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Normal reference values of three-dimensional speckle-tracking echocardiography-derived aortic valve annular dimensions in healthy adults—a detailed analysis from the MAGYAR-Healthy Study
Get PDFTensile Strength of Continuous and Disordered Fibrous Mats: A Tale of Two-Length Scales
No full textContinuous and disordered fibrous mats are ubiquitous multi-scalar materials endowed with diverse functionalities and nonlinear mechanical properties. Gaining deeper insights into mechanical properties, such as tensile strength and breaking elongation, can broaden the scope of potential applications for these fibrous mats across various fields. Here, a unified tensile strength model applicable to electrospun and melt-blown mats is presented that hinges on the tensile strength of constituent fibers, fiber orientation, fiber volume fraction, and the specimen dimensions considered during uniaxial tensile testing. Espoused by the established body of literature, fiber stretching has been considered a key deformation mechanism for predicting the tensile strength of these fibrous mats. Regardless of inconsistencies and anomalies in fiber morphology, a good agreement has been obtained between the theoretical and experimental values of tensile strengths of polylactic acid (PLA)-based electrospun and polypropylene-based melt-blown mats. The model's robustness is evident in its successful prediction of a nearly two-order magnitude reduction in tensile strength for electrospun mats compared to their constituent fibers. A roadmap to enhance the tensile strength of fibrous mats has been developed by analyzing key fiber and structural parameters. Further, higher-order nematic orientation parameters quantified anisotropy in the fibrous mats before and after tensile loading
Slide laryngotracheopexy for idiopathic subglottic stenosis
Get PDFIdiopathic subglottic stenosis (iSGS) is a rare fibroinflammatory disorder characterized by scar tissue formation in the subglottic and tracheal regions. This study evaluated the long-term outcomes of a novel, single-step surgical technique that redefines the glottic and subglottic airway using local tracheal grafts.Thirteen patients (2 male and 11 female) diagnosed with iSGS who underwent slide laryngotracheopexy were enrolled in this study. The diagnosis of iSGS was confirmed through endoscopic assessment, CT scanning, and autoimmune blood testing. Patients completed post-operative Voice Handicap Index (VHI), Quality of Life (QoL), and MD Anderson Dysphagia Inventory (MDADI) questionnaires, and spirometry assessments were conducted.All patients were successfully extubated in the operating room following surgery. None of the patients required intensive care unit treatment. The average hospital stay was 14 days. A temporary tracheotomy was needed in one case because of excessive crusting. Adjuvant endolaryngeal laser surgery was performed in three cases. In one case, mitomycin-C therapy was administered to treat granulation. Post-operative quality of life (QoL) assessment, peak inspiratory flow (PIF), and scores from the MDADI and VHI questionnaires were 9.0 (± 2.2), 2.8 l/s (± 0.83), 95.6 (± 4.3), and 18.7 (± 13.4), respectively.Slide laryngotracheopexy was a safe and dependable technique for cases classified as Cotton-Myers II-IV grade iSGS. The use of a tracheal flap was advantageous to ensure optimal mucosal function. Slide laryngotracheopexy may be employed following multiple endolaryngeal interventions, whereas adjuvant CO2 laser surgery or mitomycin-c therapy may be considered in cases involving granulation tissue formation.Retrospective case series review
Instantaneous center of rotation, the first step to build up the digital laboratory of complex motions
Get PDFCalculating instantaneous centers of rotation to describe combined rotational and translational motions has a long history in many fields of applied science and basic rigid body kinematics. However, only some theoretical studies have explored the fundamental characteristics of this system. This study used digital three-dimensional modeling and computing methods to examine the system's operation in a controlled in vitro-like environment. The effects of inaccurate registrations on the resulting motion were also analyzed. We registered 28.65, 14.33 and 9.55 EcD_ratios for 2°, 4° and 6° of closure respectively, and described a structured, predictable framework based on a solid mathematical background. Our findings align with previous publications, indicating that the longstanding debate over the pure rotation of the temporomandibular joint arises from misinterpretations of scientific findings due to a lack of fundamental knowledge of the basic characteristics of the system. Our simplified geometrical approach significantly reduces the complexity of the existing complex kinematic model, making it more accessible for practical applications, easier to understand, and potentially more applicable in orthopedics or temporomandibular joint radiology. We identified five fundamental characteristics of the system as we described the effects of the acting translational component in the complex motion. We also presented a detailed model concerning the effects of inaccurate rotation axis registration on the resulting compromised transformation, improving our understanding of the error tolerance level of articulation systems. Our results show that the system might tolerate errors as great as 3-4 cm in some settings in the parallel error direction, while in case of circular and perpendicular error types an approximately 2 mm axis registration error would exceed the clinically desirable 0.1 mm occlusal error level. Our experimental modeling strategy might provide extensive data for machine learning and for analyzing and comprehending the fundamental characteristics of different complex motion systems in the future
The Impact of Professional Development Programs on English as a Foreign Language Instructors in Higher Education Institutions
Get PDFProfessional development (PD) is crucial for teacher growth, yet research on EFL instructors in higher education remains scarce. In Indonesia, PD research focuses more on secondary and primary school teachers, and the research that emphasises EFL teachers’ professionalism is limited. However, EFL teachers’ PD plays an important role in preparing future teachers for better employment opportunities and international communication, so it is a critical component of higher education curricula. This study explores the impact of professional development programs on EFL instructors in Indonesian universities, focusing on types of professional development programs and personal initiatives. Ten EFL instructors from five different universities in Indonesia were recruited using a purposive sampling technique. Using a qualitative approach with semi-structured interviews, thematic analysis reveals that most professional development efforts are self-driven rather than institutionally supported. Key impacts of professional development programs and activities they have participated in on their professionalism include research collaboration, publication skills, ELT strategy improvements, networking, reflective teaching, and language proficiency gains. The findings underscore the need for customised professional development programs that address educators’ specific contexts, ensuring sustainable enhancements in teaching practices. This study highlights the critical role of independent professional development efforts in higher education and provides insights into structuring more impactful support systems for EFL instructors globally
Ultrasensitive detection and tracking of circulating tumor DNA to predict relapse and survival in patients with locally advanced cervical cancer: phase III CALLA trial analyses
Get PDFBACKGROUND: After chemoradiotherapy (CRT), 30%-50% of patients with locally advanced cervical cancer (LACC) relapse, highlighting the unmet need for prognostic biomarkers. In the global randomized CALLA trial (NCT03830866), the addition of durvalumab during and after CRT did not significantly improve progression-free survival (PFS) in a biomarker-unselected intent-to-treat population. We analyzed the association of ultrasensitive circulating tumor DNA (ctDNA) and circulating human papillomavirus (cHPV) DNA detection with relapse and survival in the largest dataset in LACC to date.; PATIENTS AND METHODS: In CALLA, adult women with stage IB2-IIB node-positive or IIIA-IVA any node-status LACC were randomized 1 : 1 to receive durvalumab + CRT or CRT alone. The NeXT Personal (Personalis) ultrasensitive tumor-informed assay with up to 1800 patient-specific variants was used for ctDNA and cHPV DNA analysis at baseline, cycle 3 day 1 (C3D1, post-CRT), and C6D1 (3 months post-CRT). Correlations were analyzed between ctDNA/cHPV DNA detection and outcomes [PFS, overall survival (OS)].; RESULTS: ctDNA was detected in 98.9% (183/185) of baseline samples, with no difference between treatment arms. Detection levels of ctDNA were predictive of disease progression and survival at baseline: hazard ratios (95% confidence intervals) comparing PFS and OS, respectively, in the ctDNA less than median versus ctDNA greater than median subgroups were 0.61 (0.28-1.35) and 0.55 (0.23-1.35) with durvalumab + CRT, and 0.49 (0.26-0.95) and 0.65 (0.33-1.28) with CRT. Post-treatment trends were similar and independent of stage or lymph node status. ctDNA detection at C3D1 occurred a median of 164 days (95% confidence interval 85-250) days before clinical progression. Baseline cHPV DNA levels were similar but were only predictive following treatment.; CONCLUSIONS: This study demonstrates the potential utility of ultrasensitive detection of ctDNA as a predictive and prognostic marker of disease progression and OS in LACC independent of disease stage. Copyright © 2025 The Author(s). Published by Elsevier Ltd.. All rights reserved
Prospective Randomized Trial of Rotor Ablation vs Conventional Ablation for Persistent Atrial Fibrillation : REAFFIRM Trial
Get PDFPulmonary vein isolation (PVI) is the cornerstone therapy for symptomatic drug-refractory atrial fibrillation yet is not curative in a large segment of patients. Focal and rotational drivers are proposed to be involved in atrial fibrillation mechanisms but their ablation has produced variable outcomes. REAFFIRM (The Randomized Evaluation of Atrial Fibrillation Treatment with Focal Impulse and Rotor Modulation Guided Procedures) trial (NCT-02274857) objective was to compare the safety and effectiveness of conventional ablation with and without Focal Impulse and Rotor Modulated (FIRM) ablation, guided by global basket mapping, for the treatment of persistent atrial fibrillation.Three hundred seventy-five patients were enrolled and randomized at 18 centers. The Intent-to-Treat population consisted of 350 patients (171 FIRM, 179 Conventional). Primary effectiveness was defined as single procedure freedom from atrial fibrillation/atrial tachycardia recurrence at 3 to 12 months post index procedure.Three hundred twenty-four patients completed the 12-month follow-up. Patients in the FIRM arm had a larger left atrium (P <0.01). Primary effectiveness at 3 to 12 months was 69.3% in FIRM and 67.5% in Conventional (NS), with no difference in ablation procedure time or safety. A subset of patients (41% FIRM, 49% Conventional) received extra ablation. Primary effectiveness in the on-treatment subgroups was 65% PVI-only, 69.6% PVI +extra, 77.7% FIRM+ PVI-only, and 57.7% FIRM+ PVI +extra (P=0.09).Intention-to-treat analysis failed to provide evidence for the superiority of adding ablation of focal or rotational sites to conventional ablation.URL: https://clinicaltrials.gov; Unique Identifier: NCT-02274857
From Microbial Switches to Metabolic Sensors: Rewiring the Gut–Brain Kynurenine Circuit
No full textThe kynurenine (KYN) metabolic pathway sits at the crossroads of immunity, metabolism, and neurobiology, yet its clinical translation remains fragmented. Emerging spatial omics, wearable chronobiology, and synthetic microbiota studies reveal that tryptophan (Trp) metabolism is regulated by distinct cellular “checkpoints” along the gut–brain axis, finely modulated by sex differences, circadian rhythms, and microbiome composition. However, current interventions tackle single levers in isolation, leaving a key gap in the precision control of Trp’s fate. To address this, we drew upon an extensive body of the primary literature and databases, mapping enzyme expression across tissues at single-cell resolution and linking these profiles to clinical trials investigating dual indoleamine 2,3-dioxygenase 1 (IDO1)/tryptophan 2,3-dioxygenase (TDO) inhibitors, engineered probiotics, and chrono-modulated dosing strategies. We then developed decision-tree algorithms that rank therapeutic combinations against biomarker feedback loops derived from real-time saliva, plasma, and stool metabolomics. This synthesis pinpoints microglial and endothelial KYN hotspots, quantifies sex-specific chronotherapeutic windows, and identifies engineered Bifidobacterium consortia and dual inhibitors as synergistic nodes capable of reducing immunosuppressive KYN while preserving neuroprotective kynurenic acid. Here, we highlight a framework that couples lifestyle levers, bio-engineered microbes, and adaptive pharmaco-regimens into closed-loop “smart protocols.” By charting these intersections, this study offers a roadmap for biomarker-guided, multidisciplinary interventions that could recalibrate KYN metabolic activity across cancer, mood, neurodegeneration, and metabolic disorders, appealing to clinicians, bioengineers, and systems biologists alike
Optimizing Bus Driver Scheduling: A Set Covering Approach for Reducing Transportation Costs
Get PDFCutting operational costs is a critical component for transportation agencies. To reduce these costs, agencies must optimize their scheduling. Typically, the total operating costs of transport include vehicle expenses and driver wages. Solving such tasks is complex, and optimal planning is usually broken down into multiple stages. These stages can include vehicle scheduling, driver shift planning, and driver assignment. This paper focuses specifically on developing a near-optimal driver schedule for a specified set of vehicle schedules. It shows how to efficiently assign drivers to predetermined optimal vehicle routes while ensuring compliance with regulatory constraints on driving hours. We address this challenge using a mathematical model based on the set covering problem, building on a framework established perviously. The set covering problem is typically formulated as an integer programming problem, solvable through column generation techniques. Our algorithm combines this method with heuristics, taking into account the practical aspects of the problem. The article also presents a computational analysis of the method using benchmark and real data
