bluuebunny/crossref_metadata_2025_split huggingface dataset:
Individual and environmental determinants associated with longer times to access pediatric rheumatology centers for patients with juvenile idiopathic arthritis, a JIR cohort study
Authors: Chausset Aurélie , Lambert Céline , Belot Alexandre , Merlin Etienne , Cannizzaro Elvira , Kone-Paut Isabelle , Ballot Claire , Devauchelle Valérie , Poignant Sylvaine , Carlomagno Raffaella , Lohse Anne , Barbier Catherine , Despert Véronique , Carbasse Aurélia , Sparsa Laetitia , Adank Eva , Vanoni Federica , Reumaux Héloise , Pillet Pascal , Kaiser Daniela , Hofer Michael , Freychet Caroline , Schott Anne-Marie 
Published: March 2023

Abstract
Background
Despite guidelines, poor access to appropriate care for juvenile idiopathic arthritis (JIA) patients remains a global issue. Prompt referral to a pediatric rheumatology (PR) center and effective care is known to be critical for changing the natural history of the disease and improving long-term prognosis. This project assesses socio-economic factors of delayed referral to a pediatric rheumatologist (PRst) for JIA patients in France and Switzerland within the Juvenile Inflammatory Rheumatism (JIR) Cohort.

Methods
All patients diagnosed with JIA, presenting at one center of the JIRcohort in France or Switzerland with additional data on referral pathway were included. Patient characteristics at first visit to the PR center, dates of visits to healthcare providers during referral, and parent characteristics were extracted from the JIRcohort database.

Results
Two hundred fifty children were included. The overall median time to first PR assessment was 2.4 months [1.3; 6.9] and ranged widely across the JIA subtypes, from 1.4 months [0.6; 3.8] for children with systemic juvenile idiopathic arthritis (sJIA) to 5.3 months [2.0; 19.1] for children with enthesitis-related arthritis (ERA). A diagnosis of ERA and an appointment with an orthopedist during the referral pathway were significantly associated with a longer time before the first PR visit (hazard ratio HR 0.50 [95% CI: 0.29; 0.84]) and HR 0.68 [95% CI: 0.49; 0.93], respectively) in multivariable analysis. Having a mother with a post-graduate educational attainment level was tendentially associated with a shorter time before the first PR visit, (HR 1.32 [95% CI: 0.99; 1.78]).

Conclusions
Time to first PRst visit was most often short compared to other studies and close to the British recommendations. However, this time remained too long for many patients. We observed no social inequities in access to a PRst, but we show the need to improve effective pathway and access to a PR center for JIA patients.
Illicit drug use in university students in the UK and Ireland: a PRISMA-guided scoping review
Authors: Boden Maeve , Day Ed 
Published: March 2023

Abstract
Background
Interest in the health and well-being of university students has increased in the UK and Ireland in the past two decades as their numbers have grown. Recent high-profile deaths of students after using illicit drugs have highlighted the importance of the topic for policy makers. This scoping review maps the state of the existing literature evaluating use of illicit drugs in university students in the UK and Ireland. It aims to highlight research gaps and inform policy.

Method
We conducted a systematic search of papers related to psychoactive drug use in university students in the UK and Ireland published before August 2021. The 18 extracted study characteristics included author(s); year of publication; journal; location of data collection; study design; delivery method (e.g., online survey, in-person, postal survey); number of participants; response rate; participant course of study, year of study, degree level (i.e., undergraduate, postgraduate), gender and age; time-period assessed (e.g., lifetime, current use, past 12 months); primary aim; primary outcome; ethical approval; and funding source.

Results
The PRISMA-guided search strategy identified 1583 papers for abstract review; of 110 papers retained for full-text review, 54 studies met criteria for inclusion for this paper. Primary outcomes were coded into five groups: prevalence and patterns of drug use; factors associated with drug use; attitudes and knowledge about, and motivation for, drug use; supply of drugs; consequences of drug use. The results show that there is no coherent body of research in this area. The prevalence of reported drug use has crept up and the range of substances reported has broadened over time, and attitudes to drugs on average have normalised. However, there are significant methodological limitations that limit the utility of these findings. There was little evidence of published work on prevention of, or intervention to reduce, drug-related harms.

Conclusion
The domains identified offer a framework for university administrators, researchers and policy makers to understand the potential response to drug use in university students in the UK and Ireland. Recommendations are made to fill the gaps in the research evidence base.
Cell-specific clock-controlled gene expression program regulates rhythmic fiber cell growth in cotton
Authors: Wang Dehe , Hu Xiao , Ye Hanzhe , Wang Yue , Yang Qian , Liang Xiaodong , Wang Zilin , Zhou Yifan , Wen Miaomiao , Yuan Xueyan , Zheng Xiaomin , Ye Wen , Guo Boyu , Yusuyin Mayila , Russinova Eugenia , Zhou Yu , Wang Kun 
Published: March 2023

AbstractBackgroundThe epidermis of cotton ovule produces fibers, the most important natural cellulose source for the global textile industry. However, the molecular mechanism of fiber cell growth is still poorly understood.ResultsHere, we develop an optimized protoplasting method, and integrate single-cell RNA sequencing (scRNA-seq) and single-cell ATAC sequencing (scATAC-seq) to systematically characterize the cells of the outer integument of ovules from wild type and fuzzless/lintless (fl) cotton (Gossypiumhirsutum). By jointly analyzing the scRNA-seq data from wildtype and fl, we identify five cell populations including the fiber cell type and construct the development trajectory for fiber lineage cells. Interestingly, by time-course diurnal transcriptomic analysis, we demonstrate that the primary growth of fiber cells is a highly regulated circadian rhythmic process. Moreover, we identify a small peptide GhRALF1 that circadian rhythmically controls fiber growth possibly through oscillating auxin signaling and proton pump activity in the plasma membrane. Combining with scATAC-seq, we further identify two cardinal cis-regulatory elements (CREs, TCP motif, and TCP-like motif) which are bound by thetrans factors GhTCP14sto modulate the circadian rhythmic metabolism of mitochondria and protein translation through regulating approximately one third of genes that are highly expressed in fiber cells.ConclusionsWe uncover a fiber-specific circadian clock-controlled gene expression program in regulating fiber growth. This study unprecedentedly reveals a new route to improve fiber traits by engineering the circadian clock of fiber cells.
Clearance of bacteria from lymph nodes in sheep immunized with Brucella suis S2 vaccine is associated with M1 macrophage activation
Authors: Chen Si , Chen Yuanyuan , Jiao Zizhuo , Wang Chengqiang , Zhao Dantong , Liu Yongbin , Zhang Wenguang , Zhao Shihua , Yang Bin , Zhao Qinan , Fu Shaoyin , He Xiaolong , Chen Qiaoling , Man Churiga , Liu Guoying , Wei Xuefeng , Du Li , Wang Fengyang 
Published: March 2023

AbstractOvine brucellosis is a global zoonotic disease of sheep caused by Brucella melitensis, which inflicts a significant burden on human and animal health. Brucella suis strain S2 (B. suis S2) is a smooth live attenuated vaccine for the prevention of ovine brucellosis in China. However, no previous studies have assessed the immunogenicity of B. suis S2 vaccine after oral immunization in sheep. Here, we attempted to evaluate the ovine immune response over the course of B. suis S2 immunization and to identify in vivo predictors for vaccine development. Body temperature, serum Brucella antibodies, serum cytokines (IL-12p70 and interferon [IFN]-γ), and bacterial load in the mandibular lymph nodes (LN), superficial cervical LN, superficial inguinal LN, and spleen were investigated to determine the safety and efficacy of the vaccine. The abnormal body temperature of sheep occurred within 8 days post-infection (dpi). Brucella suis S2 persisted for a short time (< 21 dpi) in the mandibular LN. The highest level of IL-12p70 was observed at 9 dpi, whereas serum IFN-γ levels peaked at 12 dpi. Transcriptome analysis and quantitative reverse transcription PCR were performed to determine gene expression profiles in the mandibular LN of sheep. Antigen processing and presentation pathway was the dominant pathway related to the dataset. Our studies suggest that the immune response in ovine LN resembled type 1 immunity with the secretion of IL-12p70 and IFN-γ after B.suis S2 immunization and the vaccine may eliminate Brucella via stimulation of M1 macrophages through the course of Th cells.
Contraceptive dynamics among women with disabilities in low- and middle-income countries: a scoping review protocol
Authors: Beyene Getalem Aychew , Abebe Solomon Mekonnen , Fekadu Gedefaw Abeje , Muche Achenef Asmamaw , Geremew Bisrat Misganaw 
Published: March 2023

Abstract
Introduction
Contraceptive dynamics is the use of contraception, unmet need, discontinuation, and/or switching of contraception. Women with disabilities (WWDs) in low- and middle-income countries (LMICs) face a common problem: a low prevalence of contraceptive usage and a high unmet need. Even though certain studies have been conducted in high-income countries, research is scarce on the degree of contraceptive method mix, unmet needs, contraception discontinuation, and switching among WWDs in LMICs. As a result, the scoping review’s goal is to investigate, map available evidence, and identify knowledge gaps on contraceptive dynamics within LMICs WWDs.

Methods
The scoping review is guided by the six-stage Arksey and O’Malley methodology framework. Published articles will be retrieved from databases such as PubMed (MEDLINE), the Cochrane Library, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Global Health. Grey literature databases will be searched using electronic search engines such as Google Scholar, Google, OpenGrey, and Worldcat. In addition, a manual search of reference lists from recognized studies will be conducted, as well as a hand search of the literature. Any type of study design (e.g., randomized controlled trials, quasi-experimental studies, prospective and retrospective cohort studies, case-control or nested case-control studies, qualitative, cross-sectional studies) will be included in this scoping review. There will be no restrictions on publication year. Two independent reviewers will screen relevant publications, and data will be charted accordingly. The Preferred Reporting Items for Systematic Review and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) checklist and reporting guidelines will be used to report all parts of the protocol and scoping review.

Discussion
When compared to non-disabled women, WWDs had a lower prevalence of contraceptive usage and a higher unmet need in LMICs. Despite these facts, they are the most marginalized people on the planet. This is, therefore, critical to map available evidence and identify knowledge gaps on contraceptive dynamics. As a result, the findings of this scoping review will be significant in terms of the contraceptive dynamic among WWDs in LMICs.

Systematic review registration
Open Science Framework (OSF), with registration number; DOI/10.17605/OSF.IO/XCKPT.
Facial nerve in skullbase tumors: imaging and clinical relevance
Authors: Yao Longping , Wang Baoyan , Lu Fengfei , He Xiaozheng , Lu Guohui , Zhang Shizhong 
Published: March 2023

AbstractFacial nerve, the 7th cranial nerve, is a mixed nerve composed of sensory and motor fibers, and its main branch is situated in the cerebellopontine angle. Facial nerve dysfunction is a debilitating phenomenon that can occur in skullbase tumors and Bell’s pals. Recovery of the facial nerve dysfunction after surgery for skullbase tumors can be disappointing, but is usually favorable in Bell’s palsy. Advances in magnetic resonance imaging (MRI) allow to visualize the facial nerve and its course in the cerebellopontine angle, also when a large tumor is present and compresses the nerve. Here, we describe the anatomical, neurochemical and clinical aspects of the facial nerve and highlight the recent progress in visualizing the facial nerve with MRI.
Assessment of integrated patterns of human-animal-environment health: a holistic and stratified analysis
Authors: Guo Zhao-Yu , Feng Jia-Xin , Ai Lin , Xue Jing-Bo , Liu Jing-Shu , Zhang Xiao-Xi , Cao Chun-Li , Xu Jing , Xia Shang , Zhou Xiao-Nong , Chen Jin , Li Shi-Zhu 
Published: March 2023

Abstract
Background
Data-driven research is a very important component of One Health. As the core part of the global One Health index (GOHI), the global One Health Intrinsic Drivers index (IDI) is a framework for evaluating the baseline conditions of human-animal-environment health. This study aims to assess the global performance in terms of GOH-IDI, compare it across different World Bank regions, and analyze the relationships between GOH-IDI and national economic levels.

Methods
The raw data among 146 countries were collected from authoritative databases and official reports in November 2021. Descriptive statistical analysis, data visualization and manipulation, Shapiro normality test and ridge maps were used to evaluate and identify the spatial and classificatory distribution of GOH-IDI. This paper uses the World Bank regional classification and the World Bank income groups to analyse the relationship between GOH-IDI and regional economic levels, and completes the case studies of representative countries.

Results
The performance of One Health Intrinsic Driver in 146 countries was evaluated. The mean (standard deviation, SD) score of GOH-IDI is 54.05 (4.95). The values (mean SD) of different regions are North America (60.44, 2.36), Europe and Central Asia (57.73, 3.29), Middle East and North Africa (57.02, 2.56), East Asia and Pacific (53.87, 5.22), Latin America and the Caribbean (53.75, 2.20), South Asia (52.45, 2.61) and sub-Saharan Africa (48.27, 2.48). Gross national income per capita was moderately correlated with GOH-IDI (R2 = 0.651, Deviance explained = 66.6%, P < 0.005). Low income countries have the best performance in some secondary indicators, including Non-communicable Diseases and Mental Health and Health risks. Five indicators are not statistically different at each economic level, including Animal Epidemic Disease, Animal Biodiversity, Air Quality and Climate Change, Land Resources and Environmental Biodiversity.

Conclusions
The GOH-IDI is a crucial tool to evaluate the situation of One Health. There are inter-regional differences in GOH-IDI significantly at the worldwide level. The best performing region for GOH-IDI was North America and the worst was sub-Saharan Africa. There is a positive correlation between the GOH-IDI and country economic status, with high-income countries performing well in most indicators. GOH-IDI facilitates researchers' understanding of the multidimensional situation in each country and invests more attention in scientific questions that need to be addressed urgently.

Graphical Abstract
Adherence to standard of care (SOC) therapy for the treatment of metastatic hormone-sensitive prostate cancer (mHSPC): A single-institution analysis.
Authors: Dhillon Puneet , Ornstein Moshe Chaim , Gupta Shilpa , Nizam Amanda , Gilligan Timothy D. , Martin Allison , Bonham Amanda , Maroli Kimberly , Wee Christopher Eing 
Published: March 2023

103 Background: Androgen deprivation therapy (ADT) has been the backbone of treatment for mHSPC for decades. In recent years, multiple randomized controlled trials demonstrating an overall survival (OS) benefit of combination treatment (e.g. ADT + novel hormonal agent and/or chemotherapy) has made this the current SOC. Large real-world reports have shown a significant number of patients are still being treated below the SOC with ADT alone, but these databases do not include patient level data to help understand the rationale for treatment decisions. We reviewed our institution’s treatment patterns for mHSPC to better understand why some patients are being treated with ADT alone. Methods: We conducted a retrospective analysis on patients who initiated treatment for mHSPC from 2017-2021 at Cleveland Clinic. Patient characteristics were recorded, including age and histology. Treatment characteristics, including location of treatment, treatment regimen, and treatment rationale (if not treated with SOC) were noted. Results: Four hundred forty-nine patients were included, with diagnosis of metastatic disease made at a median of 63 years, of which 446 started treatment with systemic therapy. The vast majority of patients were managed by a medical oncologist (95.5%). About half of the patients (49.8%) received treatment at the main campus, with the remaining patients being treated at an affiliated regional hospital (28.7%) or outpatient medical center (21.5%). Additional characteristics are shown. Out of the 446, 40 (9.0%) patients received ADT alone. Reasons for ADT monotherapy included patient preference (n = 13), cost (n = 2), and poor functional status/comorbidities (n = 4). Twenty (50%) of the patients who got ADT alone had no documented rationale for why this treatment plan was elected. One patient was lost to follow-up. For patients who received only ADT, 12 were treated at main campus, 20 were treated at a regional hospital, and 8 were treated at an outpatient medical center. Conclusions: At our institution, adherence to treatment up to SOC for mHSPC was better than previous real-world reports. There were documented reasons for not treating mHSPC up to SOC combination therapy for half of the patients who got ADT monotherapy. It remains unclear why the remaining half did not get combination therapy up to the SOC. [Table: see text]
First UK experience of apalutamide in metastatic and non-metastatic prostate cancer outside of clinical trials.
Authors: Das Prantik , Mohammed Rania , Sarwar Naveed , Din Omar , Jain Ankit , Davies Jessica , Mugunthan Thangrarajh , Nair Ajith , Ghose Aruni , Bandyopadhyay Seheli , Krishnappa Roopesh , Iyer Pooja , Jones Lauren , Vasdev Nikhil , Moldawa Maja , Devine Rebecca , Hughes Robert , Sharma Anand 
Published: March 2023

106 Background: Apalutamide plus androgen deprivation therapy(ADT) has been approved as a treatment option for castrate resistant non metastatic prostate cancer (nmCRPC) with a high risk of developing metastatic disease. It has also demonstrated benefit in patients with metastatic, castration-sensitive prostate (mHSPC) cancer, with improvement in overall and radiographic progression–free survival. Here we report our first experience of using Apalutamide in real life clinical practice. Methods: A cohort of 108 patients from 5 UK centres were included, among them 68 were metastatic and 40 non metastatic. All patients were treated with Apalutamide 240 mg along with ADT until disease progression. The primary endpoint was objective rate (ORR) and secondary endpoints included treatment duration and safety. Results: The median age for the whole cohort was 71 years (interquartile range 43-91), 73 years for nmCRPC and 69 years for mHSPC respectively. 81% had biopsy proven malignancy. A total of 11.7% with mHSPC had received prior radical treatment (prostatectomy or radiotherapy for localised disease), compared to 92.5% patients in the non-metastatic cohort. PSA reached undetectable levels (<0.04 ng per ml) in 67% of the patients in the metastatic and 60% in non-metastatic subset respectively. In patients with mHSPC, who had radiological assessments performed, the response rates at 6 months were as follows: partial response (24%), stable disease (74%) and progressive disease (4%).39% of the whole cohort, reported grade 2 and above toxicities. The commonest were skin rash, thyroid dysfunction, hypertension, lethargy and hot flushes. Adverse events led to discontinuation in 1 patient and dose reduction in 1 patient. Conclusions: Our experience of using Apalutamide has shown good biochemical and radiological response in both nmCRPC and mHSPC. Treatment was well tolerated with low rates of treatment discontinuation. Further follow up of these patients will guide us in terms of overall survival.
Association of baseline inflammatory biomarkers with outcomes in penile squamous cell carcinoma (pSCC) treated with immune checkpoint inhibitors (ICI).
Authors: Zhuang Tony , Goyal Subir , Brown Jacqueline T , Carthon Bradley Curtis , Kucuk Omer , McClintock Greta Russler , Yantorni Lauren Beth , Bilen Mehmet Asim , Master Viraj A. , Nazha Bassel 
Published: March 2023

11 Background: Penile squamous cell carcinoma (pSCC) is a rare neoplasm with a poor prognosis and a need for biomarkers to guide treatment selection. We report an association of baseline inflammatory markers with outcomes in pSCC treated with immune checkpoint inhibitors (ICI). Methods: We performed a retrospective review of patients with pSCC from 2012-2022 at the Winship Cancer Institute at Emory University. Demographics, disease characteristics, and optimal cutoffs of biomarkers prior to ICI initiation were described. Neutrophil-to-lymphocyte (NLR), monocyte-to-lymphocyte (MLR), platelet-to-lymphocyte (PLR), and neutrophil-to-eosinophil ratios (NER) were obtained from complete blood count data. Clinical benefit with ICI was defined as complete response, partial response, or stable disease based on RECIST 1.1 criteria. Overall survival (OS) and progression-free survival (PFS) were assessed by the Kaplan-Meier method and univariate Cox regression (UVA) using SAS software with significance level set at p<0.05. Results: Twenty-one patients were included in which 71.4% were white and 28.6% were black. Median age at ICI initiation was 56 years (38-76). Most patients (65%) had an ECOG PS ≥2. Four patients (19.1%) had clinical benefit at best response to ICI. Most patients (76.2%) had disease progression and 14.3% were alive at last contact. Median OS was 8.4 months (mo) (95%CI: 2.3-15.7), and median PFS was 2.0 mo (95%CI: 1.3-3.2). Of 9 patients with available HPV status, 8 were HPV+. Of 12 patients with available PD-L1 status, 8 were PD-L1+. Median follow-up was 8.4 mo and median time to ICI treatment from diagnosis was 15.6 mo. High baseline NLR, MLR, PLR, and NER above optimal cut were significantly associated with shorter OS on UVA (Table,all p<0.05). High baseline NLR was associated with shorter PFS (p=0.003). Baseline NLR groups were similar except for age and without differences in race, ECOG, BMI, PD-L1, and HPV status. Conclusions: Our real-world analysis reports a potential association of baseline inflammatory biomarkers with clinical outcomes in ICI-treated pSCC. More prospective and multicenter studies are needed for further confirmation. [Table: see text]