bluuebunny/crossref_metadata_2025_split huggingface dataset:
Outcomes of Palatal Fistula Closure with Tongue Flap Using a Parachute Technique
Authors: Khalili Neda , Hassanpour Seyed Esmail , Rouientan Abdolreza 
Published: November 2024

Objective To evaluate the efficacy of tongue flaps in closing large palatal fistulas secondary to cleft palate repair in terms of functionality, esthetics, and donor site morbidity. Design Tertiary academic center. Setting We report our 8-year surgical experience with tongue flaps, with our parachute suture technique in flap inset, and not using tongue fixation methods or feeding tubes. Participants Nineteen patients having recurrent secondary palatal fistula, post-cleft treatment were treated with anteriorly based dorsal tongue flaps. Main outcome measure Patients were evaluated for outcome in terms of flap uptake and effectiveness, correction of oronasal regurgitation, speech and nasality improvement, donor site morbidity, and esthetics. Results A total of 19 patients in the age range of 1.5 to 34 years were treated with anteriorly based tongue flap. Detachment of the tongue flap was observed in 1 patient. Furthermore, tongue flap necrosis was not observed in any of the patients. Nasal regurgitation was resolved completely in 15 cases (78.9%), and 2 out of 4 failed cases were due to fistula presence in a position out of flap territory. In addition, fistula persists in the case of flap detachment and another case at the location of pedicle division. Speech intelligibility and hypernasality changes were reported as noticeable improvement in 9 (47.4%) and no obvious change in 10 patients (52.6%). Conclusion Using parachute suturing technique can facilitate successful lingual tissue inset in palatal defects with negligible remnant fistula. Moreover, avoiding tongue fixation methods and nasogastric tube-assisted feeding wasn’t associated with increased flap dehiscence or suture loosening.
Two Years Post-COVID-19: An Ecologic Study Evaluating the Impact on Brazil’s Mammographic Screening Program
Authors: Antonini Marcelo , Mattar André , Pinheiro Denise Joffily Pereira da Costa , Teixeira Marina Diógenes , Amorim Andressa Gonçalves , Ferraro Odair , Cavalcante Francisco Pimentel , Zerwes Felipe , Madeira Marcelo , Millen Eduardo de Camargo , Frasson Antônio Luiz , Lopes Reginaldo Guedes Coelho , Brenelli Fabrício Palermo , Leite Renata Montarroyos , Gebrim Luiz Henrique , Freitas-Junior Ruffo 
Published: November 2024

Objectives The objective of this study was to assess the impact of the COVID-19 pandemic, after 2 years, on mammographic screening in Brazil evaluating BIRADS® results, breast cancer diagnosis rates, and breast cancer stage. Study Design This was an ecological observational study based on retrospective data from Brazil’s mammographic screening program from 2015 to 2023. Methods Data were obtained from the national screening database DATASUS – SISCAN (Cancer System Information) and retrieved in March 2024. Inclusion criteria comprised completeness of mammogram data (incomplete records were excluded), female participants aged 50 to 69 years, and mammograms exclusively performed for screening purposes. The study analyzed the number of mammograms conducted during the specified period, focusing on BIRADS® test results. Results Out of 23,851,371 mammograms performed between 2015 and 2023, 15,000,628 were included for analysis. A significant reduction of 39.6% in mammograms was observed in 2020 compared to 2019, followed by a 12.6% decrease in 2021. Notably, a substantial rise in BIRADS categories 4 and 5 examinations was seen post-pandemic. Breast cancer staging analysis revealed a shift towards more advanced stages (III and IV) diagnosed post-pandemic, suggesting potential delays in detection and diagnosis. Conclusions In conclusion, the study highlighted significant discrepancies in mammographic screenings and breast cancer diagnosis rates over 9 years. The pandemic reflected significant influence on the timing and stage at diagnosis, suggesting potential delays in detection and diagnosis that resulted in later identification of more advanced disease stages.
Efficacy and safety of daratumumab for the treatment of refractory/relapsed multiple myeloma. A systematic review of meta-analyses
Authors: Moustafa Diala Alhaj , Shafei Laila , Sulaiman Ruba , Yassin Mohamed A , Abushanab Dina , Algarabli Yousef , Al-Badriyeh Daoud 
Published: November 2024

Introduction Several meta-analyses (MAs) of the efficacy and safety of daratumumab in refractory/relapsed multiple myeloma (RRMM) exist. They include different types of populations, Daratumumab regimens, and outcomes. Moreover, there is a wide variation in methodological quality and risk of bias. Objective This study aimed to conduct a systematic review of MAs to summarize the literature on the efficacy and safety profile of daratumumab use in RRMM, and also provide an assessment of the quality and risk of bias of the MAs if sufficient data is available. Methods The literature databases Pubmed, Embase, Web of Science, and Cochrane were searched since inception. The quality of methodology was assessed by the AMSTAR-2 tool, and the risk of bias was assessed by the ROBIS tool. Results Eight MAs were included in the SR. Most studies reported ORR and CR improvement by adding daratumumab to the chemotherapy regimen. Five MAs reported improvement in PFS in daratumumab-based regimens compared to non- daratumumab-based regimens. Only two MAs reported molecular response, favoring daratumumab. Dara was associated with adverse drug events (ADEs), including pneumonia and diarrhea. Conflicting evidence regarding hematological ADEs association with daratumumab exists. The overall quality of the studies is poor, but the MAs had a low risk of bias overall. Conclusion Despite including low-quality MAs, this SR provides a summary that simplifies clinicians’ access to efficacy and safety outcomes of daratumumab in RRMM patients. Future studies are required to reduce the uncertainty and produce higher-quality Mas, particularly regarding daratumumab's safety.
The impact of pathogenic BRCA1/2 tumor mutation status on high grade serous epithelial ovarian cancer survival outcome: A multicenter study from Indonesia
Authors: Sutrisno Sutrisno , Marlina Dina , Tjandraprawira Kevin Dominique , Adinda Adriansyah Putri Nadhira 
Published: November 2024

Introduction: Ovarian cancer is still a major health problem in Indonesia. development of breast cancer gene-related personalized medicine to increase the survival outcome of epithelial ovarian cancer patients in Indonesia is expected to be achieved. This research aims to evaluate the impact of pathogenic breast cancer gene 1 and breast cancer gene 2 tumor mutation on high-grade serous epithelial ovarian cancer survival outcome. Methods: This study is an observational analytic study, using a historical cohort study design. A total of 68 from 144 patients diagnosed with International Federation of Gynecology and Obstetrics 2014 stage IIB-IV high-grade serous epithelial ovarian cancer between January 1st, 2015 until March 31st, 2021, at three centers in Jakarta. Next-generation sequencing tumor breast cancer gene 1 and breast cancer gene 2 testing and were included in this cohort historical study. We compared patient’s overall survival outcomes, according to pathogenic breast cancer gene 1 and breast cancer gene 2 tumor mutational status. Clinicopathological characteristic factors that might affect patient’s survival outcomes were also investigated. Results: In the group of individuals with pathogenic breast cancer gene 1 and breast cancer gene 2 tumour mutations, the risk of death was significantly lower by 86% (adjusted RR 0.149; 95% CI: 0.046–0.475; p-value = 0.001), and the median survival time was significantly better (median 46 months; 95% CI: 34.009–57.991; p-value = 0.001) compared to the group without pathogenic breast cancer gene 1 and breast cancer gene 2 tumor mutations (median 23 months; 95% CI: 15.657–30.343; p-value = 0.001). The multivariate analysis revealed that the presence of a pathogenic breast cancer gene 1 and breast cancer gene 2 tumor mutation is an independent and positive prognostic factor for survival outcome. The adjusted relative risk was 0.149, with a 95% CI of 0.046–0.475, p-value = 0.001. Conclusions: In high-grade serous ovarian cancer patients, the pathogenic breast cancer gene 1 and breast cancer gene 2 tumor mutations group have a better prognosis with longer survival outcomes than those without pathogenic breast cancer gene 1 and breast cancer gene 2 tumor mutations.
High security and privacy protection model for STI/HIV risk prediction
Authors: Tang Zhaohui , Van Nguyen Thi Phuoc , Yang Wencheng , Xia Xiaoyu , Chen Huaming , Mullens Amy B. , Dean Judith A. , Osborne Sonya R , Li Yan 
Published: November 2024

Introduction Applying and leveraging artificial intelligence within the healthcare domain has emerged as a fundamental pursuit to advance health. Data-driven models rooted in deep learning have become powerful tools for use in healthcare informatics. Nevertheless, healthcare data are highly sensitive and must be safeguarded, particularly information related to sexually transmissible infections (STIs) and human immunodeficiency virus (HIV). Methods We employed federated learning (FL) in combination with homomorphic encryption (HE) for STI/HIV prediction to train deep learning models on decentralized data while upholding rigorous privacy. The dataset included 168,459 data entries collected from eight countries between 2013 and 2018. The data for each country was split into two groups, with 70% allocated for training and 30% for testing. Our strategy was based on two-step aggregation to enhance model performance and leverage the area under the curve (AUC) and accuracy metrics and involved a secondary aggregation at the local level before utilizing the global model for each client. We introduced a dropout approach as an effective client-side solution to mitigate computational costs. Results Model performance was progressively enhanced from an AUC of 0.78 and an accuracy of 74.4% using the local model to an AUC of 0.94 and an accuracy of 90.7% using the more advanced model. Conclusion Our proposed model for STI/HIV risk prediction surpasses those achieved by local models and those constructed from centralized data sources, highlighting the potential of our approach to improve healthcare outcomes while safeguarding sensitive patient information.
Clonal hematopoiesis of indeterminate potential: a risk factor for future exacerbation in patients with COPD
Authors: Lee Jung-Kyu , An Hongyul , Koh Youngil , Lee Chang-Hoon 
Published: November 2024

BackgroundThere is limited data regarding the clinical significance of clonal hematopoiesis of indeterminate potential (CHIP) in patients with COPD. We aimed to evaluate whether CHIP could serve as a biomarker for the long-term prognosis of patients with COPD.MethodsNext-generation sequencing was used to detect CHIP in peripheral blood mononuclear cell samples. Participants with COPD were enrolled in a prospective observational cohort between January 2013 and December 2023. We investigated the association of CHIP status with the risk of subsequent acute exacerbation and longitudinal changes in lung function, by using negative binomial regression and linear mixed regression models, respectively.ResultsAmong 125 patients with COPD, the CHIP-positive group was 32 (25.6%). Higher smoking intensity and CAT score were significantly associated with increased risk of positive CHIP status, especially in current smokers. Positive CHIP of specific genes was significantly associated with a higher risk of subsequent mild and total acute exacerbation. Positive CHIP of ASXL transcriptional regulator 1 (ASXL1) had a lower risk of subsequent total acute exacerbation (aOR, 0.19; 95% CI, 0.04–0.95). The CHIP status did not show a statistically significant association with longitudinal changes in lung function.ConclusionsIn patients with COPD, CHIP positivity was significantly associated with an increased risk of subsequent acute exacerbations, but not with longitudinal changes in lung function.
Magnesium degradation-induced variable fixation plates promote bone healing in rabbits
Authors: Wen Jian , Zeng Yu , Su Shenghui , Song Meiling , Wang Zhe , Chen Xiaofan , Dong Xieping 
Published: November 2024

Abstract
Background
Both initial mechanical stability and subsequent axial interfragmentary micromotion at fracture ends play crucial roles in fracture healing. However, the conversion timing of variable fixation and its effect on and mechanism of fracture healing remain inadequately explored.

Methods
A magnesium degradation-induced variable fixation plate (MVFP) for femurs was designed, and its conversion timing was investigated both in vitro and in vivo. Then, locking plates and MVFPs with and without a magnesium shim were implanted in rabbit femur fracture models. X-ray photography and micro computed tomography (micro-CT) were performed to observe the healing of the fracture. Toluidine blue and Masson’s trichrome staining were performed to observe new bone formation. The torsion test was used to determine the strength of the bone after healing. Finally, reverse transcription-polymerase chain reaction (RT-PCR) and western blotting were used to detect the expression of osteogenesis-related genes in the three groups.

Results
The MVFP with sample 3 magnesium shim showed greater axial displacement within 15 days in vitro, and its variable capability was likewise confirmed in vivo. X-ray photography and micro-CT indicated increased callus formation in the variable fixation group. Toluidine blue and Masson’s trichrome staining revealed less callus formation on the rigid fixation side of the locking plate, whereas the variable fixation group presented more callus formation, more symmetrical intraosseous calli, and greater maturity. The torsion test indicated greater torsional resistance of the healed bone in the variable fixation group. RT-PCR and western blotting revealed that the expression levels of BMP2 and OPG increased during early fracture stages but decreased in late fracture stages, whereas RANKL expression showed the opposite trend in the variable fixation group.

Conclusions
MVFP promoted faster and stronger bone healing in rabbits, potentially by accelerating the expression of BMP2 and modulating the OPG/RANKL/RANK signaling axis. This study offers valuable insights for the clinical application of variable fixation technology in bone plates and contributes to the advancement of both internal fixation technology and theory.
Level of evidence: level V.

Graphical Abstract
A computationally efficient algorithm to leverage average information REML for (co)variance component estimation in the genomic era
Authors: Strandén Ismo , Mäntysaari Esa A. , Lidauer Martin H. , Thompson Robin , Gao Hongding 
Published: November 2024

Abstract
Background
Methods for estimating variance components (VC) using restricted maximum likelihood (REML) typically require elements from the inverse of the coefficient matrix of the mixed model equations (MME). As genomic information becomes more prevalent, the coefficient matrix of the MME becomes denser, presenting a challenge for analyzing large datasets. Thus, computational algorithms based on iterative solving and Monte Carlo approximation of the inverse of the coefficient matrix become appealing. While the standard average information REML (AI-REML) is known for its rapid convergence, its computational intensity imposes limitations. In particular, the standard AI-REML requires solving the MME for each VC, which can be computationally demanding, especially when dealing with complex models with many VC. To bridge this gap, here we (1) present a computationally efficient and tractable algorithm, named the augmented AI-REML, which facilitates the AI-REML by solving an augmented MME only once within each REML iteration; and (2) implement this approach for VC estimation in a general framework of a multi-trait GBLUP model. VC estimation was investigated based on the number of VC in the model, including a two-trait, three-trait, four-trait, and five-trait GBLUP model. We compared the augmented AI-REML with the standard AI-REML in terms of computing time per REML iteration. Direct and iterative solving methods were used to assess the advances of the augmented AI-REML.

Results
When using the direct solving method, the augmented AI-REML and the standard AI-REML required similar computing times for models with a small number of VC (the two- and three-trait GBLUP model), while the augmented AI-REML demonstrated more notable reductions in computing time as the number of VC in the model increased. When using the iterative solving method, the augmented AI-REML demonstrated substantial improvements in computational efficiency compared to the standard AI-REML. The elapsed time of each REML iteration was reduced by 75%, 84%, and 86% for the two-, three-, and four-trait GBLUP models, respectively.

Conclusions
The augmented AI-REML can considerably reduce the computing time within each REML iteration, particularly when using an iterative solver. Our results demonstrate the potential of the augmented AI-REML as an appealing approach for large-scale VC estimation in the genomic era.
ClassifieR 2.0: expanding interactive gene expression-based stratification to prostate and high-grade serous ovarian cancer
Authors: McCabe Aideen , Quinn Gerard P. , Jain Suneil , Ó Dálaigh Micheál , Dean Kellie , Murphy Ross G. , McDade Simon S. 
Published: November 2024

Abstract
Background
Advances in transcriptional profiling methods have enabled the discovery of molecular subtypes within and across traditional tissue-based cancer classifications. Such molecular subgroups hold potential for improving patient outcomes by guiding treatment decisions and revealing physiological distinctions and targetable pathways. Computational methods for stratifying transcriptomic data into molecular subgroups are increasingly abundant. However, assigning samples to these subtypes and other transcriptionally inferred predictions is time-consuming and requires significant bioinformatics expertise. To address this need, we recently reported “ClassifieR,” a flexible, interactive cloud application for the functional annotation of colorectal and breast cancer transcriptomes. Here, we report “ClassifieR 2.0” which introduces additional modules for the molecular subtyping of prostate and high-grade serous ovarian cancer (HGSOC).

Results
ClassifieR 2.0 introduces ClassifieRp and ClassifieRov, two specialised modules specifically designed to address the challenges of prostate and HGSOC molecular classification. ClassifieRp includes sigInfer, a method we developed to infer commercial prognostic prostate gene expression signatures from publicly available gene-lists or indeed any user-uploaded gene-list. ClassifieRov utilizes consensus molecular subtyping methods for HGSOC, including tools like consensusOV, for accurate ovarian cancer stratification. Both modules include functionalities present in the original ClassifieR framework for estimating cellular composition, predicting transcription factor (TF) activity and single sample gene set enrichment analysis (ssGSEA).

Conclusions
ClassifieR 2.0 combines molecular subtyping of prostate cancer and HGSOC with commonly used sample annotation tools in a single, user-friendly platform, allowing scientists without bioinformatics training to explore prostate and HGSOC transcriptional data without the need for extensive bioinformatics knowledge or manual data handling to operate various packages. Our sigInfer method within ClassifieRp enables the inference of commercially available gene signatures for prostate cancer, while ClassifieRov incorporates consensus molecular subtyping for HGSOC. Overall, ClassifieR 2.0 aims to make molecular subtyping more accessible to the wider research community. This is crucial for increased understanding of the molecular heterogeneity of these cancers and developing personalised treatment strategies.
The gut microbiota of three avian species living in sympatry
Authors: Pereira Hugo , Chakarov Nayden , Caspers Barbara A. , Gilles Marc , Jones William , Mijoro Tafitasoa , Zefania Sama , Székely Tamás , Krüger Oliver , Hoffman Joseph I. 
Published: November 2024

Abstract
Background
Evolutionary divergence and genetic variation are often linked to differences in microbial community structure and diversity. While environmental factors and diet heavily influence gut microbial communities, host species contributions are harder to quantify. Closely related species living in sympatry provide a unique opportunity to investigate species differences without the confounding effects of habitat and dietary variation. We therefore compared and contrasted the gut microbiota of three sympatric plover species: the widespread Kittlitz’s and white-fronted plovers (Anarhynchus pecuarius and A. marginatus) and the endemic and vulnerable Madagascar plover (A. thoracicus).

Results
We found no significant differences in the beta diversity (composition) of the gut microbiota of the three species. However, A. thoracicus exhibited higher intraspecific compositional similarity (i.e. lower pairwise distances) than the other two species; this pattern was especially pronounced among juveniles. By contrast, microbial alpha diversity varied significantly among the species, being highest in A. pecuarius, intermediate in A. marginatus and lowest in A. thoracicus. This pattern was again stronger among juveniles. Geographical distance did not significantly affect the composition of the gut microbiota, but genetic relatedness did.

Conclusion
While patterns of microbial diversity varied across species, the lack of compositional differences suggests that habitat and diet likely exert a strong influence on the gut microbiota of plovers. This may be enhanced by their precocial, ground-dwelling nature, which could facilitate the horizontal transmission of microbes from the environment. We hypothesise that gut microbiota diversity in plovers primarily reflects the ecological pool of microbiota, which is subsequently modified by host-specific factors including genetics. The reduced microbial and genetic diversity of the endemic A. thoracicus may hinder its ability to adapt to environmental changes, highlighting the need for increased conservation efforts for this vulnerable species.