrics (CFI = 0.847; TLI = 0.862) and good fit in root mean square error (RMSEA = 0.072; p(χ2) < 0.001). A scale reliability was calculated using Cronbach's α (0.93), beta (0.86), G6 (0.95) and omega (0.93).

Conclusions
The questionnaire showed average psychometric properties and can be used among adolescents in Slovenia to find out about their quality of life. Further research is needed to explore why fit in user model metrics is poor.
Gut microbiota modulation: a tool for the management of colorectal cancer
Authors: Wang Yan , Li Hui 
Published: April 2022

AbstractColorectal cancer (CRC) is the second cause of cancer death and the third most frequently diagnosed cancer. Besides the lifestyle, genetic and epigenetic alterations, and environmental factors, gut microbiota also plays a vital role in CRC development. The interruption of the commensal relationship between gut microbiota and the host could lead to an imbalance in the bacteria population, in which the pathogenic bacteria become the predominant population in the gut. Different therapeutic strategies have been developed to modify the gut immune system, prevent pathogen colonization, and alter the activity and composition of gut microbiota, such as prebiotics, probiotics, postbiotics, antibiotics, and fecal microbiota transplantation (FMT). Even though the employed strategies exhibit promising results, their translation into the clinic requires evaluating potential implications and risks, as well as assessment of their long-term effects. This study was set to review the gut microbiota imbalances and their relationship with CRC and their effects on CRC therapy, including chemotherapy and immunotherapy. More importantly, we reviewed the strategies that have been used to modulate gut microbiota, their impact on the treatment of CRC, and the challenges of each strategy.
The “Great Debate” at Immunotherapy Bridge 2021, December 1st–2nd, 2021
Authors: Ascierto Paolo A. , Butterfield Lisa H. , Finn Olivera J. , Futreal Andrew , Hamid Omid , LaVallee Theresa , Postow Michael A. , Puzanov Igor , Sosman Jeffrey , Fox Bernard A. , Hwu Patrick 
Published: April 2022

AbstractAs part of the 2021 Immunotherapy Bridge virtual congress (December 1–2, Naples, Italy), the Great Debate sessions featured experts who were assigned counter opposing views on four important questions in immunotherapy today. The first topic was whether oncolytic viruses or other specific immunomodulators were the more promising approach for intralesional therapy. The second was whether early surrogate endpoints, such as response rate or progression-free survival, correlate with long-term overall survival was considered. Thirdly, whether vaccines can transform cold into hot tumors was discussed and, finally, broad versus deep analytic profiling approaches to gain insights into immune-oncology development were compared. As with previous Bridge congresses, presenters were invited by the meeting Chairs and positions taken during the debates may not have reflected their respective personal view. In addition, the views summarised in this article are based on available evidence but may reflect personal interpretation of these data, clinical experience and subjective opinion of the speaker.
circMAP3K4 regulates insulin resistance in trophoblast cells during gestational diabetes mellitus by modulating the miR-6795-5p/PTPN1 axis
Authors: Du Runyu , Wu Na , Bai Yu , Tang Lei , Li Ling 
Published: April 2022

Abstract
Background
Insulin resistance (IR) during gestational diabetes mellitus (GDM) has been linked to dysregulated insulin-PI3K/Akt pathway. A defective insulin-PI3K/Akt pathway and dysregulated circular RNA (circRNA) levels have been observed in the placentas of patients with GDM; however, the mechanisms underlying this association remain unclear.

Methods
circRNAs potentially associated with GDM were selected through bioinformatics analysis and initially identified by quantitative real-time PCR (qPCR) in 9 GDM patients and 9 healthy controls, of which circMAP3K4 was further validated in additional 84 samples by qPCR. circMAP3K4 identity and localization were verified. Pearson correlation analysis was applied to evaluate the correlation between circMAP3K4 expression in the placental tissues of GDM patients and IR-related indicators. An IR model of trophoblasts was constructed using glucosamine. Interactions between miR-6795-5p and circMAP3K4 or PTPN1 were confirmed using a dual-luciferase reporter assay. The circMAP3K4/miR-6795-5p/PTPN1 axis and key markers in the insulin-PI3K/Akt pathway in placentas and trophoblasts were evaluated through qRT-PCR, immunofluorescence, and western blotting. The role of circMAP3K4 in glucose metabolism and cell growth in trophoblasts was determined using the glucose uptake and CCK8 assay, respectively.

Results
circMAP3K4 was highly expressed in the placentas of patients with GDM and the IR trophoblast model; this was associated with a dysregulated insulin-PI3K/Akt pathway. circMAP3K4 in the placentas of GDM patients was positively correlated with weight gain during pregnancy and time-glucose area under the curve of OGTT. circMAP3K4 and PTPN1 could both bind to miR-6795-5p. miR-6795-5p and PTPN1 were downregulated and upregulated, respectively, in the placentas of GDM patients and the IR trophoblast model. circMAP3K4 silencing or miR-6795-5p overexpression partially reversed the decrease in glucose uptake, inhibition in cell growth, and downregulated IRS1 and Akt phosphorylation in IR-trophoblasts; this restoration was reversed upon co-transfection with an miR-6795-5p inhibitor or PTPN1.

Conclusion
circMAP3K4 could suppress the insulin-PI3K/Akt signaling pathway via miR-6795-5p/PTPN1 axis, probably contributing to GDM-related IR.
Impact of contextual factors on patient outcomes following conservative low back pain treatment: systematic review
Authors: Sherriff Bronwyn , Clark Carol , Killingback Clare , Newell Dave 
Published: April 2022

Abstract
Background and objective
Chronic low back pain is pervasive, societally impactful, and current treatments only provide moderate relief. Exploring whether therapeutic elements, either unrecognised or perceived as implicit within clinical encounters, are acknowledged and deliberately targeted may improve treatment efficacy. Contextual factors (specifically, patient’s and practitioner’s beliefs/characteristics; patient-practitioner relationships; the therapeutic setting/environment; and treatment characteristics) could be important, but there is limited evidence regarding their influence. This research aims to review the impact of interventions modifying contextual factors during conservative care on patient’s pain and physical functioning.

Databases and data treatment
Four electronic databases (Medline, CINAHL, PsycINFO and AMED) were searched from 2009 until 15th February 2022, using tailored search strategies, and resulted in 3476 unique citations. After initial screening, 170 full-text records were potentially eligible and assessed against the inclusion–exclusion criteria. Thereafter, studies were assessed for methodological quality using a modified Downs and Black scale, data extracted, and synthesised using a narrative approach.

Results
Twenty-one primary studies (N = 3075 participants), were included in this review. Eight studies reported significant improvements in pain intensity, and seven in physical functioning, in favour of the contextual factor intervention(s). Notable contextual factors included: addressing maladaptive illness beliefs; verbal suggestions to influence symptom change expectations; visual or physical cues to suggest pain-relieving treatment properties; and positive communication such as empathy to enhance the therapeutic alliance.

Conclusion
This review identified influential contextual factors which may augment conservative chronic low back pain care. The heterogeneity of interventions suggests modifying more than one contextual factor may be more impactful on patients’ clinical outcomes, although these findings require judicious interpretation.
Increased estimated remnant-like particle cholesterol is associated with impaired coronary collateralization in patients with coronary chronic total occlusions
Authors: Gao Ang , Liu Jinxing , Liu Yan , Hu Chengping , Zhu Yong , Zhou Yujie , Han Hongya , Zhao Yingxin 
Published: April 2022

Abstract
Aims
This study intends to explore whether, or to what extent, the estimated remnant-like particle cholesterol was associated with coronary collateralization in patients with chronic total occlusion lesions.

Methods
792 patients with at least one coronary chronic total occlusion lesion were enrolled. Serum level of lipid profiles were determined and the estimated remnant-like particle cholesterol was calculated. The development of coronary collateralization was graded as low (Rentrop score 0–1) or high (Rentrop score 2–3) collateralization according to the Rentrop classification system and then the association between the estimated remnant-like particle cholesterol and collateralization was assessed.

Results
222 participants were classified into low collateralization group. The estimated remnant-like particle cholesterol level was significantly higher in low collateralization (P < 0.001) and type 2 diabetes mellitus (P = 0.009) group. To further explore the association between the estimated remnant-like particle cholesterol and the development of coronary collateralization, these patients were divided into 3 groups based on the estimated remnant-like particle cholesterol tertiles. The prevalence of low collateralization increased stepwise with the tertile groups (T1 12.5% vs. 27.1% vs. 45.3%, P < 0.001). Multivariate logistic regression analysis showed that the estimated remnant-like particle cholesterol was independently associated with the under-developed collateralization, with an OR and 95%CI of 2.34 (1.46–3.74) and 4.91 (3.01–8.02) in the T2 and T3 group, respectively. The following receiver-operating characteristic analysis indicated that the diagnostic value of estimated remnant-like particle cholesterol for the low collateralization was 0.696, with a cut-off value of 0.485, and its sensitivity was 82.88%. Besides, the addition of the estimated remnant-like particle cholesterol into the baseline model consisting of traditional risk factors could improve the incremental value of the discrimination of impaired collateralization only in overall and type 2 diabetes mellitus populations.

Conclusions
The increased estimated remnant-like particle cholesterol is independently associated with impaired collateralization in patients with coronary chronic total occlusion lesions. Therapies targeting at remnant-like particle cholesterol may be needed in advanced coronary artery disease patients with type 2 diabetes mellitus not suitable for vascular revascularization.