Search Results (1,891)

Although robust observational data have long associated physical activity with improved colon cancer survival, the lack of randomized evidence has perpetuated a “causality gap,” confining exercise to supportive lifestyle advice and creating a clinical dilemma for surgeons. This paradigm has been fundamentally reshaped by the landmark phase III CHALLENGE trial. This review synthesizes the clinical, epidemiological, and translational evidence establishing exercise as a validated, disease-modifying intervention. In the CHALLENGE trial, a 3-year structured physical activity program significantly improved both disease-free survival (HR 0.72) and overall survival (HR 0.63) in patients with resected stage III or high-risk stage II colon cancer post-adjuvant chemotherapy, demonstrating a clinically meaningful additive benefit following completion of standard adjuvant chemotherapy. Mechanistically, exercise drives a multi-layered host–tumor reprogramming. Each acute exercise bout triggers transient surges of muscle-derived myokines (e.g., IL-6, SPARC) and immune-cell mobilization, enhancing natural killer and CD8⁺ T cell tumor infiltration. Cumulatively, these repeated acute pulses drive chronic adaptations, including downregulation of the pro-proliferative insulin/IGF-1 axis, attenuation of pro-tumor systemic inflammation, and microenvironmental remodeling at metastatic sites. To bridge the implementation gap, exercise oncology must transition from vague recommendations to structured, biomarker-driven clinical prescriptions defining type, dose, and duration. Mirroring the institutional success of Enhanced Recovery After Surgery (ERAS) protocols, physical activity should be systematically embedded into multidisciplinary, post-adjuvant oncologic care pathways. As the primary coordinators of colorectal cancer care, gastrointestinal surgeons must lead the transformation of exercise from optional supportive care into a validated, disease-modifying standard of care. Full article

Understanding the genomic basis of environmental adaptation is essential for the conservation and genetic improvement of domestic camels. In this study, we investigated the population structure, genetic diversity, and genomic variation potentially associated with environmental adaptation of Kazakh dromedary and Bactrian camels using whole-genome sequencing. Whole-genome sequencing data were generated for Kazakh camels (15 dromedaries and 16 Bactrian camels) and integrated with 131 publicly available genomes representing camel populations from the Arabian Peninsula, Iran, Xinjiang, Inner Mongolia, and Mongolian wild camels. Population structure, genetic diversity, and genome-wide selection were evaluated using principal component analysis, ADMIXTURE, nucleotide diversity, linkage disequilibrium, runs of homozygosity, genomic inbreeding (FROH), and selection scans based on F_ST, θπ ratio, and XP-EHH. Population genomic analyses revealed clear differentiation between dromedary and Bactrian camels, whereas Kazakh camel populations exhibited higher nucleotide diversity (θπ = 1.307–1.551 × 10⁻³), and lower genomic inbreeding (median FROH: 0.037–0.056) than Arabian populations. Genome-wide selection analyses identified MC4R as the prominent candidate gene in Kazakh dromedaries and RYR1 as a prominent candidate gene in Kazakh Bactrian camels. Functional enrichment analyses highlighted pathways related to energy metabolism, thermogenesis, calcium signaling, skeletal muscle function, mitochondrial activity, and oxidative stress response. These findings provide new insights into genomic variation potentially associated with environmental adaptation in Kazakh camels and offer valuable genomic resources for future conservation, breeding, and evolutionary studies. Full article

Progressive resistance exercise training (RET) enhances skeletal muscle mass in healthy postmenopausal women (HEAs) and breast cancer survivors (BCSs) undergoing endocrine therapy. MicroRNAs (miRNAs) are recognized as key epigenetic regulators of exercise-induced adaptations, functioning as tumor suppressors, oncomiRs, and modulators of skeletal muscle homeostasis. Nevertheless, the impact of RET on circulating miRNA profiles in this population remains largely unexplored. This study aimed to explore the effects of a 12-week progressive RET program on plasma miRNAs associated with tumor biology and skeletal muscle regulation in HEAs and BCSs. Five HEAs and five BCSs undergoing endocrine therapy completed a 12-week supervised progressive RET program (3 sessions/week, 60–80% 1RM). Plasma samples were collected before and after intervention, and candidate miRNA expression was quantified by qRT-PCR, normalized to hsa-miR-16-5p, and analyzed using the 2^−ΔΔCt method. At baseline, no significant differences were observed between HEA and BCS in tumor suppressor miRNAs (miR-let-7f-5p, miR-125a-5p, miR-342-3p), oncomiRs (miR-21-5p, miR-155-5p, miR-221-3p), or skeletal muscle–related miRNAs (miR-206-3p, miR-486-5p) (p > 0.05). The only exception was miR-375-3p, which showed increased expression in HEA vs BCS (p = 0.037). After 12 weeks of RET, The BCS group showed increases in miR-125a-5p (p = 0.050) and miR-342-3p (p = 0.048) with significant group × time interactions that remained significant after Benjamini–Hochberg False Discovery Rate (BH-FDR) correction (FDR-adjusted p = 0.042 for both). Both groups displayed a nominal increase in miR-375-3p (p = 0.042), which did not remain significant after FDR correction. No significant changes were detected for miR-let-7f-5p or the analyzed oncomiRs in either group. Both miR-206-3p and miR-486-5p exhibited upward trends in the BCS group (p > 0.05). In this exploratory study, 12-week RET program was associated with selective changes in plasma miRNA expression in the HEA and BCS groups, suggesting that this training regimen may act as an epigenetic modulator of circulating miRNAs involved in tumor suppression and skeletal muscle homeostasis. Full article

Background/Objectives: Conventional clinical and dermoscopic assessment may overestimate treatment response in locally advanced basal cell carcinoma (laBCC) treated with Hedgehog pathway inhibitors due to treatment-induced fibrosis, pigment retention, and stromal remodeling. Reflectance confocal microscopy (RCM) enables noninvasive, near-histologic resolution skin imaging and may improve response evaluation accuracy. This study evaluated the role of RCM in monitoring treatment response and guiding presurgical planning in laBCC patients treated with sonidegib. Methods: In this prospective, single-center, observational pilot study, 15 consecutive patients with laBCC unsuitable for upfront surgery received sonidegib 200 mg daily. Treatment response was assessed using integrated clinical examination and RCM at baseline and follow-up. Study-specific response categories (complete response [CR], partial response [PR], stable disease [SD], progressive disease [PD]) were adapted from RECIST principles. Presurgical RCM mapping was performed in partial responders. Interobserver agreement between two blinded RCM readers was assessed using Cohen’s kappa (κ). Results: The objective response rate was 93.3% (CR: 26.7%; PR: 66.7%; PD: 6.7%). Dose modifications were required in 73.3% of patients; adverse events occurred in 60.0%, most commonly dysgeusia (33.3%) and muscle cramps (20.0%). Clinical–RCM discordance was identified in 13.3% of patients: lesions classified as CR by conventional evaluation were reclassified as PR after RCM detected persistent basaloid tumor nests, prompting treatment continuation (Interobserver agreement: κ = 0.62–0.86). Conclusions: RCM identified residual disease missed by conventional assessment, directly influencing treatment decisions. These findings support integrating RCM into a multimodal, response-adapted management strategy for laBCC. However, the limited sample size warrants cautious interpretation, and larger multicenter studies are required before broad clinical implementation. Full article

Barth syndrome (BTHS) is a rare, X-linked genetic disorder caused by mutations in the enzyme TAFAZZIN (TAZ), resulting in insufficient cardiolipin (CL) remodeling and mitochondrial dysfunction. While BTHS respiratory distress and breathing difficulties are commonly reported, the precise role of intrinsic respiratory tissue vulnerabilities has only recently begun to be appreciated. Historically, BTHS respiratory distress is frequently attributed to secondary consequences like cardiomyopathy or generalized skeletal myopathy, leaving the intrinsic vulnerability of vital respiratory muscles poorly understood. Using a patient-tailored point mutant knock-in mouse model (Taz^PM) harboring a stable but enzymatically deficient Taz^D75H protein, we investigated the autonomous physiological and metabolic responses in the diaphragm and lungs. Contrary to the paradigm that respiratory muscles are unaffected, Taz^PM diaphragms exhibit structurally abnormal mitochondria and undergo a survival-critical, bifurcated compensatory remodeling response to prevent fatal respiratory failure under severe bioenergetic stress. The Taz^PM adaptive mechanism is orchestrated by chronic activation of the mitochondrial Integrated Stress Response (ISR) via the Gcn2/eIF2α signaling pathway. This stress pathway halts global translation to conserve cellular ATP at the expense of reduced NAD+ levels, while selectively upregulating defensive mitokines and metabolic sirtuins and structural muscle remodeling. Furthermore, the Taz^PM diaphragm transitions into a highly specialized, slow-twitch motor system that is expected to reduce the energy cost per contraction. Concurrently, despite Taz^PM lungs exhibiting structurally abnormal mitochondria, they resist generalized mitochondrial collapse despite ADP reduction, executing tissue-specific metabolic reprogramming and localized biochemical adaptations to sustain respiratory homeostasis. Full article

Cervical dystonia (CD) is a hyperkinetic movement disorder characterized by involuntary muscle contractions leading to abnormal postures of the head and neck. The injection of botulinum neurotoxin type A (BoNT-A) into the muscles involved is the treatment of choice for CD. BoNT-A therapy of CD requires appropriate training, which has not been standardized in Germany. To address the key challenges in BoNT-A education, an expert panel developed a simplified step-by-step treatment guideline for beginners, adapted from the established Col-Cap-Concept (“Dystonia 3×3”). Based on expert consensus, recommendations were developed for the core clinical elements of BoNT-A treatment in CD—recognition of the movement pattern, identification of target muscles, development of an injection plan, ultrasound-guided injection, and dosing, taking into account the target audience of the guideline. As such, Dystonia 3×3 provides a user-friendly beginner’s guidebook, enhancing accessibility and standardization of CD treatment training. Further research is required to evaluate its clinical efficacy and suitability for training. Full article

Compliant muscle–tendon mechanics can improve terrain adaptation in musculoskeletal robots, but heterogeneous terrains impose competing requirements on compliance, propulsion, foot clearance, and support transfer. This paper proposes Value-Gradient Generalist Design (VGGD), a framework for selecting one fixed physiological muscle–tendon parameterization for cross-terrain locomotion while preserving skeletal topology and muscle routing. VGGD searches a compact PCA-based manifold that coordinates bounded scale factors for muscle strength, contraction-velocity capacity, and passive elastic response. A design- and terrain-conditioned value proxy is learned from sampled latent designs and then optimized by proximity-regularized projected value-gradient ascent under a soft-worst objective. Independent proxy validation uses 50 random designs solely for calibration and 100 separately sampled test designs excluded from fitting and Stage-B optimization. On the 100-design test set, the proxy shows positive agreement with mean cross-terrain return (Pearson $r=0.580$, Spearman $\rho =0.565$) and worst-terrain return ($r=0.583$, $\rho =0.551$), with all bootstrap intervals above zero and Holm-adjusted permutation $p=0.0006$. A separate paired local-direction test uses 60 previously unused evaluation seeds and equal feasible-space perturbation radii; at the nominal, midpoint, and selected designs, the proxy-gradient direction agrees with improvements in mean and seed-wise worst-terrain rollout return. After design selection, the muscle–tendon parameters are fixed, and a terrain-aware controller is trained with variational information-bottleneck regularization and auxiliary expert distillation. Checkpoint-resolved evaluation records identify 216/300 successes and an overall mean distance of 12.14 m for the complete pipeline, compared with 57/300 and 6.20 m for nominal-body PPO. The three checkpoint success rates are 84%, 78%, and 54% for Proposed and 49%, 0%, and 8% for PPO; exact two-sided policy-level permutation tests yield $p=0.10$ for success rate and $p=0.20$ for mean distance. All methods receive the same nominal 100-million-step final-controller budget per training run, while the 10 M Stage-A budget and expert-pretraining costs are reported separately. Full article

The Chinese longsnout catfish is a typical carnivorous fish with a relatively weak ability to utilize glucose. However, the genomic basis for its glucose metabolic adaptation remains unclear. In this study, we used comparative genomics methods to systematically analyze the evolutionary characteristics of glucose metabolism-related genes in the Chinese longsnout catfish, focusing on gene family evolution, patterns of expansion and contraction, and selective pressures. The results indicate that glucose metabolism-related genes have undergone significant reshaping during evolution. Genes involved in glucose digestion, absorption, and insulin signaling pathways demonstrate a tendency toward contraction, while those associated with protein and lipid metabolism exhibit expansion. This pattern is consistent with the species’ long-term adaptation to a high-protein, high-fat diet. Comparative analysis further revealed that, compared to fish with different dietary habits, certain key genes involved in glycolysis in the Chinese longsnout catfish exhibit a reduction in copy number. Molecular evolutionary analysis showed that key genes involved in glycolysis and gluconeogenesis (including hexokinase 2 (hk2), phosphofructokinase, muscle/platelet (pfkm/p)) exhibit signs of accelerated evolution or positive selection. Notably, the PFK gene family exhibits complex evolutionary characteristics resulting from the combined effects of gene contraction, rapid evolution, and positive selection. In summary, this study reveals the genomic evolutionary basis for the glucose metabolic adaptation of the Chinese longsnout catfish and identifies the PFK gene family as a key candidate for elucidating its unique glucose metabolic characteristics. Full article

Chronic kidney disease (CKD) promotes progressive renal dysfunction through a complex interplay of oxidative stress, chronic inflammation, apoptosis, and metabolic disturbances. This systematic review and meta-analysis aimed to evaluate the effects of exercise training on systemic adaptations as well as tissue-specific renal and muscular mechanisms in CKD rat models. In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, PubMed, Embase, and Web of Science were searched from 2000 to 2026. Of 1287 records, 11 studies were included in the systematic review, of which 8 studies were evaluated in the meta-analysis. Methodological quality was assessed using the Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies (CAMARADES) checklist, with scores ranging from 5 to 7 out of 10. Exercise interventions included resistance training, treadmill running, aerobic exercise, and wheel climbing. Exercise training enhanced endothelial function and improved metabolic homeostasis while attenuating reactive oxygen species (ROS) generation and lipid peroxidation through augmentation of endogenous antioxidant defenses. Restoration of redox balance suppressed nuclear factor kappa B (NF-κB) and NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome signaling pathways, resulting in reductions in pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6). These effects subsequently mitigated mitochondrial dysfunction, caspase activation, and apoptosis-related signaling, thereby preserving renal cellular viability. These adaptations translated into substantial histopathological protection, characterized by reduced inflammatory cell infiltration, glomerular sclerosis, tubular degeneration, and extracellular matrix deposition. Preservation of renal microarchitecture contributed to improved filtration capacity and overall renal function. Furthermore, exercise promoted mitochondrial biogenesis and anabolic signaling in skeletal muscle via activation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α)/transcription factor A, mitochondrial (TFAM) pathways, enhancing protein synthesis and attenuating CKD-associated muscle wasting, thereby contributing to tissue-level protection and systemic physiological improvement. Full article

Three-dimensional comparative descriptions of the ossa cranii across representatives of the Camelidae, Giraffidae, and Bovidae remain limited despite their relevance to comparative veterinary anatomy and clinical practice. Given the distinct structural variations and functional adaptations of these families, a descriptive comparison of ossa cranii morphology is needed to advance anatomical knowledge and establish species-specific reference data. This study compared the principal ossa cranii of camel, giraffe, cattle, sheep, and goat to identify conserved anatomical features and species-specific adaptations. High-resolution three-dimensional digital skull models were generated with a Creality Raptor blue laser scanner and processed using 3D Slicer (Version 5.6.2). Due to marked interspecific differences in skull size and cranial capacity, quantitative morphometric analyses were not feasible; therefore, comparisons were based on qualitative gross anatomical evaluation of the os occipitale, os sphenoidale, os parietale, os temporale, os frontale, os pterygoideum, os ethmoidale, and os vomer. Although the overall organization of the ossa cranii was conserved, distinct species-specific adaptations were identified. Camels exhibited a prominent crista sagittalis externa, a broad nuchal surface, an elongated os vomer, and the absence of the tuber faciale and processus cornualis. Giraffes showed well-developed ossicones, a pronounced frontoparietal prominence, enlarged frontal sinuses, modified occipital condyles, and elongated ethmoid and vomer bones. Bovids were distinguished by horn-related structures, frontal sinus configuration, the processus jugularis, bulla tympanica, and foramen supraorbitale. Ossa cranii morphology reflects both anatomic relationships and functional adaptations associated with feeding behavior, head posture, and muscle attachment. These findings provide comparative anatomical reference data that support veterinary anatomy education, diagnostic imaging, species-specific surgical planning, and future studies in functional morphology and paleontology. Full article

Background: Circulating tumor DNA (ctDNA) analysis has emerged as a promising tool for real-time disease monitoring in muscle-invasive bladder cancer (MIBC). This narrative review summarizes current clinical evidence regarding ctDNA across disease stages. Methods: We examine recent translational and clinical findings, incorporating key prospective data from practice-changing trials, as well as insights into minimal residual disease (MRD) detection, treatment escalation and de-escalation strategies, and systemic barriers to adoption. Results: Postoperative ctDNA positivity consistently identifies patients with molecular residual disease (MRD) who face a substantially higher risk of recurrence and mortality, frequently preceding radiographic relapse by several months. Prospective evidence now validates ctDNA as a predictive biomarker to guide adjuvant immunotherapy escalation, while sustained ctDNA negativity correlates with high long-term disease-free survival. Beyond plasma ctDNA, emerging multi-compartment liquid biopsies—integrating urinary tumor DNA (utDNA)—demonstrate enhanced sensitivity, particularly in bladder-sparing and local surveillance settings. Furthermore, integrating genomic ctDNA profiling with novel post-transcriptional layers like epitranscriptomics offers a functional framework to capture tumor adaptation under therapeutic pressure. However, clinical translation remains constrained by a lack of assay harmonization, variable analytical sensitivity, and the need for standardized intervention thresholds. Conclusions: Longitudinal liquid biopsies are rapidly shifting MIBC management from static, stage-based paradigms toward dynamic, molecularly informed precision oncology. While ctDNA-guided strategies show robust clinical utility, prospective interventional validation and technical standardization are required before widespread routine integration. Full article

Background: Persistent quadriceps weakness is a common consequence of joint injury, particularly following anterior cruciate ligament (ACL) injury and reconstruction. While traditionally attributed to muscle atrophy and disuse, growing evidence suggests that neural mechanisms play a central role. Arthrogenic Muscle Inhibition (AMI) is a neurally mediated impairment in the ability to voluntarily activate periarticular musculature following joint injury, occurring within a broader neurophysiological response involving altered joint-related afferent input, spinal mechanisms, and supraspinal adaptations. Methods: A narrative review of the literature was conducted using PubMed and Scopus databases. Studies investigating the peripheral, spinal, and supraspinal mechanisms of AMI, as well as its clinical manifestations, assessment methods, and rehabilitation strategies, were reviewed. Experimental, observational, and neurophysiological studies focusing on ACL injury and related joint disorders were included. Results: Current evidence indicates that AMI is a multifactorial neurophysiological process involving altered afferent signaling, spinal reflex inhibition, and central nervous system adaptations. These mechanisms contribute to persistent quadriceps activation failure, impaired motor control, biomechanical asymmetries, and functional and biomechanical alterations that may persist during recovery. Neuroimaging and electrophysiological studies further demonstrate cortical reorganization and neuroplastic changes that may persist despite restoration of joint stability and muscle strength. Conclusions: AMI should be considered a multilevel sensorimotor dysfunction rather than an isolated muscular deficit. Recognition of its neurophysiological basis may improve rehabilitation strategies by promoting interventions that target both neural and muscular components of recovery. Full article

This study compared elbow flexor hypertrophy and maximal strength adaptations after eight weeks of resistance training performed either to momentary muscular failure or with 1–3 repetitions in reserve (RIR). Nineteen resistance-trained adults completed a unilateral within-participant protocol in which one arm trained to failure and the contralateral arm trained with 1–3 RIR. Participants trained twice weekly using the unilateral preacher curl exercise at 70–80% one-repetition maximum (1RM). Elbow flexor muscle thickness and 1RM strength were assessed before and after the intervention. Bayesian mixed-effects models estimated between-condition differences. Both protocols increased muscle thickness and 1RM strength. The estimated between-condition differences for muscle thickness were 0.032 cm (95% highest density interval [HDI]: −0.044 to 0.113) while the estimated difference in 1RM strength was 0.588 kg (85% HDI: −0.491 to 1.66), with both 95% HDIs spanning zero and including values favoring either protocol. Sex-specific analyses showed the same general patter of responses. Overall, resistance training performed with 1–3 RIR produces similar elbow flexor hypertrophy and maximal strength adaptations to training performed to momentary muscular failures under the loading and volume conditions examined. Full article

Autophagy plays a central role in cellular homeostasis and metabolic adaptation, and its dysregulation has been implicated in metabolic disorders, including non-alcoholic fatty liver disease (NAFLD). This study investigated the biological effects of a chemically characterised multi-component nutraceutical formulation using an integrated in vitro gut–liver–muscle axis model under lipotoxic and inflammatory conditions induced by free fatty acids (FFAs) and lipopolysaccharide (LPS). The principal bioactive constituents were quantified in both the individual extracts and the final formulation before biological testing. Caco-2, HepG2, and C2C12 cells were sequentially exposed to conditioned media to reproduce inter-organ metabolic interactions. The Supplement preserved intestinal barrier integrity by maintaining transepithelial electrical resistance and tight junction protein expression. In HepG2 cells, it preserved telomerase levels, improved markers of cellular metabolic adaptation, modulated AMPK/mTOR and SIRT1 signalling, and promoted autophagy-related responses, including increased LC3-II/I ratio, reduced p62 accumulation, and preservation of lysosomal markers. In skeletal muscle cells, exposure to conditioned medium derived from formulation-treated compartments was associated with improved cellular bioenergetics, reduced oxidative stress and inflammatory mediators, and enhanced ATP and glycogen levels under exercise-like conditions. Overall, these findings provide preliminary evidence that the chemically characterised formulation modulates interconnected pathways involved in intestinal barrier function, hepatic autophagy-related processes, and skeletal muscle metabolic adaptation under the experimental conditions employed. Full article

Background: Nutritional support in critically ill patients remains one of the most debated aspects of intensive care medicine. Although international guidelines have long recommended early nutritional support with progressive protein delivery, recent clinical evidence has questioned the benefit of aggressive early calorie and protein provision during the acute phase of critical illness, highlighting the need for phase-adapted nutritional strategies. Methods: This narrative review summarizes current evidence on individualized, phase-adapted nutritional therapy in critically ill adults and post-ICU survivors, focusing on protein dose and timing, anabolic resistance, muscle wasting, and nutritional management during recovery. Relevant studies published between January 2011 and June 2026 were identified through structured searches of PubMed/MEDLINE, supplemented by reference screening and forward citation tracking. A total of 59 publications were included in the final narrative synthesis. Results: Recent clinical trials indicate that early high-dose protein administration does not consistently improve survival or functional outcomes and may be associated with harm in selected patient subgroups, particularly those with acute kidney injury, severe organ dysfunction, or shock. More conservative early calorie and protein delivery during the early acute phase has been associated with improved gastrointestinal tolerance and faster clinical stabilization without increasing mortality. Complementary mechanistic evidence supports these findings, highlighting persistent endogenous energy production, anabolic resistance, impaired protein utilization, and reduced autophagy during early critical illness. In contrast, the post-ICU recovery phase is characterized by ongoing muscle wasting, weakness, reduced oral intake, and persistent nutritional deficits, while structured nutritional support after ICU discharge remains inconsistently implemented. Conclusions: Current evidence increasingly supports an individualized, phase-adapted approach to nutritional therapy rather than uniform early aggressive calorie and protein targets. Nutritional strategies should consider illness severity, metabolic phase, organ dysfunction, gastrointestinal tolerance, and recovery trajectory. Further studies are needed to define optimal nutritional targets during post-ICU recovery. An evidence-informed practical framework for phase-adapted nutritional therapy is proposed. Full article