Browse Articles

Machine learning-based high-benefit approach versus traditional high-risk approach in statin therapy: the Shizuoka Kokuho database study

Risk of recurrence and bleeding in patients with cancer-associated venous thromboembolism in the direct oral anticoagulants era: Findings from the TULIPE registry

Background The introduction of direct oral anticoagulants (DOACs) for venous thromboembolism (VTE) treatment has led to their widespread adoption in clinical practice, potentially influencing management strategies and patient outcomes. However, real-world data on cancer-associated VTE in the DOAC era remain limited. This study aimed to evaluate the clinical characteristics and long-term outcomes of patients with cancer- and non-cancer-associated VTE in a real-world setting. Methods We retrospectively analyzed patients diagnosed with deep vein thrombosis (DVT) using lower-extremity venous ultrasound between January 2015 and August 2020 at the University of Tsukuba Hospital, a tertiary academic referral center in Japan. Results The cohort included 2,281 patients with DVT, comprising 1,152 with active cancer (cancer group) and 1,129 without cancer (non-cancer group). The cumulative 5-year incidence of recurrent VTE was significantly higher in the cancer group than in the non-cancer group (25% vs. 10%, P < 0.001). After adjusting for confounders and accounting for the competing risk of mortality, cancer remained a significant risk factor for recurrence (adjusted subdistribution hazard ratio [sHR]: 2.00; 95% confidence interval [CI]: 1.46–2.74). Similarly, the cumulative 5-year incidence of major bleeding was significantly higher in the cancer group (30% vs. 9.6%, P < 0.001). After adjustment, the risk of major bleeding remained significantly elevated in the cancer group compared to that in the non-cancer group (adjusted sHR: 2.69; 95% CI: 1.90–3.81). In the cancer group, discontinuation of bleeding-related anticoagulation therapy was associated with increased VTE recurrence (P < 0.001), whereas no such association was observed in the non-cancer group (P = 0.716). Conclusions In the DOAC era, similar to the warfarin era, patients with cancer exhibited significantly higher rates of VTE recurrence and major bleeding than those without cancer.

Influence of surface quality on corrosion resistance of stainless steel and aluminum alloy butt welds after innovative finishing

Study on energy evolution and crack propagation of filling mortar-rock at different loading rates

Shotcrete, as a highly efficient reinforcement material widely used in geotechnical engineering, demonstrates irreplaceable advantages in projects such as tunnel excavation, mine roadway support, and slope protection. However, when shotcrete becomes tightly bonded with rock masses, the energy evolution and crack initiation mechanisms between the two materials exhibit remarkable complexity. Different loading rates significantly alter the internal stress distribution and deformation characteristics within the composite system, thereby influencing the patterns of energy evolution and crack propagation. Consequently, it is essential to investigate the mechanical behavior of filling mortar-rock under varying loading rates. Firstly, uniaxial tests with four loading rates were conducted for the composite specimens, and the effects of loading rate on the mechanical parameters, energy evolution and fracture modes were analyzed. The results show that the mechanical parameters of the composite decrease with the rise of loading rate, and the decrease reaches the maximum when the mortar strength is M20. All three types of energies decreased exponentially with increasing loading rate. The decrease reaches the maximum at a mortar strength of M40. Subsequently, a damage model applicable to the composite specimens was established based on the development rules of the dissipated energy and the compaction coefficient. Finally, PFC2D was used to simulate and analyze the specimens with mortar grade of M30 to investigate the crack propagation and stress evolution process at four loading rates. The results show that tensile stress is the causative factor of crack propagation. The cracks first appeared at the interface, and were mainly distributed on both sides of the specimen after cracking.

Stromatolites and pulsed oxygenation events in the Mesoproterozoic Longjiayuan formation of western Henan: evidence for life-environment co-evolution

Abstract The oxygen level in the ocean and atmosphere played a crucial role in the development of Precambrian stromatolites. The Mesoproterozoic represents a critical interval in Earth’s history, characterized by persistently low atmospheric and oceanic oxygen levels under which stromatolites flourished. Stromatolites are particularly abundant in Member II of the Mesoproterozoic Longjiayuan formation in western Henan Province. To investigate the relationship between stromatolites and redox conditions, petrographic and geochemical analyses were conducted on siliceous-banded dolomites and stromatolitic dolomites from the Longjiayuan Formation. The results show that the macromorphology of stromatolites in Member II is classified into stratiform, undulatory, domical, conical, and columnar morphologies. Microscopically, the stromatolites exhibit alternating light and dark laminae, with occasional ooids and spherules. The CeSN/CeSN* values recorded in carbonate rocks from Member II show negative anomalies, reflecting oxidizing conditions influenced by environmental changes and microbial activity. These stromatolite records and oxygen fluctuations in the Mesoproterozoic shallow marine environment provide a valuable basis for studying the co-evolution of early life and the environment.

Associations of estimated glucose disposal rate with kidney stones in U.S. non-diabetic adults and possible mediating mechanisms: NHANES 2009–2020

Background Kidney stone formation has been linked to insulin resistance (IR). However, the association between the estimated glucose disposal rate (eGDR) – a novel surrogate marker for IR – and kidney stone occurrence in non-diabetic adults remains unclear. Methods We analyzed data from adult participants in the National Health and Nutrition Examination Survey (NHANES) collected between 2009 and 2020 who self-reported a history of kidney stones. To assess the relationship between eGDR and kidney stones, we applied a range of statistical methods, including weighted proportions, multivariable logistic regression, restricted cubic splines (RCS), receiver operating characteristic (ROC) curve analysis, subgroup analysis, and mediation analysis. Results The final analysis included 8,051 participants, of whom 8.71% reported a history of kidney stones. Multivariable logistic regression revealed that, compared to the lowest eGDR quartile, the fully adjusted odds ratios (95% confidence intervals) for kidney stone in the second, third, and fourth quartiles were 0.87 (0.61–1.26), 0.54 (0.34–0.85), and 0.46 (0.28–0.77), respectively. The RCS plot indicated a significant non-linear inverse association between eGDR and kidney stone risk. ROC curve analysis showed that the association between eGDR and the risk of kidney stones was more pronounced compared to the other five IR indicators, as evidenced by a higher area under the curve. Mediation analysis identified albumin (ALB) and red cell distribution width (RDW) as partial mediators in the association between IR and kidney stones. Conclusion Our research results indicate that lower levels of eGDR are associated with an increased risk of developing kidney stones in non-diabetic adults. Furthermore, ALB and RDW may partially mediate the relationship between IR and kidney stones.

FTO-mediated MMP1 m6A modification promotes osteogenic differentiation of bone marrow mesenchymal stem cells via the ERK pathway in congenital scoliosis

Retraction: Bidirectional rotating flow of nanofluid over a variable thickened stretching sheet with non-Fourier’s heat flux and non-Fick’s mass flux theory

A computational pipeline for image-based statistical analysis of biomolecular condensates dynamics using morphological descriptors

Implementation of Point-of-Care PCR-testing for the diagnosis of respiratory infections in vulnerable patient populations

Background Point-of-Care (POC) PCR-testing provides accurate, and timely results in diagnosing respiratory viral infections. Despite these benefits, stakeholder perceptions and its potential for improving health outcomes remain insufficiently explored. Therefore, we aim to explore the acceptability and feasibility of POC PCR-testing implementation in settings attended by vulnerable populations. Methods We conducted semi-structured interviews with stakeholders from ambulatory settings, including decision makers, molecular diagnostics experts, healthcare workers, and patients. Study settings included two emergency departments (one adult, one pediatric), two oncology units, and two dialysis units, including both POC PCR implementors and non-implementors. We thematically analyzed our data, drawing on components of the Thematic Framework of Acceptability, the CFIR, and the Consolidated Framework for Sustainability Constructs in Healthcare. Results Stakeholders recognized COVID-19, influenza A&B, and RSV as significant healthcare challenges and generally viewed POC PCR-testing as fit to address them. Stakeholders exhibited varying levels of knowledge about POC PCR-testing, with lower levels among non-implementors. While perceived benefits included rapid results, accuracy, and automation, concerns regarding cost, workload, and device throughput remained. Stakeholders recognized testing’s clinical impact in terms of transmission prevention and patient management. Perceived infection risk, disease prevalence, governmental regulations, and funding availability further influenced implementation decisions. Implementation processes were deemed straightforward, but limited involvement in decision-making processes dissatisfied some healthcare providers. End-users valued POC PCR-devices’ ease-of-use, while molecular diagnostics experts stressed that testing should be performed by medical staff. Sustainability considerations emphasized the stepwise development of testing guidelines, adaptation to local workflows, and continuous evaluation and quality control. Conclusion POC PCR-testing for respiratory viral infections is generally accepted. Knowledge, cost, workload and perceived benefit of testing guide decisions, while testing upon suspicion is favored over screening strategies due to per-test-cost and low device throughput. Sustainability requires cost-efficiency through guidelines and outcome monitoring. While test accuracy and turnover-time are valued, clinical impact requires further investigation.

Effects of neoadjuvant immunotherapy on hearing in patients with head and neck squamous cell carcinoma

Abstract Immune checkpoint blockade (ICB) is a commonly used treatment modality for cancer with a growing list of oncologic indications. Ototoxicity is a potential immune-related adverse event of ICB treatment, but the risk of hearing loss after ICB remains unknown. This retrospective chart review sought to identify individuals who received ICB and had available audiometric data before and after treatment in order to identify clinically meaningful changes in hearing. This single center, institutional chart review examined hearing function data in patients who underwent audiometry before and after ICB treatment. Measures included pure tone thresholds, distortion product otoacoustic emissions (DPOAEs), tympanometry, and word recognition scores. Ototoxicity was assessed using the American Speech-Language-Hearing-Association (ASHA) and Common Terminology Criteria for Adverse Events (CTCAEv5.0) guidelines where applicable. We identified twelve individuals with newly diagnosed, advanced-stage Head and Neck Squamous Cell Carcinoma (HNSCC) who received neoadjuvant ICB on a clinical trial. Eleven of twelve (92%) patients (8 male, 4 female, age 41–79 years) did not meet criteria for hearing threshold changes. One patient demonstrated a 10 dB shift at two consecutive frequencies in one ear, meeting the minimum ASHA criteria for significant change. Speech audiometry and tympanometry identified no differences in speech understanding or middle ear function pre-and post-treatment. Variations in DPOAE amplitudes were noted, potentially indicating early outer hair cell damage despite stable audiometric thresholds. In this small data set of newly diagnosed advanced-stage HNSCC, there appears to be a low incidence of significant hearing changes following neoadjuvant ICB treatment. Larger, prospective studies with long-term follow-up are needed to evaluate late-onset ototoxicity. Cancer survivors treated with neoadjuvant immune checkpoint blockade for advanced-stage head and neck squamous cell carcinoma (HNSCC) appear to have a low risk of acute hearing loss based on this study. While significant changes in hearing thresholds were not observed, subtle alterations in cochlear outer hair cell function were detected, suggesting the importance of long-term monitoring to capture potential delayed effects on hearing. This insight helps reassure patients about the immediate ototoxic risks while highlighting the need for continued vigilance in hearing assessment during follow-up.

Molecular and morphological alterations in breast tissue of transgender patients undergoing dihydrotestosterone therapy

Many patients undergoing gender-affirming surgery (GAS) opt for reconstructive procedures rather than total mastectomy to achieve a more masculine chest contour. The impact of dihydrotestosterone (DHT) treatment on breast tissue remains unclear. This study evaluates the morphological changes and protein expression levels in breast tissue associated with hormonal and molecular pathways in patients receiving short-term or long-term DHT treatment before GAS. A total of 230 breast tissue samples were categorized into three groups: nontreatment, short-term treatment (STT, < 12 months), and long-term treatment (LTT, ≥ 12 months). Paired samples (n = 33) were stained for estrogen receptor (ER) and androgen receptor (AR). NanoString Digital Spatial Profiling (DSP) analysis was conducted on a subset (n = 17), including two incidental breast cancer (BC) cases. Among morphological parameters assessed, atrophy and secretory changes differed significantly among groups. In the LTT group, ER-alpha expression was elevated in lactiferous ducts, while AR H-scores were higher in both STT and LTT groups. ER and AR expression levels were strongly correlated in the STT and LTT groups (r = 0.93–0.99). DSP analysis revealed increased ER expression in the treated groups and higher AR expression in peripheral lobules of the LTT group (log2FC = 1.3, p = 0.03). Ki-67, CDK6, and CD45 levels decreased in the LTT group, while INPP4B and BCL6 increased. DHT treatment leads to significant morphological and molecular changes in both benign and cancerous breast tissue. Altered expression of biomarkers such as INPP4B and CD45 in the LTT group and breast cancer samples suggests a potential role in BC development, warranting further investigation.

An improved lightweight tongue segmentation model with self-attention parallel network and progressive upsampling

Identification of differentially expressed genes associated with ferroptosis in ulcerative colitis

Purpose To identify ferroptosis-related genes associated with the development of Ulcerative colitis (UC), through bioinformatics and basic experiments. Methods Ferroptosis-related genes were identified from UC microarray data extracted from the GEO database and FerrDb. GO and KEGG pathway enrichment analyses were performed. Hub genes were identified through PPI analysis, leading to TF-hub gene and miRNA-hub gene regulatory network, predicting potential drug candidates by DSigDB. RT-qPCR, WB and IHC were employed to validate hub gene expression in animal samples. Clinical samples were gathered from Normal examiners and UC patients and IHC was performed to verify SLC7A5. Results Eleven ferroptosis-related DEGs were identified (nine upregulated and two downregulated genes) in UC, with eight genes chosen from the PPI network. MCC algorithm demonstrated that SLC7A11, PSAT1, SLC7A5, ACSF2, and ACSL4 were hub genes, predicting TFs, miRNAs and drugs. RT-qPCR confirmed significant differential expression of SLC7A5, ACSL4, and ACSF2. WB and IHC of mouse samples, as well as IHC of clinical samples, revealed significantly elevated SLC7A5 expression in the UC group compared to controls. Conclusion SLC7A5 emerged as a potential focus for understanding UC pathogenesis, potentially influencing ferroptosis. FOXP3, STAT6, and hsa-miR-186-5p are implicated in UC and ferroptosis, with minocycline identified as a potential treatment by inhibiting ferroptosis.

A dual input dual spliced network with data augmentation for robust modulation recognition in communication countermeasures

A novel incision design for Vibrant SoundBridge®︎ implantation prior to auricular reconstruction for microtia

Objective This study aimed to present and evaluate a surgical approach for placing a Vibrant Soundbridge® (VSB) device prior to auricular reconstruction in patients with microtia atresia. The goal was to determine whether an incision line for VSB implantation, located sufficiently posterior to the planned area of auricular reconstruction, could prevent interference with subsequent auricular surgeries and ensure stable hearing outcomes. Methods We retrospectively examined four patients with unilateral microtia who underwent VSB implantation before auricular reconstruction. The incision line was placed approximately 5 cm posterior to the posterior edge of the temporomandibular joint, ensuring that it remained at least 2 cm away from the future area of auricular reconstruction. The VSB implantation procedure involved skin incision, subperiosteal dissection, mastoidectomy, and placement of the VSB implant, with a floating mass transducer attached to the head of the stapes. More than a year later, two-stage auricular reconstruction was performed. Results All patients underwent successful auricular reconstruction after VSB implantation. During the first stage of costal cartilage grafting, subcutaneous pockets were created without encountering congestion or compromised skin flaps, and the grafted cartilage maintained a good contour. In the second stage of auricular elevation, the mastoid fascial flap was elevated with adequate blood flow, and careful dissection prevented exposure or damage to the VSB device. Postoperatively, the reconstructed auricles exhibited stable contour. Audiometric evaluation revealed no deterioration in hearing outcomes, indicating that the VSB device worked well. Conclusion This method allows safe and effective VSB implantation prior to auricular reconstruction, without hindering subsequent procedures. By maintaining an appropriate distance between the incision line and planned area of reconstruction, early hearing rehabilitation and successful auricular reconstruction can be achieved. This approach may serve as a practical standard for treating patients with microtia atresia who require early hearing intervention.

Nutrient dynamics in the berry, bean, and husk of six Coffea canephora genotypes throughout fruit maturation

Evidence Based Gait Analysis Interpretation Tools (EB-GAIT) treatment recommendation and outcome prediction models to support decision-making based on clinical gait analysis data

Clinical gait analysis (CGA) has historically relied on clinician experience and judgment, leading to modest, stagnant, and unpredictable outcomes. This paper introduces Evidence-Based Gait Analysis Interpretation Tools (EB-GAIT), a novel framework leveraging machine learning to support treatment decisions. The core of EB-GAIT consists of two key components: (1) treatment recommendation models, which are models that estimate the probability of specific surgeries based on historical standard-of-practice (SOP), and (2) treatment outcome models, which predict changes in patient characteristics following treatment or natural history. Using Bayesian Additive Regression Trees (BART), we developed and validated treatment recommendation models for 12 common surgeries that account for more than 95% of the surgery recorded in our CGA center’s database. These models demonstrated high balanced accuracy, sensitivity, and specificity. We used Shapley values for the models to enhances interpretability and allow clinicians and patients to understand the factors driving treatment recommendations. We also developed treatment outcome models for over 20 common outcome measures. These models were found to be unbiased, with reliable prediction intervals and accuracy comparable to experimental measurement error. We illustrated the application of EB-GAIT through a case study, showcasing its utility in providing treatment recommendations and outcome predictions. We then use simulations to show that combining recommendation and outcome models offers the possibility to improve outcomes for treated limbs, maintain outcomes for untreated limbs, and reduce the number of surgeries performed. For example, under the counterfactual situation where femoral derotation osteotomies are administered only when they align with historical standard of practice (> 50% probability of surgery) and are predicted to improve the Gait Deviation Index (change > 7.5 points), the model predicts a 11 percentage point reduction in surgeries (26% limbs currently, 15% limbs simulated), a 6 point improvement in Gait Deviation Index among treated limbs (6 currently, 12 simulated), and no change in Gait Deviation Index for untreated limbs (2 currently, 2 simulated). EB-GAIT represents a significant step toward precision medicine in CGA, offering a promising tool to enhance treatment outcomes and patient care. The EB-GAIT approach addresses the limitations of the conventional CGA interpretation method, offering a more structured and data-driven decision-making process. EB-GAIT is not intended to replace clinical judgment but to supplement it, providing clinicians with a second opinion grounded in historical data and predictive analytics. While the models perform well, their effectiveness is constrained by historical variability in treatment decisions and the inherent complexity of patient outcomes. Future efforts should focus on refining model inputs, incorporating surgical details, and pooling data from multiple centers to improve generalizability.

In vitro haploid plantlet regeneration through anther culture in some local types of Syrian cauliflower (Brassica Oleracea var. botrytis L.)

Fractionation mechanisms of rare earth element speciation in granitic weathering profiles: Metallogenic implications for the kuanyu ion-adsorption REE deposit, dechang, SW China

The Kuanyu ion-adsorption rare earth element (REE) deposit, Sichuan’s first economically viable resource of its type, remains underexplored in terms of REE fractionation and enrichment mechanisms within its weathering profiles. This study systematically resolves REE speciation patterns and light-to-heavy REE (LREE/HREE) differentiation processes, advancing the metallogenic framework fo r such deposits. Analytical results demonstrate: (1) A vertically progressive enrichment of LREE-dominated REE concentrations from bedrock to topsoil, with the fully weathered layer serving as the primary enrichment zone; (2) Weathering of primary REE-bearing minerals and subsequent secondary mineral formation as drivers of elemental redistribution; (3) Contrasting controls by clay minerals, iron-manganese oxides, and humic acids—clay minerals preferentially adsorb LREEs, while iron-manganese oxides exhibit stronger HREE affinity through inner-sphere complexation, and humic acids enhance HREE mobility via stable complex formation. These findings establish iron-manganese oxides and organic ligands as dual regulators of REE fractionation, refining predictive models for ion-adsorption REE exploration in granitic weathering systems.