bluuebunny/crossref_metadata_2025_split huggingface dataset:
Urocortin-positive nerve fibres and cells are present in the human choroid
Authors: Kaser-Eichberger Alexandra , Platzl Christian , Wolfmeier Heidi , Trost Andrea , Horn Anja , Barnerssoi Miriam , Strohmaier Clemens , Schroedl Falk 
Published: February 2022

BackgroundChoroidal vascular regulation is mediated by the autonomic nervous system in order to gain proper blood flow control. While the mechanisms behind this control are unknown, neuroregulatory peptides are involved in this process. To better understand choroidal function, we investigate the presence of urocortin-1 (UCN), a neuroregulatory peptide with vascular effects, in the human choroid and its possible intrinsic and extrinsic origin.MethodsHuman choroid and eye-related cranial ganglia (superior cervical ganglion- SCG, ciliary ganglion-CIL, pterygopalatine ganglion-PPG, trigeminal ganglion-TRI) were prepared for immunohistochemistry against UCN, protein–gene product 9.5 (PGP9.5), substance P (SP), tyrosine hydroxylase (TH) and vesicular acetylcholine transporter (VAChT). For documentation, confocal laser scanning microscopy was used.ResultsIn choroidal stroma, UCN-immunoreactivity was present in nerve fibres, small cells and intrinsic choroidal neurons (ICN). Some UCN+ nerve fibres colocalised for VAChT, while others were VAChT. A similar situation was found with SP: some UCN+ nerve fibres showed colocalisation for SP, while others lacked SP. Colocalisation for UCN and TH was not observed. In eye-related cranial ganglia, only few cells in the SCG, PPG and TRI were UCN+, while many cells of the CIL displayed weak UCN immunoreactivity.ConclusionUCN is part of the choroidal innervation. UCN+/VAChT+ fibres could derive from the few cells of the PPG or cells of the CIL, if these indeed supply the choroid. UCN+/SP+ fibres might originate from ICN, or the few UCN+ cells detected in the TRI. Further studies are necessary to establish UCN function in the choroid and its implication for choroidal autonomic control.
The effects of plasma exchange in patients with ANCA-associated vasculitis: an updated systematic review and meta-analysis
Authors: Walsh Michael , Collister David , Zeng Linan , Merkel Peter A , Pusey Charles D , Guyatt Gordon , Au Peh Chen , Szpirt Wladimir , Ito-Hara Toshiko , Jayne David R W 
Published: February 2022

AbstractObjectiveTo assess the effects of plasma exchange on important outcomes in anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV).DesignSystematic review and meta-analysis of randomised controlled trials.Eligibility criteriaRandomised controlled trials investigating effects of plasma exchange in patients with AAV or pauci-immune rapidly progressive glomerulonephritis and at least 12 months’ follow-up.Information sourcesPrior systematic reviews, updated by searching Medline, Embase, and CENTRAL to July 2020.Risk of biasReviewers independently identified studies, extracted data, and assessed the risk of bias using the Cochrane Risk of Bias tool.Synthesis of resultsMeta-analyses were conducted using random effects models to calculate risk ratios and 95% confidence intervals. Quality of evidence was summarised in accordance with GRADE methods. Outcomes were assessed after at least12 months of follow-up and included all-cause mortality, end stage kidney disease (ESKD), serious infections, disease relapse, serious adverse events, and quality of life.ResultsNine trials including 1060 participants met eligibility criteria. There were no important effects of plasma exchange on all-cause mortality (relative risk 0.90 (95% CI 0.64 to 1.27), moderate certainty). Data from seven trials including 999 participants that reported ESKD demonstrated that plasma exchange reduced the risk of ESKD at 12 months (relative risk 0.62 (0.39 to 0.98), moderate certainty) with no evidence of subgroup effects. Data from four trials including 908 participants showed that plasma exchange increased the risk of serious infections at 12 months (relative risk 1.27 (1.08 to 1.49), moderate certainty). The effects of plasma exchange on other outcomes were uncertain or considered unimportant to patients.Limitations of evidenceThere is a relative sparsity of events, and treatment effect estimates are therefore imprecise. Subgroup effects at the participant level could not be evaluated.InterpretationFor the treatment of AAV, plasma exchange has no important effect on mortality, reduces the 12 month risk of ESKD, but increases the risk of serious infections.FundingNo funding was received.RegistrationThis is an update of a previously unregistered systematic review and meta-analysis published in 2014.
Comparative efficacy and safety of alternative glucocorticoids regimens in patients with ANCA-associated vasculitis: a systematic review
Authors: Xiao Yingqi , Guyatt Gordon , Zeng Linan , RW Jayne David , A Merkel Peter , AC Siemieniuk Reed , Dookie Jared E , A Buchan Tayler , Ahmed Muhammad Muneeb , J Couban Rachel , Mahr Alfred , Walsh Michael 
Published: February 2022

ObjectiveTo compare the efficacy and safety of alternative glucocorticoids (GCs) regimens as induction therapy for patients with antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis.DesignSystematic review of randomised controlled trials (RCTs).Data sourcesMedline, Embase, Clinicaltrials.gov and Cochrane Central Register of Controlled Trials up to 10 April 2020.Study selection and review methodsRCTs comparing two (or more) different dose regimens of GC in ANCA-associated vasculitis during induction of remission, regardless of other therapies. Pairs of reviewers independently screened records, extracted data and assessed risk of bias. Two reviewers rated certainty of evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach.ResultsOf 3912 records identified, the full texts of two records met the eligibility criteria. Due to the heterogeneity of population and dose regimen of GCs between the two trials, we descriptively presented the two trials and did not combine the results using meta-analysis. Compared with the standard-dose regimen, the reduced-dose regimen of GC may reduce death risk difference (RD): from −1.7% to −2.1%, low certainty), while not increasing end-stage kidney disease (ESKD) (RD: from −1.5% to 0.4%, moderate certainty). The reduced-dose regimen probably has an important reduction in serious infections at 1 year (RD: from −12.8% to −5.9%, moderate certainty). Reduced-dose regimen of GCs probably has trivial or no effect in disease remission, relapse or health-related quality of life (moderate to high certainty).ConclusionsThe reduced-dose regimen of GC may reduce death at the follow-up of 6 months to longer than 1 year and serious infections while not increasing ESKD.PROSPERO registration numberCRD42020179087.
Australian Parkinson’s Genetics Study (APGS): pilot (n=1532)
Authors: Bivol Svetlana , Mellick George D , Gratten Jacob , Parker Richard , Mulcahy Aoibhe , Mosley Philip E , Poortvliet Peter C , Campos Adrian I , Mitchell Brittany L , Garcia-Marin Luis M , Cross Simone , Ferguson Mary , Lind Penelope A , Loesch Danuta Z , Visscher Peter M , Medland Sarah E , Scherzer Clemens R , Martin Nicholas G , Rentería Miguel E 
Published: February 2022

PurposeParkinson’s disease (PD) is a neurodegenerative disorder associated with progressive disability. While the precise aetiology is unknown, there is evidence of significant genetic and environmental influences on individual risk. The Australian Parkinson’s Genetics Study seeks to study genetic and patient-reported data from a large cohort of individuals with PD in Australia to understand the sociodemographic, genetic and environmental basis of PD susceptibility, symptoms and progression.ParticipantsIn the pilot phase reported here, 1819 participants were recruited through assisted mailouts facilitated by Services Australia based on having three or more prescriptions for anti-PD medications in their Pharmaceutical Benefits Scheme records. The average age at the time of the questionnaire was 64±6 years. We collected patient-reported information and sociodemographic variables via an online (93% of the cohort) or paper-based (7%) questionnaire. One thousand five hundred and thirty-two participants (84.2%) met all inclusion criteria, and 1499 provided a DNA sample via traditional post.Findings to date65% of participants were men, and 92% identified as being of European descent. A previous traumatic brain injury was reported by 16% of participants and was correlated with a younger age of symptom onset. At the time of the questionnaire, constipation (36% of participants), depression (34%), anxiety (17%), melanoma (16%) and diabetes (10%) were the most reported comorbid conditions.Future plansWe plan to recruit sex-matched and age-matched unaffected controls, genotype all participants and collect non-motor symptoms and cognitive function data. Future work will explore the role of genetic and environmental factors in the aetiology of PD susceptibility, onset, symptoms, and progression, including as part of international PD research consortia.
Measuring health service providers’ attitudes towards the provision of youth-friendly sexual and reproductive health services: a psychometric study to develop and validate a scale in Jordan
Authors: Gausman Jewel , Othman Areej , Al-Qotob Raeda , Shaheen Abeer , Aldiqs Mohannad , Hamad Iqbal Lutfi , Dabobe Maysoon , Langer Ana 
Published: February 2022

ObjectivesThe aim of this study is to develop and validate a scale to measure provider attitudes towards provision of youth-friendly sexual and reproductive health (SRH) services in a conservative setting in the Middle East.DesignCross-sectional, psychometric validation study.SettingPublic health facilities in Amman, Irbid, Mafraq and Zarqa in Jordan.Participants552 healthcare providers were recruited by convenience. Providers were eligible if they were a practising midwife, nurse or physician in one of the selected health facilities.MethodsAn initial pool of 52 items was generated using theory and local expert input. We evaluated the psychometric properties of the scale using factor analysis. We assessed internal consistency reliability by calculating Cronbach’s alpha and convergent construct validity using linear regression to assess the association between a provider’s score on the scale and whether they had ever received training on SRH issues.ResultsOur final scale consisted of 3 dimensions and 29 items corresponding to the constructs of: (1) Attitudes towards Information and Services Offered to Youth (11 items) (2) norms and personal beliefs (10 items) and (3) attitudes towards the service delivery environment (8 items). Cronbach’s alpha was estimated at 0.72 for the full scale, and between 0.70 and 0.73 for each subscale. The scale demonstrated high construct validity. The results of the linear regression analysis suggest that respondents who had received SRH training had a mean score that was 16% higher (0.64 points; 95% CI 0.2 to 11.2; p<0.01) on the full attitudes scale compared with those who did not.ConclusionsThis paper describes a study to formally develop and validate a scale to measure healthcare provider attitudes in support of youth-friendly SRH services, thus providing an important tool to identify areas for improvement of youth SRH programmes in the Middle East and globally.
Outpatient healthcare use before and during a long-term sickness absence spell: a register-based follow-up study comparing healthcare use by the length of sickness absence and transition to disability pension in Finland
Authors: Perhoniemi Riku , Blomgren Jenni 
Published: February 2022

ObjectivesThe objective of the study was to examine outpatient healthcare use before and during a long-term sickness absence (LTSA), and to compare the development of healthcare use between groups defined through LTSA lengths and disability pension (DP) transition.DesignRegister-based longitudinal study with five 6-month periods before and after the start of the LTSA spell in early 2016.LTSA groups 1 (N=210) and 2 (N=187) went on to reach the statutory maximum LTSA length, with group 1 transitioning to DP. Group 3 (N=3082) had a shorter LTSA spell. Control group 4 (N=92 921) had no LTSA.Setting and participantsNon-retired individuals aged 20–59, with no LTSA during 2015 (N=96 400) were included from the total population of the city of Oulu, Finland. Register data were linked on LTSA spells and outpatient healthcare use 2013–2018, DP status in 2018, and various covariates.Main outcome measuresNegative binomial regression models were used to examine the covariate-adjusted number of healthcare visits, and to examine the association of the LTSA groups with healthcare use before and after the start of LTSA (incidence rate ratios and predicted means).ResultsIndividuals eventually reaching the maximum LTSA length (groups 1 and 2) had a higher level of healthcare use before the LTSA and especially after the start of LTSA than others. Individuals transferring to DP after the maximum LTSA (group 1) used healthcare the most after the start of LTSA.ConclusionsThe risk for at least 1 year’s disability may be identified by frequent outpatient healthcare use years before LTSA. However, future disability retirees could not be identified through their pre-LTSA healthcare use. Instead, their high use of healthcare after the start of the LTSA was consistent with their increasing health problems leading to retirement.
Educational status and COVID-19 related outcomes in India: hospital-based cross-sectional study
Authors: Sharma Arvind K , Gupta Rajeev , Baig Vaseem Naheed , Singh Veer Teja , Chakraborty Surabhi , Sunda Jagdish P , Dhakar Prahalad , Sharma Shiv Prakash , Panwar Raja Babu , Katoch Vishwa Mohan 
Published: February 2022

ObjectiveAssociation of educational status, as marker of socioeconomic status, with COVID-19 outcomes has not been well studied. We performed a hospital-based cross-sectional study to determine its association with outcomes.MethodsSuccessive patients of COVID-19 presenting at government hospital were recruited. Demographic and clinical details were obtained at admission, and in-hospital outcomes were assessed. Cohort was classified according to self-reported educational status into group 1: illiterate or ≤primary; group 2: higher secondary; and group 3: some college. To compare intergroup outcomes, we performed logistic regression.Results4645 patients (men 3386, women 1259) with confirmed COVID-19 were recruited. Mean age was 46±18 years, most lived in large households and 30.5% had low educational status. Smoking or tobacco use was in 29.5%, comorbidities in 28.6% and low oxygen concentration (SpO2 <95%) at admission in 30%. Average length of hospital stay was 6.8±3.7 days, supplemental oxygen was provided in 18.4%, high flow oxygen or non-invasive ventilation 7.1% and mechanical ventilation 3.6%, 340 patients (7.3%) died. Group 1 patients had more tobacco use, hypoxia at admission, lymphocytopaenia, and liver and kidney dysfunction. In group 1 versus groups 2 and 3, requirement of oxygen (21.6% vs 16.7% and 17.0%), non-invasive ventilation (8.0% vs 5.9% and 7.1%), invasive ventilation (4.6% vs 3.5% and 3.1%) and deaths (10.0% vs 6.8% and 5.5%) were significantly greater (p<0.05). OR for deaths were higher in group 1 (1.91, 95% CI 1.46 to 2.51) and group 2 (1.24, 95% CI 0.93 to 1.66) compared with group 3. Adjustment for demographic and comorbidities led to some attenuation in groups 1 (1.44, 95% CI 1.07 to 1.93) and 2 (1.38, 95% CI 1.02 to 1.85); this persisted with adjustments for clinical parameters and oxygen support in groups 1 (1.38, 95% CI 0.99 to 1.93) and 2 (1.52, 95% CI 1.01 to 2.11).ConclusionLow educational status patients with COVID-19 in India have significantly greater adverse in-hospital outcomes and mortality.Trial registration numberREF/2020/06/034036.
Development of a psychosocial functioning questionnaire for patients with major depressive disorder
Authors: Zhang Xiujuan , Yang Hua , Ma Hui , Teng Changjun , Wang Hui , Diao Kaili , Zhang Ning 
Published: February 2022

BackgroundThe importance of psychosocial functioning in the assessment, diagnosis and treatment of major depressive disorder (MDD) is widely recognised. However, there is a lack of effective scales to assess psychosocial functioning in patients with MDD.AimsTo develop a professional questionnaire to evaluate the psychosocial functioning of patients with MDD.MethodsUsing a literature review, an open-ended questionnaire survey, and patient interviews, a theoretical model of psychosocial functioning was constructed, and an initial questionnaire was formed which included four dimensions. After two rounds of testing, using items analysis and exploratory factor analysis, a finalized questionnaire was created. There were 460 patients with MDD selected from six psychiatric hospitals for formal testing using a convenience sampling method. Forty patients were randomly selected and retested one week later to evaluate the test-retest reliability of the scale. The Patient Health Questionnaire-9 (PHQ-9), Short Form of Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q-SF), Sheehan Disability Scale (SDS), and Dysfunctional Attitudes Scale (DAS) provided major standards to check the criterion validity of this questionnaire. Correlation analysis, confirmatory factor analysis, and internal consistency reliability testing were used to examine other psychometric characteristics of the finalized questionnaire.ResultsThe Psychosocial Functioning Questionnaire (PFQ) for patients with MDD included three dimensions: psychological cognitive functioning, subjective well-being, and social functioning, with a total of 18 items. The overall internal consistency reliability of the questionnaire was 0.957, and the test-retest reliability was 0.840. Confirmatory factor analysis showed that the model fitted well: Goodness of Fit Index (GFI)=0.888; Root Mean SquareError of Approximation (RMSEA)=0.085. The total score of PFQ was significantly correlated with the total score of PHQ-9, DAS, SDS and Q-LES-Q-SF (|r|=0.599–0.870, p<0.001).ConclusionsThe Psychosocial Functioning Questionnaire has good reliability and validity. It can be used to measure the psychosocial functioning of patients with MDD.
Peptidic microarchitecture-trapped tumor vaccine combined with immune checkpoint inhibitor or PI3Kγ inhibitor can enhance immunogenicity and eradicate tumors
Authors: Du Yang , Liu Ye , Wang Di , Bai Hua , Wang Zhijie , He Xiran , Zhang Pei , Tian Jie , Wang Jie 
Published: February 2022

BackgroundWith the rapid development of immune checkpoint inhibitors and neoantigen (NeoV)-based personalized tumor vaccines, tumor immunotherapy has shown promising therapeutic results. However, the limited efficacy of available tumor vaccines impedes the development of personalized tumor immunotherapy. In this study, we developed a novel tumor vaccine system and proposed combined therapeutic strategies for improving treatment effects.MethodsWe developed a novel tumor vaccine system comprising a newly synthesized peptidic microarchitecture (PMA) with high assembly efficacy. The PMA-trapped neoantigen vaccine was developed to codeliver tumor neoantigen and the Toll-like receptor 9 agonist CpG (NeoV), abbreviated as PMA-NeoV. A microfluidic chip was used to produce PMA particles in a uniform and precise manner. Vaccine effectiveness was investigated both in vitro and in vivo. The combined immunotherapeutic effect of PMA-NeoV with anti-programmed cell death ligand 1 antibody (aPD-L1) or with the phosphatidylinositol 3‑kinase γ (PI3Kγ) inhibitor IPI-549 was further tested in MC38 mouse tumor model.ResultsPMA-NeoV not only promoted codelivery of the tumor vaccine but also potentiated vaccine immunogenicity. Moreover, compared with free NeoV, PMA-NeoV significantly increased the number of tumor-infiltrating lymphocytes, promoted the neoantigen-specific systemic immune response, and suppressed murine colon MC38 tumor growth. Furthermore, PMA-NeoV increased the expression of programmed cell death receptor-1 on T lymphocytes, and in combination with aPD-L1 eradicated seven of eight MC38 tumors by rescuing exhausted T lymphocytes. Moreover, we combined the PMA-NeoV with the IPI-549, a molecular switch that controls immune suppression, and found that this combination significantly suppressed tumor growth and eradicated five of eight inoculated tumors, by switching suppressive macrophages to their active state and activating T cells to prime a robust tumor immune microenvironment.ConclusionsWe developed a tumor vaccine delivery system and presented a promising personalized tumor vaccine-based therapeutic regimen in which a tumor vaccine delivery system is combined with an aPD-L1 or PI3Kγ inhibitor to improve tumor immunotherapy outcomes.
Tumor-specific T cells support chemokine-driven spatial organization of intratumoral immune microaggregates needed for long survival
Authors: Abdulrahman Ziena , Santegoets Saskia J , Sturm Gregor , Charoentong Pornpimol , Ijsselsteijn Marieke E , Somarakis Antonios , Höllt Thomas , Finotello Francesca , Trajanoski Zlatko , van Egmond Sylvia L , Mustafa Dana A M , Welters Marij J P , de Miranda Noel F C C , van der Burg Sjoerd H 
Published: February 2022

BackgroundThe composition of the tumor immune microenvironment (TIME) associated with good prognosis generally also predicts the success of immunotherapy, and both entail the presence of pre-existing tumor-specific T cells. Here, the blueprint of the TIME associated with such an ongoing tumor-specific T-cell response was dissected in a unique prospective oropharyngeal squamous cell carcinoma (OPSCC) cohort, in which tumor-specific tumor-infiltrating T cells were detected (immune responsiveness (IR+)) or not (lack of immune responsiveness (IR−)).MethodsA comprehensive multimodal, high-dimensional strategy was applied to dissect the TIME of treatment-naive IR+and IR−OPSCC tissue, including bulk RNA sequencing (NanoString), imaging mass cytometry (Hyperion) for phenotyping and spatial interaction analyses of immune cells, and combined single-cell gene expression profiling and T-cell receptor (TCR) sequencing (single-cell RNA sequencing (scRNAseq)) to characterize the transcriptional states of clonally expanded tumor-infiltrating T cells.ResultsIR+patients had an excellent survival during >10 years follow-up. The tumors of IR+patients expressed higher levels of genes strongly related to interferon gamma signaling, T-cell activation, TCR signaling, and mononuclear cell differentiation, as well as genes involved in several immune signaling pathways, than IR−patients. The top differently overexpressed genes includedCXCL12andLTB,involved in ectopic lymphoid structure development. Moreover, scRNAseq not only revealed that CD4+T cells were the main producers ofLTBbut also identified a subset of clonally expanded CD8+T cells, dominantly present in IR+tumors, which secreted the T cell and dendritic cell (DC) attracting chemokine CCL4. Indeed, immune cell infiltration in IR+tumors is stronger, highly coordinated, and has a distinct spatial phenotypical signature characterized by intratumoral microaggregates of CD8+CD103+and CD4+T cells with DCs. In contrast, the IR−TIME comprised spatial interactions between lymphocytes and various immunosuppressive myeloid cell populations. The impact of these chemokines on local immunity and clinical outcome was confirmed in an independent The Cancer Genome Atlas OPSCC cohort.ConclusionThe production of lymphoid cell attracting and organizing chemokines by tumor-specific T cells in IR+tumors constitutes a positive feedback loop to sustain the formation of the DC–T-cell microaggregates and identifies patients with excellent survival after standard therapy.