bluuebunny/crossref_metadata_2025_split huggingface dataset:
Homelessness and health-related outcomes: an umbrella review of observational studies and randomized controlled trials
Authors: Fornaro Michele , Dragioti Elena , De Prisco Michele , Billeci Martina , Mondin Anna Maria , Calati Raffaella , Smith Lee , Hatcher Simon , Kaluzienski Mark , Fiedorowicz Jess G. , Solmi Marco , de Bartolomeis Andrea , Carvalho André F. 
Published: July 2022

AbstractBackgroundHomelessness has been associated with multiple detrimental health outcomes across observational studies. However, relatively few randomized controlled trials (RCTs) have been conducted on people who experience homelessness (PEH). Thus, this umbrella review ranked the credibility of evidence derived from systematic reviews (SRs) and meta-analyses (MAs) of observational studies investigating the associations between homelessness and any health outcome as well as RCTs targeting health needs in this population.MethodsSeveral databases were systematically searched from inception through April 28, 2021. Any SR and/or MA reporting quantitative data and providing a control group were eligible for inclusion. The credibility of the evidence derived from observational studies was appraised by considering the significance level of the association and the largest study, the degree of heterogeneity, the presence of small-study effects as well as excess significance bias. The credibility of evidence was then ranked in five classes. For SRs and/or MAs of RCTs, we considered the level of significance and whether the prediction interval crossed the null. The AMSTAR-2 and AMSTAR-plus instruments were adopted to further assess the methodological quality of SRs and/or MAs. The Newcastle-Ottawa Scale (NOS) was employed to further appraise the methodological quality of prospective cohort studies only; a sensitivity analysis limited to higher quality studies was conducted.ResultsOut of 1549 references, 8 MAs and 2 SRs were included. Among those considering observational studies, 23 unique associations were appraised. Twelve of them were statistically significant at thep≤0.005 level. Included cases had worst health-related outcomes than controls, but only two associations reached a priori-defined criteria for convincing (class I) evidence namely hospitalization due to any cause among PEH diagnosed with HIV infection, and the occurrence of falls within the past year among PEH. According to the AMSTAR-2 instrument, the methodological quality of all included SRs and/or MAs was “critically low.” Interventional studies were scant.ConclusionWhile homelessness has been repeatedly associated with detrimental health outcomes, only two associations met the criteria for convincing evidence. Furthermore, few RCTs were appraised by SRs and/or MAs. Our umbrella review also highlights the need to standardize definitions of homelessness to be incorporated by forthcoming studies to improve the external validity of the findings in this vulnerable population.
The effects of greenness exposure on hypertension incidence among Chinese oldest-old: a prospective cohort study
Authors: Wensu Zhou , Wenjuan Wang , Fenfen Zhou , Wen Chen , Li Ling 
Published: July 2022

AbstractBackgroundAlthough the oldest-old (those aged over 80 years) are vulnerable to environmental factors and have the highest prevalence of hypertension, studies focusing on greenness exposure and the development of hypertension among them are insufficient. The aim of this study was to explore the association between residential greenness and hypertension in the oldest-old population.MethodsThis cohort study included data from the Chinese Longitudinal Healthy Longevity Survey (CLHLS). The oldest-old were free of hypertension at baseline (2008), and hypertension events were assessed by follow-up surveys in 2011, 2014, and 2018. The one-year averages of the normalized difference vegetation index (NDVI) and enhanced vegetation index (EVI) at 500-m buffer before the interview year of incident hypertension or last censoring interview were collected at the level of 652 residential units (district or county). The linear or nonlinear association between greenness and hypertension incidence was analyzed using the Cox proportional hazards model with penalized splines. The linear links between greenness and hypertension incidence were determined using the Cox proportional hazards model included a random effect term.ResultsAmong 5253 participants, the incidence rate of hypertension was 7.25 (95% confidence interval [CI]: 6.83–7.67) per 100 person-years. We found a nonlinear association between greenness exposure and hypertension risk, and the exposure-response curve showed that 1 change point existed. We examined the linear effect of greenness on hypertension by categorizing the NDVI/EVI into low and high-level exposure areas according to the change point. We found more notable protective effects of each 0.1-unit increase in greenness on hypertension incidence for participants living in the high-level greenness areas (hazard ratio (HR) = 0.60; 95% CI: 0.53–0.70 for NDVI; HR = 0.46; 95% CI: 0.37–0.57 for EVI). In contrast, no significant influence of greenness exposure on hypertension risk was found for participants living in the low-level greenness areas (HR = 0.77; 95% CI: 0.38–1.55 for NDVI; HR = 0.73; 95% CI: 0.33–1.63 for EVI).ConclusionsGreenness exposure is nonlinearly associated with hypertension risk among the oldest-old, presenting its relationship in an inverse “U-shaped” curve. Greenness is a protective factor that decreases the risk of hypertension.
A process for creating data report-back tools to improve equity in environmental health
Authors: Tomsho Kathryn S. , Polka Erin , Chacker Stacey , Queeley David , Alvarez Marty , Scammell Madeleine K. , Emmons Karen M. , Rudd Rima E. , Adamkiewicz Gary 
Published: July 2022

AbstractBackgroundAlthough there is increasing interest in reporting results of environmental research efforts back to participants, evidence-based tools have not yet been applied to developed materials to ensure their accessibility in terms of literacy, numeracy, and data visualization demand. Additionally, there is not yet guidance as to how to formally assess the created materials to assure a match with the intended audience.MethodsRelying on formative qualitative research with participants of an indoor air quality study in Dorchester, Massachusetts, we identified means of enhancing accessibility of indoor air quality data report-back materials for participants. Participants (n = 20) engaged in semi-structured interviews in which they described challenges they encountered with scientific and medical materials and outlined written and verbal communication techniques that would help facilitate engagement with and accessibility of environmental health report-back materials. We coupled these insights from participants with best practice guidelines for written materials by operationalizing health literacy tools to produce accessible audience-informed data report-back materials.ResultsThe resulting data report-back materials had a 7th -grade reading level, and between a 4th -8th grade level of overall document complexity. The numeracy skills required to engage with the material were of the lowest demand, and we incorporated best practices for risk communication and facilitating understanding and actionability of the materials. Use of a rigorous assessment tool provides evidence of accessibility and appropriateness of the material for the audience.ConclusionsWe outline a process for developing and evaluating environmental health data reports that are tailored to inspire risk-reduction actions, and are demonstrably accessible in terms of their literacy, numeracy, and data visualization demand. Adapting health literacy tools to create and evaluate environmental data report-back materials is a novel and evidence-based means of ensuring their accessibility.
Alternative splicing patterns reveal prognostic indicator in muscle-invasive bladder cancer
Authors: AZhaTi BaiHeTiYa , Wu Gaoliang , Zhan Hailun , Liang Wei , Song Zhijian , Lu Leilei , Xie Qichao 
Published: July 2022

Abstract
Background
Bladder cancer is one of the most lethal malignancy in urological system, and 20–25% of bladder cancer patients are muscle invasive with unfavorable prognosis. However, the role of alternative splicing (AS) in muscle-invasive bladder cancer (MIBC) remains to be elucidated.

Methods
Percent spliced in (PSI) data obtained from the Cancer Genome Atlas (TCGA) SpliceSeq database (n = 394) were utilized to evaluate the AS events in MIBC. Prognosis-associated AS events were screened out by univariate Cox regression. LASSO Cox regression was used to identify reliable prognostic patterns in a training set and further validated in a test set. Splicing regulatory networks were constructed by correlations between PSI of AS events and RNA expression of splicing factors.

Results
As a result, a total of 2589 prognosis-related AS events in MIBC were identified. Pathways of spliceosomal complex (FDR = 0.017), DNA-directed RNA polymerase II, core complex (FDR = 0.032), and base excision repair (FDR = 0.038) were observed to be significantly enriched. Additionally, we noticed that most of the prognosis-related AS events were favorable factors. According to the LASSO and multivariate Cox regression analyses, 15-AS-based signature was established with the area under curve (AUC) of 0.709, 0.823, and 0.857 at 1-, 3-, and 5- years, respectively. The MIBC patients were further divided into high- and low-risk groups based on median risk sores. Interestingly, we observed that the prevalence of FGFR3 with mutations and focal amplification was significantly higher in low-risk group. Functional and immune infiltration analysis suggested potential signaling pathways and distinct immune states between these two groups. Moreover, splicing correlation network displayed a regulatory mode of prognostic splicing factors (SF) in MIBC patients.

Conclusions
This study not only provided novel insights into deciphering the possible mechanism of tumorgenesis and pathogenesis but also help refine risk stratification systems and potential treatment of decision-making for MIBC.
MST4 negatively regulates type I interferons production via targeting MAVS-mediated pathway
Authors: Liu Wei , Ma Zhenling , Wu Yaru , Yuan Cui , Zhang Yanyan , Liang Zeyang , Yang Yu , Zhang Wenwen , Jiao Pengtao 
Published: July 2022

Abstract
Background
Cytosolic RNA sensing can elicit immune responses against viral pathogens. However, antiviral responses must be tightly regulated to avoid the uncontrolled production of type I interferons (IFN) that might have deleterious effects on the host. Upon bacterial infection, the germinal center kinase MST4 can directly phosphorylate the adaptor TRAF6 to limit the inflammatory responses, thereby avoiding the damage caused by excessive immune activation. However, the molecular mechanism of how MST4 regulates virus-mediated type I IFN production remains unknown.

Methods
The expression levels of IFN-β, IFIT1, and IFIT2 mRNA were determined by RT-PCR. The expression levels of p-IRF3, IRF3, RIG-I, MAVS, and MST4 proteins were determined by Western blot. The effect of secreted level of IFN-β was measured by ELISA. The relationship between MST4 and MAVS was investigated by immunofluorescence staining and coimmunoprecipitation.

Results
In this study, we reported that MST4 can act as a negative regulator of type I IFN production. Ectopic expression of MST4 suppressed the Poly (I:C) (polyino-sinic-polycytidylic acid)- and Sendai virus (SeV)-triggered production of type I IFN, while the knockdown of MST4 enhanced the production of type I IFN. Mechanistically, upon SeV infection, the MST4 competed with TRAF3 to bind to the 360–540 domain of MAVS, thereby inhibiting the TRAF3/MAVS association. Additionally, MST4 facilitated the interaction between the E3 ubiquitin ligase Smurf1 and MAVS. This promoted the K48-linked ubiquitination of MAVS, thereby accelerating the ubiquitin-mediated proteasome degradation of MAVS.

Conclusions
Our findings showed that MST4 acted as a crucial negative regulator of RLR-mediated type I IFN production.
Predominantly epithelial-type synovial sarcoma with overwhelming neuroendocrine differentiation: a potential diagnostic pitfall
Authors: Chen Ying , Zhou Ning , Guo Deyu , Wang Xiaodong , He Xin , Xu Yujuan 
Published: July 2022

Abstract
Background
Synovial sarcoma is an uncommon soft tissue tumor of soft tissue, characterized by a specific SS18 rearrangement. It generally manifests as a lesion composed of monomorphic spindle cells and sometimes shows variable epithelial differentiation. Epithelial-type synovial sarcoma is rare, and synovial sarcoma with overwhelming neuroendocrine differentiation has not been reported previously.

Case presentation
Here, we present a case of a young man with an epithelial-type synovial sarcoma of the right leg that showed an overwhelming neuroendocrine differentiation. The diagnosis was confirmed by the detection of targeted fusion re-arrangement associated with synovial sarcoma.

Conclusions
This study emphasizes the importance of molecular approaches in modern soft tissue pathology. Detecting the expression of neuroendocrine antigens in synovial sarcoma is a pre-requisite to avoid misdiagnosis of metastatic neuroendocrine tumor, malignant peripheral nerve sheath tumor with glandular differentiation, and carcinosarcoma.
Bu Shen Huo Xue decoction promotes functional recovery in spinal cord injury mice by improving the microenvironment to promote axonal regeneration
Authors: Hou Yonghui , Luo Dan , Hou Yu , Luan Jiyao , Zhan Jiheng , Chen Zepeng , E Shunmei , Xu Liangliang , Lin Dingkun 
Published: July 2022

Abstract
Background
Bu-Shen-Huo-Xue (BSHX) decoction has been used in the postoperative rehabilitation of patients with spinal cord injury in China. In the present study, we aim to reveal the bioactive compounds in BSHX decoction and comprehensively explore the effects of BSHX decoction and the underlying mechanism in spinal cord injury recovery.

Methods
The main chemical constituents in BSHX decoction were determined by UPLC–MS/MS. SCI mice were induced by a pneumatic impact device at T9–T10 level of the vertebra, and treated with BSHX decoction. Basso–Beattie–Bresnahan (BBB) score, footprint analysis, hematoxylin–eosin (H&E) staining, Nissl staining and a series of immunofluorescence staining were performed to investigate the functional recovery, glial scar formation and axon regeneration after BSHX treatment. Immunofluorescent staining of bromodeoxyuridine (BrdU), neuronal nuclei (NeuN) and glial fibrillary acidic protein (GFAP) was performed to evaluate the effect of BSHX decoction on neural stem cells (NSCs) proliferation and differentiation.

Results
We found that the main compounds in BSHX decoction were Gallic acid, 3,4-Dihydroxybenzaldehyde, (+)-Catechin, Paeoniflorin, Rosmarinic acid, and Diosmetin. BSHX decoction improved the pathological findings in SCI mice through invigorating blood circulation and cleaning blood stasis in the lesion site. In addition, it reduced tissue damage and neuron loss by inhibiting astrocytes activation, and promoting the polarization of microglia towards M2 phenotype. The functional recovery test revealed that BSHX treatment improved the motor function recovery post SCI.

Conclusions
Our study provided evidence that BSHX treatment could improve the microenvironment of the injured spinal cord to promote axonal regeneration and functional recovery in SCI mice.
Conceptualization, detection, and management of psychological distress and mental health conditions among people with tuberculosis in Zambia: a qualitative study with stakeholders’ and TB health workers
Authors: Mainga T. , Gondwe M. , Stewart R. C. , Mactaggart I. , Shanaube K. , Ayles H. , Bond V. 
Published: July 2022

Abstract
Background
In recent years, there has been increased recognition of the need to integrate mental health services into routine tuberculosis (TB) care. For successful integration, policymakers need to first understand the practices of TB health workers in the management of mental health conditions, including depression, anxiety, and psychological distress, and use this to decide how best mental health services could be delivered in tandem with TB services. In this qualitative study we aimed to understand how TB health workers and other stakeholders viewed mental health conditions linked to TB and how they screened and treated these in their patients.

Methods
The study draws on qualitative data collected in 2018 as part of the Tuberculosis Reduction through Expanded Antiretroviral Treatment and Screening for active TB trial (TREATS), conducted in eight urban communities in Zambia. Data were collected through 17 focus group discussions with local health committee members (n = 96) and TB stakeholders (n = 57) present in the communities. Further in-depth interviews were held with key TB health workers (n = 9). Thematic analysis was conducted.

Results
TB stakeholders and health workers had an inadequate understanding of mental health and commonly described mental health conditions among TB patients by using stigmatizing terminology and overtones, for example “madness”, which often implied a characterological flaw rather an actual illness. Psychological distress was also described as “overthinking”, which participants attributed to psychosocial stressors, and was not perceived as a condition that would benefit from mental health intervention. There were no standard screening and treatment options for mental health conditions in TB patients and most TB health workers had no mental health training. TB Stakeholders and health workers understood the negative implications of mental health conditions on TB treatment adherence and overall wellbeing for TB patients.

Conclusions
TB stakeholders and health workers in Zambia have a complex conceptualisation of mental health and illness, that does not support the mental health needs of TB patients. The integration of mental health training in TB services could be beneficial and shift negative attitudes about mental health. Further, TB patients should be screened for mental health conditions and offered treatment.
Trial registration number NCT03739736-Registered on the 14th of November 2018- Retrospectively registered-
https://clinicaltrials.gov/ct2/results?cond=&term=NCT03739736&cntry=&state=&city=&dist
High AUF1 level in stromal fibroblasts promotes carcinogenesis and chemoresistance and predicts unfavorable prognosis among locally advanced breast cancer patients
Authors: Al-Tweigeri Taher , AlRaouji Noura N. , Tulbah Asma , Arafah Maria , Aboussekhra Mouad , Al-Mohanna Falah , Gad Ahmed Mostafa , Eldali Abdelmonneim M. , Elhassan Tusneem A. , Aboussekhra Abdelilah 
Published: July 2022

Abstract
Background
Locally advanced breast cancer (LABC), the most aggressive form of the disease, is a serious threat for women's health worldwide. The AU-rich RNA-binding factor 1 (AUF1) promotes the formation of chemo-resistant breast cancer stem cells. Thereby, we investigated the power of AUF1 expression, in both cancer cells and their stromal fibroblasts, as predictive biomarker for LABC patients’ clinical outcome following neoadjuvant treatment.

Methods
We have used immunohistochemistry to assess the level of AUF1 on formalin-fixed paraffin-embedded tissues. Immunoblotting was utilized to show the effect of AUF1 ectopic expression in breast stromal fibroblasts on the expression of various genes both in vitro and in orthotopic tumor xenografts. Cytotoxicity was evaluated using the WST1 assay, while a label-free real-time setting using the xCELLigence RTCA technology was utilized to assess the proliferative, migratory and invasive abilities of cells.

Results
We have shown that high AUF1 immunostaining (≥ 10%) in both cancer cells and their adjacent cancer-associated fibroblasts (CAFs) was significantly associated with higher tumor grade. Kaplan–Meier univariate analysis revealed a strong correlation between high AUF1 level in CAFs and poor patient’s survival. This correlation was highly significant in patients with triple negative breast cancer, who showed poor disease-free survival (DFS) and overall survival (OS). High expression of AUF1 in CAFs was also associated with poor OS of ER+/Her2− patients. Similarly, AUF1-positive malignant cells tended to be associated with shorter DFS and OS of ER+/Her2+ patients. Interestingly, neoadjuvant therapy downregulated AUF1 to a level lower than 10% in malignant cells in a significant number of patients, which improved both DFS and OS. In addition, ectopic expression of AUF1 in breast fibroblasts activated these cells and enhanced their capacity to promote, in an IL-6-dependent manner, the epithelial-to-mesenchymal transition and stemness processes. Furthermore, these AUF1-expressing cells enhanced the chemoresistance of breast cancer cells and their growth in orthotopic tumor xenografts.

Conclusions
The present findings show that the CAF-activating factor AUF1 has prognostic/predictive value for breast cancer patients and could represent a great therapeutic target in order to improve the precision of cancer treatment.
An ORFeome of rice E3 ubiquitin ligases for global analysis of the ubiquitination interactome
Authors: Wang Ruyi , You Xiaoman , Zhang Chongyang , Fang Hong , Wang Min , Zhang Fan , Kang Houxiang , Xu Xiao , Liu Zheng , Wang Jiyang , Zhao Qingzhen , Wang Xuli , Hao Zeyun , He Feng , Tao Hui , Wang Debao , Wang Jisong , Fang Liang , Qin Mengchao , Zhao Tianxiao , Zhang Pingping , Xing Hefei , Xiao Yunping , Liu Wende , Xie Qi , Wang Guo-Liang , Ning Yuese 
Published: July 2022

Abstract
Background
Ubiquitination is essential for many cellular processes in eukaryotes, including 26S proteasome-dependent protein degradation, cell cycle progression, transcriptional regulation, and signal transduction. Although numerous ubiquitinated proteins have been empirically identified, their cognate ubiquitin E3 ligases remain largely unknown.

Results
Here, we generate a complete ubiquitin E3 ligase-encoding open reading frames (UbE3-ORFeome) library containing 98.94% of the 1515 E3 ligase genes in the rice (Oryza sativa L.) genome. In the test screens with four known ubiquitinated proteins, we identify both known and new E3s. The interaction and degradation between several E3s and their substrates are confirmed in vitro and in vivo. In addition, we identify the F-box E3 ligase OsFBK16 as a hub-interacting protein of the phenylalanine ammonia lyase family OsPAL1–OsPAL7. We demonstrate that OsFBK16 promotes the degradation of OsPAL1, OsPAL5, and OsPAL6. Remarkably, we find that overexpression of OsPAL1 or OsPAL6 as well as loss-of-function of OsFBK16 in rice displayed enhanced blast resistance, indicating that OsFBK16 degrades OsPALs to negatively regulate rice immunity.

Conclusions
The rice UbE3-ORFeome is the first complete E3 ligase library in plants and represents a powerful proteomic resource for rapid identification of the cognate E3 ligases of ubiquitinated proteins and establishment of functional E3–substrate interactome in plants.