bluuebunny/crossref_metadata_2025_split huggingface dataset:
START – physical exercise and person-centred cognitive skills training as treatment for adult ADHD: protocol for a randomized controlled trial
Authors: Lindvall Mialinn Arvidsson , Holmqvist Kajsa Lidström , Svedell Lena Axelsson , Philipson Anna , Cao Yang , Msghina Mussie 
Published: September 2023

Abstract
Background
Core symptoms in attention deficit hyperactivity disorder (ADHD) are inattention, impulsivity and hyperactivity. Many individuals with this disorder also have a sedentary lifestyle, co-morbid mental illness such as depressive and anxiety disorders, and reduced quality of life. People with ADHD often have impaired executive function, which among other things may include difficulty in time management and structuring of everyday life. Pharmacological treatment is often the first-line option, but non-pharmacological treatment is also available and is used in clinical settings. In children and adolescents with ADHD, physical exercise is used as a non-pharmacological treatment. However, the evidence for the effectiveness of exercise in adults is sparse.

Objective
To implement the START intervention (START = Stöd i Aktivitet, Rörelse och Träning [Support in activity, movement and exercise]) consisting of a 12-week, structured mixed exercise programme with or without a cognitive intervention, in adults with ADHD, and study whether it has an effect on core symptoms of ADHD as well as physical, cognitive, mental and everyday functioning compared with usual treatment. A secondary aim is to investigate the participants’ experiences of the intervention and its possible benefits, and to evaluate the cost-effectiveness of START compared with usual treatment.

Methods
This is a randomized controlled trial planned to be conducted in 120 adults with ADHD, aged 18–65. The intervention will be given as an add-on to standard care. Participants will be randomized to three groups. Group 1 will be given a physiotherapist-led mixed exercise programme for 12 weeks. Group 2 will receive the same intervention as group 1 with the addition of occupational therapist-led cognitive skills training. Group 3 will be the control group who will receive standard care only. The primary outcome will be reduction of ADHD symptoms measured using the World Health Organization (WHO) Adult ADHD Self-Report Scale (ASRS-v1.1), Clinical Global Impression-Severity scale (CGI-S) and CGI-Improvement scale (CGI-I). The effect will be measured within 1 week after the end of the intervention and 6 and 12 months later.

Discussion
Data collection began in March 2021. The final 12-month follow-up is anticipated to be completed by autumn 2024.

Trial registration
ClinicalTrials.gov (Identifier: NCT05049239). Registered on 20 September 2021 (last verified: May 2021).
Likelihood of identifying autistic traits with the autism spectrum quotient (AQ) in male juveniles with autism spectrum disorder (ASD) and severe behavioral problems (SBPs)
Authors: Rutten Alexa X. , Vermeiren Robert R. J. M. , Bongers Ilja L. , Van Nieuwenhuizen Chijs 
Published: September 2023

Abstract
Background
When screening for autism spectrum disorders (ASD), the Autism Spectrum Quotient (AQ) is generally considered to be useful. Whether the AQ is also a suitable screener for ASD in juveniles with severe behavioral problems (SBPs) is unknown. Due to the overlap of symptoms between ASD and SBPs, particularly in juveniles low on empathy, the screening capacity of the AQ might be constrained. The aim of the present study was to investigate whether (comorbid) SBPs affect the screening capacity of the AQ. The hypothesis is that male juveniles with SBPs - but without a diagnosis of ASD - will score higher than male juveniles without both SBPs and ASD.

Method
The AQ was completed by 216 male juveniles aged 15–18 years treated at an outpatient department of child and adolescent psychiatry. The 216 participants were categorized into four groups according to a clinical diagnosis of ASD and SBPs (defined as disruptive behavior disorder and/or delinquent behavior). Using multinomial logistic regression, we investigated whether the four identified groups, based on a diagnosis of ASD and SBPs, scored differently for the total score and subscales of the AQ.

Results
Participants in the group with ASD (ASD+) but without SBPs (SBP-) were more likely to report higher levels of autistic traits than the reference group without both ASD and SBPs (ASD-SBP-), except for the subscale on attention to detail (ASD+SBP- OR = 1.04; 95%CI = 0.98–1.11). Participants in the group with both ASD and SBPs were more likely to report higher levels for the total AQ score (ASD+SBP+ OR = 1.03; 95%CI = 1.00–1.05) and the communication subscale of the AQ (ASD+SBP+ OR = 1.18; 95%CI = 1.07–1.31) than the reference group without both ASD and SBPs.

Conclusion
In outpatient male juveniles, SBPs do not affect the screening capacity of the AQ for autistic traits. In spite of the well-known overlap of symptoms between ASD and SBPs, male juveniles with SBPs but without a diagnosis of ASD do not score higher on the AQ than male juveniles without SBPs and without a diagnosis of ASD.
A multisectoral and multidisciplinary endeavor: a review of diabetes self-management apps in China
Authors: Chen Meifang , Weissglass Daniel , Li Chengyi , Li Di , Wu Zixuan , Zhang Li 
Published: September 2023

Abstract
Background
While the use of self-management apps has considerable promise to efficiently reduce the diabetes burden that disproportionally affects low- and middle-income countries (LMICs), and the multisectoral and multidisciplinary approaches have been encouraged to be used in diabetes management, little is known about the status of the integration of these approaches in the existing diabetes self-management apps. This review examines the diabetes apps in China as an indication of the current status of integrating multisectoral and multidisciplinary approaches in diabetes mHealth care in LMICs.

Methods
Eligible diabetes apps were searched on major Chinese app stores up to December 23, 2022. The app comprehensiveness index (ranging 0–80) regarding the app functions and diabetes management domains was created. The multisectoral and multidisciplinary features were summarized using indices derived from current guidance.

Results
Sixty-six apps were reviewed, all developed by private companies. The average comprehensiveness score was 16, with many major self-management domains and functions not represented among the reviewed apps. Forty apps (61%) involved multiple sectoral entities, with public/private and private/private collaborations being the most common collaborative combinations. Thirty-seven apps (56%) involved multiple disciplines, among which endocrinology/metabolism, nutrition, and cardiovascular medicine were the top three most common disciplines. Compared to non-multidisciplinary apps, multidisciplinary apps tended to provide more comprehensive services in apps (6.14 vs. 5.18, p = 0.0345). Different sectors and disciplines tended to work independently, without robust interactions, in providing diabetes management services in the reviewed apps.

Conclusion
Multisectoral and multidisciplinary features has presented in the current diabetes self-management apps in China; however, it is still in its infancy and significant limitations existed. More engagement of civil society organizations and community groups and innovative collaborations between sectors and disciplines are needed to provide comprehensive, continuous, and patient-centered mHealth care for patients with diabetes in LMICs like China. Clear guidance for integrating and evaluating the multisectoral and multidisciplinary efforts in self-management apps is necessary to ensure the effective use of mHealth solutions for diabetes management in LMICs.
Mobility and HIV vulnerabilities among female sex workers in Guinea-Bissau: findings from an integrated bio-behavioral survey
Authors: Gorin Emma M. , Lyons Carrie E. , Jarrett Brooke A. , Djalo Mamadu A. , Barreto Kátia , Drame Fatou M. , Baral Stefan 
Published: September 2023

Abstract
Background
Mobility is an important risk determinant for HIV given the potential for intermittent access to HIV services. Mobility may be particularly relevant among female sex workers, (FSW) who have been shown to be at high risk for HIV in settings around the world. Data regarding the role mobility plays in exacerbating HIV risks among FSW across Sub-Saharan Africa remains limited, and data on FSW in Guinea-Bissau is sparse.

Methods
FSW in four regions of Guinea-Bissau were recruited with a respondent-driven sampling (RDS) method and participated in an integrated bio-behavioral survey between September 27, 2017 and January 26, 2018. Associations between reported general mobility, mobility to or residence in Bissau, and social and HIV vulnerabilities among FSW in Guinea-Bissau were assessed using multivariable logistic regression models. Population proportions were weighted for RDS sampling, while logistic regression models were not.

Results
Survey respondents included 323 individuals in Bissau, 45 in Bissorã, 140 in Bafatá, and 59 in Gabu. Statistical analyses demonstrated that mobility to more than one destination was significantly associated with recent sex without a condom (ie, sex without a condom within the last three sex acts) with both clients (aOR: 2.47 (95% CI: 1.08, 5.64)) and non-paying partners (aOR: 5.39 (95% CI: 2.61, 11.15)) compared to non-mobility. However, mobility to one or more locations was also associated with higher odds of receiving HIV prevention information, and mobility to more than one location was associated with participating in programming with HIV-related organizations.

Conclusions
These results suggest that while some prevention services including HIV prevention information reach mobile FSW in Guinea-Bissau more than their non-mobile counterparts, the higher rates of condomless sex among mobile FSW suggest that HIV prevention needs may remain unmet for mobile FSW in Guinea-Bissau. Additionally, the results suggest a nuanced relationship between mobility, place of residence, and HIV and social vulnerabilities and prevention indicators.
Metformin induces ferroptosis through the Nrf2/HO-1 signaling in lung cancer
Authors: Deng Chengmin , Xiong Lin , Chen Yang , Wu Kaifeng , Wu Jie 
Published: September 2023

Abstract
Background
Metformin is the most frequently prescribed medication for the treatment of type II diabetes mellitus and has played an anti-tumor potential in a variety of cancer types. Metformin can inhibit the growth of many cancer cells through various mechanisms, including ferroptosis. However, it is still unclear whether metformin can induce ferroptosis in lung cancer.

Methods
This study evaluated the anti-tumor effect of metformin by detecting the levels of oxidative stress factors, the levels of ferrous ions, and the expression of ferroptosis-related genes in A549 and H1299 lung cancer cell lines treated with or without metformin.

Results
The results showed that metformin treatment increased the levels of MDA, ROS and iron ions, while decreased the levels of GSH, T-SOD and CAT. Meanwhile, metformin treatment reduced the protein expression levels of Gpx4 and SLC7A11, Nrf2 and HO-1, while the addition of ferroptosis inhibitor ferrostatin-1 reversed the reduction.

Conclusions
These results demonstrated that metformin exerts anti-tumor effects by inducing ferroptosis through the Nrf2/HO-1 signaling pathway in lung cancer cells, providing a theoretical basis for drug therapy of lung cancer patients.
Serum prolactin and gonadal hormones in hemodialysis women: a meta-analysis
Authors: Zhang Kailu , Zhao Lanbo , Bin Yadi , Guo Miao , Zhou Xue , Li Min , Han Lu , Li Qiling 
Published: September 2023

Abstract
Background
A meta-analysis followed by PRISMA 2020 statement was performed aiming to present a whole prolactin and sex hormone profile in hemodialysis women.

Methods
Literatures were searched in PubMed, Cochrane library, Embase, and Web of science before March 11, 2023. Trial sequential analysis (TSA) was performed to test the conclusiveness of this meta-analysis. Egger’s test and trim-and-fill analysis was used to test publication bias. We took standardized mean difference (SMD) as pool effect of hormones values including prolactin (PRL), follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2) and progesterone (P). This study was registered in PROSPERO and the number was CRD42023394503.

Results
Twenty-two articles from 13 countries were analyzed. Combining the results of TSA and meta-analysis, we found that compared with healthy control, hemodialysis women had higher PRL, follicular FSH and LH values and lower P levels (PRL: I2 = 87%, SMD 1.24, 95% CI: 0.79–1.69, p < 0.00001; FSH: I2 = 0%, SMD 0.34, 95% CI: 0.13–0.55, p = 0.002; LH: I2 = 39%, SMD 0.64, 95% CI: 0.34–0.93, p < 0.00001; P: I2 = 30%, SMD − 1.62, 95% CI: -2.04 to -1.20, p < 0.00001). What’s more, compared with women after renal transplantation, hemodialysis women had higher PRL levels (I2 = 0%, SMD 0.51, 95% CI: 0.25–0.78, p = 0.0001). There was not enough evidence to draw a conclusion on the comparison of hormones between regular and irregular menses hemodialysis women. Egger’s test and trim-and-fill analysis didn’t show significant publication bias.

Conclusions
Hemodialysis women had higher serum PRL, follicular phase FSH, LH and lower serum P values compared with healthy control. PRL values of hemodialysis women were also higher than that of women after renal transplantation.
Cone-beam computed tomography assessment of the root canal morphology of primary molars
Authors: Rahmati Afsaneh , Khoshbin Elham , Shokri Abbas , Yalfani Hadis 
Published: September 2023

Abstract
Background
This study aimed to assess the root canal morphology of primary molars using cone-beam computed tomography (CBCT).

Methods
This cross-sectional study evaluated 60 maxillary and mandibular primary first and second molars on CBCT scans of patients retrieved from the archives of Hamadan School of Dentistry between 2018–2020. The teeth were evaluated regarding the number of roots and canals, canal type according to the Vertucci’s classification, and root surface concavities. Data were analyzed descriptively and by independent t-test.

Results
The most frequent number of canals and roots in the maxillary right and left first molars was 3 canals (60%) and 3 roots (80%). These values were 4 canals (80%) and 5 canals (50%) with 3 roots in the maxillary right and left second molars, respectively, 4 canals (100%) and 2 roots (50%), and 3 canals (60%) and 2 roots (50%) in mandibular right and left first molars, respectively, and 4 canals (92.3%) and 3 roots (61.5%) in mandibular right and left second molars. Vertucci’s type IV was the most common canal type in mesial and distal canals, type I was the most common in mesiobuccal, mesiolingual, distobuccal, and distolingual, and types I and II were the most common in the palatal canal. The maximum and minimum concavities were noted in the buccal (26.7%) and mesial (8.3%) surfaces, respectively.

Conclusions
A wide variation exists in the number of roots and canals of maxillary and mandibular primary molars, which calls for further attention in treatment of such teeth.
Meta-analysis reveals the vaginal microbiome is a better predictor of earlier than later preterm birth
Authors: Huang Caizhi , Gin Craig , Fettweis Jennifer , Foxman Betsy , Gelaye Bizu , MacIntyre David A. , Subramaniam Akila , Fraser William , Tabatabaei Negar , Callahan Benjamin 
Published: September 2023

Abstract
Background
High-throughput sequencing measurements of the vaginal microbiome have yielded intriguing potential relationships between the vaginal microbiome and preterm birth (PTB; live birth prior to 37 weeks of gestation). However, results across studies have been inconsistent.

Results
Here, we perform an integrated analysis of previously published datasets from 12 cohorts of pregnant women whose vaginal microbiomes were measured by 16S rRNA gene sequencing. Of 2039 women included in our analysis, 586 went on to deliver prematurely. Substantial variation between these datasets existed in their definition of preterm birth, characteristics of the study populations, and sequencing methodology. Nevertheless, a small group of taxa comprised a vast majority of the measured microbiome in all cohorts. We trained machine learning (ML) models to predict PTB from the composition of the vaginal microbiome, finding low to modest predictive accuracy (0.28–0.79). Predictive accuracy was typically lower when ML models trained in one dataset predicted PTB in another dataset. Earlier preterm birth (< 32 weeks, < 34 weeks) was more predictable from the vaginal microbiome than late preterm birth (34–37 weeks), both within and across datasets. Integrated differential abundance analysis revealed a highly significant negative association between L. crispatus and PTB that was consistent across almost all studies. The presence of the majority (18 out of 25) of genera was associated with a higher risk of PTB, with L. iners, Prevotella, and Gardnerella showing particularly consistent and significant associations. Some example discrepancies between studies could be attributed to specific methodological differences but not most study-to-study variations in the relationship between the vaginal microbiome and preterm birth.

Conclusions
We believe future studies of the vaginal microbiome and PTB will benefit from a focus on earlier preterm births and improved reporting of specific patient metadata shown to influence the vaginal microbiome and/or birth outcomes.
Diagnostic and societal impact of implementing the syncope guidelines of the European Society of Cardiology (SYNERGY study)
Authors: Ghariq M. , van den Hout W. B. , Dekkers O. M. , Bootsma M. , de Groot B. , Groothuis J. G. J. , Harms M. P. M. , Hemels M. E. W. , Kaal E. C. A. , Koomen E. M. , de Lange F. J. , Peeters S. Y. G. , van Rossum I. A. , Rutten J. H. W. , van Zwet E. W. , van Dijk J. G. , Thijs R. D. ,   on behalf of the SYNERGY Consortium, Tuinema R. M. , Voet W. , Boerman D. B. , Firouzi M. , Fokke C. 
Published: September 2023

Abstract
Background
Syncope management is fraught with unnecessary tests and frequent failure to establish a diagnosis. We evaluated the potential of implementing the 2018 European Society of Cardiology (ESC) Syncope Guidelines regarding diagnostic yield, accuracy and costs.

Methods
A multicentre pre-post study in five Dutch hospitals comparing two groups of syncope patients visiting the emergency department: one before intervention (usual care; from March 2017 to February 2019) and one afterwards (from October 2017 to September 2019). The intervention consisted of the simultaneous implementation of the ESC Syncope Guidelines with quick referral routes to a syncope unit when indicated. The primary objective was to compare diagnostic accuracy using logistic regression analysis accounting for the study site. Secondary outcome measures included diagnostic yield, syncope-related healthcare and societal costs. One-year follow-up data were used to define a gold standard reference diagnosis by applying ESC criteria or, if not possible, evaluation by an expert committee. We determined the accuracy by comparing the treating physician’s diagnosis with the reference diagnosis.

Results
We included 521 patients (usual care, n = 275; syncope guidelines intervention, n = 246). The syncope guidelines intervention resulted in a higher diagnostic accuracy in the syncope guidelines group than in the usual care group (86% vs.69%; risk ratio 1.15; 95% CI 1.07 to 1.23) and a higher diagnostic yield (89% vs. 76%, 95% CI of the difference 6 to 19%). Syncope-related healthcare costs did not differ between the groups, yet the syncope guideline implementation resulted in lower total syncope-related societal costs compared to usual care (saving €908 per patient; 95% CI €34 to €1782).

Conclusions
ESC Syncope Guidelines implementation in the emergency department with quick referral routes to a syncope unit improved diagnostic yield and accuracy and lowered societal costs.

Trial registration
Netherlands Trial Register, NTR6268
ACVRL1 drives resistance to multitarget tyrosine kinase inhibitors in colorectal cancer by promoting USP15-mediated GPX2 stabilization
Authors: Lu Xiaolin , Liu Ruiqi , Liao Yuanyu , Cui Luying , Sun Haoxiu , Zhang Dongzhi , Wang Bojun , Fang Lin , Guan Xin , Yao Yuanfei , Liu Chao , Zhang Yanqiao 
Published: September 2023

Abstract
Background
Multitarget tyrosine kinase inhibitors (mTKIs) such as Regorafenib and Sorafenib have already been approved for the treatment of many solid tumours. However, the efficacy of mTKIs in colorectal cancer (CRC) is limited; the underlined mechanism remains largely elusive. Our study was aimed to find out the resistance mechanism of mTKIs in CRC.

Methods
RNA sequencing was used to identify the expression of Activin A receptor-like type 1 (ACVRL1) under the treatment of mTKIs. Gain/loss-of-function experiments were performed to assess the biological function of ACVRL1 in resistance to mTKIs. The underlying mechanisms of ACVRL1-mediated mTKI resistance were investigated by using liquid chromatography-mass spectrometry assays (LC-MS), co-immunoprecipitation assays (Co-IP), chromatin immunoprecipitation assays, ubiquitination assays, dual luciferase reporter assays, etc.

Results
RNA sequencing identified the activation of ACVRL1 under the treatment of mTKIs in CRC cells. ACVRL1 knockdown and overexpression significantly affects the sensitivity of CRC cells to mTKIs both in vitro and vivo. Mechanistically, we found the β-catenin/TCF-1-KCNQ1OT1/miR-7-5p axis mediated the activation of ACVRL1.
Furthermore, LC-MS assays indicated the interaction between ACVRL1 and glutathione peroxidase 2(GPX2) protein. IP assay defined ACVRL1 truncation (282–503aa) could be responsible for interacting with GPX2, and rescue experiments with ACVRL1 truncations confirmed the importance of this interaction in driving mTKI resistance. Co-IP assays confirmed that ACVRL1 associates with ubiquitin-specific peptidase 15(USP15) which directly deubiquinates GPX2 at the K187(K, lysine) site, leading to the accumulation of GPX2 protein. Rescue experiments performed with the lysine mutants in GPX2 CRISPR knockout cell model confirmed the importance of GPX2 K187 mutant. As a result, the increased ROS clearance and decreased cell apoptosis eventually lead to mTKI resistance in CRC.

Conclusions
Our results demonstrate that the Wnt/β-catenin/KCNQ1OT1/miR-7-5p/ACVRL1/GPX2 biological axis plays a vital role in CRC, targeting which may be an effective approach for overcoming mTKI resistance.