bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multi-omics revealed that the postbiotic of hawthorn-probiotic alleviated constipation caused by loperamide in elderly mice
Authors: Wei Yu , Chen Shuai , Ling Ying , Wang Wei , Huang Yali 
Published: February 2025

BackgroundConstipation is a prevalent and recurrent gastrointestinal disorder causing significant discomfort. However, current treatments often prove ineffective. Previous research indicates that the postbiotic derived from a combination of hawthorn and probiotics can alleviate constipation. This study aimed to investigate its mechanisms using loperamide-induced constipation in aged KM mice.MethodsConstipated mice were divided into groups receiving 10% lactulose (Y), hawthorn extract (S), probiotics (F), and the postbiotic of hawthorn-probiotic (FS). UPLC–MS metabolomics identified constituents of F, S, and FS. Network pharmacological analysis identified targets affected by FS. RT-qPCR assessed target expression in mouse colons, along with IL-6 and IL-17A levels. Molecular docking with AutoDock Tools1.5.6 evaluated interactions between FS components and targets. ex vivo colonic organ culture and RT-qPCR assessed target changes. Molecular dynamics analysis further scrutinized interactions. Targeted metabolomics measured short-chain fatty acid levels in mouse stool.ResultsUPLC–MS metabolomics revealed distinct profiles for F, S, and FS, with FS showing decreased toxic substances and increased beneficial ones compared to S. Network pharmacology identified 20 cross-targets of FS in constipation. RT-qPCR showed decreased NR1I2 and SULT1A1 and increased GLP-2r in FS-treated mice. Inflammatory cytokines IL-6 and IL-17A were also reduced. ex vivo colonic organ culture and molecular docking identified effective combinations such as TNF-Baicalin and AQP3-Quinacridone. RMSD, RMSF, and RG analyses indicated favorable interactions between small molecules and targets. Targeted metabolomics revealed differing short-chain fatty acid contents in feces among groups.ConclusionThe postbiotic of hawthorn-probiotic alleviates constipation by regulating intestinal water and sodium metabolism, maintaining the intestinal barrier and gut flora, promoting epithelial cell proliferation, reducing inflammatory responses, and improving short-chain fatty acid metabolism.
Reclassification of variants of uncertain significance by race, ethnicity, and ancestry for patients at risk for breast cancer
Authors: Pleasant Versha , Boggan Jordyn , Richards Blair , Milliron Kara J. , Purrington Kristen S. , Simon Michael , Merajver Sofia 
Published: February 2025

IntroductionAlthough most variants of uncertain significance (VUS) in breast cancer susceptibility genes are eventually downgraded to benign or likely benign in individuals of European ancestry, it is unclear if this also applies to non-European populations. This study examines the time to and type of VUS reclassification among a diverse cohort at risk for breast cancer.MethodsA multicenter retrospective analysis examined people assigned female at birth (AFAB) who underwent genetic testing from 2013 to 2021 with VUS in ATM, BARD1, BRCA1/2, CDH1, CHEK2, NF1, PALB2, PTEN, RAD51C/D, STK11, and/or TP53. Demographic data were collected [including race, ethnicity, and ancestry (REA)], as well as time to and type of reclassification. Frequency data and univariable and multivariable analyses were performed (p &lt; 0.05 was considered statistically significant).ResultsThere were 932 participants who had a total of 1,032 VUS (905 unique variants), with 20% who underwent reclassification of their results. The proportion of reclassified VUS among the largest represented REA groups was 19%, 23%, and 27% for White, Black or African American, and Asian people, respectively. REA was not associated with VUS reclassification (p = 0.25). The mean time to VUS reclassification was 2.8 years and was not significantly associated with REA (p = 0.16). Most VUS were downgraded to benign/likely benign (n = 187, 92%).DiscussionOur findings demonstrate that REA is not significantly associated with VUS reclassification or time to reclassification, with the majority of VUS being downgraded across REA. This study allows for improved and more equitable genetic counseling. It may also provide more reassurance to those groups that may have a higher likelihood of VUS results.
Identification of benign and malignant breast nodules on ultrasound: comparison of multiple deep learning models and model interpretation
Authors: Wen Xi , Tu Hao , Zhao Bingyang , Zhou Wenbo , Yang Zhuo , Li Lijuan 
Published: February 2025

Background and PurposeDeep learning (DL) algorithms generally require full supervision of annotating the region of interest (ROI), a process that is both labor-intensive and susceptible to bias. We aimed to develop a weakly supervised algorithm to differentiate between benign and malignant breast tumors in ultrasound images without image annotation.MethodsWe developed and validated the models using two publicly available datasets: breast ultrasound image (BUSI) and GDPH&amp;SYSUCC breast ultrasound datasets. After removing the poor quality images, a total of 3049 images were included, divided into two classes: benign (N = 1320 images) and malignant (N = 1729 images). Weakly-supervised DL algorithms were implemented with four networks (DenseNet121, ResNet50, EffientNetb0, and Vision Transformer) and trained using 2136 unannotated breast ultrasound images. 609 and 304 images were used for validation and test sets, respectively. Diagnostic performances were calculated as the area under the receiver operating characteristic curve (AUC). Using the class activation map to interpret the prediction results of weakly supervised DL algorithms.ResultsThe DenseNet121 model, utilizing complete image inputs without ROI annotations, demonstrated superior diagnostic performance in distinguishing between benign and malignant breast nodules when compared to ResNet50, EfficientNetb0, and Vision Transformer models. DenseNet121 achieved the highest AUC, with values of 0.94 on the validation set and 0.93 on the test set, significantly surpassing the performance of the other models across both datasets (all P &lt; 0.05).ConclusionThe weakly supervised DenseNet121 model developed in this study demonstrated feasibility for ultrasound diagnosis of breast tumor and showed good capabilities in differential diagnosis. This model may help radiologists, especially novice doctors, to improve the accuracy of breast tumor diagnosis using ultrasound.
Ivabradine in treatment of symptomatic heart failure and supraventricular tachycardias in patients under six months of age
Authors: Gómez-Ganda L. , Parramón-Teixidó C. J. , Giralt-García G. , Fernández-García C. , Ferrer-Menduiña Q. , Cabañas-Poy M. J. 
Published: February 2025

BackgroundAlthough heart failure (HF) and supraventricular tachycardias (SVT) are associated with high morbidity and mortality in pediatrics, especially, in children under 6 months; the efficacy of available treatments is limited, requiring the use of off-label therapies. The aim of the study is to investigate the efficacy, dosage, and safety of off-label ivabradine in patients under 6 months of age with HF or SVT.MethodsRetrospective observational study, which included patients under 6 months of age with HF or SVT who received ivabradine between January 2020 - May 2024. Demographic, clinical, and treatment-related variables were collected. Response variables were established according to indication, HF: heart rate (HR) and left ventricular ejection fraction (LVEF); SVT: HR.ResultsThirteen patients (nine women) with a median age of 1.4 (1-4) months were included. Ivabradine was discontinued in five of the seven HF patients due to resolution of HF, control of HR, and improvement of LVEF. One patient discontinued ivabradine because of bradycardia. In the SVT group, four of the seven patients discontinued ivabradine after the resolution of tachyarrhythmia and improvement of HR. Two patients experienced bradycardia but did not require treatment discontinuation. HR reduction was statistically significant in both groups. In HF, the median initial ivabradine dose was 0.06 mg/kg/day and the maintenance dose was 0.2 mg/kg/day. In SVT, the initial and maintenance doses were 0.1 mg/kg/day and 0.24 mg/kg/day, respectively.ConclusionIvabradine demonstrated favorable efficacy and safety results in patients under 6 months of age with HF or SVT.
Brigatinib can inhibit proliferation and induce apoptosis of human immortalized keratinocyte cells
Authors: Yang Qi , Zhao Dan , Ju Linjie , Cao Peng , Wei Jifu , Liu Zhixian 
Published: February 2025

BackgroundBrigatinib is approved in multiple countries for the treatment of patients with anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC). Despite its superior efficacy, the dermal toxicities caused by brigatinib cannot be overlooked. However, its underlying mechanism remains unknown.MethodsThe effects of brigatinib on the proliferation ability of human immortalized keratinocyte (HaCaT) cells were evaluated using Cell Counting Kit-8 (CCK-8) proliferation, colony formation, and 5-ethynyl-2′-deoxyuridine (EdU) incorporation assays. The effects of brigatinib on apoptosis were detected using Annexin FITC/PI and Acridine Orange (AO) staining assays. Cell cycle was assessed with flow cytometry. An analysis of transcriptome by RNA sequencing procedures (RNA-seq) was performed to reveal the key regulatory genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to find out the biological function and related signal pathways. The expressions of amphiregulin, epiregulin and transforming growth factor alpha (TGFA) and the protein levels of Phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) and Cleaved-Caspase three were measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot assay.ResultsBrigatinib inhibits cell proliferation with an IC50 value of 2.9 μmol/L and significantly increases apoptosis rates. Transcriptome sequencing (RNA-seq) indicates that brigatinib could significantly downregulate the expression of amphiregulin, epiregulin and TGFA. In addition, we demonstrated that brigatinib reduced the protein expression of amphiregulin, epiregulin, TGFA, PI3K, AKT and phosphorylated AKT (p-AKT).ConclusionThis study confirms the inhibition of HaCaT cells growth and progression by brigatinib and highlights the potential value of the PI3K/AKT pathway as a therapeutic target for brigatinib-induced dermal toxicities.
Potential activity of Ferula macrecolea essential oil for treating Giardia lamblia infection through modulating electrolytes and suppressing NF-κB p65 pathway
Authors: Salimikia Iraj , Yaghoubi Seyed Ehsan , Khalaf Amal Khudair , Masoori Leila , Ghasemian Yadegari Javad , Mahmoudvand Hossein 
Published: February 2025

BackgroundThe pharmacological treatment of Giardia lamblia infection involves the use of chemical agents, such as metronidazole (MNZ). However, these medications are associated with a range of adverse effects, and their effectiveness is not definitively established. In light of the previously discussed information and the recognized antimicrobial properties of Ferula macrecolea, this study aims to investigate both the in vitro and in vivo anti-giardial effects of F. macrecolea essential oil (FME) on G. lamblia infection.MethodsGas chromatography-mass spectrometry (GC-MS) was utilized to analyze the chemical composition of the prepared FME. The MTT colorimetric assay was employed to assess FME’s in vitro anti-giardial and cytotoxic activities. FME’s in vivo effects were evaluated compared to MNZ in mice infected with G. lamblia. Additionally, the effects of FME therapy on serum electrolyte levels and the expression levels of inflammatory cytokines were assessed.ResultsThe primary components of FME were identified as terpinolene (78.72%), n-nonanal (4.47%), and linalool (4.35%). FME significantly reduced the viability and growth rate of G. lamblia trophozoites (IC50 = 21.6 μg/mL) and cysts (IC50 = 27.6 μg/mL) in a dose-dependent manner compared to the control group (p &lt; 0.001). The CC50 value for FME against normal intestinal cells was determined to be 207.4 μg/mL. In vivo, assays demonstrated that the administration of various doses of FME, particularly in combination with MNZ over 7 days, resulted in a statistically significant reduction in the mean number and viability of Giardia cysts, serum level electrolytes (sodium and potassium), and the expression levels of interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-α), nuclear factor κB p65 (NF-κB p65), and Toll-like receptor 4 (TLR-4) in mice with giardiasis (p &lt; 0.001).ConclusionThis study’s results demonstrate the extract’s efficacy in vitro against G. lamblia, exhibiting minimal cytotoxicity towards normal cells. Furthermore, the extract was shown to manage giardiasis in murine models by modulating electrolyte levels and inflammatory responses via suppressing the NF-κB p65/TLR pathways. However, further research is necessary to clarify the specific efficacy and mechanisms of action of the extract in combating G. lamblia infection.
Dynamic changes in the transcriptome of tropical region-originated king grasses in response to cold stress
Authors: Lai Xianjun , Yan Junfeng , Chen Zihan , Zhang Yizheng , Luo Fan , Cai Guangze , Yan Lang 
Published: February 2025

IntroductionCold acclimatization in tropical region-originated plants involves complex gene expression reprogramming to adapt to fluctuating temperatures. However, the molecular mechanisms and gene networks regulating cold tolerance in king grass remain largely unknown.MethodsTo address this, we established a full-length reference transcriptome of king grass to enhance assembly quality and performed multiple time-point transcriptomic analyses following cold treatment at 4°C. Differentially expressed genes (DEGs) and transcription factors (TFs) involved in cold stress response were identified and analyzed through clustering and co-expression network analysis.ResultsA total of 13,056 DEGs were identified and classified into nine clusters via k-means analysis. The cold response exhibited three distinct phases: early (before 3 h), middle (6–24 h), and late (48–72 h). Early-responsive genes were enriched in glycolipid metabolism and photosynthesis, middle-stage genes in carbohydrate metabolism, and late-stage genes in cold stress, osmotic stress, and endogenous stimuli responses. Key regulators of the ICE-CBF-COR signaling module, including 13 positive and negative regulators, were identified. The co-expression network further revealed mutual regulatory interactions within this module, highlighting its role in cold stress adaptation.DiscussionOur findings provide insights into the cold tolerance mechanisms of king grass, offering a genetic basis for modifying cold stress regulators. This research contributes to the broader understanding of low-temperature adaptive mechanisms in tropical plants and supports future breeding strategies for improved cold tolerance.
Ensiling characteristics, in vitro digestibility and bacterial community structure of mulberry leaf silage with or without the addition of cellulase, protease, and starch
Authors: Zhao Guoqiang , Wu Hao , Li Yangyuan , Huang Zhiyi , He Jiajun , Xie Xiangxue 
Published: February 2025

ObjectiveThis study aimed to investigate the effects of cellulase, protease, and starch on the fermentation quality, in vitro digestibility, and microbial community of mulberry leaf silage after 30d of ensiling.MethodsMulberry leaves (376 g/kg dry matter (DM)) were ensiled with four experimental treatments: i) CON, no additives; ii) CEL, added cellulase (120 U/g fresh matter [FM]); iii) CPR, added cellulase (120 U/g FM) and protease (50 U/g FM); and iv) CPS, added cellulase (120 U/g FM), protease (50 U/g FM), and starch (2% FM).ResultsAll treatments with additives improved fermentation quality, showing higher DM (353 ~ 378 vs. 341 g/kg DM), lactic acid (LA) content (51.6 ~ 64.6 vs. 40.2 g/kg DM), lactic acid bacteria (LAB) counts (7.63 ~ 7.73 vs. 7.49 log10 CFU /g of FM), along with lower pH values (4.29 ~ 4.60 vs. 5.09), and DM losses (124 ~ 130 vs. 134 g/kg DM) compared to the CON group. All the additive treated groups showed higher in vitro digestibility of DM (698 ~ 720 vs. 618 g/kg DM), in vitro digestibility of NDF (395 ~ 412 vs. 336 g/kg DM), and ADF (277 ~ 298 vs. 232 g/kg DM) than CON. Among all the groups, the CPS group exhibited the highest DM content (378 g/kg DM), LA content (64.6 g/kg DM) and LAB counts (7.73 log10 CFU /g of FM), with the lowest pH value (4.29) and DM losses (124 g/kg DM). Additionally, the additive treatments increased abundance of bacteria like Firmicutes and Enteroccocus, while reducing Proteobacteria abundance, and resulted in lower diversity and richness of the microbial community. Specifically, CPR and CPS silages showed increased Pediococcus and decreased Enterobacter compared to CON and CEL, and CPS silage had a relatively high abundance of favorable Bacteroidota. Furthermore, the CPS silage exhibited upregulated genetic functions, energy and lipid metabolism, as well as metabolism of cofactors and vitamins compared to the other groups.ConclusionThe combined application of cellulase, protease, and starch effectively improved the fermentation quality, in vitro digestibility, and microbial community of mulberry leaf silage over the 30-day ensiling period.
Mental imagery and stress: the mediating role of self-efficacy in competitive martial arts athletes
Authors: Di Corrado Donatella , Tortella Patrizia , Coco Marinella , Guarnera Maria , Tusak Matej , Parisi Maria Chiara 
Published: February 2025

IntroductionMartial arts are diverse systems of combat practices, each with its unique techniques, philosophies, and histories. Mental imagery is a multisensory experience that integrates various senses to create vivid mental representations, evoking the physical attributes of people, places, or objects not currently within our perception. In sports contexts, studies have indicated that martial arts often use imagery to enhance performance.MethodsThis study aimed to investigate the mediating role of self-efficacy in the relationship between static (visualizing still scenes or concepts) and dynamic (focusing on motion and action) vividness, controllability (manipulating the imagery experience), and the degree of stress, in a group of 110 martial arts athletes (61 males and 49 females), aged between 21 and 23 years old (M = 22.47, SD = 0.75). Participants were competitive athletes of karate, taekwondo and judo, having a minimum of 13 years of training skill in the sport. They completed the Vividness of Visual Imagery Questionnaire, the Vividness of Movement Imagery Questionnaire-2, the Mental Image Transformation Task, The General Self-Efficacy Scale, and Measuring Psychological Stress Test.ResultsA 2 × 3 (gender × sport type) between groups MANOVA showed significant differences in imagery dimensions by sport type. The results of the mediation analysis showed that self-efficacy plays a mediating role between imagery and stress.DiscussionThe study advanced exploration in the field of mental imagery training, providing additional evidence for its importance in improving performance and managing stress in athletes.
Association between psychological depression and physical health in Chinese empty-nesters during the COVID-19 pandemic
Authors: Wang Shiyi , Fan Xiaojing , Li Fang , Zhou Zhongliang 
Published: February 2025

ObjectivesWith the aging of the population becoming increasingly serious, the phenomenon of empty-nesters is also becoming more and more serious. The psychological problems of the empty-nester elderly are becoming more and more prominent, which may affect their physical health. This study aimed to quantify the association between psychological depression and physical health in the background of the COVID-19 pandemic.MethodsA total of 7,835 empty-nesters over 60 years old were selected from the China Health and Retirement Longitudinal Study in 2020. Depressive symptoms were applied to measure psychological health. The outcome variables of physical health were measured by self-rated health (SRH), chronic disease, and limited basic activities of daily living (BADLs). Binary logistic regression models with odds ratios and 95% confidence intervals (CI) were applied to explore the association between psychological and physical health.ResultsEmpty-nesters with depressive symptoms were 72% less likely to rate their health as good than empty-nesters without depressive symptoms (95%CI: 0.242–0.328). The rates of chronic disease for empty-nesters with depressive symptoms were 1.45 (95%CI: 1.300–1.622) times higher than those without depressive symptoms, and those with depressive symptoms were more likely to have limited BADLs than elderly without depressive symptoms (OR = 3.125, 95%CI: 2.757–3.543).ConclusionWe found that among empty-nesters in China, depressive symptoms were negatively associated with good self-rated health and positively associated with chronic diseases and limitations in BADLs.
Tourette syndrome and brain stimulation therapy: a systematic review and meta-analysis of current evidence
Authors: Aloufi Alwaleed K. , Zahhar Jalal A. , Bader Mahmoud W. , Almutairi Maher B. , Alaaldeen Abdulqader , Hetta Omar E. , Gammash Abdulaziz M. , Almuntashiri Saleh , Binrabaa Ibrahim S. , Alsaleh Ahmad , AlSalem Moayyad 
Published: February 2025

BackgroundTourette syndrome (TS) is a neurological disorder characterized by tics, often associated with obsessive-compulsive disorder (OCD). Severe cases may require interventions such as deep brain stimulation (DBS) or repetitive transcranial magnetic stimulation (rTMS).MethodsA thorough search was performed across PubMed/Medline, Embase, (CENTRAL), and Google Scholar. Studies comparing DBS and rTMS efficacy for TS were included if they reported YGTSS before and after treatment. Two independent reviewers screened the search results, extracted data, and assessed study quality using standardized tools.Results22 studies met the inclusion criteria, with a total of 222 participants. Analysis of RCTs investigating post-intervention rTMS vs baseline showed a statistically insignificant decrease in YGTSS (MD = -5.01, 95% CI: [-10.8, 0.79], P= 0.090) but a statistically significant decrease in YBOCS (MD = -6.6; 95% CI: [-11.64, -1.55], P= 0.010). However, post-intervention rTMS in RCT and non-randomized trials vs baseline showed a significant decrease in YGTSS (MD = -11.6; 95% CI: [-18.25, -4.94], P &lt; 0.001) and YBOCS (MD = -7.5; 95% CI: [-11.85, -3.15], P &lt; 0.001). Post-intervention DBS in RCT and non-RCTs vs baseline showed a significant decrease in YGTSS (MD = -18.29; 95% CI: [-24.93, -11.64], P &lt; 0.001) and YBOCS (MD = -4.76; 95% CI: [-7.30, -2.21], P &lt; 0.001). Analysis of RCTs investigating Post-intervention DBS vs baseline showed a significant decrease in YGTSS (MD = -14.71; 95% CI: [-19.78, -9.63], P &lt;0.001) and YBOCS (MD = -5.04; 95% CI: [-8.28, -1.80], P = 0.002).ConclusionOur analysis revealed both DBS and rTMS improved TS and OCD symptoms, however the effect of rTMS on TS in RCTs was insignificant, suggesting DBS stimulation is more effective. Despite this, clinicians may still opt for rTMS before DBS due to its less invasive nature, the limited number of high-quality RCTs, and the lack of studies directly comparing rTMS and DBS.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023386856, identifier CRD42023386856.