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Enhancing the Nucleoside Analog Response with Translational Therapeutic Approaches to Overcome Resistance
No full textNucleoside analogs remain central to the treatment of hematologic malignancies and solid tumors, yet resistance frequently occurs, contributing to relapse and disease-related mortality. Rather than arising from a single mechanism, effective nucleoside analog activity requires successful navigation of multiple biological barriers, including cellular uptake, intracellular activation, nucleotide pool balance, genome surveillance, and mitochondrial stress responses. This review integrates recent advances describing how alterations at each of these levels contribute to resistance to nucleoside analog therapies. We further highlight emerging therapeutic strategies centered on small-molecule inhibitors that exploit these vulnerabilities to enhance the efficacy of nucleoside analogs. Together, this integrative perspective supports the need for development of small molecule inhibitors and design of combination approaches aimed at restoring apoptotic competence and improving the use of nucleoside analog-based therapies for the treatment of cancer
Temporal Trends in Lower Respiratory Infection Mortality in Ecuador, 2012–2022
No full textLower respiratory infections (LRIs) are responsible for significant morbidity and mortality in Ecuador; however, evidence to support prevention strategies is limited. This study aimed to identify age-specific trends, spatial patterns, and sociodemographic risk factors of LRI mortality in Ecuador between 2012–2022, utilizing national mortality data sourced from the Ecuadorian National Institute for Statistics and Censuses (INEC). Age-sex-specific trend analysis was performed using Joinpoint regression. LRI age-standardized mortality rates (ASMRs) were mapped by province of death, and percentage change was calculated between 2012 and 2019. Multivariable logistic regression was performed to assess risk factors pre- and post-2020. A change in trend in LRI mortality rate, from a decreasing trend to a marginal increasing trend, was identified for both genders in children aged 0–4 and 5–15 years. There were significant increasing trends for males (2014–2019 APC: 2.21%, 95% CI: 0.57, 6.70) and females (2016–2019 APC: 4.62%, 95% CI: 0.84, 10.58) aged ≥ 70 years. From 2012 to 2019, the highest average LRI ASMR was in Guayas (30.90 deaths per 100,000 inhabitants), and the greatest percentage increase was observed in Orellana (419.54%). Before 2020, LRI mortality, compared to deaths of other causes, was significantly associated with sex, age, education, ethnicity, place of death and climate region, with major shifts post COVID-19 pandemic
Effect of Matric Suction and Drying-Wetting Cycles on the Strength of Granite Residual Soil in Fujian Pumped Storage Power Station Slopes, China
No full textThe stability of bank slopes in pumped storage power stations is crucial, particularly in regions where frequent water level fluctuations occur. This study aims to investigate the degradation mechanism of bank slope under such fluctuating conditions, focusing on granite residual soil from the pumped storage power stations in Fujian, China. To explore the effects of drying-wetting cycles and matric suction on soil shear strength, drying and wetting cycles were conducted with unsaturated triaxial shear tests. The results revealed that the shear parameter strengthening effect occurs when the matric suction increases from 50 kPa to 200 kPa. Moreover, during the first five drying-wetting cycles, soil shear strength decreased sharply, with cohesion and internal friction angle decreasing by approximately 15.4% and 11.2%, respectively. This degradation trend stabilized in the later cycles. Scanning Electron Microscopy (SEM) analysis of the soil microstructure showed an evolution from a dense structure to a penetrating cavity during the cycles. This change reflects that the strength degradation characteristics of granite residual soils are controlled by the synergistic effects of structural and frictional mechanisms, manifesting as initial degradation followed by stabilization. Additionally, by fitting the nonlinear characteristics of the experimental data, shear strength evolution functions for matric suction and drying-wetting cycles were established, revealing the effect of these factors on strength degradation. These findings provide a theoretical basis for the stability analysis of bank slopes in pumped storage power stations, offering insights into soil behavior under fluctuating water levels
Experimental Evaluation of the Bioenergy Potential of Enterolobium cyclocarpum (Orejero) Fruit Peel Residue
No full textThis study presents an experimental evaluation of the bioenergy potential of Enterolobium cyclocarpum (“orejero”) fruit peel residue, an underutilized agroforestry by-product in tropical America. Although the species is widely used for shade and fodder in livestock systems, its fruit peel has not yet been characterized for energy recovery purposes. Fruit samples were collected in rural areas of Tesalia (Huila, Colombia), and the peel fraction was analyzed in certified laboratories. The moisture content of the peel was determined as 11 wt%, and the lower heating value was measured as 0.015 TJ/t following ASTM E711-06. Elemental analysis according to ASTM D5373-16 yielded (dry basis): 37.2 wt% C, 4.09 wt% H, 0.45 wt% N and 0.13 wt% S. Based on Colombian cultivation and production data, the theoretical energy potential was estimated as 3.6 TJ/year per hectare. The technical energy potential reached 0.18 and 0.21 TJ/year per hectare for combustion and gasification, respectively. CO2-equivalent emissions were also estimated for both conversion routes, revealing a trade-off between the higher energy yield and higher specific emissions associated with gasification. Overall, the results show that E. cyclocarpum fruit peel residue has a calorific value comparable to widely used agri-food residues in Colombia (e.g., sugarcane bagasse and oil palm fiber), but with a substantially higher per-hectare energy potential due to its large residue fraction. Its high availability, favorable fuel properties, and compatibility with decentralized combustion and gasification technologies support its use as a promising feedstock for bioenergy generation in rural or off-grid areas, in line with circular economy and sustainable energy transition strategies
Loaded Single-Leg Roman Chair Hold Preferentially Increases Biceps Femoris Activation, Whereas the Nordic Hamstring Exercise Emphasises Semitendinosus Activation in Professional Athletes
No full textBackground and Objectives: Hamstring strain injuries (HSIs) are frequent and recurrent in athletes who perform high-speed running. The long head of the biceps femoris (BFlh) is often affected by HSIs. While the Nordic hamstring exercise (NHE) is used for prevention, evidence shows it mainly activates the semitendinosus (ST) instead of the biceps femoris (BF). It was argued that hamstrings may contract isometrically during sprinting’s late swing phase; exercises like the single-leg Roman Chair-Hold (RCH) might better mimic sprinting. Limited electromyographic (EMG) data compare NHE and RCH. This study examined EMG activation of BF and ST during both exercises in athletes. Materials and Methods: Thirty-six professional handball players (17 females, 19 males) were randomly assigned to NHE (n = 18; mean age 22.1 ± 3.9 years) or RCH (n = 18; mean age 22.6 ± 4.9 years). A wireless EMG system recorded dominant leg BFlh and ST activity, normalised to maximal voluntary isometric contraction (MVIC%). NHE participants completed one set of ten repetitions; RCH participants performed three sets of ten repetitions with progressive loads (bodyweight, +10 kg, +20 kg). Results: RCH led to a significantly higher mean BFlh activation in the third set with +20 kg weight compared to NHE (72.9% versus 46.5%; p < 0.001, g = 1.52). BFlh activation steadily increased across RCH sets, coinciding with additional load increments (p < 0.001). Conversely, NHE produced greater ST activation than the RCH at the first set, where RCH was performed with only bodyweight (p < 0.001). Conclusions: NHE primarily activates the ST, while RCH gradually increases BFlh activation, particularly under load. Future research should investigate which exercises are more effective at reducing HSIs to draw more robust conclusions based on the study’s findings
A Novel ECG Score for Predicting Left Ventricular Systolic Dysfunction in Stable Angina: A Pilot Study
No full textBackground: Left ventricular systolic dysfunction (LVSD) is a major determinant of prognosis in patients with ischemic heart disease. Electrocardiography (ECG) is widely available, inexpensive, and may aid in identifying patients at risk. We hypothesized that a composite score derived from multiple established ECG markers could improve the detection of LVSD in patients with stable angina. Methods: In this single-center, cross-sectional study, 177 patients undergoing elective coronary angiography for stable angina were included. Patients were classified as LVSD-negative (n = 123) or LVSD-positive (n = 54) based on echocardiographic ejection fraction. ECG parameters, including fragmented QRS, pathologic Q waves, R-wave peak time, QRS duration, and frontal QRS–T angle, were assessed. Independent predictors of LVSD were identified using multivariate logistic regression. A composite ECG score was constructed by assigning one point to each abnormal parameter. Model robustness was evaluated using bootstrap resampling (1000 iterations) and 10-fold cross-validation. Results: Multivariable analysis identified prior stent implantation, fragmented QRS, pathological Q waves, R-wave peak time, frontal QRS–T angle (log-transformed), and QRS duration as independent predictors of LVSD. ROC analysis demonstrated good discriminatory performance for R-wave peak time (AUC 0.804), QRS duration (AUC 0.649), and frontal QRS–T angle (AUC 0.825) measurements. The composite ECG score showed a stepwise association with LVSD: a score of ≥2 yielded high sensitivity (88%) and negative predictive value (97%), whereas a score of ≥3 provided high specificity (100%) and positive predictive value (100%). Bootstrap resampling and cross-validation confirmed model stability and strong discriminatory performance (mean AUC, 0.964; accuracy, 0.91). Conclusions: A simple composite ECG score integrating multiple established ECG markers is associated with the robust detection of LVSD in patients with stable angina. Although not a substitute for echocardiography, this score may support early risk stratification and help identify patients who warrant further imaging evaluations. External validation in larger and more diverse populations is required before routine clinical implementation of this model
Determinants of Telemedicine Satisfaction in Inflammatory Bowel Disease Patients: A Multi-Centre Cross-Sectional Study
No full textBackground and Objectives: Telemedicine has become an essential component of chronic Inflammatory Bowel Disease (IBD) care, yet the factors that shape patient satisfaction with remote consultations remain only partially understood. This study aimed to assess satisfaction with institutional telemedicine services among Italian patients with ulcerative colitis (UC) and Crohn’s disease (CD), and to identify sociodemographic, clinical and organisational predictors to inform more person-centred telehealth models. Materials and Methods: We conducted a prospective, multi-centre, cross-sectional study in three IBD units in northern, central and southern Italy between June and October 2024. Consecutive adult patients who had completed a scheduled, non-emergency telemedicine visit were invited within 24–48 h to complete an online questionnaire including the Italian Telemedicine Satisfaction Questionnaire (I-TSQ), sociodemographic items, IBD-related variables, and telemedicine process indicators (accessibility, technology usability, technical support, time saved). Data were analysed descriptively and with multivariable linear regression to determine independent predictors of satisfaction, adjusting for recruiting centre. Results: A total of 705 patients participated (54.9% UC; 55.3% disease duration > 10 years). Overall, telemedicine satisfaction was high (mean I-TSQ total 57.5 ± 4.9; range 35–70), and all respondents reported reduced indirect costs compared with in-person visits. Greater ease of technology use, more frequent contact with the care team, male sex, older age, and employment were independently associated with higher satisfaction scores. Conversely, first-ever teleconsultations, CD, subcutaneous therapies, more difficult platform access, and the need for technical support were linked to lower satisfaction. Model fit was modest (R2 up to 0.20), suggesting the presence of additional unmeasured relational and contextual factors. Conclusions: Telemedicine for IBD is widely accepted in Italy, but satisfaction is strongly conditioned by digital usability, previous experience, and clinical complexity. Tailored telehealth pathways that incorporate user-friendly platforms, proactive technical support, and attention to vulnerable subgroups are needed to translate high satisfaction into sustained, equitable remote care
A Pragmatic Two-Step Screening Algorithm for Sarcopenia and Frailty in Community-Dwelling Older Adults: A Cross-Sectional Population-Based Study
No full textSarcopenia and physical frailty are interconnected geriatric syndromes that frequently coexist in older adults, sharing common pathophysiological pathways. However, their early detection in community settings is limited by resource constraints and by the lack of simplified, scalable diagnostic tools. This cross-sectional study aimed to estimate the prevalence and overlap of sarcopenia and frailty in a real-world public health screening programme and to evaluate the diagnostic performance of a pragmatic two-step algorithm. In September 2025, a total of 256 consecutive community-dwelling adults aged ≥65 years underwent standardized assessment using the SARC-F questionnaire, handgrip strength dynamometry, and selective bioelectrical impedance analysis (BIA). Sarcopenia was defined according to 2019 EWGSOP2 criteria, and frailty according to the Fried phenotype. Confirmed sarcopenia was identified in 37 participants (14.5%, 95% CI 10.7–19.1%) and frailty in 31 (12.1%, 95% CI 8.6–16.7%), with substantial overlap (77.4% of frail individuals also had sarcopenia; Cohen’s κ = 0.62). The two-step algorithm (Step 1: SARC-F ≥ 4; Step 2: handgrip strength and BIA only in screen-positive participants) demonstrated excellent accuracy for confirmed sarcopenia (AUC 0.913, 95% CI 0.871–0.955), with sensitivity 91.9%, specificity 81.3%, and a 53.9% reduction in BIA use. Factors independently associated with confirmed sarcopenia included older age, BMI < 22 kg/m2, physical inactivity, and higher SARC-F score. A simple, function-centered two-step approach enables efficient and scalable identification of sarcopenia and frailty in community settings, supporting early preventive strategies to preserve physical function
AI-Assisted Double-Headed Capsule Endoscopy: Multicentre Prospective Diagnostic Accuracy Study Across Small Bowel Indications
No full textBackground/Aims: Double-headed capsule endoscopy enhances visualization and diagnostic yield in small bowel evaluation but increases reading time. This study aimed to assess the diagnostic performance of AI-assisted double-headed capsule endoscopy (MiroCam MC2000) across all small bowel indications and to compare its reading efficiency with the standard manual reading mode. Methods: From May to December 2023, 242 consecutive patients (mean age 50.17 years, SD 18.3; 53% female) underwent small bowel capsule endoscopy at two UK centres for suspected Crohn’s disease (48.8%), iron-deficiency anemia (23.6%), bleeding (18.6%), or other (9%). Seven experienced readers reviewed videos in standard mode (blinded to clinical data), then AI-assisted (MiroCam AI Scan) methods were applied after de-identification/randomization. Two experts provided reference standards. No adverse events occurred. Results: AI-assisted reading had sensitivity 95.3% (95% CI 90.1–98.3%) and specificity 96.5% (95% CI 91.3–99.0%) for diagnostic findings, vs. standard reading: 96.5% (95% CI 91.2–99.0%) and 85.3% (95% CI 78.0–90.9%). The positive findings rate was 83.6% vs. 80.2% (p = 0.040). Reading time decreased by 52% (38.1 vs. 18.26 min; p < 0.001). Conclusions: AI-assisted reading offers high diagnostic accuracy, superior specificity and reduced reading times, supporting its adjunctive role with expert oversight. Registered: ERGO ID 82419
School Administrator and Food Vendor Perspectives on Stocking and Promoting Healthier Offerings in Indonesian Primary Schools: Findings from a Pilot Study
No full textChildhood overweight and obesity is a growing public health challenge in Indonesia, affecting approximately one in five school-aged children. Because children spend substantial time at school and frequently obtain meals and snacks from on-site canteens, these settings represent an important opportunity for nutrition-focused interventions. As an initial step towards understanding factors influencing canteen stocking decisions, we assessed perceived taste, acceptability, and feasibility of healthier local foods and beverages from the perspectives of canteen owners and school administrators (n = 10) across five primary schools (n = 2 urban, n = 3 rural) in Magelang, Indonesia. Participants completed in-person taste tests of selected food and beverage options and participated in in-depth interviews exploring drivers of stocking decisions. IndoMilk (multi-cereal, reduced-sugar dairy beverage) received the most favorable taste ratings and was perceived as the most feasible option to sell, followed by sate telur puyuh (braised quail eggs) and sate buah (fresh fruit skewers). In contrast, gethuk (cassava/coconut cake) and polo pendem (steamed tubers with boiled peanuts) were viewed as less appealing to children and unlikely to be sold. Participants identified children’s taste preferences, affordability, visual appeal, and profitability as key considerations influencing stocking decisions, while perceptions of nutrition varied. Findings from this pilot study highlight contextual factors shaping school canteen food environments and may inform future interventions aimed at introducing healthier options while accounting for children’s preferences and canteen operational constraints