bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improved polygenic risk prediction in migraine-first patients
Authors: Torok Dora , Petschner Peter , Baksa Daniel , Juhasz Gabriella 
Published: September 2024

Abstract
Background
Recent meta-analyses estimated 14.6% and 11.2% SNP-based heritability of migraine, compared to twin-heritability estimates of 30–60%. This study aimed to investigate heritability estimates in “migraine-first” individuals, patients for whom G43 (migraine with or without aura) was their first medical diagnosis in their lifetime.

Findings
Using data from the UK Biobank (N = 199,929), genome-wide association studies (GWAS) were conducted on 6,139 migraine-first patients and 193,790 healthy controls. SNP-based heritability was estimated using SumHer, yielding 19.37% (± 0.019) for all SNPs and 21.31% (± 0.019) for HapMap3 variants, substantially surpassing previous estimates. Key risk loci included PRDM16, FHL5, ASTN2, STAT6/LRP1, and SLC24A3, and pathway analyses highlighted retinol metabolism and steroid hormone biosynthesis as important pathways in these patients.

Conclusions
The findings underscore that excluding comorbidities at onset time can enhance heritability estimates and genetic signal detection, significantly reducing the extent of “missing heritability” in migraine.
A novel protein SPECC1-415aa encoded by N6-methyladenosine modified circSPECC1 regulates the sensitivity of glioblastoma to TMZ
Authors: Wei Cheng , Peng Dazhao , Jing Boyuan , Wang Bo , Li Zesheng , Yu Runze , Zhang Shu , Cai Jinquan , Zhang Zhenyu , Zhang Jianning , Han Lei 
Published: September 2024

Abstract
Background
Circular RNAs (circRNAs) can influence a variety of biological functions and act as a significant role in the progression and recurrence of glioblastoma (GBM). However, few coding circRNAs have been discovered in cancer, and their role in GBM is still unknown. The aim of this study was to identify coding circRNAs and explore their potential roles in the progression and recurrence of GBM.

Methods
CircSPECC1 was screened via circRNAs microarray of primary and recurrent GBM samples. To ascertain the characteristics and coding ability of circSPECC1, we conducted a number of experiments. Afterward, through in vivo and in vitro experiments, we investigated the biological functions of circSPECC1 and its encoded novel protein (SPECC1-415aa) in GBM, as well as their effects on TMZ sensitivity.

Results
By analyzing primary and recurrent GBM samples via circRNAs microarray, circSPECC1 was found to be a downregulated circRNA with coding potential in recurrent GBM compared with primary GBM. CircSPECC1 suppressed the proliferation, migration, invasion, and colony formation abilities of GBM cells by encoding a new protein known as SPECC1-415aa. CircSPECC1 restored TMZ sensitivity in TMZ-resistant GBM cells by encoding the new protein SPECC1-415aa. The m6A reader protein IGF2BP1 can bind to circSPECC1 to promote its expression and stability. Mechanistically, SPECC1-415aa can bind to ANXA2 and competitively inhibit the binding of ANXA2 to EGFR, thus resulting in the inhibition of the phosphorylation of EGFR (Tyr845) and its downstream pathway protein AKT (Ser473). In vivo experiments showed that the overexpression of circSPECC1 could combine with TMZ to treat TMZ-resistant GBM, thereby restoring the sensitivity of TMZ-resistant GBM to TMZ.

Conclusions
CircSPECC1 was downregulated in recurrent GBM compared with primary GBM. The m6A reader protein IGF2BP1 could promote the expression and stability of circSPECC1. The sequence of SPECC1-415aa, which is encoded by circSPECC1, can inhibit the binding of ANXA2 to EGFR by competitively binding to ANXA2 and inhibiting the phosphorylation of EGFR and AKT, thereby restoring the sensitivity of TMZ-resistant GBM cells to TMZ.
GenRCA: a user-friendly rare codon analysis tool for comprehensive evaluation of codon usage preferences based on coding sequences in genomes
Authors: Fan Kunjie , Li Yuanyuan , Chen Zhiwei , Fan Long 
Published: September 2024

Abstract
Background
The study of codon usage bias is important for understanding gene expression, evolution and gene design, providing critical insights into the molecular processes that govern the function and regulation of genes. Codon Usage Bias (CUB) indices are valuable metrics for understanding codon usage patterns across different organisms without extensive experiments. Considering that there is no one-fits-all index for all species, a comprehensive platform supporting the calculation and analysis of multiple CUB indices for codon optimization is greatly needed.

Results
Here, we release GenRCA, an updated version of our previous Rare Codon Analysis Tool, as a free and user-friendly website for all-inclusive evaluation of codon usage preferences of coding sequences. In this study, we manually reviewed and implemented up to 31 codon preference indices, with 65 expression host organisms covered and batch processing of multiple gene sequences supported, aiming to improve the user experience and provide more comprehensive and efficient analysis.

Conclusions
Our website fills a gap in the availability of comprehensive tools for species-specific CUB calculations, enabling researchers to thoroughly assess the protein expression level based on a comprehensive list of 31 indices and further guide the codon optimization.
Investigating causal links between gallstones, cholecystectomy, and 33 site-specific cancers: a Mendelian randomization post-meta-analysis study
Authors: Teng Fei , Tang Youyin , Lu Zhangyu , Chen Kefei , Chen Zheyu 
Published: September 2024

Abstract
Background and aim
The association between gallstones/cholecystectomy and cancer remains inconclusive in the current literature. This study aimed to explore the causal connections between gallstones/cholecystectomy and cancer risk by utilizing a bidirectional two-sample multivariable Mendelian randomization approach with Genome-Wide Association Studies data.

Methods
Utilizing Genome-Wide Association Studies data from the UK Biobank and FinnGen, this research employed multivariable Mendelian randomization analyses to explore the impact of gallstones and cholecystectomy on the risk of 33 distinct cancer types. Instrumental variables for gallstones and cholecystectomy were carefully selected to ensure robust analyses, and sensitivity and heterogeneity tests were conducted to verify the findings’ validity.

Results
Multivariable Mendelian randomization analysis, incorporating data from more than 450,000 individuals for gallstones and cholecystectomy, revealed nuanced associations with cancer risk. Cholecystectomy was associated with a significantly increased risk of nonmelanoma skin cancer (OR = 1.59, 95% CI: 1.21 to 2.10, P = 0.001), while gallstones were linked to a decreased risk of the same cancer type (OR = 0.63, 95% CI: 0.47 to 0.84, P = 0.002). Interestingly, the analysis also suggested that cholecystectomy may lower the risk of small intestine tumors (OR = 0.18, 95% CI: 0.043 to 0.71, P = 0.015), with gallstones showing an inverse relationship, indicating an increased risk (OR = 6.41, 95% CI: 1.48 to 27.80, P = 0.013).

Conclusions
The multivariable Mendelian randomization analysis highlights the differential impact of gallstones and cholecystectomy on cancer risk, specifically for nonmelanoma skin cancer and small intestine tumors. These results underscore the importance of nuanced clinical management strategies and further research to understand the underlying mechanisms and potential clinical implications of gallstone disease and cholecystectomy on cancer risk.
Association between hydroxychloroquine intake and damage to the outer nuclear layer in eyes without manifest retinal toxicity
Authors: Salameh Nagib , Doumit Carla Abi , Jalkh Edmond , Nehme Joseph 
Published: September 2024

Abstract
Background
Hydroxychloroquine (HCQ) is widely used to treat various autoimmune diseases but carries a risk of retinal toxicity, particularly with prolonged use. Despite advancements, uncertainty persists regarding optimal screening methods. Recent advances in OCT have enabled early detection of retinal damage, with studies suggesting that thinning of specific retinal layers may be an early indicator of toxicity. However, there is a gap in research on outer nuclear layer (ONL) thinning in HCQ users without apparent retinal toxicity. This information is crucial for improving screening and identifying the ONL as a reliable biomarker for screening. Therefore, this study aimed to investigate the association between HCQ intake and ONL damage in eyes without manifest retinal toxicity.

Methods
A case‒control study was conducted at the ophthalmology department of Eye and Ear Hospital International from July 2022 to June 2023. The study included 20 individuals on HCQ and 20 age-matched controls. The data were obtained through chart reviews, and participants underwent comprehensive ophthalmic assessments.

Results
A total of 80 eyes were analyzed. Patients on HCQ exhibited significantly thinner perifoveal, parafoveal, and overall ONL compared to controls (P < .001, P < .012, and P < .004, respectively). Similarly, this association was found in the nasal, inferior, and temporal quadrants of both the inner (region 3: P < .01, region 4: P < .001, and region 5: P < .03) and outer zones (region 7: P < .04, region 8: P < .001, region 9: P < .02), most pronounced in the inferior regions. The cumulative dose was weakly associated with decreased ONL thickness only in the nasal quadrant of the inner zone (region 3: P < .047). Correlation analysis of the initial and most recent OCT scans in the same individuals revealed a weak association with ONL thinning in the central zone (region 1: P < .0048).

Conclusion
The thickness of the ONL can significantly decrease in patients taking HCQ, even in the absence of of manifest retinal toxicity. This study is the first to evaluate this association in eyes with negative screening and diagnostic tests for HCQ retinopathy. The findings suggest that ONL thickness could serve as an early diagnostic indicator for HCQ retinal toxicity.
Psychometric properties of the German version of the brief resilience scale in persons with mental disorders
Authors: Broll Jan , Schäfer Sarah K. , Chmitorz Andrea , Meule Adrian , Voderholzer Ulrich , Helmreich Isabella , Lieb Klaus 
Published: September 2024

AbstractThe Brief Resilience Scale (BRS) was developed to assess individual differences in the ability to recover from stress despite adversity and has been translated into several languages. This study aimed to examine the psychometric properties (i.e., item characteristics, reliability, factor structure, measurement invariance, and validity) of the German version of the BRS in persons with mental disorders. A total of N = 5,986 persons admitted to inpatient treatment completed the German version of the BRS and other questionnaires. The discriminating power of the items, the difficulty of the items, and the internal consistency were all sufficient. Moreover, confirmatory factor analysis supported the two–factor structure of the BRS, consistent with the findings of the German validation study in a non–clinical sample. The BRS also had strict measurement invariance across diagnostic groups for mental disorders according to ICD–10. Validity was examined using a network analysis, in which the BRS demonstrated positive correlations with life satisfaction, self–efficacy and optimism and negative correlations with somatic symptoms, anxiety, insomnia, and depression. The BRS can serve as a reliable and valid tool for assessing resilience in clinical settings, facilitating the identification of persons with potentially lower psychosocial resources.
Dissemination of colorectal cancer information among Hispanic patients and their social network
Authors: Ko Linda K. , Jang Sou Hyun , Rodriguez Edgar , Buta Miruna , Ibarra Genoveva , Reuland Daniel 
Published: September 2024

Abstract
Background
Colorectal cancer (CRC) screening decision aids can inform patients about CRC screening benefits, costs, and procedures. Patients who receive the decision aid report wanting to share the information with their families and friends. We evaluated a CRC screening decision aid on Hispanic patients’ communication to their alters and whether patient-alter communication leads to alters’ CRC screening intention.

Methods
We conducted a one-arm pre/post study of Hispanic patients and their alters; patients (n = 42) and their alters (n = 19) were recruited from a clinic site in Yakima County, Washington State. Patients viewed a CRC screening decision aid at the clinic site. Survey data from patients and alters were collected via telephone including patients’ communication with their alters about CRC screening after viewing the decision aid and alters’ intention to be screened for CRC after talking to the patient.

Results
Most participants reported sharing CRC information with their alters after viewing the decision aid, and most alters confirmed they had received CRC information from participants (68%). The decision aid was associated with participants' own intention to undergo CRC screening and with alters' intention to be screened for CRC using a fecal occult blood test (p = 0.014) and sigmoidoscopy (p = 0.011).

Conclusions
Patient decision aids have the potential to increase CRC screening behavior beyond the decision aid recipients to their social network.

Trial registration
Trials Registration Number: NCT04444232 “Retrospectively registered.”
MINISTOP 3.0: Implementation of a mHealth obesity prevention program within Swedish child healthcare – study protocol for a cluster randomized controlled trial
Authors: Thomas Kristin , Löf Marie , Lundgren Maria , Fagerström Maria , Hesketh Kylie D. , Brown Vicki , Häbel Henrike , Delisle Nyström Christine 
Published: September 2024

Abstract
Background
Previously, we have reported on the efficacy and real-world effectiveness of a parent-oriented mobile health intervention (MINISTOP 1.0 and 2.0), which have shown improvements in pre-school children’s lifestyle behaviours. However, there is a need for implementation evidence. The overall aims of this study are to: (i) compare two different implementation strategies for MINISTOP 3.0 (Basic vs. Enhanced) on: acceptability, appropriateness, feasibility, organizational readiness to implement MINISTOP 3.0 within Swedish child healthcare (primary outcomes) as well as reach, costs, and adoption of MINISTOP 3.0 (secondary outcomes); (ii) evaluate cost-effectiveness of MINISTOP 3.0; (iii) explore the sustainability of MINISTOP 3.0; (iv) evaluate the determinants of effectiveness of MINISTOP 3.0 on children’s key lifestyle behaviours; and (v) investigate the long-term effects of MINISTOP 3.0 on children’s body mass index.

Methods
A hybrid type III implementation-effectiveness design will be used. A cluster randomized controlled trial will be conducted to compare the effects of basic versus enhanced implementation strategies on the outcomes at the child healthcare level. A minimum of 50 child healthcare centers across Sweden will participate and we aim to recruit 120 nurses. Child healthcare nurses in both groups will offer the MINISTOP 3.0 app to the families at the 2.5/3-year routine visit. Basic implementation strategies include educational meeting with nurses, formal implementation blueprint, develop/distribute educational materials and enhanced implementation includes all aforementioned strategies plus auditing/providing feedback and ongoing training for nurses. All outcomes will be assessed at baseline and 12 months post-implementation. Implementation outcomes will be assessed quantitatively using questionnaires and sustainability will be assessed qualitatively at 12 months. Children’s key lifestyle behaviours will be collected through a parental questionnaire within the MINISTOP app at baseline and 6 months after they have received the app. Children’s weight/height will be measured at routine visits at 2.5/3 (baseline), 4 and 5 years of age.

Discussion
This study will provide important implementation evidence with regards to implementing mHealth interventions within Swedish child healthcare at scale and these results have the potential to be generalized to other digital interventions being implemented in child healthcare.

Trial registration
ClinicalTrials.gov, NCT05667753. Registered December 29, 2022.
Exceeding the guideline-recommended maximum daily dose of opioids for long-term treatment of non-cancer pain in Germany – a large retrospective observational study
Authors: Schrader Nils Frederik , Niemann Anja , Weitzel Milena , Speckemeier Christian , Abels Carina , Blase Nikola , Giebel Godwin Denk , Riederer Cordula , Nadstawek Joachim , Straßmeir Wolfgang , Wasem Jürgen , Neusser Silke 
Published: September 2024

Abstract
Background
High-dose long-term opioid therapy (LTOT) has been associated with increased mortality and hospitalizations. Therefore, the evidence-based German guideline on LTOT for chronic non-cancer pain (CNCP) recommends to only exceed the maximum daily dose (MDD) of opioids in exceptional cases. This study aimed to determine the portion of LTOT patients who exceeded the guideline-recommended MDD and identify predictors of exceeding in administrative claims data.

Methods
The retrospective observational analysis of opioid prescriptions in patients receiving LTOT for CNCP was based on administrative claims by a large German statutory health insurance company. Patients with at least two quarters of opioid prescriptions between January 2018 and June 2019 were included and followed up for two years. Predictors were identified by logistic regression. In addition, the number of patients still in opioid therapy and the extent of exceeded MDDs were analyzed over time.

Results
The sample consisted of 113,475 patients. Overall, 10.5% of the patients exceeded the guideline-recommended MDD averaged over the observation period. Strong predictors for exceeding the MDD were receiving opioid prescriptions from > 7 physicians (OR = 7.66, p < .001), receiving predominantly strong opioids (OR = 6.79, p < .001) and receiving opioids for at least one year prior to inclusion (OR = 5.35, p < .001). Within the non-exceeding group, 28.1% discontinued opioid therapy. In contrast, 9.9% of patients in the exceeding group discontinued opioid therapy, whereas the vast majority remained on treatment until the end of the observation period. Furthermore, a slight increase in prescribed doses was observed over time.

Conclusions
The results indicate that a moderate proportion of patients exceeded the guideline-recommended MDD. However, certain patient groups were more likely to receive high doses. This applied in particular to those who were already on treatment at the time of inclusion and continued to receive opioids until the end of the observation period. Further research should examine whether the continuous opioid therapy among the patients with exceeding the guideline-recommended MDD might be related to specific indications, a lack of therapeutic options or avoidance of withdrawal.

Trial registration
German Clinical Trials Register (drks.de/search/en). Identifier: DRKS00024854. Registered 28 April 2021.
Integrating early child development into an existing health and nutrition program: evidence from a cluster-randomized controlled trial
Authors: Hemlock Caitlin , Galasso Emanuela , Weber Ann M. , Randriamiarisoa Tsirery Christian , Col Mathilde , Dieci Maria , Ratsifandrihamanana Lisy , Fernald Lia C.H. 
Published: September 2024

Abstract
Introduction
In low-resource settings, introducing child health programs into community services may compete for caregiver time. We analyzed the impact of a new early childhood development (ECD) program in rural Madagascar on family attendance at other health services and of adding at-home play materials on program attendance.

Methods
We randomized 75 communities where community health workers (CHWs) implement an existing child health and nutrition program (Projet d’Amélioration des Résultats Nutritionnels or PARN), the status quo. We offered two 6-month cycles of 12 ECD sessions to eligible caregiver-child dyads (6–30 months) in 25 sites [T]; we added take-home play materials in Cycle 2 to 25 sites [T+]. We used differences-in-differences with administrative data to analyze the effect of offering ECD sessions on monthly PARN attendance (T+/T vs. C) among age-eligible children and the impact of toy boxes/libraries on monthly ECD session attendance (T + vs. T). We used random intercept models to analyze characteristics associated with program registration.

Results
We analyzed data for 9,408 dyads; 30% and 32% registered for the program in Cycle 1 and 2 (respectively). On average, CHWs delivered 11.4 sessions (SD: 1.5). Children from wealthier households who already attended PARN sessions were more likely to register, and we found no effect of T or T + on PARN attendance. Adding play materials did not affect monthly ECD session attendance. Children from more populated sites were less likely to participate in both ECD and PARN sessions.

Conclusions
Integrating new services for ECD into the health system was feasible and did not reduce dyad participation in existing services. Investment in health services in more populated areas is needed to provide coverage to all eligible children. Novel strategies should be explored to engage the most vulnerable children in new and existing health services.

Trial registration
AEA Social Science Registry (AEARCTR-0004704) on November 15, 2019 (prospective registration) and ClinicalTrials.gov (NCT05129696) on November 22, 2021 (retrospective registration).
Kinetics of cellulase-free endo xylanase hyper-synthesis by Aspergillus Niger using wheat bran as a potential solid substrate
Authors: Ali Sikander , Noor Pakeeza , Ahmad Muhammad Usman , Khan Qaiser Farid , William Kaynat , Liaqat Iram , Shah Tawaf Ali , Alsahli Abdulaziz Abdullah , Younous Youssouf Ali , Bourhia Mohammed 
Published: September 2024

AbstractThe present study deals with the production of cellulase-free endoxylanase by Aspergillus niger ISL-9 using wheat bran as a solid substrate. Endoxylanase was produced under a solid-state fermentation. Various growth parameters were optimized for the improved production of the enzyme. The Substrate level of 15 g was optimized as it provided the fungus with balanced aeration and nutrition. Among the six moisture contents investigated, Moisture Content 5 (MC5) was optimized (g/l: malt extract, 10; (NH4)2HPO4, 2.5; urea, 1.0) and 10 mL of MC5 was found to give the highest production of endoxylanase. The pH and time of incubation were optimized to 6.2 and 48 h respectively. The Inoculum size of 2 mL (1.4 × 106 spores/mL) gave the maximum enzyme production. After optimization of these growth parameters, a significantly high endoxylanase activity of 21.87 U/g was achieved. Very negligible Carboxymethylcellulase (CMCase) activity was observed indicating the production of cellulase-free endoxylanase. The notable finding is that the endoxylanase activity was increased by 1.4-fold under optimized conditions (p ≤ 0.05). The overall comparison of kinetic parameters for enhanced production of endoxylanase by A. niger ISL-9 under Solid State Fermentation (SSF) was also studied. Different kinetic variables which included specific growth rate, product yield coefficients, volumetric rates and specific rates were observed at 48, 72 and 96 h incubation time and were compared for MC1 and MC5. Among the kinetic parameters, the most significant result was obtained with volumetric rate constant for product formation (Qp) that was found to be optimum (1.89 U/h) at 72 h incubation period and a high value of Qp i.e.1.68 U/h was also observed at 48 h incubation period. Thus, the study demonstrates a cost-effective and environmentally sustainable process for xylanase production and exhibits scope towards successful industrial applications.