bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrated single-cell and bulk RNA sequencing analysis identifies a cancer-associated fibroblast-related gene signature for predicting survival and therapy in gastric cancer
Authors: Zhou Zhiyang , Guo Sixuan , Lai Shuhui , Wang Tao , Du Yao , Deng Junping , Zhang Shun , Gao Ge , Zhang Jiangnan 
Published: January 2023

AbstractAs the dominant component of the tumor microenvironment, cancer-associated fibroblasts (CAFs), play a vital role in tumor progression. An increasing number of studies have confirmed that CAFs are involved in almost every aspect of tumors including tumorigenesis, metabolism, invasion, metastasis and drug resistance, and CAFs provide an attractive therapeutic target. This study aimed to explore the feature genes of CAFs for potential therapeutic targets and reliable prediction of prognosis in patients with gastric cancer (GC). Bioinformatic analysis was utilized to identify the feature genes of CAFs in GC by performing an integrated analysis of single-cell and transcriptome RNA sequencing using R software. Based on these feature genes, a CAF-related gene signature was constructed for prognostic prediction by LASSO. Simultaneously, survival analysis and nomogram were performed to validate the prognostic predictive value of this gene signature, and qRT–PCR and immunohistochemical staining verified the expression of the feature genes of CAFs. In addition, small molecular drugs for gene therapy of CAF-related gene signatures in GC patients were identified using the connectivity map (CMAP) database. A combination of nine CAF-related genes was constructed to characterize the prognosis of GC, and the prognostic potential and differential expression of the gene signature were initially validated. Additionally, three small molecular drugs were deduced to have anticancer properties on GC progression. By integrating single-cell and bulk RNA sequencing analyses, a novel gene signature of CAFs was constructed. The results provide a positive impact on future research and clinical studies involving CAFs for GC.
Mental health professionals’ expectations and efforts to include employment for people with moderate to severe mental illness in treatment settings
Authors: Finne Joakim , Holt Karin 
Published: January 2023

Abstract
Background
Research suggests that employment is an important factor for recovery and improved quality of life for people with mental illnesses. Mental health professionals often serve as gatekeepers for employment interventions, yet little is known about their expectations about employment for people with mental illness in Norway. The purpose of this study is to examine mental health professionals’ expectations and efforts to include employment for people with moderate to severe mental illness in treatment settings.

Methods
Two hundred seven mental health professionals were recruited from municipal mental health services, specialized clinics, social media, and professionals’ networks across Norway. Participants completed a survey package comprising demographic questions, current practices and a revised version of the self-reported measure Expectations for the Employability of People with Serious Mental Illness (EESMI), a validated measure consisting of three subscales.

Results
Results suggested overall favorable expectations of employment for people with moderate to severe mental illness. Analyses revealed that patients participating more frequently in collaborative meetings predicted more favorable expectations about employment among mental health professionals compared to less frequent meetings. In addition, findings suggest that psychiatrist hold more negative expectations about employment in comparison to the other educational groups. Lastly, more than half of mental health professionals reported that they have integrated discussions about employment, and routines to address work-oriented activity in consultations with patients, however, there are substantial variations in routines for addressing work or work-oriented activity as a topic in consultations with patients.

Conclusions
These results suggest that efforts are being made to integrate employment in treatment settings for people with mental illness in Norway; however, more work is needed to remove barriers and facilitate evidence-based approaches.
Barriers to simultaneous multilocus integration in Bacillus subtilis tumble down: development of a straightforward screening method for the colorimetric detection of one-step multiple gene insertion using the CRISPR-Cas9 system
Authors: Ferrando Jordi , Filluelo Oriana , Zeigler Daniel R. , Picart Pere 
Published: January 2023

Abstract
Background
Despite recent advances in genetic engineering tools for effectively regulating and manipulating genes, efficient simultaneous multigene insertion methods have not been established in Bacillus subtilis. To date, multilocus integration systems in B. subtilis, which is one of the main industrial enzyme producers and a GRAS (generally regarded as safe) microbial host, rely on iterative rounds of plasmid construction for sequential insertions of genes into the B. subtilis chromosome, which is tedious and time consuming.

Results
In this study, we present development and proof-of-concept of a novel CRISPR-Cas9-based genome-editing strategy for the colorimetric detection of one-step multiple gene insertion in B. subtilis. First, up to three copies of the crtMN operon from Staphylococcus aureus, encoding a yellow pigment, were incorporated at three ectopic sites within the B. subtilis chromosome, rendering engineered strains able to form yellow colonies. Second, a single CRISPR-Cas9-based plasmid carrying a highly specific single guide RNA (sgRNA) targeting crtMN operon and a changeable editing template was constructed to facilitate simultaneous insertion of multiple gene-copies through homology-directed repair (HDR). Upon transformation of engineered strains with engineered plasmids, strains harboring up to three gene copies integrated into the chromosome formed white colonies because of the removal of the crtMN operon, clearly distinguishable from yellow colonies harboring undesired genetic modifications. As a result, construction of a plasmid-less, marker-free, high-expression stable producer B. subtilis strain can be completed in only seven days, demonstrating the potential that the implementation of this technology may bring for biotechnology purposes.

Conclusions
The novel technology expands the genome-editing toolset for B. subtilis and means a substantial improvement over current methodology, offering new application possibilities that we envision should significantly boost the development of B. subtilis as a chassis in the field of synthetic biology.
Investigating people’s attitudes towards participating in longitudinal health research: an intersectionality-informed perspective
Authors: Merz Sibille , Jaehn Philipp , Pischon Tobias , Fischer Beate , Wirkner Kerstin , Rach Stefan , Guenther Kathrin , Obi Nadia , Holmberg Christine ,   the AdvanceGender Study Group, Bolte Gabriele , Mena Emily , Rommel Alexander , Saß Anke-Christine , Pöge Kathleen , Strasser Sarah 
Published: January 2023

Abstract
Background
Increasing evidence suggests that participation proportions in longitudinal health research vary according to sex/gender, age, social class, or migration status. Intersectionality scholarship purports that such social categories cannot be understood in isolation and makes visible the co-dependent nature of the social determinants of health and illness. This paper uses an intersectionality-informed approach in order to expand the understanding of why people participate in health research, and the impact of intersecting social structures and experiences on these attitudes.

Methods
A sample of 80 respondents who had previously either accepted or declined an invitation to participate in the German National Cohort (NAKO) participated in our interview study. Interviews were semi-structured and contained both narrative elements and more structured probes. Data analysis proceeded in two steps: first, the entire data set was analysed thematically (separately for participants and non-participants); second, key themes were compared across self-reported sex/gender, age group and migration status to identify differences and commonalities.

Results
Respondents’ attitudes towards study participation can be categorised into four themes: wanting to make a contribution, seeking personalised health information, excitement and feeling chosen, and seeking social recognition. Besides citing logistical challenges, non-participants narrated adverse experiences with or attitudes towards science and the healthcare system that deterred them from participating. A range of social experiences and cultural value systems shaped such attitudes; in particular, this includes the cultural authority of science as an arbiter of social questions, transgressing social categories and experiences of marginalisation. Care responsibilities, predominantly borne by female respondents, also impacted upon the decision to take part in NAKO.

Discussion
Our findings suggest that for participants, health research constitutes a site of distinction in the sense of making a difference and being distinct or distinguishable, whereas non-participants inhabited an orientation towards science that reflected their subjective marginalisation through science. No clear relationship can thereby be presumed between social location and a particular attitude towards study participation; rather, such attitudes transgress and challenge categorical boundaries. This challenges the understanding of particular populations as more or less disadvantaged, or as more or less inclined to participate in health research.
Methylphenidate use and misuse among medical residents in Israel: a cross-sectional study
Authors: Zahavi Eden , Lev-Shalem Liat , Yehoshua Ilan , Adler Limor 
Published: January 2023

Abstract
Background
Methylphenidate (MPH) and other stimulants may be misused, mainly as cognitive enhancers and recreational drugs. Data regarding misuse among medical residents are scarce. This study aimed to evaluate the prevalence of and main reasons for methylphenidate (MPH) use and misuse among Israeli medical residents.

Methods
In this cross-sectional study, we sent an online questionnaire to medical residents who had completed their first residency exam and specialists with up to 2 years of experience. We asked about the use of MPH before and during residency and attitudes toward the use of MPH as a cognitive enhancer. We also added the Adult ADHD Self-Report Scale (ASRS) questionnaire, a validated tool used to screen for the presence of attention deficit hyperactivity disorder (ADHD). Users and misusers were classified based on self-report of use and formal ADHD diagnosis. Logistic regression analysis was used to evaluate factors associated with MPH misuse.

Results
From March 2021 to August 2021, 370 physicians responded to our questionnaire (response rate 26.4%). Twenty-eight met the exclusion criteria and were not included. The respondents’ average age was 36.5 years. Women comprised 63.5% of the respondents. Of the participants, 16.4% were classified as users and 35.1% as misusers. The prevalence of misusers was 45.6% among surgery and OB/GYN physicians, 39.4% among pediatricians and internists, and 24% among family physicians (P < 0.001). Misusers had a more liberal approach than others to MPH use as a cognitive enhancer. Factors associated with misuse of MPH included not being a native-born Israeli (OR-1.99, 95% CI 1.08, 3.67) and type of residency (OR-2.33, 95% CI 1.22, 4.44 and OR-4.08, 95% CI 2.06, 8.07 for pediatrics and internal medicine and surgery, respectively).

Conclusion
Very high levels of MPH misuse during residency may be related to stress, long working hours, night shifts, and the academic burden of the residency period. We believe that our findings should be considered by healthcare policymakers as they make decisions regarding the conditions of medical residencies. The use of MPH as a cognitive enhancer should be further studied and discussed.
High proportion of circulating CD8 + CD28- senescent T cells is an independent predictor of distant metastasis in nasopharyngeal carcinoma after radiotherapy
Authors: Xu Xiaotian , Wei Fangze , Xiao Lin , Wu Runye , Wei Baojun , Huang Shengkai , Yi Junlin , Cui Wei 
Published: January 2023

AbstractBackgroundNasopharyngeal carcinoma (NPC) is a kind of epithelial carcinoma that is common in East and Southeast Asia. Distant metastasis after radiotherapy remains the main cause of treatment failure and preradiotherapy immune system function can influence prognosis. Our study aimed to identify immune-related prognostic factors for NPC after radiotherapy and establish a prognostic model to predict progression-free survival (PFS) and distant metastasis-free survival (DMFS).MethodsWe enrolled NPC patients and divided them into training and validation cohorts with follow-up. We collected clinical information and investigated immune cells, EBV DNA and cytokines in the peripheral blood of NPC patients before radiotherapy and EBV DNA after radiotherapy. Among these immune cells, we included CD8+CD28−T cells, which are a unique T-cell immunosenescent subset that increases in human peripheral blood with increasing age and declining immune function. Based on the detection results and clinical information, we utilized Cox regression and least absolute shrinkage and selection operator (LASSO) regression to screen the PFS and DMFS prognostic factors and build nomograms to predict the PFS and DMFS of NPC. We also verified the results in the validation set.ResultsThree factors associated with PFS were selected: proportion of CD8+CD28−T cells posttreatment EBV and N stage. Three factors associated with DMFS were screened: proportion of CD8+CD28−T cells, posttreatment EBV and N stage. CD8+CD28−T cells are correlated with systemic inflammation and posttreatment immunosuppression. The C-indexes were 0.735 and 0.745 in the training and validation cohorts for predicting PFS. For DMFS, the C-indexes were 0.793 and 0.774 in the training and validation cohorts.ConclusionsThe pretreatment proportion of CD8+CD28−T cells is a candidate prognostic biomarker for NPC after radiotherapy. The constructed nomogram models based on CD8+CD28−T cells have good predictive value.
Two-year changes in body composition and future cardiovascular events: a longitudinal community-based study
Authors: Hu Tingting , Shen Yun , Cao Weijie , Xu Yiting , Wang Yufei , Ma Xiaojing , Bao Yuqian 
Published: January 2023

AbstractBackgroundThe risk of cardiovascular diseases has rapidly increased among middle-aged and elderly. However, little is known about the relationship of body composition changes with the risk of cardiovascular events among this population in China.We explored the associations of 2-year changes in fat percentage (fat%) and fat-free mass percentage (FFM%) with subsequent cardiovascular events in a middle-aged and elderly community-based cohort.MethodsThis study included 1048 participants (456 men [43.51%], aged 50–80 years) without overt cardiovascular disease, who underwent two examinations during 2013–2014 and 2015–2016. All participants were followed up until 2022 for cardiovascular events. A bioelectrical impedance analyzer was used to calculate fat% and FFM% change.ResultsAt baseline, the median body mass index (BMI), fat%, and FFM% were 23.9 (22.1–25.9) kg/m2, 27.2 (20.8–33.6)%, and 72.8 (66.4–79.2)%, respectively. Two-year changes in fat% and FFM% were 0.31 (− 5.53 to 6.87)% and − 0.12 (− 2.36 to 2.06)%. During an average follow-up of 5.5 years, 86 cardiovascular events (8.21%) occurred. Cox regression models showed that hazard ratios (HRs) of every 2% change in fat% and FFM% for cardiovascular events were 1.04 (95% confidence interval [CI] 1.01–1.07) and 0.84 (95% CI 0.74–0.95), respectively. Compared with participants with stable fat% (–2% ≤ ⊿fat% < 2%), those with fat% gain ≥ 2% had an increased risk of cardiovascular events (HR 2.07, 95% CI 1.08–3.97). FFM% loss > 8% was associated with a higher risk of cardiovascular events (HR 3.83, 95% CI 1.29–11.4).ConclusionsIn a middle-aged and elderly community-based Chinese population, fat% gain or FFM% loss was associated with an increased risk of cardiovascular events.
Experimental and Numerical Assessments of Slab-Column Connections Strengthened Using Bonded Hemp Fiber Fabric Sheets
Authors: Al-Mawed Loai Khaled , Hamad Bilal Salim 
Published: January 2023

AbstractThe replacement of synthetic fibers with natural fibers in concrete has been recently investigated to counter the growing environmental and sustainable issues. Hemp fibers are environmentally friendly and are used in the manufacturing of composite materials. This paper reports on the experimental assessment of using hemp fiber reinforced polymer (HFRP) fabric sheets as an alternative to carbon fiber reinforced polymer (CFRP) sheets to strengthen interior slab-column connections. Small-scale interior slab-column connections were loaded centrally through the column stub up to failure. The main test variables were slab thickness, HFRP sheet width, number of HFRP layers, type of strengthening material (HFRP or CFRP sheets), and HFRP sheet's location relative to the column’s face. Assessment of the strengthening material was based on a comparison of load capacity, mode of failure, load–displacement history, and cracking patterns. The experimental results demonstrated that HFRP strengthening sheets led to improvement in the structural behavior of the slab-column connections depending on the slab thickness, width and configuration for HFRP sheets. Although the HFRP sheets led to lower improvement as compared to the synthetic CFRP sheets, however, the same improvement could be reached by the HFRP sheets if they are applied in larger width or different configurations. A finite-element model was developed using ABAQUS software to predict the behavior of simulated specimens. The numerical findings showed that the models predicted the connection behavior in good agreement with the experimental test results. In addition, an analytical model was calibrated to simulate the behavior of the tested specimens.
Effect of Chitosan nanoparticles on quality indices, metabolites, and vase life of Rosa hybrida cv. Black magic
Authors: Seyed Hajizadeh Hanifeh , Dadashzadeh Roya , Azizi Sahar , Mahdavinia Gholam Reza , Kaya Ozkan 
Published: January 2023

Abstract
Background
Chitosan nanoparticles (CTS-NPs) protect the active ingredients from the environment for a specific period and reduces sweating, control weight loss, delay ripening, and increase vase life. So, a factorial experiment was carried out as a randomized complete design in three replications to investigate the efficiency of CTS-NPs in quality improvement and longevity extension of cut rose flowers.

Results
The 15-day maximum vase life was attained by the rose placed in a preservative solution containing 10 mg L−1 CTS-NPs. CTS-NPs also reduced microbial growth as compared to controls. Total phenolics, total flavonoids, and amount of anthocyanin in treated petals were dramatically increased. CTS-NPs solutions especially at 10 and 15 mg L−1 concentrations, markedly reduced the H2O2 and malondialdehyde at the end of 15th day and maintained the membrane index. The protein and carbohydrate and petals anthocyanin content and enzymatic activities such as superoxide dismutase, polyphenol oxidase, peroxidase, catalase and ascorbate peroxidase increased in cut roses placed in 10 mg L−1 CTS-NPs vase solution which in turn caused to increase in vase life.

Conclusion
CTS-NPs especially at a level of 10 mg L−1 can assist plants to enhance light usage efficiency, as well as promote photosynthetic carbon fixation and the production of additional carbohydrate products for plant growth and development.

Graphical Abstract
Forkhead box P3 gene polymorphisms predispose to type 2 diabetes and diabetic nephropathy in the Han Chinese populations: a genetic-association and gender-based evaluation study
Authors: Wang Xiaorong , Liu Zejing , Zhang Shangdi , Yang Yinfeng , Wu Xue , Liu Xinyue 
Published: January 2023

Abstract
Background
Functional mutations or polymorphisms affecting forkhead box P3 (FOXP3) can lead to their abnormal FOXP3 gene expression and/or defective Treg cells generation, thus resulting in autoimmune disease and inflammatory disorders. FOXP3 also plays a key role in Type 2 diabetes mellitus (T2DM) and its complications, because the disease usually involves chronic low-grade inflammatory disorders and is associated with long-term immune system imbalance. This study aimed to investigate the association between FOXP3 polymorphisms and the susceptibility to T2DM and type 2 diabetes nephropathy (T2DN) within the Han Chinese populations.

Methods
Polymorphisms in rs3761548C/A and rs2294021C/T were examined in 400 patients (which include an equal number of T2DM and T2DN groups) and 200 healthy controls using PCR-HRM and sequence analysis.

Results
The genotype and allelic frequencies of the two single nucleotide polymorphisms (SNPs) were significantly different in T2DM and the progression of diabetes developing to T2DN. The further gender-based evaluation showed that in female subjects, rs3761548C/A was associated with an approximately 3-fold higher threat for T2DM and 4.5-fold for T2DN, while there was no noticeable association with rs2294021C/T; in males, the promoter polymorphism showed an increased predisposition of 5.4-fold and 3.4-fold predisposition to T2DM and T2DN, respectively, while rs2294021 polymorphism could impart a nearly 2-fold risk of developing T2DN. An additional analysis of combined genotypes (rs3761548 C/A-rs2294021C/T) revealed that CC-CC and CC-CT can be considered protective combinations in the predisposition of males with diabetes towards T2DN, while AA-CC and AA-TT have the opposite effect.

Conclusions
This study demonstrated the possible involvement of individual and combined genetic associations of rs3761548C/A and rs2294021C/T polymorphisms with the susceptibility to diabetes and diabetic nephropathy in the Han Chinese population, as well as gender bias.
The Stanniocalcin-PAPP-A-IGFBP-IGF Axis
Authors: Oxvig Claus , Conover Cheryl A 
Published: January 2023

Abstract
The pappalysin metalloproteinases, PAPP-A and PAPP-A2, have emerged as highly specific proteolytic enzymes involved in the regulation of insulin-like growth factor (IGF) signaling. The only known pappalysin substrates are a subset of the IGF binding proteins (IGFBPs), which bind IGF-I or IGF-II with high affinity to antagonize receptor binding. Thus, by cleaving IGFBPs, the pappalysins have the potential to increase IGF bioactivity and hence promote IGF signaling. This is relevant both in systemic and local IGF regulation, in normal and several pathophysiological conditions. Stanniocalcin-1 and -2 were recently found to be potent pappalysin inhibitors, thus comprising the missing components of a complete proteolytic system, the stanniocalcin-PAPP-A-IGFBP-IGF axis. Here, we provide the biological context necessary for understanding the properties of this molecular network, and we review biochemical data, animal experiments, clinical data, and genetic data supporting the physiological operation of this branch as an important part of the IGF system. However, although in vivo data clearly illustrate its power, it is a challenge to understand its subtle operation, for example, multiple equilibria and inhibitory kinetics may determine how, where, and when the IGF receptor is stimulated. In addition, literally all of the regulatory proteins have suspected or known activities that are not directly related to IGF signaling. How such activities may integrate with IGF signaling is also important to address in the future.