bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rationale and design of a prospective, multicenter, phase II clinical trial of safety and efficacy evaluation of long course neoadjuvant chemoradiotherapy plus tislelizumab followed by total mesorectal excision for locally advanced rectal cancer (NCRT-PD1-LARC trial)
Authors: Yang Zhengyang , Zhang Xiao , Zhang Jie , Gao Jiale , Bai Zhigang , Deng Wei , Chen Guangyong , An Yongbo , Liu Yishan , Wei Qi , Han Jiagang , Li Ang , Liu Gang , Sun Yi , Kong Dalu , Yao Hongwei , Zhang Zhongtao 
Published: April 2022

Abstract
Background
Long course radiotherapy plus neoadjuvant chemotherapy followed by resection (total mesorectal excision, TME) has accepted widespread recognized in the treatment of locally advanced rectal cancer (LARC). Tislelizumab, an anti-PD1 humanized IgG4 monoclonal antibody, has been demonstrated with clinical activity and is approved for treating recurrent/refractory classical Hodgkin lymphoma and locally advanced/metastatic urothelial carcinoma in China. However, the safety and efficacy of long course (neoadjuvant chemoradiotherapy, NCRT) plus tislelizumab followed by TME for LARC is still uncertain.

Methods
This NCRT-PD1-LARC trial will be a prospective, multicenter and phase II clinical trial designed to evaluate the safety and efficacy of LARC patients treated with long course NCRT plus tislelizumab followed by TME. This trial will consecutively enroll 50 stage II/III LARC patients (cT3N0M0 and cT1-3N1-2M0) with the tumor distal location ≤ 7 cm from anal verge at 7 centers in China. The enrolled patients will receive long course radiotherapy (50 Gy/25 f, 2 Gy/f, 5 days/week) and three 21-day cycles capecitabine (1000 mg/m2, bid, po, day1-14) plus three 21-day cycles tislelizumab (200 mg, iv.gtt, day8), followed by TME 6–8 weeks after the end of radiotherapy. The primary efficacy endpoint will be the pathological complete response (pCR) rate, which is defined as absence of viable tumor cells in the primary tumor and lymph nodes.

Discussion
To our knowledge, this trial is the first multicenter clinical trial in China to assess the safety and efficacy of NCRT plus anti-PD1 therapy followed by TME to treat patients with LARC. NCRT followed by TME was recognized as the most recommended treatment against LARC while could not be completely satisfied in clinic. This study expects to provide a solid basis and encouraging outcomes for this promising combination of radiotherapy, chemotherapy and immunotherapy in LARC.

Trial registration
Name of the registry: ClinicalTrials.gov. Trial
registration number: NCT04911517. Date of registration: 23 May 2021. URL of
trial registry record: https://www.clinicaltrials.gov/ct2/show/NCT04911517?id=BFH-NCRTPD&draw=2&rank=1.
The identification of liver metastasis- and prognosis-associated genes in pancreatic ductal adenocarcinoma
Authors: Luan Hong , He Ye , Zhang Tuo , Su Yanna , Zhou Liping 
Published: April 2022

Abstract
Background
Pancreatic ductal adenocarcinoma (PDAC) is an often fatal malignancy with an extremely low survival rate. Liver metastasis, which causes high mortality, is the most common recurring metastasis for PDAC. However, the mechanisms underlying this liver metastasis and associated candidate biomarkers are unknown.

Methods
We performed mRNA profiling comparisons in 8 primary tumors (T) and 12 liver metastases (M) samples using the Gene Expression Omnibus (GEO) database. After determining differentially expressed genes (DEG), gene ontology (GO), pathway enrichment and protein–protein interaction (PPI) network analyses were performed to determine DEG functions. Then, Cytoscape was used to screen out significant hub genes, after which their clinical relevance was investigated using The Cancer Genome Atlas (TCGA) resources. Furthermore, prognosis-associated gene expression was validated using Oncomine and TCGA database. Lastly, associations between prognosis-associated genes, immune cells and immunological checkpoint genes were evaluated using the Tumor Immune Estimation Resource (TIMER).

Results
In total, 102 genes were related to liver metastasis and predominantly involved in cell migration, motility, and adhesion. Using Cytoscape, this number was narrowed down to 16 hub genes. Elevated mRNA expression levels for two of these genes, SPARC (P = 0.019) and TPM1 (P = 0.037) were significantly correlated with poor disease prognosis. For the remaining 14, expression was not related to overall patient survival. SPARC had higher expression in patients with metastatic PDAC than those with non-metastatic PDAC in TCGA dataset. SPARC and TPM1 levels were also positively correlated with the immune infiltration of specific cell types. Additionally, both genes exhibited strong co-expression associations with immune checkpoint genes.

Conclusions
Combined, we suggest SPARC has high potential as biomarker to predict liver metastasis during PDAC. Additionally, both SPARC and TPM1 appeared to recruit and regulate immune-infiltrating cells during these pathophysiological processes.
The relationship between occupational physical activity and dyslipidaemia in farmers with varying working modes in southwest China: the China multi-ethnic cohort study
Authors: Du Lunwei , Hong Feng , Luo Peng , Wang Ziyun , Zeng Qibing , Guan Han , Liu Haiyan , Yuan Zhiping , Xu Degan , Nie Fang , Wang Junhua 
Published: April 2022

Abstract
Background
Farmers are the integral members of rural communities. In the present study, we determined the association between occupational physical activity (OPA) of farmers and dyslipidaemia.

Methods
We included 7649 farmers from The China Multi-Ethnic Cohort (CMEC) Study. The working modes of all farmers were divided into four types according to their self-reported seasonal changes in farming work and/or other job changes (1: no change; 2: changing job; 3: seasonal changes; and 4: seasonal and job changes). OPA was self-reported, and the OPA levels in the four groups were classified as Q1, Q2–Q3, and Q4 by quantile. Dyslipidaemia was defined as the presence of abnormalities in lipid indicators. Binary logistic regression was used to estimate the association between OPA and dyslipidaemia.

Results
Compared with those in the no change group, the participants in other three groups were younger with lower level of education, annual income, and leisure-time physical activity (LTPA). Active OPA could reduce the risk of dyslipidaemia in the no change [men: odds ratios (OR) = 0.21, 95% confidence intervals (CI): 0.07–0.64; women: OR = 0.43, 95% CI: 0.20–0.93] and seasonal change (men: OR = 0.46, 95% CI: 0.27–0.77; women: OR = 0.59, 95% CI: 0.41–0.86) groups. However, in the seasonal and job change group (men: OR = 3.23, 95% CI: 1.06–9.80; women: OR = 3.24, 95% CI: 1.42–7.41), active OPA increased the risk of dyslipidaemia.

Conclusions
Different OPA levels might lead to differences in association with blood lipid levels. Thus, OPA guidelines must be developed for farmers, especially for those who experience seasonal changes in farming work and job changes.
Relationship between bone mineral density and ovarian function and thyroid function in perimenopausal women with endometriosis: a prospective study
Authors: Uehara Mari , Wada-Hiraike Osamu , Hirano Mana , Koga Kaori , Yoshimura Noriko , Tanaka Sakae , Osuga Yutaka 
Published: April 2022

Abstract
Background
In women with endometriosis, the association between ovarian function, hormones, and bone mineral density (BMD) is unclear. Therefore, this study aimed to elucidate the association between changes in bone mineral density (BMD) and clinical data, such as ovarian reserves, in perimenopausal women with endometriosis.

Methods
In this prospective study, we evaluated 207 female patients who visited the Department of Obstetrics and Gynecology at the University of Tokyo Hospital between December 2015 and December 2020. We included patients aged ≥ 40 years with a history of endometriosis or who presented with endometriosis lesions. Patients with a history of smoking, steroid administration, autoimmune diseases, dyslipidaemia, and heart disease were excluded. During the study period, patients who underwent two tests, an initial and a follow-up test (n = 142, average age: 45.02 years, average BMD: 1.16 g/cm2), were evaluated at regular intervals based on the annual rate of change in BMD.

Results
There was a weak negative correlation between the follicle-stimulating hormone (FSH) and BMD and a weak positive correlation between the anti-Müllerian hormone (AMH) and BMD. The annual rate of change in BMD showed a very weak correlation with thyroid-stimulating hormone (TSH) levels. A large decline in BMD was associated with high TSH levels and higher average age at menopause. Patients with higher TSH exhibited a higher rate of decrease in BMD than those without.

Conclusions
High FSH or low AMH levels are associated with decreased BMD. Decreased ovarian reserve is associated with decreased BMD in perimenopausal women with endometriosis. High TSH levels increase the risk of BMD loss. This finding may suggest that women with endometriosis should undergo bone scanning to rule out the possibility of reduced bone mass and subsequent increased risk of fracture.
How does interprofessional education influence students’ perceptions of collaboration in the clinical setting? A qualitative study
Authors: Teuwen Carolyn , van der Burgt Stéphanie , Kusurkar Rashmi , Schreurs Hermien , Daelmans Hester , Peerdeman Saskia 
Published: April 2022

Abstract
Background
Interprofessional education (IPE) aims to improve students’ collaborative competencies and behaviour. The effect of classroom IPE on students’ perceptions of collaboration in clinical practice, and how knowledge is possibly transferred, has yet to be investigated. The research question of this study was: How does IPE in a classroom setting influence students’ perceptions of collaboration in clinical practice? Social capital theory is used as the theoretical lens. Social capital theory describes how social relationships generate benefits for the individuals involved. Social capital can be divided into three forms of social cohesion: bonding, bridging and linking social capital. Bonding refers to connections that are close and strong, such as family. Bridging social capital occurs in more distant relationships. Linking social capital refers to relationships between individuals with different power or social status.

Methods
A qualitative study with semi-structured face-to-face interviews was conducted to explore students’ perceptions and experiences. Nursing and medical students who had participated in four classroom IPE-sessions were asked about the perceived influence of the IPE-sessions they had attended on their interprofessional collaboration. Thematic analysis was conducted, with sensitising concepts of ‘bonding’, ‘bridging’ and ‘linking social capital’ from the social capital theory.

Results
Twenty-two interviews were conducted. Students experienced: 1) exchange of discipline specific knowledge, 2) general knowledge about each other’s responsibilities, 3) reduction of hierarchy, and 4) improvement in patient care. The first two themes reflect bridging social capital, since students experience that the other student is from a different group. The third theme reflects linking social capital, since students experience a difference in (social) status. The fourth theme most explicitly reflects ‘getting ahead’ or doing better, what is referred to as an effect of increased social capital.

Conclusion
This study reveals new insights regarding how increased social capital of undergraduate students after IPE-sessions in a classroom setting influences the way they conceptualise and experience interprofessional collaboration in clinical practice. These insights contribute to the understanding of the effectiveness of IPE in undergraduate curricula. Further research on long-term effects is underway.
Reporting characteristics of journal infographics: a cross-sectional study
Authors: Ferreira Giovanni E. , Elkins Mark R. , Jones Caitlin , O’Keeffe Mary , Cashin Aidan G. , Becerra Rosa E. , Gamble Andrew R. , Zadro Joshua R. 
Published: April 2022

Abstract
Background
Infographics have become an increasingly popular method to present research findings and increase the attention research receives. As many scientific journals now use infographics to boost the visibility and uptake of the research they publish, infographics have become an important tool for medical education. It is unknown whether such infographics convey the key characteristics that are needed to make useful interpretations of the data such as an adequate description of the study population, interventions, comparators and outcomes; methodological limitations; and numerical estimates of benefits and harms. This study described whether infographics published in peer-reviewed health and medical research journals contain key characteristics that are needed to make useful interpretations of clinical research.

Methods
In this cross-sectional study, we identified peer-reviewed journals listed in the top quintile of 35 unique fields of medicine and health research listed in the Journal Citation Reports database. Two researchers screened journals for the presence of infographics. We defined an infographic as a graphical visual representation of research findings. We extracted data from a sample of two of the most recent infographics from each journal. Outcomes were the proportion of infographics that reported key characteristics such as study population, interventions, comparators and outcomes, benefits, harms, effect estimates with measures of precision, between-group differences and conflicts of interest; acknowledged risk of bias, certainty of evidence and study limitations; and based their conclusions on the study’s primary outcome.

Results
We included 129 infographics from 69 journals. Most infographics described the population (81%), intervention (96%), comparator (91%) and outcomes (94%), but fewer contained enough information on the population (26%), intervention (45%), comparator (20%) and outcomes (55%) for those components of the study to be understood without referring to the main paper. Risk of bias was acknowledged in only 2% of infographics, and none of the 69 studies that had declared a conflict of interest disclosed it in the infographics.

Conclusions
Most infographics do not report sufficient information to allow readers to interpret study findings, including the study characteristics, results, and sources of bias. Our results can inform initiatives to improve the quality of the information presented in infographics.
Factors influencing bedtime procrastination in junior college nursing students: a cross-sectional study
Authors: Chen Dong , Zhang Yuhuan , Lin Jie , Pang Dong , Cheng Dongyang , Si Daiwei 
Published: April 2022

Abstract
Background
Sleep quality is related to physical and mental health. Though bedtime procrastination has been identified as a potentially key source of poor sleep quality, related research is scarce. The goal of our study was to determine bedtime procrastination among nursing students and identify its influencing factors.

Methods
This cross-sectional study comprised 1827 junior college nursing students. The data were collected from November to December 2021 using a mobile app-based survey. We evaluated demographic factors, Big Five personality traits, self-regulatory fatigue, future time perspective, and problematic mobile phone use. Multiple linear regression analysis was used to identify independent characteristics that influence bedtime procrastination among junior college nursing students.

Results
The mean bedtime procrastination score in junior college nursing students was 25.11 ± 6.88. Family monthly income of 3000–6000 RMB (β = 0.740; p = 0.015), as well as that of > 6000 RMB (β = 1.708; p = 0.001), and an extroverted personality (β = 0.225; p = 0.001), self-regulatory fatigue (β = 0.135; p < 0.001), and problematic mobile phone use (β = 0.078; p < 0.001) had significant positive effects on bedtime procrastination. Conscientious personality (β = − 0.284; p = 0.003), neurotic personality (β = − 0.203; p = 0.031), and future time perspective (β = − 0.141; p < 0.001) had significant negative effects on bedtime procrastination.

Conclusion
The nursing students who participated in this study had moderate levels of bedtime procrastination. Bedtime procrastination was predicted by higher monthly household income; personality traits of extroversion, conscientiousness, and neuroticism; self-regulatory fatigue; future time perspective; and problematic mobile phone use.

Practical implications
We recommend that effective measures are needed to help alleviate bedtime procrastination and improve the health and well-being of nursing students.
Evaluation of’the Buddy Study’, a peer support program for second victims in healthcare: a survey in two Danish hospital departments
Authors: Schrøder Katja , Bovil Tine , Jørgensen Jan Stener , Abrahamsen Charlotte 
Published: April 2022

Abstract
Background
Healthcare professionals involved in adverse events may suffer severe physical and emotional distress in the aftermath. Adequate support is critical to an overall culture of safety for any healthcare institution. This study evaluates a formalised peer support program, ‘the Buddy Study’, in two Danish university hospital departments. The program consists of a 2-h seminar about second victims and self-selected buddies to provide peer support after adverse events.

Methods
The study design involved a cross-sectional survey comprised of two close-ended questionnaires evaluating the Buddy Study seminar (Q1) and the Buddy Study program (Q2), along with two open-ended questions and three individual interviews for more elaborate answers.

Results
Out of the 250 HCPs employed in both departments, 191 midwives, physicians, and nursing assistants completed Q1 and 156 completed Q2. The seminars were evaluated positively; 91.6% were satisfied with the overall content of the seminar, and 69.1% agreed that insight into how other people may react to adverse events has helped them contain their own reactions or emotions. Assessments of having the Buddy Study program in the department or using or being used as a buddy were more diverse, yet overall positive. Three benefits of the program were identified: the program i) has encouraged an open and compassionate culture; ii) has caused attentiveness to the wellbeing of colleagues; and iii) the self-selected buddy relationship has created a safe space for sharing. Additionally, three challenges or shortcomings were identified: i) although peer support is valuable, it should not stand alone; ii) informal peer support is already in place, hence making a formalised system redundant; and iii) the buddy system requires continuous maintenance and visibility.

Conclusions
The overall evaluation of the Buddy Study program was positive, suggesting that this type of formalised peer support may contribute to a rapid and accessible second-victim support program in healthcare institutions. A key principle for the Buddy Study program is that relationships are crucial, and all buddy relationships are based on self-selection. This seems to offer a safe space for health care professionals to share emotional vulnerability and professional insecurity after an adverse event.
The effects of oclacitinib treatment on antimicrobial usage in allergic dogs in primary practice: an Australia wide case-control study
Authors: Rynhoud Hester , Croton Catriona , Henry Grace , Meler Erika , Gibson Justine S. , Soares Magalhaes Ricardo J. 
Published: April 2022

Abstract
Background
Canine allergic dermatitis is a common diagnosis in veterinary practices which can lead to secondary infections requiring treatment with antimicrobials. A previous study suggested that dogs treated with oclacitinib in an Australian referral hospital required fewer courses of antimicrobial therapy compared to dogs receiving other anti-pruritic treatments. This study aimed to quantify the effect of oclacitinib treatment on the use of antimicrobials and other therapies in general practice veterinary clinics across Australia. A retrospective case-controlled review of patient records was designed to investigate the number of courses of antimicrobials and other therapies in dogs that received oclacitinib (Apoquel®), compared with those who received an anti-pruritic treatment that was not oclacitinib.

Results
The target population included canine patients with a presumptive diagnosis of allergic dermatitis presenting between 2008 and 2018 to general practices contributing to the VetCompass Australia database. Patient records of interest were identified using search terms relating to allergic dermatitis, resulting in over 700,000 observations. Multivariable logistic regression models were developed to determine whether cases were prescribed fewer antimicrobial courses than controls, after adjusting for the presence of concurrent skin infections or infectious agents in ears. Our results indicate that fewer antimicrobial courses were prescribed in the cases compared to the controls. After adjusting for the concurrent skin infections, there was a significant reduction in the use of cefovecin [OR:0.62(0.39–0.98), P = 0.043], chlorhexidine [OR:0.57(0.42–0.77), P < 0.001], neomycin [OR:0.4(0.28–0.56), P < 0.001] and amoxycillin clavulanic acid (AMC) [OR: 0.55(0.39–0.78), P = 0.001] in cases compared to controls.

Conclusion
This study demonstrates a potential sparing effect of oclacitinib on the prescription of antimicrobials for the treatment of allergic skin diseases in dogs. This information may assist in the planning of treatment for canine allergic dermatitis, with consideration for antimicrobial stewardship.
The fciTABC and feoABI systems contribute to ferric citrate acquisition in Stenotrophomonas maltophilia
Authors: Liao Chun-Hsing , Lu Hsu-Feng , Huang Hsin-Hui , Chen Yu , Li Li-Hua , Lin Yi-Tsung , Yang Tsuey-Ching 
Published: April 2022

AbstractBackgroundStenotrophomonas maltophilia, a member of γ-proteobacteria, is a ubiquitous environmental bacterium that is recognized as an opportunistic nosocomial pathogen. FecABCD system contributes to ferric citrate acquisition inEscherichia coli. FeoABC system, consisting of an inner membrane transporter (FeoB) and two cytoplasmic proteins (FeoA and FeoC), is a well-known ferrous iron transporter system in γ-proteobacteria. As revealed by the sequenced genome,S. maltophiliaappears to be equipped with several iron acquisition systems; however, the understanding of these systems is limited. In this study, we aimed to elucidate the ferric citrate acquisition system ofS. maltophilia.MethodsCandidate genes searching and function validation are the strategy for elucidating the genes involved in ferric citrate acquisition. The candidate genes responsible for ferric citrate acquisition were firstly selected using FecABCD ofE. colias a reference, and then revealed by transcriptome analysis ofS. maltophiliaKJ with and without 2,2′-dipyridyl (DIP) treatment. Function validation was carried out by deletion mutant construction and ferric citrate utilization assay. The bacterial adenylate cyclase two-hybrid system was used to verify intra-membrane protein–protein interaction.ResultsSmlt2858 and Smlt2356, the homologues of FecA and FecC/D ofE. coli, were first considered; however, deletion mutant construction and functional validation ruled out their involvement in ferric citrate acquisition.FciA(Smlt1148), revealed by its upregulation in DIP-treated KJ cells, was the outer membrane receptor for ferric citrate uptake. ThefciAgene is a member of thefciTABCoperon, in whichfciT, fciA,andfciCparticipated in ferric citrate acquisition. Uniquely, the Feo system ofS. maltophiliais composed of a cytoplasmic protein FeoA, an inner membrane transporter FeoB, and a predicted inner membrane protein FeoI. The intra-membrane protein–protein interaction between FeoB and FeoI may extend the substrate profile of FeoB to ferric citrate. FeoABI system functioned as an inner membrane transporter of ferric citrate.ConclusionsThe FciTABC and FeoABI systems contribute to ferric citrate acquisition inS. maltophilia.