bluuebunny/crossref_metadata_2025_split huggingface dataset:
The significance of structural stigma towards transgender people in health care encounters across Europe: Health care access, gender identity disclosure, and discrimination in health care as a function of national legislation and public attitudes
Authors: Falck Felicitas , Bränström Richard 
Published: May 2023

Abstract
Background
According to the minority stress theory, stigma affects the health of marginalized populations. Previous stigma research has focused on the health effects of individual and interpersonal stigma, paying less attention to structural factors. Laws on legal gender recognition affect the lives of transgender individuals in unique ways. The fact that these laws and population attitudes vary greatly between European countries, offer a unique opportunity to study the role of structural stigma in the lives of transgender individuals. Little is known about how transgender specific structural stigma relates to individual health determinants. Consequently, the aim of this study was to explore the association between structural stigma and access to gender affirming care, gender identity disclosure in health care, and experiences of discrimination in health care across 28 European countries.

Methods
By using multilevel regression, we combined data on health seeking behavior, transgender identity disclosure to health care providers, and experiences of discrimination in health care from 6,771 transgender individuals participating in the 2012 European Union Lesbian, Gay, Bisexual and Transgender survey with a structural stigma measure, consisting of population attitudes towards transgender individuals as well as national legislation on gender recognition. Reasons to refrain from seeking care and discrimination in health care were assessed by categorizing countries as low or high in structural stigma and using Chi-square statistics.

Results
Country-level structural stigma was negatively associated experiences of seeking gender affirming care and positively associated with concealment of being transgender to health care providers. Identity concealment was associated with a lower likelihood of exposure to discrimination in the health care setting across countries regardless of their level of structural stigma. The most prevalent reasons to forgo gender affirming care were shared between low and high structural stigma country groups and centered around fear.

Conclusion
The results highlight the importance of changing stigmatizing legislation and population attitudes to promote access to gender affirming care as well as openness of being transgender towards providers. Measures to decrease discrimination in the health care setting are warranted in high as well as in low structural stigma countries.
Birthweight, gestational age, and early school trajectory
Authors: Gansaonré Rabi Joël , Moore Lynne , Kobiané Jean-François , Sié Ali , Haddad Slim 
Published: May 2023

Abstract
Background
Birthweight and gestational age are important factors of not only newborn health by also child development and can contribute to delayed cognitive abilities. However, no study has analyzed the association of birthweight and gestational age with school trajectory measured simultaneously by school entry, grade repetition, and school dropout. This study aims, first, to analyze the association of birthweight or gestational age with school entry, and second, to explore the relationship between birthweight or gestational age and grade repetition and school dropout among children in Ouagadougou, Burkina Faso.

Methods
This study used longitudinal data from the Ouagadougou Health and Demographic Surveillance System. Our samples consisted of children born between 2008 and 2014 who were at least three years old at the beginning of the 2017–18 school year. Samples included 13,676, 3152, and 3498 children for the analysis of the school entry, grade repetition, and dropout, respectively. A discrete-time survival model was used to examine the relationship between birthweight or gestational age and school entry, grade repetition, and dropout. The association between birthweight or gestational age and age at school entry were assessed using a Poisson regression.

Results
The incidence rate of school entry was 18.1 per 100 people-years. The incidence of first repetition and dropout were 12.6 and 5.9, respectively. The probability of school entry decreased by 31% (HR:0.69, 95%CI: 0.56–0.85) and 8% (HR:0.92, 95%CI: 0.85–0.99) for children weighing less than 2000 g and those weighing between 2000 and 2499 g, respectively, compared to those born with a normal weight (weight ≥ 2500 g). The age at school entry of children with a birthweight less than 2000 g and between 2000 and 2499 g was 7% (IRR: 1.07, 95%CI: 1.06–1.08) and 3% (IRR: 1.03, 95%CI: 1.00-1.06) higher than children born at a normal birthweight, respectively. Gestational age was not associated with school entry or age at school entry. Similarly, birthweight and gestational age were not associated with grade repetition or dropout.

Conclusion
This study shows that low birthweight is negatively associated with school entry and age at school entry in Ouagadougou. Efforts to avoid low birthweights should be part of maternal and prenatal health care because the associated difficulties may be difficult to overcome later in the child’s life. Further longitudinal studies are needed to better understand the relationship between development at birth and school trajectory.
Relationship among symptoms, quality of life, and complementary and alternative medicines use among patients undergoing hemodialysis in French-speaking Switzerland
Authors: Kemnitz Marie , Antonini Matteo , Delmas Philippe 
Published: May 2023

AbstractBackgroundChronic renal disease is considered a main public health problem due to its high prevalence in the population. The solution of choice currently available is kidney transplantation but when this option is not available, blood purification treatments, notably haemodialysis (HD), are necessary. The presence of chronic renal disease combined with this demanding medical procedure leads to a hard symptomatology. To face this situation, HD patients often resort to complementary and alternative medicines (CAM) as they perceive that the healthcare professionals aren’t paying enough attention to their quality of life.Given this background, we aim to describe the prevalence and the type of the CAM used among HD patients and their possible relations with patients’ symptomatology and quality of life.MethodsWe interviewed 88 patients, undergoing hemodialysis in three hemodialysis centers in French-speaking Switzerland, about the presence of symptoms, their quality of life, and the possible use of CAM. Cluster analysis was used to create patients’ profiles about CAM use and regression analysis to explore the links between symptoms’ presence, patients’ quality of life, and CAM use.ResultsOur results show a large use of CAM: almost two HD patients out of three uses at least one CAM. Using cluster analysis, we were able to identify five patients’ profiles: non-users (37.5% of our sample), users of herbal medicine (20.5%), users of prayer-based practices (18.2%), people mainly using massages (9.1%), and a residual group including the users of other CAMs, with a predominance of meditation (14.8%). As expected, we observe a negative relation between the number of declared symptoms and patients' quality of life. Contrarily, we observe no relation between the use of CAM and the presence of symptoms. Our results show a positive relationship between the use of CAM and patients’ overall perception of health as well as the psychological dimension of their quality of life. No relationship is observed with other dimensions of quality of life, notably the physical dimension.ConclusionsOur results suggests that CAMs aren’t used as a substitute of official medicine but as a parallel support to HD patients’ quality of life.
Social prescribing practices and learning across the North West Coast region: essential elements and key challenges to implementing effective and sustainable social prescribing services
Authors: Hassan Shaima M. , Ring Adele , Goodall Mark , Abba Katharine , Gabbay Mark , van Ginneken Nadja 
Published: May 2023

Abstract
Introduction
Social prescribing has become an important feature of the UK primary care offer. However, there remains limited evidence on how best to implement and deliver social prescribing programmes to maximise effectiveness and long-term sustainability.

Aim
To explore social prescribing practices and experience of implementing social prescribing programmes across National Institute for Health and Social Care Research (NIHR) Collaborative Leadership for Applied Health and Care Research (CLAHRC) North West Coast (NWC) and NIHR Applied Research Collaboration (ARC) NWC region to identify key learning points that can be applied to other settings.

Method
We held a learning exchange workshop attended by practitioners and Public Advisors who had been involved in implementing and evaluating eight different social prescribing programmes with the support of NIHR CLAHRC NWC. We followed this with an online survey of social prescribing practice and priorities within the NIHR ARC NWC area. We used the findings from the workshop and survey to develop an initial model of the elements needed to successfully implement and sustain a working social prescribing programme.

Findings
We identified three core essential elements for a successful social prescribing programme: a personalised approach; meaningful service-user and community involvement; and whole systems working. These core elements need to be supported with adequate resources in the form of continuity of funding and adequate community resources to refer people to, capacity building and appropriate evaluation.

Conclusion
We were able to use a learning exchange workshop to both facilitate learning between practitioners and begin the process of identifying the ingredients needed for a successful social prescribing programme, which may be built on with further research.
An ICD-Associated DAMP Gene signature predicts survival and immunotherapy response of patients with lung adenocarcinoma
Authors: Wu Yuxin , Li Kexin , Liang Shuang , Lou Xiaoying , Li Yiling , Xu Danfei , Wu Yue , Wang Yuan , Cui Wei 
Published: May 2023

Abstract
Background
While some lung adenocarcinoma (LUAD) patients benefit long-term from treatment with immune checkpoint inhibitors, the sad reality is that a considerable proportion of patients do not. The classification of the LUAD tumor microenvironment (TME) can be used to conceptually comprehend primary resistance mechanisms. In addition, the most recent research demonstrates that the release of damage-associated molecular pattern (DAMP) in TME by immunogenic cell death (ICD) may contribute to the adaptive immune response. Currently, however, there is no such comprehensive research on this topic in LUAD patients. Therefore, we set out to investigate how to reverse the poor infiltration characteristics of immune cells and boost antitumor immunity by identifying DAMP model.

Methods
In this study, ICD-related DAMP genes were selected to investigate their effects on the prognosis of LUAD. To create a risk signature using the TCGA-LUAD cohort, the univariate COX regression and the least absolute shrinkage and selection operator regression were carried out, and the results were verified in a GEO dataset. Subsequently, the multivariate COX regression was applied to establish a prognostic nomogram. And the ESTIMATE and ssGSEA algorithms were utilized to analyze immune activity and the TIDE algorithm was for responsiveness to immunotherapy. Moreover, clinical tissue samples were used to verify the differential expression of 9 DAMP genes in the signature.

Results
We identified two distinct DAMP molecular subtypes, and there are remarkable differences in survival probability between the two subtypes, and patients with higher levels of DAMP-related genes are “hot tumors” with increased immune activity. In addition, 9 DAMP genes were selected as prognostic signature genes, and clinical outcomes and immunotherapy response were better for participants in the low-risk group. Importantly, according to the area under the curve (AUC) value in evaluating the efficacy of immunotherapy, this signature is superior to existing predictors, such as PD-L1 and TIDE.

Conclusions
Our study suggests ICD plays an important part in modeling the TME of LUAD patients. And this signature could be utilized as a reliable predictor to estimate clinical outcomes and predict immunotherapy efficacy among LUAD patients.
A cost-effectiveness analysis of ruxolitinib versus best alternative therapy for patients with steroid-refractory chronic graft-versus-host disease aged > 12 years in Singapore
Authors: Ong Jian Chun Matthew , Than Hein , Tripathi Sandeep , Gkitzia Christina , Wang Xiaojun 
Published: May 2023

AbstractBackgroundApproximately 30–70% of patients who have undergone allogeneic (allo) hematopoietic stem cell transplantation (HSCT) eventually experience chronic graft-versus-host disease (cGVHD). Patients who develop steroid-refractory (SR)-cGVHD are the most severely impacted due to significant disease and financial burden. There remains an unmet need for safe, efficacious, and accessible treatments for these patients. The objective of this study was to determine the cost effectiveness of ruxolitinib for treatment of SR-cGvHD from the Singapore healthcare system perspective.MethodsBased on data from the REACH3 randomized open-label trial, a semi-Markov model was developed to evaluate cost-effectiveness of ruxolitinib compared with investigators' choice of best alternative therapy (BAT) for treatment of patients > 12 years of age with SR-cGVHD in Singapore over a 40-year time horizon. The model only considered direct medical-care costs related to the treatment of SR-cGVHD and reported them in Singapore Dollars (SGD). Half-cycle correction was applied to all costs and outcomes, which were discounted at 3%. Probabilistic sensitivity analysis (PSA), one-way sensitivity analysis (OWSA), and scenario analysis were conducted to explore the drivers of uncertainty in the model.ResultsIn the deterministic base case, more life years (LY; 10.28 vs. 9.42) and quality-adjusted life years (QALYs; 7.31 vs. 6.51) were gained with ruxolitinib than BAT at higher costs (SGD 303,214 vs. SGD 302,673) leading to an incremental cost-effectiveness ratio (ICER) of SGD 677/QALY. At a willingness-to-pay threshold of SGD 75,000/QALY gained, PSA found that ruxolitinib had a 78.52% probability of being cost-effective. Findings were sensitive to variations in non-responder utilities in the BAT arm and duration of BAT treatment in the OWSA, or comparison to either methotrexate (MTX) or mycophenolic acid as a single comparator in the scenario analysis. ICERs remained lower than SGD 75,000/QALY in all other tested variations and scenarios.ConclusionRuxolitinib is likely to be cost-effective from Singapore healthcare system’s perspective for patients with SR-cGVHD, which is promising in the management of patients with unmet clinical needs.
Spatial analysis of stromal signatures identifies invasive front carcinoma-associated fibroblasts as suppressors of anti-tumor immune response in esophageal cancer
Authors: He Jian-Zhong , Chen Yang , Zeng Fa-Min , Huang Qing-Feng , Zhang Hai-Feng , Wang Shao-Hong , Yu Shuai-Xia , Pang Xiao-Xiao , Liu Ye , Xu Xiu-E , Wu Jian-Yi , Shen Wen-Jun , Li Zhan-Yu , Li En-Min , Xu Li-Yan 
Published: May 2023

Abstract
Background
Increasing evidence indicates that the tumor microenvironment (TME) is a crucial determinant of cancer progression. However, the clinical and pathobiological significance of stromal signatures in the TME, as a complex dynamic entity, is still unclear in esophageal squamous cell carcinoma (ESCC).

Methods
Herein, we used single-cell transcriptome sequencing data, imaging mass cytometry (IMC) and multiplex immunofluorescence staining to characterize the stromal signatures in ESCC and evaluate their prognostic values in this aggressive disease. An automated quantitative pathology imaging system determined the locations of the lamina propria, stroma, and invasive front. Subsequently, IMC spatial analyses further uncovered spatial interaction and distribution. Additionally, bioinformatics analysis was performed to explore the TME remodeling mechanism in ESCC. To define a new molecular prognostic model, we calculated the risk score of each patient based on their TME signatures and pTNM stages.

Results
We demonstrate that the presence of fibroblasts at the tumor invasive front was associated with the invasive depth and poor prognosis. Furthermore, the amount of α-smooth muscle actin (α-SMA)+ fibroblasts at the tumor invasive front positively correlated with the number of macrophages (MØs), but negatively correlated with that of tumor-infiltrating granzyme B+ immune cells, and CD4+ and CD8+ T cells. Spatial analyses uncovered a significant spatial interaction between α-SMA+ fibroblasts and CD163+ MØs in the TME, which resulted in spatially exclusive interactions to anti-tumor immune cells. We further validated the laminin and collagen signaling network contributions to TME remodeling. Moreover, compared with pTNM staging, a molecular prognostic model, based on expression of α-SMA+ fibroblasts at the invasive front, and CD163+ MØs, showed higher accuracy in predicting survival or recurrence in ESCC patients. Regression analysis confirmed this model is an independent predictor for survival, which also identifies a high-risk group of ESCC patients that can benefit from adjuvant therapy.

Conclusions
Our newly defined biomarker signature may serve as a complement for current clinical risk stratification approaches and provide potential therapeutic targets for reversing the fibroblast-mediated immunosuppressive microenvironment.
Efficacy of CytoSorb®: a systematic review and meta-analysis
Authors: Becker Sören , Lang Hannah , Vollmer Barbosa Clara , Tian Zhejia , Melk Anette , Schmidt Bernhard M. W. 
Published: May 2023

Abstract
Introduction
Cytokine adsorption using the CytoSorb® adsorber has been proposed in various clinical settings including sepsis, ARDS, hyperinflammatory syndromes, cardiac surgery or recovery after cardiac arrest. The aim of this analysis is to provide evidence for the efficacy of the CytoSorb® adsorber with regard to mortality in various settings.

Methods
We searched PubMed, Cochrane Library database and the database provided by Cytosorbents™ (01.1.2010–29.5.2022). We considered randomized controlled trials and observational studies with control groups. The longest reported mortality was defined as the primary endpoint. We computed risk ratios and 95%-confidence intervals and used DerSimonian and Lairds random effects model. We analysed all studies combined and divided them into the subgroups: sepsis, cardiopulmonary bypass surgery (CPB), other severe illness, SARS-CoV-2 infection and recovery from cardiac arrest. The meta-analysis was registered in advance (PROSPERO: CRD42022290334).

Results
Of an initial 1295 publications, 34 studies were found eligible, including 1297 patients treated with CytoSorb® and 1314 controls. Cytosorb® intervention did not lower mortality (RR [95%-CI]: all studies 1.07 [0.88; 1.31], sepsis 0.98 [0.74; 1.31], CPB surgery 0.91 [0.64; 1.29], severe illness 0.95 [0.59; 1.55], SARS-CoV-2 1.58 [0.50; 4.94]). In patients with cardiac arrest, we found a significant survival advantage of the untreated controls (1.22 [1.02; 1.46]). We did not find significant differences in ICU length of stay, lactate levels, or IL-6 levels after treatment. Of the eligible 34 studies only 12 were randomized controlled trials. All observational studies showed moderate to serious risk of bias.

Interpretation
To date, there is no evidence for a positive effect of the CytoSorb® adsorber on mortality across a variety of diagnoses that justifies its widespread use in intensive care medicine.
A peripheral signature of Alzheimer’s disease featuring microbiota-gut-brain axis markers
Authors: Marizzoni Moira , Mirabelli Peppino , Mombelli Elisa , Coppola Luigi , Festari Cristina , Lopizzo Nicola , Luongo Delia , Mazzelli Monica , Naviglio Daniele , Blouin Jean-Louis , Abramowicz Marc , Salvatore Marco , Pievani Michela , Cattaneo Annamaria , Frisoni Giovanni B. 
Published: May 2023

Abstract

Background
Increasing evidence links the gut microbiota (GM) to Alzheimer’s disease (AD) but the mechanisms through which gut bacteria influence the brain are still unclear. This study tests the hypothesis that GM and mediators of the microbiota-gut-brain axis (MGBA) are associated with the amyloid cascade in sporadic AD.

Methods
We included 34 patients with cognitive impairment due to AD (CI-AD), 37 patients with cognitive impairment not due to AD (CI-NAD), and 13 cognitively unimpaired persons (CU). We studied the following systems: (1) fecal GM, with 16S rRNA sequencing; (2) a panel of putative MGBA mediators in the blood including immune and endothelial markers as bacterial products (i.e., lipopolysaccharide, LPS), cell adhesion molecules (CAMs) indicative of endothelial dysfunction (VCAM-1, PECAM-1), vascular changes (P-, E-Selectin), and upregulated after infections (NCAM, ICAM-1), as well as pro- (IL1β, IL6, TNFα, IL18) and anti- (IL10) inflammatory cytokines; (3) the amyloid cascade with amyloid PET, plasma phosphorylated tau (pTau-181, for tau pathology), neurofilament light chain (NfL, for neurodegeneration), and global cognition measured using MMSE and ADAScog. We performed 3-group comparisons of markers in the 3 systems and calculated correlation matrices for the pooled group of CI-AD and CU as well as CI-NAD and CU. Patterns of associations based on Spearman’s rho were used to validate the study hypothesis.

Results
CI-AD were characterized by (1) higher abundance of Clostridia_UCG-014 and decreased abundance of Moryella and Blautia (p < .04); (2) elevated levels of LPS (p < .03), upregulation of CAMs, Il1β, IL6, and TNFα, and downregulation of IL10 (p < .05); (3) increased brain amyloid, plasma pTau-181, and NfL (p < 0.004) compared with the other groups. CI-NAD showed (1) higher abundance of [Eubacterium] coprostanoligenes group and Collinsella and decreased abundance of Lachnospiraceae_ND3007_group, [Ruminococcus]_gnavus_group and Oscillibacter (p < .03); (2) upregulation of PECAM-1 and TNFα (p < .03); (4) increased plasma levels of NfL (p < .02) compared with CU. Different GM genera were associated with immune and endothelial markers in both CI-NAD and CI-AD but these mediators were widely related to amyloid cascade markers only in CI-AD.

Conclusions
Specific bacterial genera are associated with immune and endothelial MGBA mediators, and these are associated with amyloid cascade markers in sporadic AD. The physiological mechanisms linking the GM to the amyloid cascade should be further investigated to elucidate their potential therapeutic implications.
Infinitely many homoclinic solutions for fractional discrete Kirchhoff–Schrödinger equations
Authors: Ju Chunming , Molica Bisci Giovanni , Zhang Binlin 
Published: May 2023

AbstractIn the present paper, we consider a fractional discrete Schrödinger equation with Kirchhoff term. Through the fountain theorem and the dual fountain theorem, we obtain two different conclusions about infinitely many homoclinic solutions to this equation.