bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circulating miRNA-486 as a novel diagnostic biomarker for right ventricular remodeling
Authors: Cai Huiling , Yu Cheng , Li Xiuchuan , Wang Xuenan , Yang Yongjian , Lan Cong 
Published: January 2025

ObjectiveClinical practice currently faces a significant shortfall in specific biomarkers needed for diagnosing right ventricular (RV) remodeling in patients with pulmonary hypertension (PH). While small noncoding microRNAs (miRNAs) are crucial regulators of RV remodeling, the biomarker potential of serum miRNAs in this process is little known. This study systematically screened and identified candidate serum miRNAs as potential diagnostic biomarkers for RV remodeling in PH patients.MethodsPulmonary artery banding (PAB) was performed in Sprague-Dawley (SD) rats and RV modeling was measured by echocardiographic and histological analyses 4 weeks after surgery. High-throughput miRNA sequencing of serum samples was performed to profile differentially-expressed miRNAs (dif-miRNAs) and preliminarily screen candidate miRNAs. The diagnostic power of the candidate miRNA was further validated in 100 patients [20 with adaptive RV pressure overload; 20 with maladaptive RV pressure overload; 20 with left heart failure (LHF); 19 with left ventricular hypertrophy and 21 controls].ResultsPAB rats exhibited severe RV hypertrophy, fibrosis and enlargement of RV cardiomyocytes compared with sham group. MiRNA sequencing analyses revealed 19 dif-miRNAs (12 upregulated and 7 downregulated) between the two groups. Among the 12 upregulated miRNAs, miRNA-486 exhibited highest elevation in PAB group and was supposed to be the candidate biomarker for RV modeling. Serum miRNA-486 levels were lower in control and left ventricular hypertrophy (LVH) patients compared to PH patients, and significantly higher in maladapted RV patients than in adapted RV patients. Serum miRNA-486 was significantly higher in LHF patients compared to controls, but still significantly lower than in PH patients. In receiver operating characteristic (ROC) analysis, serum miRNA-486 was a good predictor of RV maladaptation in PH patients (cut-off value 3.441, AUC 0.8625), which was not significantly different from B-type natriuretic peptide (BNP). Elevated serum miRNA-486 levels (≥3.441) were associated with reduced TAPSE/PASP ratios and increased BNP levels.ConclusionsSerum miRNA-486 has the potential to be a valuable noninvasive biomarker for diagnosing RV remodeling in patients with PH.
Quadratic descriptors and reduction methods in a two-layered model for compound inference
Authors: Zhu Jianshen , Azam Naveed Ahmed , Cao Shengjuan , Ido Ryota , Haraguchi Kazuya , Zhao Liang , Nagamochi Hiroshi , Akutsu Tatsuya 
Published: January 2025

Compound inference models are crucial for discovering novel drugs in bioinformatics and chemo-informatics. These models rely heavily on useful descriptors of chemical compounds that effectively capture important information about the underlying compounds for constructing accurate prediction functions. In this article, we introduce quadratic descriptors, the products of two graph-theoretic descriptors, to enhance the learning performance of a novel two-layered compound inference model. A mixed-integer linear programming formulation is designed to approximate these quadratic descriptors for inferring desired compounds with the two-layered model. Furthermore, we introduce different methods to reduce descriptors, aiming to avoid computational complexity and overfitting issues during the learning process caused by the large number of quadratic descriptors. Experimental results show that for 32 chemical properties of monomers and 10 chemical properties of polymers, the prediction functions constructed by the proposed method achieved high test coefficients of determination. Furthermore, our method inferred chemical compounds in a time ranging from a few seconds to approximately 60 s. These results indicate a strong correlation between the properties of chemical graphs and their quadratic graph-theoretic descriptors.
Location and natural history are key to determining impact of the 2021 atmospheric heatwave on Pacific Northwest rocky intertidal communities
Authors: Miner C. Melissa , Berry Helen D. , Bohlmann Heath , Dethier Megan N. , Fradkin Steven C. , Gaddam Rani , Raymond Wendel W. , Raimondi Peter T. 
Published: January 2025

IntroductionIn late June 2021, the Pacific Northwest region of the United States and Canada experienced an unprecedented atmospheric heatwave that co-occurred with one of the lowest day-time tide series of the year. Several consecutive days of air temperatures 10-20°C above normal, coupled with mid-afternoon low tides proved deadly for many rocky intertidal organisms, which live at the margin of land and sea.MethodsTo assess short (weeks) and longer-term (1 year) impacts of the heatwave on rocky intertidal communities, we used long-term monitoring data collected annually at 16 sites throughout Washington State.Results and discussionOur findings indicate that impacts were most severe at sites within the Salish Sea region of WA, where peak low tides occurred during the hottest, mid-afternoon hours. Focal species assemblages at Olympic coast sites, where low tides occurred in the morning, were largely spared. In addition, while the heatwave was associated with substantial short-term changes in acorn barnacle, rockweed, and California mussel assemblages, lasting impacts (1 year) were only observed in the mussel assemblage at the one Salish Sea site where this species is common. These findings will aid in forecasting both short-term and longer lasting impacts of future heatwave events and help direct potential mitigation efforts to regions and species assemblages where impacts will likely be greatest.
Inspiratory muscle training facilitates liberation from mechanical ventilation in subacute critically ill patients—a randomized controlled trial
Authors: Wang Shu-Jane , Fang Tien-Pei , Rowley Daniel D. , Liu Nan-Wei , Chen Jui-O , Liu Jui-Fang , Lin Hui-Ling 
Published: January 2025

BackgroundPatients undergoing mechanical ventilation often develop rapid diaphragmatic atrophy, respiratory muscle weakness, and dysfunction, which are associated with prolonged duration of ventilation. This study aimed to evaluate whether Inspiratory Muscle Training (IMT) facilitates weaning from mechanical ventilation and enhances muscle strength in critically ill, subacute adult patients, while examining the relationship between IMT and relevant clinical laboratory values.MethodsIn this randomized clinical trial, patients admitted to the intensive care unit requiring mechanical ventilation for more than 2 days, with stable hemodynamics and resolved acute conditions, were enrolled. Participants were randomly assigned to the IMT or no-IMT group. The IMT group received training twice daily, 5 days a week, for three consecutive weeks. The primary outcome was ventilator duration. The primary outcome measure was the number of days until liberation from mechanical ventilation. The secondary outcomes of interest were respiratory muscle strength and biomarker levels.ResultsThirty-three subjects (17 in the IMT group, 16 in the no-IMT group) were included in the final analysis. The IMT group had significantly shorter ventilator days (12.6 ± 5.2 vs. 18.1 ± 8.8, p = 0.04). IMT intervention significantly reduced rapid shallow breathing index and improved respiratory muscle strength, with greater maximum inspiratory pressure (p &lt; 0.01), maximum expiratory pressure (p = 0.03), and peak expiratory flow (p = 0.01). A moderate positive correlation was observed between IMT and increased creatinine levels (rs = 0.54, p = 0.01), whereas the no-IMT group showed a reduction.ConclusionIMT significantly shortened ventilator duration and improved respiratory muscle strength. A moderate correlation between increased creatinine levels and respiratory muscle strength was observed, suggesting that creatinine may be a potential biomarker for muscle recovery during IMT.Clinical trial registrationThis study was registered at ClinicalTrials.gov (NCT06611683).
Meta-analysis of the efficiency and safety of neoadjuvant therapy with immune checkpoint inhibitors in resectable hepatocellular carcinoma
Authors: Tuersun Adili , Yasen Yadikaer , Mohetaer Munire , Hou Guanxin , Cheng Gang , Zhao Xin 
Published: January 2025

PurposeImmunotherapy as a neoadjuvant treatment approach has achieved certain therapeutic effects in various types of cancer. However, in the specific cancer type of hepatocellular carcinoma (HCC), standardized protocols for neoadjuvant immunotherapy remain to be defined. This systematic review and meta-analysis focus on evaluating the efficacy and safety of neoadjuvant immunotherapy in the treatment of HCC, aiming to provide a robust basis for clinical decision-making.MethodsThis study systematically searched databases such as PubMed, EMBASE, the Cochrane Library, and conference proceedings to identify clinical trials focusing on patients with HCC undergoing neoadjuvant immunotherapy. The Review Manager 5.4 software was applied to estimate the odds ratio (OR) of effect sizes and their corresponding 95% confidence intervals (CI).ResultsImmune checkpoint inhibitors (ICIs) demonstrate significant efficacy in improving pathological outcomes and safety profiles in patients with resectable hepatocellular carcinoma (HCC). Specifically, ICIs significantly increase the pathological complete response (pCR) rate (OR = 0.23, 95% CI [0.14, 0.37], p &lt; 0.00001) and major pathological response (MPR) rate (OR = 0.47, 95% CI [0.32, 0.70], p = 0.0002). They also markedly enhance the objective response rate (ORR) (OR = 0.42, 95% CI [0.28, 0.63], p &lt; 0.0001). Furthermore, ICIs potentially improve the surgical resection rate (OR = 3.91, 95% CI [2.05, 7.45], p &lt; 0.0001) and reduce the incidence of grade 3–4 treatment-related adverse events (TRAEs) (OR = 0.27, 95% CI [0.17, 0.44], p &lt; 0.00001), indicating both therapeutic benefits and acceptable toxicity profiles.ConclusionNeoadjuvant immunotherapy shows promise in the treatment of resectable HCC. Nonetheless, to further validate its efficacy, more large-scale, well-designed clinical trials are necessary to provide conclusive evidence.Systematic review registrationThis comprehensive review adheres to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) standards and has been carried out as per a preregistered protocol (PROSPERO registration number: CRD42024560660).
Application of 2D polymerase chain reaction for single-tube detection of high-risk human papillomaviruses
Authors: Wang Weifeng , Jiang Min , Liu Ying , Wu Xuan , Chen Yan , Zhang Xiaoyun , Liu Weiwei 
Published: January 2025

PurposeThe persistent infection of high-risk HPV (HR-HPV) is intricately linked to the onset and progression of cervical cancer. This research endeavored to develop a high-throughput 2D PCR method for closed-tube genotyping of 11 HR-HPVs.MethodsBase-quenched probes were specifically designed for FAM, VIC, and CY5 channels. The 2D PCR system underwent optimization, with its detection performance assessed in terms of specificity and sensitivity. Plasmid mixtures was used to simulate multiple infections of HPV, providing preliminary insights into the detection efficacy and throughput of the 2D PCR technology. Ultimately, the detection capability of this method was assessed using clinical samples.ResultsThe sequenced tags, when paired with primers, could generate Tm differences exceeding 3°C. These were then integrated with a fluorescent channel and Tm to differentiate and identify target genes upon detection. The refined 2D PCR system was confirmed to be free from cross-reactions and exhibited high specificity, capable of detecting 12 target genes within a single tube. A total of 294 cervical exfoliated cell samples were tested using 2D PCR and flow fluorescence hybridization method. The overall concordance between the two detection methods was 96.17% (Kappa = 0.910).ConclusionThe 2D PCR method, which integrates asymmetric PCR amplification with melting curve analysis, has the capacity to detect 11 types of HR-HPVs across three channels. This closed-tube detection approach offers several benefits including high throughput, straightforward operation, and low detection cost. Consequently, it can be effectively utilized for early screening and prevention of cervical cancer.
Latencies of conditioned vocal responses to hearing test tones in killer whales (Orcinus orca)
Authors: Stephens Jared , Accomando Alyssa W. , Nease Kayla , Branstetter Brian K. , Robeck Todd R. 
Published: January 2025

IntroductionPerceived loudness is challenging to study in non-human animals. However, reaction time to an acoustic stimulus is a useful behavioral proxy for the assessment of perceived loudness. Understanding the effect of sound frequency and level on perceived loudness would improve prediction and modeling of anthropogenic noise impacts on marine mammals.MethodsIn this study, behavioral hearing tests conducted with two killer whales were analyzed to capture conditioned vocal response latency, which is the time between the onset of the acoustic signal and the onset of the response (i.e., reaction time).ResultsThe results showed that vocal reaction times decreased with increasing sensation level (i.e., sound pressure level above the baseline hearing threshold), while the effect of frequency on reaction time varied between the subjects. Reaction time as a function of sound duration is described, and equal-latency contours are presented.DiscussionThe data suggest that vocal reaction time decreases with increasing sensation level, therefore supporting the use of reaction time as a proxy for loudness perception in killer whales.
Bilateral lower limb symmetry during sit-to-stand and stand-to-sit tasks in stroke patients with hemiplegia
Authors: Hou Meijin , He Jian , Liu Dongwei , Guo Chenyi , Ma Ye , Luo Xiaobo 
Published: January 2025

IntroductionStroke patients with hemiplegia are at an increased risk of falling during sit-to-stand (Si-St) and stand-to-sit (St-Si) tasks, partly due to impaired bilateral lower limb symmetry. Maintaining symmetrical movement between the limbs in these tasks can help reduce fall incidence.MethodThis study aimed to investigate bilateral lower limb symmetry during Si-St and St-Si tasks in stroke patients with hemiplegia to compare their performance with healthy controls. Thirteen stroke patients and 13 healthy controls participated in the study. Participants were instructed to perform the 30-s chair stand test at their self-selected pace. Kinematic and kinetic parameters were calculated using OpenSim's inverse kinematics and inverse dynamics tools. Bilateral symmetry was quantified using the symmetry index (SI), with an asymmetry threshold set at 10%.ResultsThe stroke group exhibited significantly greater lower limb asymmetry in both kinematic and kinetic parameters during Si-St and St-Si tasks compared to the healthy controls, with the kinetic parameters being more pronounced. In the stroke group, notable bilateral asymmetry (SI &gt; 10%) was observed in the ankle joint angle (P &lt; 0.05) during both tasks. Furthermore, severe asymmetry (SI &gt; 30%) was identified joint moments across all lower limb joints, vertical ground reaction forces, and medial-lateral center of pressure.DiscussionThese findings highlight the need for targeted rehabilitation programs focusing on improving strength, coordination, and balance. Close monitoring of SI values, particularly for kinetic parameters, is recommended to guide and evaluate the effectiveness of these interventions.
Magnetic resonance imaging-based deep learning for predicting subtypes of glioma
Authors: Yang Zhen , Zhang Peng , Ding Yi , Deng Liyi , Zhang Tong , Liu Yong 
Published: January 2025

PurposeTo explore the value of deep learning based on magnetic resonance imaging (MRI) in the classification of glioma subtypes.MethodsThis study retrospectively included 747 adult patients with surgically pathologically confirmed gliomas from a public database and 64 patients from our hospital. Patients were classified into IDH-wildtype (IDHwt) (490 cases), IDH-mutant/1p19q-noncodeleted (IDHmut-intact) (105 cases), and IDH-mutant/1p19q-codeleted (IDHmut-codel) (216 cases) based on their pathological findings, with the public database of patients were divided into training and validation sets, and patients from our hospital were used as an independent test set. The models were developed based on five categories of preoperative T1-weighted, T1-weighted gadolinium contrast-enhanced, T2-weighted and T2-weighted fluid-attenuated inversion recovery (T1w, T1c, T2w and FLAIR) magnetic resonance imaging (MRI) of four sequences and mixed imaging of the four sequences, respectively. The receiver operating characteristic curve (ROC), area under the curve (AUC) of the ROC were generated in the jupyter notebook tool using python language to evaluate the accuracy of the models in classification and comparing the predictive value of different MRI sequences.ResultsIDHwt, IDHmut-intact and IDHmut-codel were the best classified in the model containing only FLAIR sequences, with test set AUCs of 0.790, 0.737 and 0.820, respectively; and the worst classified in the model containing only T1w sequences, with test set AUCs of 0.621, 0.537 and 0.760, respectively.ConclusionWe have developed a set of models that can effectively classify glioma subtypes and that work best when only the FLAIR sequence model is included.
Associations of comprehensive dietary antioxidant index with postmenopausal femur bone mineral density and osteoporosis: data from the national health and nutrition examination survey
Authors: Sun Jianbo , Wang Jie , Hu Wu , Huang He , Zhao Hongmou 
Published: January 2025

ObjectivesThe study aimed to explore associations of the comprehensive dietary antioxidant index (CDAI) with femur bone mineral density (BMD) and risk of osteoporosis in American postmenopausal women.MethodsA total of 2,862 participants from the National Health and Nutrition Examination Survey were included in this study. The relationship between the CDAI and femur BMD was assessed via weighted multivariate linear regression model. The odds ratios (ORs) and 95% confidence intervals (95% CIs) for the association between the CDAI and the risk of osteoporosis was assessed by weighted logistic regression model. Moreover, the nonlinear relationship was also characterized by smooth curve fitting and weighted generalized additive model. The two-piecewise linear regression models and a recursive algorithm were used to find the inflection points.ResultsAfter adjusting all covariates, the weighted multivariable linear regression models demonstrated that the CDAI was positively correlated with femur BMD. Moreover, there were nonlinear relationships between CDAI and risk of osteoporosis. In the age below 70 years, the risk of osteoporosis decreased to 60.6 and 92.2% with each unit increase in CDAI value before and after the inflection point (−2.268), respectively. In the 70 years or older, the risk of osteoporosis decreased to 80.4% with each unit increase in CDAI value before the inflection point (−1.479). The weighted logistic regression model demonstrated that compared to the first tertile of CDAI, the highest tertile of CDAI was significantly associated with a lower risk of osteoporosis, with ORs of 0.375 (95% CI 0.284, 0.495) for individuals under the age of 70, and 0.626 (95% CI 0.481, 0.814) for individuals aged 70 or above.ConclusionThe present study indicated that postmenopausal women with higher CDAI scores have a lower risk of osteoporosis. In addition, there is a non-linear relationship between CDAI and the risk of osteoporosis. This finding suggests that the adoption of a comprehensive antioxidant dietary structure represented by high CDAI scores may have a positive impact on the prevention and management of osteoporosis in postmenopausal women. Particularly for those with lower CDAI scores, early screening and intervention for osteoporosis may be necessary.
Investigating the role of cathepsins in breast cancer progression: a Mendelian randomization study
Authors: Zhou Shengyi , Sun Yizhou , Zha Wenzhang , Zhou Guangjun 
Published: January 2025

BackgroundBreast cancer, a major threat to women’s health worldwide, has mechanisms of onset that remain unclear. Within the human lysosomal system, a class of enzymes known as cathepsins exhibit elevated expression levels in various malignant tumors, suggesting that they may play key roles in cancer progression.MethodsThis study employed the two-sample Mendelian randomization (MR) approach to investigate the potential causal relationship between cathepsin levels and the risk of developing breast cancer. Furthermore, we conducted MR analysis using eQTL data to investigate how gene expression, mediated by cathepsins, affects the occurrence of different types of breast cancer and assessed the regulatory effects of cathepsins.ResultsMR analysis revealed that increased levels of cathepsin E are associated with a greater risk of malignant breast tumors (IVW: p = 0.006, OR = 1.103, 95% CI = 1.028–1.184), and increased levels of cathepsin F are associated with an increased risk of in situ breast cancer (IVW: p = 0.031, OR = 1.190, 95% CI = 1.016–1.394). Additionally, cathepsin Z has a protective effect against in situ breast cancer (IVW: p = 0.017, OR = 0.846, 95% CI = 0.737-0.971). Cathepsin E can mediate the effects of APBB1IP, NT5C3B, and ZNF66 on HER2-negative breast cancer, as well as the effects of DHRS9, CDK12, and CD247 on HER2-positive breast cancer. Cathepsin F can mediate the effects of ANXA2R and ZNF605 on in situ breast cancer. Cathepsin Z can mediate the effects of PRX, CRY2, ADCY3, and PELATON on in situ breast cancer.DiscussionThese findings highlight the dual roles of cathepsins as potential risk and protective factors for breast cancer, underscoring their potential in diagnostic and therapeutic strategies.