bluuebunny/crossref_metadata_2025_split huggingface dataset:
The BRCA2 R2645G variant increases DNA binding and induces hyper-recombination
Authors: Alvaro-Aranda Lucia , Petitalot Ambre , Djeghmoum Yasmina , Panigada Davide , Singh Jenny Kaur , Ehlén Åsa , Vugic Domagoj , Martin Charlotte , Miron Simona , Contreras-Perez Aida , Nhiri Naima , Boucherit Virginie , Lafitte Philippe , Dumoulin Isaac , Quiles Francisco , Rouleau Etienne , Jacquet Eric , Feliubadaló Lidia , del Valle Jesús , Sharan Shyam K , Stoppa-Lyonnet Dominique , Zinn-Justin Sophie , Lázaro Conxi , Caputo Sandrine M , Carreira Aura 
Published: December 2023

Abstract
BRCA2 tumor suppressor protein ensures genome integrity by mediating DNA repair via homologous recombination (HR). This function is executed in part by its canonical DNA binding domain located at the C-terminus (BRCA2CTD), the only folded domain of the protein. Most germline pathogenic missense variants are located in this highly conserved region which binds to single-stranded DNA (ssDNA) and to the acidic protein DSS1. These interactions are essential for the HR function of BRCA2. Here, we report that the variant R2645G, identified in breast cancer and located at the DSS1 interface, unexpectedly increases the ssDNA binding activity of BRCA2CTDin vitro. Human cells expressing this variant display a hyper-recombination phenotype, chromosomal instability in the form of chromatid gaps when exposed to DNA damage, and increased PARP inhibitor sensitivity. In mouse embryonic stem cells (mES), this variant alters viability and confers sensitivity to cisplatin and Mitomycin C. These results suggest that BRCA2 interaction with ssDNA needs to be tightly regulated to limit HR and prevent chromosomal instability and we propose that this control mechanism involves DSS1. Given that several missense variants located within this region have been identified in breast cancer patients, these findings might have clinical implications for carriers.
Does exogenous hormonal therapy affect the risk of glioma among females: A systematic review and meta-analysis
Authors: Alfuridy Ghady , Alghamdi Rana , Alkhoshi Abdulaziz , Mahjari Ahood , Alhussein Abdullah , Alshehri Ebtihaj , Lary Ahmed , Sabbagh Abdulrahman , Alomar Soha 
Published: December 2023

Abstract

Background
The effect of exogenous hormone replacement therapy (HRT) and oral contraceptive pills (OCPs) on glioma risk in females is unclear despite numerous studies; hence, we conducted a meta-analysis to evaluate this relationship.

Methods
Studies investigating the impact of exogenous female hormones on glioma risk were retrieved by searching 4 databases from inception until September 2022. Articles of any design, such as case–control and cohort studies, proving the relative risk (RR), odds ratio (OR), or hazard ratio were included. Summary OR values were calculated using a random effects model.

Results
Both HRT and OCP use of any duration decreased the risk of developing glioma [HRT OR = 0.78, 95% CI 0.66–0.91, P = .00; OCP: OR = 0.80, 95% CI 0.67–0.96, P = .02]. When stratified by duration of use, HRT use &gt;1 year significantly reduced glioma risk (&lt;1 year: OR = 0.82, 95% CI 0.63–1.07, P = 0.15; 1–5 years: OR = 0.79, 95% CI 0.67–0.92, P = .00; 5–10 years: OR = 0.80, 95% CI 0.66–0.97, P = .02; &gt;10 years: OR = 0.69, 95% CI 0.54–0.88, P = .00). In contrast, only OCP use for &gt;10 years significantly reduced glioma risk (&lt;1 year: OR = 0.72, 95% CI 0.49–1.05, P = .09; 1–5 years: OR = 0.88, 95% CI 0.72–1.02, P = .09; 5–10 years: OR = 0.85, 95% CI 0.65–1.1, P = 0.21; &gt;10 years: OR = 0.58, 95% CI 0.45–0.74, P = .00).

Conclusions
Our pooled results strongly suggest that sustained HRT and OCP use is associated with reduced risk of glioma development.
Root branching under high salinity requires auxin-independent modulation of LATERAL ORGAN BOUNDARY DOMAIN 16 function
Authors: Zhang Yanxia , Li Yiyun , de Zeeuw Thijs , Duijts Kilian , Kawa Dorota , Lamers Jasper , Munzert Kristina S , Li Hongfei , Zou Yutao , Meyer A Jessica , Yan Jinxuan , Verstappen Francel , Wang Yixuan , Gijsberts Tom , Wang Jielin , Gigli-Bisceglia Nora , Engelsdorf Timo , van Dijk Aalt D J , Testerink Christa 
Published: December 2023

Abstract
Salinity stress constrains lateral root (LR) growth and severely affects plant growth. Auxin signaling regulates LR formation, but the molecular mechanism by which salinity affects root auxin signaling and whether salt induces other pathways that regulate LR development remains unknown. In Arabidopsis thaliana, the auxin-regulated transcription factor LATERAL ORGAN BOUNDARY DOMAIN 16 (LBD16) is an essential player in LR development under control conditions. Here, we show that under high-salt conditions, an alternative pathway regulates LBD16 expression. Salt represses auxin signaling but, in parallel, activates ZINC FINGER OF ARABIDOPSIS THALIANA 6 (ZAT6), a transcriptional activator of LBD16. ZAT6 activates LBD16 expression, thus contributing to downstream cell wall remodeling and promoting LR development under high-salt conditions. Our study thus shows that the integration of auxin-dependent repressive and salt-activated auxin-independent pathways converging on LBD16 modulates root branching under high-salt conditions.
Molecular and phylogenetic evidence of parallel expansion of anion channels in plants
Authors: Li Shanshan , Wei Lanlan , Gao Qiang , Xu Min , Wang Yizhou , Lin Zhenguo , Holford Paul , Chen Zhong-Hua , Zhang Liangsheng 
Published: December 2023

Abstract
Aluminum-activated malate transporters (ALMTs) and slow anion channels (SLACs) are important in various physiological processes in plants, including stomatal regulation, nutrient uptake, and in response to abiotic stress such as aluminum toxicity. To understand their evolutionary history and functional divergence, we conducted phylogenetic and expression analyses of ALMTs and SLACs in green plants. Our findings from phylogenetic studies indicate that ALMTs and SLACs may have originated from green algae and red algae, respectively. The ALMTs of early land plants and charophytes formed a monophyletic clade consisting of three subgroups. A single duplication event of ALMTs was identified in vascular plants and subsequent duplications into six clades occurred in angiosperms, including an identified clade, 1-1. The ALMTs experienced gene number losses in clades 1-1 and 2-1 and expansions in clades 1-2 and 2-2b. Interestingly, the expansion of clade 1-2 was also associated with higher expression levels compared to genes in clades that experienced apparent loss. SLACs first diversified in bryophytes, followed by duplication in vascular plants, giving rise to three distinct clades (I, II, and III), and clade II potentially associated with stomatal control in seed plants. SLACs show losses in clades II and III without substantial expansion in clade I. Additionally, ALMT clade 2-2 and SLAC clade III contain genes specifically expressed in reproductive organs and roots in angiosperms, lycophytes, and mosses, indicating neofunctionalization. In summary, our study demonstrates the evolutionary complexity of ALMTs and SLACs, highlighting their crucial role in the adaptation and diversification of vascular plants.
An artificial intelligence model based on transrectal ultrasound images of biopsy needle tract tissues to differentiate prostate cancer
Authors: Li Shiyu , Ye Xiuqin , Tian Hongtian , Ding Zhimin , Cui Chen , Shi Siyuan , Yang Yang , Li Guoqiu , Chen Jing , Lin Ziwei , Ni Zhipeng , Xu Jinfeng , Dong Fajin 
Published: December 2023

Abstract

Purpose
We aimed to develop an artificial intelligence (AI) model based on transrectal ultrasonography (TRUS) images of biopsy needle tract (BNT) tissues for predicting prostate cancer (PCa) and to compare the PCa diagnostic performance of the radiologist model and clinical model.

Methods
A total of 1696 2D prostate TRUS images were involved from 142 patients between July 2021 and May 2022. The ResNet50 network model was utilized to train classification models with different input methods: original image (Whole model), BNT (Needle model), and combined image [Feature Pyramid Networks (FPN) model]. The training set, validation set, and test set were randomly assigned, then randomized 5-fold cross-validation between the training set and validation set was performed. The diagnostic effectiveness of AI models and image combination was accessed by an independent testing set. Then, the optimal AI model and image combination were selected to compare the diagnostic efficacy with that of senior radiologists and the clinical model.

Results
In the test set, the area under the curve, specificity, and sensitivity of the FPN model were 0.934, 0.966, and 0.829, respectively; the diagnostic efficacy was improved compared with the Whole and Needle models, with statistically significant differences (P &lt; 0.05), and was better than that of senior radiologists (area under the curve: 0.667). The FPN model detected more PCa compared with senior physicians (82.9% vs. 55.8%), with a 61.3% decrease in the false-positive rate and a 23.2% increase in overall accuracy (0.887 vs. 0.655).

Conclusion
The proposed FPN model can offer a new method for prostate tissue classification, improve the diagnostic performance, and may be a helpful tool to guide prostate biopsy.
Immediate implantation of ultrafine fiber slow-release system based on cell electrospinning to induce osteogenesis of mesenchymal stem cells
Authors: Lu Tao , Yang Long , Li Zhuoyang , Liu Yin , Xu Shun'en , Ye Chuan 
Published: December 2023

Abstract
This study presents the development and evaluation of a poly(3-hydroxybutyrate-co-4-hydroxybutyrate) (P34HB) ultrafine fiber slow-release system for in vivo osteogenic induction of human umbilical cord mesenchymal stem cells (HUCMSCs). Utilizing dual-nozzle and cell electrospinning techniques, the system encapsulates L-ascorbic acid-2-phosphate magnesium (ASP), β-glycerophosphate sodium and dexamethasone (DEX) within the fibers, ensuring sustained osteogenic differentiation. The scaffold’s morphology, characterization, hydrophilicity, mechanical properties and cellular behavior were examined. Immediate subcutaneous implantation in rabbits was conducted to observe its ectopic osteogenic induction effect. Successfully fabricated P34HB ultrafine fiber slow-release system. Characterization confirmed the uniform distribution of HUCMSCs and inducing components within the scaffold, with no chemical reactions affecting the active components. In vitro tests showcased a prolonged release of DEX and ASP, while biocompatibility assays highlighted the scaffold’s suitability for cellular growth. Alizarin Red, type I collagen, and osteopontin (OPN) staining verified the scaffold’s potent osteogenic induction effect on HUCMSCs. Notably, immediate implantation into New Zealand White rabbits led to significant new bone formation within 8 weeks. These findings underscore the system’s potential for immediate in vivo implantation without prior in vitro induction, marking a promising advancement in bone tissue engineering.
State of the science and recommendations for using wearable technology in sleep and circadian research
Authors: de Zambotti Massimiliano , Goldstein Cathy , Cook Jesse , Menghini Luca , Altini Marco , Cheng Philip , Robillard Rebecca 
Published: December 2023

Abstract
Wearable sleep-tracking technology is of growing use in the sleep and circadian fields, including for applications across other disciplines, inclusive of a variety of disease states. Patients increasingly present sleep data derived from their wearable devices to their providers and the ever-increasing availability of commercial devices and new-generation research/clinical tools has led to the wide adoption of wearables in research, which has become even more relevant given the discontinuation of the Philips Respironics Actiwatch. Standards for evaluating the performance of wearable sleep-tracking devices have been introduced and the available evidence suggests that consumer-grade devices exceed the performance of traditional actigraphy in assessing sleep as defined by polysomnogram. However, clear limitations exist, for example, the misclassification of wakefulness during the sleep period, problems with sleep tracking outside of the main sleep bout or nighttime period, artifacts, and unclear translation of performance to individuals with certain characteristics or comorbidities. This is of particular relevance when person-specific factors (like skin color or obesity) negatively impact sensor performance with the potential downstream impact of augmenting already existing healthcare disparities. However, wearable sleep-tracking technology holds great promise for our field, given features distinct from traditional actigraphy such as measurement of autonomic parameters, estimation of circadian features, and the potential to integrate other self-reported, objective, and passively recorded health indicators. Scientists face numerous decision points and barriers when incorporating traditional actigraphy, consumer-grade multi-sensor devices, or contemporary research/clinical-grade sleep trackers into their research. Considerations include wearable device capabilities and performance, target population and goals of the study, wearable device outputs and availability of raw and aggregate data, and data extraction, processing, and analysis. Given the difficulties in the implementation and utilization of wearable sleep-tracking technology in real-world research and clinical settings, the following State of the Science review requested by the Sleep Research Society aims to address the following questions. What data can wearable sleep-tracking devices provide? How accurate are these data? What should be taken into account when incorporating wearable sleep-tracking devices into research? These outstanding questions and surrounding considerations motivated this work, outlining practical recommendations for using wearable technology in sleep and circadian research.
Genetic Manipulation Approaches to Enhance the Clinical Application of NK Cell-Based Immunotherapy
Authors: Maia Andreia , Tarannum Mubin , Romee Rizwan 
Published: December 2023

Abstract
Natural killer (NK) cells are a subset of cytotoxic lymphocytes within the innate immune system. While they are naturally cytotoxic, genetic modifications can enhance their tumor-targeting capability, cytotoxicity, persistence, tumor infiltration, and prevent exhaustion. These improvements hold the potential to make NK-cell-based immunotherapies more effective in clinical applications. Currently, several viral and non-viral technologies are used to genetically modify NK cells. For nucleic acid delivery, non-viral methods such as electroporation, lipid nanoparticles, lipofection, and DNA transposons have gained popularity in recent years. On the other hand, viral methods including lentivirus, gamma retrovirus, and adeno-associated virus, remain widely used for gene delivery. Furthermore, gene editing techniques such as clustered regularly interspaced short-palindromic repeats-based, zinc finger nucleases, and transcription activator-like effector nucleases are the pivotal methodologies in this field. This review aims to provide a comprehensive overview of chimeric antigen receptor (CAR) arming strategies and discuss key gene editing techniques. These approaches collectively aim to enhance NK cell/NK cell CAR-based immunotherapies for clinical translation.
Evaluation of a microencapsulated form of zinc oxide on weanling pig growth performance, fecal zinc excretion, and small intestinal morphology
Authors: Dahmer Payton L , Jones Cassandra K , Ferreyra Franco M 
Published: December 2023

Abstract
A total of 300 pigs (DNA 200 × 400; initially 6.0 ± 0.08 kg body weight [BW]) were used in a 42-d study to evaluate a microencapsulated form of zinc oxide. At weaning, pigs were randomly allocated to pens, and pens were randomly assigned to dietary treatments with 5 pigs per pen and 12 pens per treatment. Dietary treatments were 1) negative control (CON; standard nursery diet containing 110 ppm Zn in the form of zinc sulfate from trace mineral premix); 2) control diet with 400 ppm added Zn from ZnO included in phases 1 and 2 (Low-ZnO); 3) control diet with 3,000 ppm added Zn from ZnO included in phase 1 and 2,000 ppm added Zn from ZnO included in phase 2 (High-ZnO); 4) control diet with 400 ppm added Zn from microencapsulated ZnO included in phases 1 and 2 (Low-MZnO; Vetagro S.p.A., Reggio Emilia, Italy); 5) control diet with 3,000 ppm added Zn from microencapsulated ZnO in phase 1 and 2,000 ppm added Zn from microencapsulated ZnO in phase 2 (high-MZnO; Vetagro S.p.A., Reggio Emilia, Italy). On days 10 and 28, fecal samples from 2 pigs per pen were collected for fecal Zn concentrations, and on day 28, 30 pigs (n = 6) were euthanized, and small intestinal tissues were collected to evaluate morphology. For the entire treatment period (days 0 to 28) there was no evidence of differences in average daily gain (ADG), average daily feed intake (ADFI), or G:F (P &gt; 0.05). During the common phase 3 (days 28 to 42) pigs fed the negative control, High-MZnO, or Low-MZnO had improved (P &lt; 0.0001) ADG and ADFI compared to pigs fed High- or Low-ZnO. For the entire experiment (days 0 to 42), pigs fed Low-ZnO or High-ZnO had reduced (P &lt; 0.0001) ADG compared to those fed the negative control. A significant treatment × day interaction (P = 0.04) was observed for fecal Zn concentrations, where the level of Zn excreted in the feces was dependent on the sampling day in pigs fed a low level of ZnO or low level of microencapsulated ZnO. There was no evidence (P &gt; 0.05) that small intestinal morphology differed significantly between treatments. In summary, feeding a microencapsulated form of ZnO did not alter piglet growth performance during the treatment period. Pigs fed a low level of ZnO or microencapsulated ZnO had reduced fecal Zn excretion by the end of the feeding period, but no significant impacts were observed on piglet small intestinal morphology.
Urine TIMP2.IGFBP7 reflects kidney injury after moderate volume paracentesis in patients with ascites: A randomized control study
Authors: Suksamai Anuchit , Khaoprasert Sanpolpai , Chaiprasert Amnart , Chirapongsathorn Sakkarin 
Published: December 2023

AbstractBackgroundPatients with cirrhosis undergoing therapeutic paracentesis are at risk of developing kidney injury, but this has not been well evaluated in a non-large volume paracentesis setting.ObjectiveThe aims of this study were to determine the risk and consequence of acute kidney injury (AKI) and its progression in patients with decompensated cirrhosis after moderate volume paracentesis by use of a urine test measuring tissue inhibitor of metalloproteinases-2 (TIMP2) and (IGFBP7).MethodsA randomized, prospective cohort study was performed. All outpatients with decompensated cirrhosis with ascites and diuretic complications were enrolled and randomized into 3 liters and 5 liters of paracentesis groups. Serial urine samples were analyzed for [TIMP2]*[IGFBP7] concentration before and after paracentesis.ResultsA total of 90 patients with decompensated cirrhosis were consecutively enrolled during the study period. After screening, 29 patients were enrolled in the 3-liter paracentesis group, and 25 patients were enrolled in the 5-liter paracentesis group. The mean of the MELD score was 8 ± 1.2. Urine TIMP2.IGFBP7>2, rising urine TIMP2, and rising urine TIMP2/urine Cr were shown in patients within the 5-liter group for 48% (p = 0.015), 32% (p = 0.049) and 76% (p =0.010), respectively. There was no statistical difference between the two groups in the rapid decline of GFR, admission, or death.ConclusionUrine TIMP2.IGFBP7>2 predicted renal tubular injury in patients in the ascites release 5 L group therefore, ascites release 5 L may not be safe. Kidney injury could occur even less than 5 liters of ascites release in decompensated cirrhosis as demonstrated.The national clinical registration number was TCTR20191116003.
Treatment preferences among people at risk of developing tuberculosis: a discrete choice experiment
Authors: Kamchedzera Wala , Quaife Matthew , Msukwa-Panje Wezi , Burke Rachael M , Macpherson Liana , Kumwenda Moses , Twabi Hussein H , Quartagno Matteo , MacPherson Peter , Esmail Hanif 
Published: December 2023

AbstractDiagnosing and treating tuberculosis (TB) early, prior to bacteriological conformation (e.g. bacteriologically-negative but radiologically-apparent TB) may contribute to more effective TB care and reduce transmission. However, optimal treatment approaches for this group are unknown. It is important to understand peoples’ preferences of treatment options for effective programmatic implementation of people-centred treatment approaches.We designed and implemented a discrete choice experiment (DCE) to solicit treatment preferences among adults (≥18 years) with TB symptoms attending a primary health clinic in Blantyre, Malawi. Quantitative choice modelling with multinomial logit models estimated through frequentist and Bayesian approaches investigated preferences for the management of bacteriologically-negative, but radiographically-apparent TB.128 participants were recruited (57% male, 43.8% HIV-positive, 8.6% previously treated for TB). Participants preferred any treatment option compared to no treatment (odds ratio [OR]: 0.17; 95% confidence interval [CI]: 0.07, 0.42). Treatments that reduced the relative risk of developing TB disease by 80% were preferred (OR: 2.97; 95% CI: 2.09, 4.21) compared to treatments that lead to a lower reduction in risk of 50%. However, there was no evidence for treatments that are 95% effective being preferred over those that are 80% effective. Participants strongly favoured the treatments that could completely stop transmission (OR: 7.87, 95% CI: 5.71, 10.84), and prioritised avoiding side effects (OR: 0.19, 95% CI: 0.12, 0.29). There was no evidence of an interaction between perceived TB disease risk and treatment preferences.In summary, participants were primarily concerned with the effectiveness of TB treatments and strongly preferred treatments that removed the risk of onward transmission. Person-centred approaches of preferences for treatment should be considered when designing new treatment strategies. Understanding treatment preferences will ensure that any recommended treatment for probable early TB disease is well accepted and utilized by the public.