bluuebunny/crossref_metadata_2025_split huggingface dataset:
LncRNA-Gm9866 promotes liver fibrosis by activating TGFβ/Smad signaling via targeting Fam98b
Authors: Liao Xiaomin , Ruan Xianxian , Yao Peishan , Yang Dan , Wu Xianbin , Zhou Xia , Jing Jie , Wei Dafu , Liang Yaodan , Zhang Taicheng , Qin Shanyu , Jiang Haixing 
Published: November 2023

Abstract
Objective
The exact mechanism and target molecules of liver fibrosis have remained largely elusive. Here, we investigated the role of long noncoding RNA Gm9866(lncRNA-Gm9866) on liver fibrosis.

Methods
The transcription of lncRNA-Gm9866 in activated cells and mouse fibrotic livers was determined by quantitative polymerase chain reaction (qRT-PCR). The effects of lentivirus-mediated knockdown or overexpression of lncRNA-Gm9866 in liver fibrosis were examined in vitro and in vivo. Furthermore, bioinformatics analysis, cell samples validation, fluorescence in situ hybridization (FISH) co-localization, RNA binding protein immunoprecipitation (RIP), actinomycin D test and Western blot (WB) were carried out to explore the potential mechanism of lncRNA-Gm9866.

Results
The expression of α-smooth muscle actin (α-SMA), Collagen I (COL-1) and lncRNA-Gm9866 were significantly increased in tissues and cells. Overexpressing lncRNA-Gm9866 promoted the activation of hepatic stellate cells (HSCs). Silencing lncRNA-Gm9866 inhibited the activation of HSCs and transforming growth factor-β1 (TGFβ1) induced fibrosis. Overexpressing lncRNA-Gm9866 promoted hepatocytes (HCs) apoptosis and the expression of pro-fibrogenic genes, inhibited the proliferation and migration of HCs. Knockdown of lncRNA-Gm9866 inhibited the apoptosis of HCs, the expression of pro-fibrogenic genes, TGFβ1 induced fibrosis and the occurrence of carbon tetrachloride (CCl4)-induced liver fibrosis, and promoted the proliferation and migration of HCs. Mechanistically, lncRNA-Gm9866 may directly bine with Fam98b. Silencing Fam98b in stably overexpressing lncRNA-Gm9866 cell lines reversed the increase of pro-fibrogenic genes and pro-apoptotic genes, fibrosis related pathway protein TGFβ1, Smad2/3, p-Smad2/3 and Notch3 induced by overexpressing lncRNA-Gm9866.

Conclusions
LncRNA-Gm9866 may regulate TGFβ/Smad and Notch pathways by targeting Fam98b to regulate liver fibrosis. LncRNA-Gm9866 may be a new target for diagnosis and treatment of liver fibrosis.
Reliability of the tunisian pediatric gait, arms, legs, and spine: toward a valid screening tool for tunisian children with musculoskeletal conditions
Authors: Hanene Lassoued Ferjani , Amdouni Narjess , Emna Rabhi , Hela Sahli , Kaouther Ben Abdelgheni , Dorra Ben Nessib , Dhia Kaffel , Kaouther Maatallah , Wafa Hamdi 
Published: November 2023

Abstract
Background
Pediatric musculoskeletal disorders account for 10% of first-line consultations in Tunisia. Referral delay and deficiencies in musculoskeletal screening raise a challenge to the early diagnosis and management of rheumatic conditions in children. The pGALS (Pediatric Gait Arms Legs Spine) was developed and translated into many languages to overcome these deficiencies. Our study aimed to adapt and validate pGALS to the Tunisian dialect for school-age children.

Methods
Using the Delphi method, we carried out a cross-cultural adaptation of the pGALS to the Tunisian dialect. This consensual version was validated in a cross-sectional study, in two pediatric centers.

Results
Ninety-two patients were enrolled, 43 females (46.7%) and 49 males (53.3%), mean age was 9.4 ± 2.6 years. The mean test duration was 3.4 ± 2.3 min, and the acceptability and comprehension of the test were good. Six patients had a musculoskeletal complaint, 19 had positive pGALS, and 14 were diagnosed with musculoskeletal disease. The internal consistency score (Cronbach’s α) was 0.852. The sensitivity of the test was 92.8%, the specificity was 92.3%, the positive likelihood ratio was 2.16, and the negative likelihood ratio was 0.01.

Conclusion
The pGALS test adapted to the Tunisian dialect is a relevant, quick, and valid tool for screening musculoskeletal abnormalities in school-age children.
A post hoc analysis of Projected Retained Ability Scores (PRAS) for the longitudinal assessment of cognitive functioning in patients with neuronopathic mucopolysaccharidosis II receiving intrathecal idursulfase-IT
Authors: Yee Karen S. , Chirila Costel , Davenport Eric , Mladsi Deirdre , Barnett Christine , Kronenberger William G. 
Published: November 2023

Abstract
Background
Norm-based scores used to assess cognitive ability have clinical value when describing functioning of patients with neuronopathic disorders compared with unaffected, same-age peers. However, they have limitations when used to assess change in cognitive ability between two timepoints, especially in children with severe cognitive decline. Calculation of Projected Retained Ability Scores (PRAS) is a novel method developed to characterize absolute change in norm-based ability test scores. In this analysis, PRAS were calculated post hoc for children with mucopolysaccharidosis II (MPS II; Hunter syndrome) and early cognitive impairment in a 52-week phase 2/3 randomized controlled trial (RCT) and its extension study of intrathecal idursulfase (idursulfase-IT). Patients completing the first year of the extension after receiving idursulfase-IT in the RCT and extension (n = 32 of 34 enrolled) or the extension only (n = 15 of 15 enrolled) were categorized according to changes in Differential Ability Scales, Second Edition, General Conceptual Ability (DAS-II GCA) scores and PRAS at 1 and 2 years. Analyses were conducted in the overall population and a subpopulation aged < 6 years at baseline (idursulfase-IT in the RCT and extension [n = 27] and extension only [n = 12]).

Results
PRAS methodology differentiated patients with decreases in DAS-II GCA scores into three separate categories reflecting below-average cognitive growth rates, plateauing cognitive development, and deteriorating cognitive functioning. After 1 year in the RCT, 72.4% of patients who initiated idursulfase-IT had above-average or average cognitive growth rates in DAS-II GCA scores compared with 53.3% of those who did not receive idursulfase-IT; 6.9% versus 20.0% experienced deteriorating cognitive functioning. Similar results were seen in children aged < 6 years: 76% (idursulfase-IT group) versus 50% (no idursulfase-IT) had above-average or average cognitive growth rates in DAS-II GCA scores; 4% versus 17% had deteriorating cognitive functioning. The difference in the distributions of cognitive categories at 1 year in children aged < 6 years was significant (p = 0.048). At 2 years, the proportions of patients in different cognitive categories were more similar between treatment groups.

Conclusions
PRAS methodology may help to differentiate changes in cognitive development in MPS II, and therefore may represent a valuable addition to existing approaches for interpreting changes in cognitive scores over time.
Trial Registration: ClinicalTrials.gov NCT02055118 (registration date: 4 February 2014) and NCT02412787 (registration date: 9 April 2015).
FAM171B stabilizes vimentin and enhances CCL2-mediated TAM infiltration to promote bladder cancer progression
Authors: Hu Wei-Min , Li Ming , Ning Jin-Zhuo , Tang Yu-Qi , Song Tian-Bao , Li Lin-Zhi , Zou Fan , Cheng Fan , Yu Wei-Min 
Published: November 2023

Abstract
Background
Invasion and metastasis are the main causes of unfavourable prognosis in patients diagnosed with bladder cancer. The efficacy of immunotherapy in bladder cancer remains suboptimal due to the presence of an immunosuppressive microenvironment. The novel protein family with sequence similarity 171B (FAM171B) has been identified, but its precise role and mechanism in bladder cancer remain unclear.

Methods
In this study, we conducted an analysis to investigate the associations between FAM171B expression and the prognosis and clinicopathological stage of bladder cancer. To this end, we utilized RNA sequencing data from the TCGA and GEO databases, as well as tumor tissue specimens obtained from our clinical centre. RNA sequencing analysis allowed us to examine the biological function of FAM171B at the transcriptional level in bladder cancer cells. Additionally, we used immunoprecipitation and mass spectrometry to identify the protein that interacts with FAM171B in bladder cancer cells. The effects of FAM171B on modulating tumor-associated macrophages (TAMs) and vimentin-mediated tumor progression, as well as the underlying mechanisms, were clarified by phalloidin staining, immunofluorescence staining, ELISA, RNA immunoprecipitation, flow cytometry and a bladder cancer graft model.

Results
FAM171B expression exhibits strong positive correlation with poor survival outcomes and advanced clinicopathological stages in patients with bladder cancer. FAM171B significantly promoted bladder cancer growth and metastasis, accompanied by TAM accumulation in the microenvironment, in vivo and in vitro. Through studies of the molecular mechanism, we found that FAM171B contributes to tumor progression by stabilizing vimentin in the cytoplasm. Additionally, our research revealed that FAM171B enhances the splicing of CCL2 mRNA by interacting with heterogeneous nuclear ribonucleoprotein U (HNRNPU), ultimately leading to increased recruitment and M2 polarization of TAMs.

Conclusions
In this study, we identified FAM171B as a potent factor that promotes the progression of bladder cancer. These findings establish a solid theoretical foundation for considering FAM171B as a potential diagnostic and therapeutic biomarker for bladder cancer.
Examining the impact of a universal social and emotional learning intervention (Passport) on internalising symptoms and other outcomes among children, compared to the usual school curriculum: study protocol for a school-based cluster randomised trial
Authors: O’Brien Annie , Hamilton Suzanne , Humphrey Neil , Qualter Pamela , Boehnke Jan R. , Santos Joao , Demkowicz Ola , Panayiotou Margarita , Thompson Alex , Lau Jennifer , Burke Lauren , Lu Yizhuo 
Published: November 2023

Abstract
Background
School-based universal social and emotional learning (SEL) interventions implemented during the transition to adolescence may be efficacious in preventing the development of mental health difficulties. This protocol describes a two-arm parallel cluster randomised controlled trial to investigate the impact of a universal SEL intervention (Passport, compared to usual provision) on internalising symptoms (primary outcome), emotion regulation, well-being, loneliness, social support, bullying, academic attainment, and health-related quality of life in English primary school pupils aged 9–11 years. A developer-led trial demonstrated the feasibility, acceptability, and utility of Passport; this will be the first independent trial.

Methods
Sixty primary schools will be recruited across the Greater Manchester city region and surrounding areas, involving 2400 pupils aged 8–9 at baseline. Schools will be allocated to the intervention arm to implement Passport over 18 weekly sessions or to the control arm to implement the usual school curriculum. Random allocation will be at school level following completion of baseline measures, with minimisation to ensure balance across trial arms in school size and free school meal eligibility. Measures will be collected at baseline, post-intervention (12 months post-baseline), and at 12 months follow-up (24 months post-baseline). The primary outcome analysis (intervention effects on internalising symptoms at post-intervention) will comprise a two-level (school, child) hierarchical linear model, following the intention-to-treat principle. Additional analyses will be undertaken to assess intervention effects on secondary outcomes, maintenance effects for all outcomes, intervention compliance moderator effects, subgroup moderator effects, and mechanisms underpinning intervention effects on the primary outcome. A mixed-methods implementation and process evaluation will examine factors that influence implementation, and a health economic evaluation will assess the cost-effectiveness of the intervention.

Discussion
Findings will provide educators with crucial knowledge of whether and how increasing emotion regulation through a universal intervention impacts internalising symptoms and a range of related outcomes. Findings will also inform policy related to the promotion of mental health among children and young people. If the intervention is found to be efficacious in reducing internalising symptoms and is also cost-effective, it may offer high potential as a preventative intervention for widespread implementation.

Trial registration
ISRCTN12875599; registered on 24 November 2022
Molecular detection of Babesia spp. in dogs in Germany (2007–2020) and identification of potential risk factors for infection
Authors: Schäfer Ingo , Helm Christina Sabine , von Samson-Himmelstjerna Georg , Krücken Jürgen , Kottmann Tanja , Holtdirk Annette , Kohn Barbara , Hendrickx Guy , Marsboom Cedric , Müller Elisabeth 
Published: November 2023

Abstract
Background
In Europe, canine babesiosis is most frequently caused by Babesia canis and Babesia vogeli, and occasionally by Babesia gibsoni.. In Germany, B. canis is recognized as endemic. The aims of this study were to assess how often Babesia spp. infections were diagnosed in a commercial laboratory in samples from dogs from Germany, and to evaluate potential risk factors for infection.

Methods
The database of the LABOKLIN laboratory was screened for Babesia spp.-positive polymerase chain reaction (PCR) tests for dogs for the period January 2007–December 2020. Sequencing was performed for positive tests from 2018 and 2019. Binary logistic regression analysis was performed to determine the effects of sex, season, and year of testing. Questionnaires were sent to the submitting veterinarians to obtain information on travel abroad, tick infestation, and ectoparasite prophylaxis of the respective dogs. Fisher’s exact test was used to calculate statistical significance and P < 0.05 was considered statistically significant.

Results
In total, 659 out of 20,914 dogs (3.2%) tested positive for Babesia spp. by PCR. Of 172 sequenced samples, B. canis was identified in 156, B. vogeli in nine, B. gibsoni in five, and B. vulpes in two. Season had a statistically significant impact on test results when summer/winter (1.6% tested positive) was compared to spring/autumn (4.7%), with peaks in April (5.2%) and October (7.4%) [P < 0.001, odds ratio (OR) = 3.16]. Sex (male 3.5%, female 2.8%; P = 0.012, OR = 1.49) and age (< 7 years old 4.0%, ≥ 7 years old 2.3%; P < 0.001, OR = 1.76) of the tested dogs also had a statistically significant effect. A statistically significant impact was demonstrated for observed tick attachment (P < 0.001, OR = 7.62) and lack of ectoparasite prophylaxis (P = 0.001, OR = 3.03). The frequency of positive Babesia spp. tests did not significantly differ between the 659 dogs that had never left Germany and the 1506 dogs with known stays abroad (P = 0.088).

Conclusions
The possibility of canine infection with B. canis needs to be especially taken into consideration in spring and autumn in Germany as the activity of the tick Dermacentor reticulatus, a potential vector for canine babesiosis, is highest in these seasons. Travel and importation of dogs are considered major factors associated with canine babesiosis in Germany. However, autochthonous Babesia spp. infections also occur in a considerable number of dogs in Germany.

Graphical Abstract
Multi-scale characterisation of homologous recombination deficiency in breast cancer
Authors: Jacobson Daniel H. , Pan Shi , Fisher Jasmin , Secrier Maria 
Published: November 2023

Abstract
Background
Homologous recombination is a robust, broadly error-free mechanism of double-strand break repair, and deficiencies lead to PARP inhibitor sensitivity. Patients displaying homologous recombination deficiency can be identified using ‘mutational signatures’. However, these patterns are difficult to reliably infer from exome sequencing. Additionally, as mutational signatures are a historical record of mutagenic processes, this limits their utility in describing the current status of a tumour.

Methods
We apply two methods for characterising homologous recombination deficiency in breast cancer to explore the features and heterogeneity associated with this phenotype. We develop a likelihood-based method which leverages small insertions and deletions for high-confidence classification of homologous recombination deficiency for exome-sequenced breast cancers. We then use multinomial elastic net regression modelling to develop a transcriptional signature of heterogeneous homologous recombination deficiency. This signature is then applied to single-cell RNA-sequenced breast cancer cohorts enabling analysis of homologous recombination deficiency heterogeneity and differential patterns of tumour microenvironment interactivity.

Results
We demonstrate that the inclusion of indel events, even at low levels, improves homologous recombination deficiency classification. Whilst BRCA-positive homologous recombination deficient samples display strong similarities to those harbouring BRCA1/2 defects, they appear to deviate in microenvironmental features such as hypoxic signalling. We then present a 228-gene transcriptional signature which simultaneously characterises homologous recombination deficiency and BRCA1/2-defect status, and is associated with PARP inhibitor response. Finally, we show that this signature is applicable to single-cell transcriptomics data and predict that these cells present a distinct milieu of interactions with their microenvironment compared to their homologous recombination proficient counterparts, typified by a decreased cancer cell response to TNFα signalling.

Conclusions
We apply multi-scale approaches to characterise homologous recombination deficiency in breast cancer through the development of mutational and transcriptional signatures. We demonstrate how indels can improve homologous recombination deficiency classification in exome-sequenced breast cancers. Additionally, we demonstrate the heterogeneity of homologous recombination deficiency, especially in relation to BRCA1/2-defect status, and show that indications of this feature can be captured at a single-cell level, enabling further investigations into interactions between DNA repair deficient cells and their tumour microenvironment.
Outer approximated projection and contraction method for solving variational inequalities
Authors: Uzor V. A. , Mewomo O. T. , Alakoya T. O. , Gibali A. 
Published: November 2023

AbstractIn this paper we focus on solving the classical variational inequality (VI) problem. Most common methods for solving VIs use some kind of projection onto the associated feasible set. Thus, when the involved set is not simple to project onto, then the applicability and computational effort of the proposed method could be arguable. One such scenario is when the given set is represented as a finite intersection of sublevel sets of convex functions. In this work we develop an outer approximation method that replaces the projection onto the VI’s feasible set by a simple, closed formula projection onto some “superset”. The proposed method also combines several known ideas such as the inertial technique and self-adaptive step size.Under standard assumptions, a strong minimum-norm convergence is proved and several numerical experiments validate and exhibit the performance of our scheme.
Strategies to support substance use disorder care transitions from acute-care to community-based settings: a scoping review and typology
Authors: Krawczyk Noa , Rivera Bianca D. , Chang Ji E. , Grivel Margaux , Chen Yu-Heng , Nagappala Suhas , Englander Honora , McNeely Jennifer 
Published: November 2023

Abstract
Background
Acute-care interventions that identify patients with substance use disorders (SUDs), initiate treatment, and link patients to community-based services, have proliferated in recent years. Yet, much is unknown about the specific strategies being used to support continuity of care from emergency department (ED) or inpatient hospital settings to community-based SUD treatment. In this scoping review, we synthesize the existing literature on patient transition interventions, and form an initial typology of reported strategies.

Methods
We searched Pubmed, Embase, CINAHL and PsychINFO for peer-reviewed articles published between 2000 and 2021 that studied interventions linking patients with SUD from ED or inpatient hospital settings to community-based SUD services. Eligible articles measured at least one post-discharge treatment outcome and included a description of the strategy used to promote linkage to community care. Detailed information was extracted on the components of the transition strategies and a thematic coding process was used to categorize strategies into a typology based on shared characteristics. Facilitators and barriers to transitions of care were synthesized using the Consolidated Framework for Implementation Research.

Results
Forty-five articles met inclusion criteria. 62% included ED interventions and 44% inpatient interventions. The majority focused on patients with opioid (71%) or alcohol (31%) use disorder. The transition strategies reported across studies were heterogeneous and often not well described. An initial typology of ten transition strategies, including five pre- and five post-discharge transition strategies is proposed. The most common strategy was scheduling an appointment with a community-based treatment provider prior to discharge. A range of facilitators and barriers were described, which can inform efforts to improve hospital-to-community transitions of care.

Conclusions
Strategies to support transitions from acute-care to community-based SUD services, although critical for ensuring continuity of care, vary greatly across interventions and are inconsistently measured and described. More research is needed to classify SUD care transition strategies, understand their components, and explore which lead to the best patient outcomes.
Signatures of adaptation in myopia-related genes on the sunlight exposure hypothesis
Authors: Xia Tian , Nakayama Kazuhiro 
Published: November 2023

Abstract
Background
Myopia is a common eye disorder that results from gene-environment interactions. The prevalence of myopia varies across populations, and exposure to bright sunlight may prevent its development. We hypothesize that local adaptation to light environments during human migration played a role in shaping the genetic basis of myopia, and we aim to investigate how the environment influences the genetic basis of myopia.

Method
We utilized the whole-genome variant data of the 1000 Genomes Project for analysis. We searched myopia-associated loci that were under selection in Europeans using population branch statistics and the number of segregating sites by length statistics. The outliers of these statistics were enriched in the Kyoto Encyclopedia of Genes and Genomes pathways and the gene ontology biological process terms in searching for pathways that were under selection. We applied Bayesian inference to estimate the correlation between environmental factors and allele frequencies of the selected loci and performed causal inference of myopia using two-sample Mendelian randomization analysis.

Results
We detected signatures of adaptation in vision and light perception pathways, supporting our hypothesis of sunlight adaptation. We discovered a strong correlation between latitude and allele frequencies in genes that are under significant selection, and we found pleiotropic effects of pigmentation or circadian rhythm genes on myopia, indicating that sunlight exposure influences the genetic diversity of myopia.

Conclusions
Myopia genes involved in light perception showed signs of selection. Local adaptation during human migration shaped the genetic basis of myopia and may have influenced its global prevalence distribution.