Aqueous Li+/Na+ hybrid-ion batteries (AIBs) have emerged as a promising alternative to address concerns regarding lithium resource scarcity and the safety issues associated with organic electrolytes. However, the development of NaTi2(PO4)3 (NTP) as a high-performance anode material for AIBs is hindered by intrinsic challenges, including material dissolution and the competitive hydrogen evolution reaction (HER) at the electrode-electrolyte interface. Meanwhile, the scalable synthesis of NTPs remains constrained by the complexity of conventional preparation methods. In this work, the N-doped carbon-coated NaTi2(PO4)3 (NTP@NC) as an advanced AIB anode material is synthesized. The carbon coating effectively suppresses HER and material dissolution while maintaining electrolyte pH stability. Remarkably, the NTP@NC demonstrates a high-capacity retention of 66% after 1000 cycles, and the assembled pouch cell retains stable performance over 300 cycles. The large-scale production of the material is successfully achieved with a batch mass of 4 kg. This work establishes a clear correlation among the microstructure, composition, and electrochemical performance, facilitating the practical development of anode materials for high-safety aqueous battery technologies.
An 8-year-old male patient with bilateral Sprengel deformity, characterized by a right-sided bony omovertebral bar and a left-sided fibrous band, in the context of Klippel-Feil syndrome is presented in this case report. The patient had limited shoulder movement, a short neck, and considerable cosmetic issues. The radiological evaluation showed the omovertebral structures to be asymmetrical and a cervical fusion at C2-C3. The patient underwent 2 separate surgical procedures: the right side was operated on when the patient was 8 years old, and the left side was operated on 8 months later. The procedures involved the resection of the omovertebral structures and modified Woodward procedures for scapular repositioning. The postoperative results showed a marked improvement in shoulder abduction and cosmetic appearance with no neurovascular complications. This report emphasizes the need for early diagnosis, comprehensive imaging, and individualized surgical planning in the management of complex congenital shoulder deformities.    Cite this article as: Güneş Z, Danışman M, Bekmez Ş. Bilateral Sprengel deformity with asymmetrical omovertebral connections in a child with Klippel-Feil syndrome: a rare case report. Acta Orthop Traumatol Turc., 2026; 60(2), 0313, doi: 10.5152/j.aott.2026.25313.
The integration of large language models (LLMs) into orthopedic surgical decision-making represents a growing area of research. This study aimed to compare the surgical recommendation capabilities of ChatGPT-4.0, ChatGPT-4o, and ChatGPT-5 models in simulated cases of hallux valgus deformity. A total of 50 simulated cases were constructed using fundamental clinical data related to hallux valgus pathology and were individually submitted to 3 models. For each case, a surgical recommendation and a brief rationale were obtained. The responses were compared based on content alignment, adequacy of justification, and consistency with established surgical algorithms. Additionally, textual outputs were evaluated using DISCERN and multiple readability indices. All 3 models demonstrated overall algorithmic consistency. However, the ChatGPT-5 model provided the most context-aware and clinically consistent recommendations, followed by ChatGPT-4o and ChatGPT-4.0. Concordance rates with surgical algorithms were 70% for ChatGPT-4.0, 82% for ChatGPT-4o, and 90% for ChatGPT-5. DISCERN scores were 51, 56, and 62, respectively. ChatGPT-5 also achieved superior performance across readability metrics, including Flesch Reading Ease Score, Simple Measure of Gobbledygook, and Gunning-Fog Index, indicating improved textual clarity and reduced complexity. The ChatGPT-5 model demonstrated the highest contextual accuracy, consistency, and readability in surgical decision support for hallux valgus surgery, highlighting the progressive improvements of newer LLMs. Nonetheless, ChatGPT-4.0 and ChatGPT-4o also exhibited compatibility with surgical algorithms, indicating potential utility in generating patient education and informational content.   Cite this article as: Karadamar ÖL, Aydilek A. Evaluation of surgical recommendation algorithms in hallux valgus cases using ChatGPT models: an artificial intelligence approach based on 50 simulated scenarios. Acta Orthop Traumatol Turc. 2026; 60(2), 0580, doi: 10.5152/j.aott.2026.25580.
PD-L1 tumor proportion score (TPS) is used to guide immunotherapy in non-small cell lung cancer (NSCLC), yet its ability to predict pathological response in the neoadjuvant setting remains limited. Thirty pathologists from 11 countries independently assessed PD-L1 TPS in pre-treatment biopsies and residual viable tumor (RVT) in matched resection specimens after neoadjuvant chemoimmunotherapy in 30 digitized cases from the ReGraDE (regression grading in Germany) study. Interobserver agreement was evaluated using intraclass correlation coefficients (ICC) and Fleiss' kappa. Associations between TPS and RVT were analyzed using Pearson correlation, and correlations derived from single-rater and averaged TPS were compared using the Williams test. Interobserver agreement was moderate for both TPS and RVT (ICC = 0.74, 95% CI 0.60-0.87, and ICC = 0.74, 95% CI 0.62-0.85, respectively) and became near-perfect when mean scores per case were calculated across observers (ICC = 0.99, for both). However, TPS remained poorly correlated with RVT for both single-rater assessment (r = -0.17, p = 0.38) and averaged TPS (r = -0.16, p = 0.39) with no significant difference between these approaches (p = 0.96). Differences in interpretation thresholds were observed particularly in borderline cases around the 1% TPS cut-off and in distinguishing 0% from minimal RVT, but did not account for the lack of association between TPS and RVT. Systematic differences were observed depending on individual professional experience, particularly in borderline cases. Interobserver variability does not explain the limited predictive value of PD-L1 TPS in the neoadjuvant setting, suggesting an intrinsic limitation of the biomarker.
The gut microbiome is increasingly recognized as a metabolically active regulator of host gene expression, translating environmental exposures-particularly diet-into epigenetic signals that shape development, immunity, metabolism, and disease susceptibility. This narrative review synthesizes current evidence for a microbiome-epigenome axis in which microbial metabolites and regulatory molecules modulate DNA methylation, histone modifications, non-coding RNA networks, RNA epitranscriptomic marks, and higher-order chromatin organization. Short-chain fatty acids act as histone deacetylase inhibitors, acyl-CoA donors, and regulators of histone acetyltransferase activity; microbially derived B vitamins influence one-carbon metabolism and S-adenosylmethionine availability; and bile acids, indoles, trimethylamine-N-oxide, and extracellular vesicle cargo signal through host metabolic, immune, and transcriptional pathways. Evidence from germ-free and recolonization models, genetic perturbation studies, in vitro systems, and human cohorts indicates that microbial signals exert particularly strong effects during developmental windows of heightened epigenetic plasticity, contributing to immune tolerance, trained innate immunity, and long-term metabolic programming. Dysbiosis may disrupt these regulatory circuits and promote inflammatory bowel disease, colorectal cancer, cardiometabolic and atherosclerotic disorders, and neurodevelopmental or neurodegenerative conditions. By integrating microbial metabolism with chromatin regulation, RNA-based control, and genome topology, this review highlights the microbiome as a dynamic epigenetic interface between environment and host physiology. Key challenges include establishing causality in humans, resolving temporal and tissue-specific mechanisms, and developing longitudinal multi-omics studies with functional validation. Targeted microbiome modulation may ultimately restore epigenetic homeostasis and support precision prevention and therapy.
A critical cardiovascular emergency is acute lower extremity ischemia (ALI). Acute kidney injury (AKI) after surgical embolectomy prolongs hospitalization and increases treatment costs. Low blood magnesium (Mg) levels were shown to be associated with renal dysfunction. In this study, the goal was to investigate the connection between AKI and preoperative Mg levels. Patients who underwent a surgical embolectomy for ALI between January 2016 and June 2024 were consecutively included in this retrospective study. After the exclusion criteria, patients were divided into 2 groups: those who developed AKI in the postoperative period (group 1) and those who did not (group 2). The median ages of the 403 patients in group 2 and the 69 patients in group 1 were 64 (39-95 years) and 67 (35-89 years), respectively (P = .098). There was no statistical difference in terms of gender, prior cerebrovascular events, hypertension, diabetes mellitus, hyperlipidemia, rates of coronary artery disease, and peripheral arterial disease between the 2 groups. Glycated hemoglobin >9 (OR: 1.350, CI 95%: 1.110-1.984,- P = .028), high creatinine (OR: 2.945, CI 95%: 1.837-3.682, P < .001), and low Mg (OR: 0.695, CI 95%: 0.550- 0.869, P = .014) values were determined as independent predictors for AKI. The current study demonstrates that preoperative low Mg levels may be a risk factor for AKI. Cite this article as: Engin M, As AK, Aydın U, Ata Y, Yavuz Ş. Association of preoperative serum magnesium levels and acute kidney injury following thromboembolectomy in acute limb ischemia. Eurasian J Med. 2026, 58(3), 1340, doi: 10.5152/ eurasianjmed.2026.251340.
Anionic phospholipids are essential for surfactant function and phosphatidylglycerol (PG) is the most abundant. Increased secretory phospholipase A2 (sPLA2) and disproportionate depletion of PG is consistently observed in patients with acute respiratory distress syndrome (ARDS), leading to speculation on their potential relationship. We hypothesized that a non-lethal murine model of acute lung injury (ALI) would demonstrate a temporal association between lung inflammation, surfactant dysfunction, PG depletion, and sPLA2 activity at peak ALI. ALI was induced in BALB/c mice by intratracheal lipopolysaccharide (IT-LPS). Markers of ALI, surfactant (function, recovery, and composition), and sPLA2 activity were assessed over a 240-h period encompassing peak ALI and resolution. During peak ALI, a separate cohort of IT-LPS mice received IT-varespladib, an sPLA2 inhibitor, with surfactant outcomes analyzed 4 h later. IT-LPS induced features of ALI, including immune cell influx, protein leak, histological injury, and respiratory dysfunction, which peaked at 48-96 h and resolved by 240 h. Impaired surfactant function at peak ALI was associated with increased sPLA2-mediated PG hydrolysis and reduced PG content. All changes were absent post-ALI resolution. Varespladib reduced alveolar sPLA2 activity, increased surfactant PG, and improved surfactant function compared to untreated LPS controls. At peak ALI after IT-LPS, depletion of PG is synchronously related to surfactant dysfunction and increased sPLA2 hydrolysis. Pharmacologic inhibition of sPLA2 at peak ALI improves PG content and surfactant function. Additional substudies to fully examine their relationships and mechanisms are warranted.
Optimizing plant architecture without compromising disease resistance is a fundamental challenge in crop breeding, particularly for space-efficient systems such as vertical farming (VF). Here, we identify the YABBY-family transcription factor SlYABBY5b as a pivotal regulator that synchronizes these traits in tomato. Through a genome-wide association study (GWAS), we establish SlYABBY5b as a major locus governing natural variation in plant height. Functional analyses reveal that SlYABBY5b directly orchestrates gibberellin (GA) metabolism by activating the inactivation gene SlGA2ox2 and repressing the biosynthetic gene SlGA3ox1, thereby reducing bioactive GA pools and causing GA-reversible dwarfism. In parallel, SlYABBY5b enhances resistance to the major greenhouse pathogen Botrytis cinerea by directly targeting the promoters of the immune genes SlNLR and SlPR1a. Evolutionary analyses reveal functional divergence: while SlYABBY5b acts redundantly with its paralog SlYABBY5a in growth regulation, it has acquired a specialized, non-redundant role in enhancing basal immunity. Furthermore, natural promoter haplotypes of SlYABBY5b associate with stature and show signs of selection during domestication, positioning SlYABBY5b as a key target for breeding compact crops. Our findings illustrate how a single transcription factor can coordinate compact architecture with enhanced immunity, offering a promising target for developing resilient, high-density crops for controlled-environment agriculture.
Marginalized populations experience increased eating disorder (ED) risk and encounter significant barriers to treatment. Intersectionality provides a framework for understanding how systemic oppression contributes to inequities in EDs; however, intersectional approaches have yet to be applied to a clinical ED sample. The current study examined inequities in ED severity and treatment outcome across the intersections of race/ethnicity, sexual orientation, and socioeconomic status (SES). Adult women (N=3016; M = 27.2 years) with transdiagnostic EDs presenting to affiliated treatment sites across the United States completed the Eating Disorder Examination-Questionnaire (EDE-Q) at admission and discharge. Race/ethnicity and sexual orientation were self-reported; SES was measured using the area deprivation index of participants' neighborhoods. Multilevel Analysis of Individual Heterogeneity and Discriminatory Accuracy (MAIHDA) was used to estimate baseline EDE-Q global score; change in EDE-Q global score and binge eating, self-induced vomiting, laxative use, and driven exercise frequency from admission to discharge; and reason for discharge (routine or non-routine) across intersectional subgroups. In this sample of women with access to treatment, MAIHDA models predicted higher baseline levels of overall ED pathology among sexual minorities (predicted M = 4.10). Few differences in ED symptom improvement were observed across intersectional subgroups, with some small yet potentially meaningful inequities. Racially/ethnically minoritized subgroups appeared slightly less likely to complete treatment (predicted percent non-routine discharge = 41.50%). Future research should build on these findings by analyzing other dimensions of inequity (e.g., gender, weight status, disability status) to further characterize and address intersecting systems of oppression that disparately influence ED outcomes.
What is the effect of adenomyosis on cumulative live birth rate (CLBR) in women undergoing single embryo transfer in donor-oocyte cycles, with specific attention to type, location and severity of disease. Retrospective observational study of 228 infertile women treated at IVI Roma between 2019 and 2024. Adenomyosis was diagnosed via ultrasound using the MUSA criteria and classified by type, location and severity. Endometrial preparation involved hormone replacement therapy or modified natural cycles. Primary outcome was CLBR per woman; secondary outcome was serum progesterone concentrations on embryo transfer day in the adenomyosis and control groups. The CLBR did not differ significantly between the adenomyosis group and controls (both 74.29%, P = 0.81). Women with adenomyosis in the outer myometrium and junctional zone had a lower CLBR (62.5%) compared with those with adenomyosis limited to the junctional zone (83.33%) or outer myometrium (78.57%). The estimated number of transfers for 50% CLBR was also higher in the outer myometrium and junctional zone group (median 3) versus junctional zone or outer myometrium alone (median 2) (P = 0.04). Multivariate analysis confirmed outer myometrium and junctional zone adenomyosis as a negative predictor of live birth (hazard ratio 0.44, P = 0.03). No significant differences were found in CLBR by type or severity of adenomyosis or in serum progesterone concentrations. Ultrasound mapping to identify adenomyosis location is crucial in fertility counselling. Adenomyosis involving outer myometrium and junctional zone presented a lower CLBR. No differences were found in serum progesterone concentrations.
Mortality is a devastating complication after primary total hip arthroplasty (THA). The aim of this study was to investigate the prevalence and risk factors associated with 1-year postoperative mortality in patients undergoing primary THA. The authors reviewed the e-health database (e-Nabız) of the Republic of Türkiye Ministry of Health to identify patients who underwent primary THA between January 2016 and June 2022. The study included 98 622 patients with a mean age of 59.9 Å} 13.6 years. Hip fractures were excluded. Demographic data, body mass index, and Charlson Comorbidity Index scores were recorded. The incidence of 1-year mortality was investigated. A multivariate Cox regression model was created to identify risk factors for 1-year postoperative mortality. The postoperative 1-year mortality of patients who underwent primary THA was 2.8%. Cox regression analysis revealed that male gender and advanced age were independent risk factors for 1-year mortality and the risk of 1-year mortality increased with comorbidities such as cancer (hazard ratio (HR) = 2.46; 95% CI = 2.21-2.71), renal disease (HR = 2.29; 95% CI = 2.1-2.5), dementia (HR = 1.83; 95% CI = 1.63- 2.05), liver disease (HR = 1.69; 95% CI = 1.25-2.27), heart failure (HR = 1.65; 95% CI = 1.49-1.83), cerebrovascular accident (CVA) (HR = 1.43; 95% CI = 1.3-1.57), and acute myocardial infarction (AMI) (HR = 1.25; 95% CI = 1.07-1.45). Advanced age, male gender, cancer, renal disease, dementia, liver disease, heart failure, CVA, and AMI were identified as risk factors for 1-year mortality in patients undergoing THA. Meticulous preoperative medical optimization and standardized postoperative care may reduce mortality among patients with these comorbidities.   Cite this article as: Artuç M, Birinci M, Hakyemez ÖS, et al. Perioperative risk factor analysis for mortality in patients undergoing total hip arthroplasty: A national database study from Türkiye. Acta Orthop Traumatol Turc., 2026; 60(2), 0052, doi:10.5152/j.aott.2026.24052.
The association between cultural identity and substance use varies across studies, highlighting the need to quantify this relationship and identify sources of variability. This meta-analysis quantified the relationship between cultural identity and substance use among North American Indigenous youth, tested potential moderators, and described measurement approaches and tribal nation representation. A systematic literature search identified 18 studies reporting a quantifiable association between cultural identity and substance use with samples of at least 75% Indigenous youth between the ages of 10 and 20 years. Random effects models were used to calculate pooled effect sizes (Pearson's r), and meta-regressions assessed for potential moderating effects of age, sex, measurement approach, and living on a reservation. Overall, there was no significant pooled association between cultural identity and substance use in Indigenous youth (r = -0.003, p = .86). Effects were similar across alcohol, tobacco, and cannabis. However, heterogeneity was high (I2=72%), and funnel plot asymmetry suggested possible publication bias (p = .04). Age, sex, living on a reservation, and measurement approach did not moderate the overall effect (p's > .49). Tribal affiliation was largely not reported. This is the first meta-analysis to quantify the association between cultural identity and substance use among Indigenous youth. Although the overall pooled association was not statistically significant, this likely reflects limitations in how cultural identity is operationalized within quantitative research, leaving the question as to how cultural identity may impact substance use among Indigenous youth as of yet unanswered. Identifying which components of cultural identity are most relevant for Indigenous youth substance use will yield a better understanding of this relationship to inform the development of culturally sensitive interventions.
Cell fate plasticity refers to the capacity of cells sharing the same genome to alter, reverse, or reconfigure their identity under physiological, pathological, or experimental conditions. This property underlies embryonic development, cellular reprogramming, and tissue regeneration, but becomes progressively restricted as lineage identity is stabilized. Embryonic development represents an intrinsic process of fate transitions, whereas reprogramming and regeneration reveal how differentiated cells can dedifferentiate or transdifferentiate under specific conditions. Across these contexts, plasticity is governed by multilayered regulatory networks involving transcription factors, epigenetic regulators, cofactors, and the core transcription machinery. Robust regulatory programs stabilize cell identity, whereas stochastic fluctuations in gene expression and chromatin state can prime cells for fate transitions, adding a tunable dimension to plasticity control. In this review, we synthesize recent advances in the regulation of cell fate plasticity across development, reprogramming, and regeneration, highlighting how transcription factors, epigenetic modifications, transcriptional cofactors, and core transcription machinery cooperate to control cell fate decisions and plasticity.
Docetaxel (DTX)-based therapy remains first-line treatment for advanced prostate cancer (PCa), yet its efficacy is often compromised by chemoresistance. Emerging evidence highlights that circular RNAs (circRNAs) contribute to the development of chemoresistance, but their specific functions in DTX-resistant PCa remain poorly understood. By integrating molecular biology, cell biology, and immunology approaches, we investigated the mechanism by which hsa_circ_0003258 drives DTX resistance in PCa. We identified that hsa_circ_0003258 was significantly elevated in DTX-resistant patients of PCa. Functional experiments confirmed that hsa_circ_0003258 enhances DTX resistance both in vitro and in vivo by promoting cancer stem-like properties, independent of its linear transcript. Mechanistically, hsa_circ_0003258 directly bound the RRMs and KH1 domains of IGF2BP3 via its CAUU motif, augmenting the non-competitive interaction between IGF2BP3's KH4 domain and the 3'UTR of PSAT1 mRNA. This led to increased PSAT1 mRNA stability and activation of the serine biosynthesis, thereby reinforcing stemness and driving DTX resistance of PCa. To explore therapeutic potential, we engineered targeted nanoliposomes (HA-LNP@si-hsa_circ_0003258/cy7) which selectively accumulated in PCa xenografts and significantly inhibited tumor growth in combination with DTX. Co-treatment with Bix, a G9a inhibitor previously reported to suppress PSAT1 expression, further enhanced the antitumor efficacy of this combination, suggesting a potential synergistic therapeutic effect. Our findings reveal a novel hsa_circ_0003258/IGF2BP3/PSAT1 axis that enhances de novo serine synthesis and drives DTX resistance in PCa, highlighting this pathway as a promising therapeutic target.
Ocean acidification (OA) exerts diverse effects on marine macroalgae, with calcified species being particularly vulnerable. Due to calcified skeletons can contribute to physical screening against solar ultraviolet radiation (UVR), OA-driven calcification loss may increase exposure of the photosynthetic apparatus to UVR. Here, we cultured Corallina officinalis under ambient CO₂ (∼420 μatm) or elevated CO₂ (∼1000 μatm), with or without UVR, under natural solar radiation. Our results confirmed that OA reduced calcification and, under UVR, enhanced donor-side impairment of photosystem II (PSII), as evidenced by an increase in the relative K-step (Wk, an indicator of OEC damage) and a decrease in the maximum quantum yield of PSII (Fᵥ/Fₘ). This donor-side injury was accompanied by a reconfiguration of energy fluxes per PSII reaction center, particularly under combined OA and UVR. These impairments further extended to intersystem electron transport and limited the linear electron flow from PSII to the intersystem chain. Photosystem I (PSI) related electron transport was also functionally constrained, as evidenced by the reduced electron transfer probability and terminal reduction yield. This, together with the reduction of cyclic electron transport around PSI, resulted in over-reduction of the intersystem chain and making PSI the limiting photosystem. Together, these results indicate that OA amplified UVR-induced net photodamage and weakened PSII repair capacity in C. officinalis, while also constraining PSI-related electron transport. These findings highlight the potential vulnerability of calcified red algae under future high-CO₂, high-UVR coastal oceans.
Cell-surface glycans play essential roles in cell communication, immune recognition, and disease progression. Their medical applications are supported by two important technological pillars: glycan recognition and glycan editing. This Review focuses on three key directions: recognition technologies, namely, in situ imaging and glycomic profiling, for detecting and profiling glycans; functional editing technologies, including genetic, enzymatic, chemical, and metabolic approaches, for precisely remodelling glycans; and medical applications driven by the synergy between recognition and editing, with a focus on four areas: biomarkers, lectin-based therapies, precision glycan editing, and cancer immunotherapy. Throughout the Review, five representative glycan classes-high-mannose N-glycans, mucin-type O-GalNAc, heparan sulfate, ganglioside GM3, and glycoRNAs-are used as recurring examples wherever possible. This Review offers an integrated perspective to navigate the process by which glycan recognition and editing technologies collectively drive the translation of cell-surface glycan research into clinical practice.
Heterogeneous outcomes were reported in studies targeting left atrial (LA) pressure reduction by interatrial shunting in heart failure (HF). Right ventricular (RV) performance and pulmonary arterial (PA) afterload are essential in assuring the efficient blood flow shunting through the pulmonary circulation. We investigated whether baseline RV-PA coupling, expressed as the tricuspid annular plane systolic excursion (TAPSE) to pulmonary artery systolic pressure (PASP) ratio, is associated with outcomes after Atrial Flow Regulator (AFR) implantation in the PRELIEVE study. In this post-hoc analysis of the multicentre, single-arm PRELIEVE study (NCT03030274), 106 patients with symptomatic HF (62 with reduced and 44 with preserved ejection fraction) underwent AFR implantation and were followed for 12 months. TAPSE/PASP was measured by echocardiography at baseline and 3 months. The primary composite endpoint was cardiovascular (CV) death or HF hospitalization (HFH).During follow-up, 19 patients (18%) experienced the composite endpoint. At baseline, these patients had higher NT-proBNP (1261 [567, 1790] vs. 317 [114, 1200] pg/mL; p=0.009) and lower TAPSE/PASP (0.43 [0.33-0.53] vs 0.53 [0.43-0.76], p=0.04). In Kaplan-Meier analysis, lowest TAPSE/PASP ratio tended to show the worst outcome (p=0.07). Using recurrent-event Poisson regression, lower baseline TAPSE/PASP was associated with a higher cumulative incidence of HFHs (incidence rate ratio 2.4 [95% CI 1.0-5.6] for lowest vs middle tertile, p=0.039). In patients with HF undergoing interatrial shunting, impaired baseline RV-PA coupling assessed by a low TAPSE/PASP ratio was associated with higher rates of CV death or recurrent HF hospitalizations. The potential value of baseline RV-PA uncoupling in identifying responders to LA shunt therapies requires prospective evaluation in adequately powered prospective studies.
Heart failure (HF) and frailty frequently coexist in older adults and are associated with poor clinical outcomes. Frailty affects 15-76% of patients with chronic HF depending on the clinical setting and assessment tool used, with prevalence approaching 90% in hospitalised patients with heart failure with preserved ejection fraction (HFpEF). This integrated review synthesises current evidence on the bidirectional relationship between frailty and HF, including shared pathophysiological mechanisms, epidemiology, prognostic implications, assessment strategies, and contemporary management approaches. Available evidence indicates that frailty independently predicts incident HF and is associated with progressive deterioration in cardiac structure and function. Conversely, HF accelerates frailty progression through systemic inflammation, skeletal muscle hypoperfusion, sarcopenia, neurohormonal activation, malnutrition, and hospital-associated deconditioning. Frailty contributes to impaired quality of life, reduced self-care capacity, prolonged hospitalisation, poorer tolerance of guideline-directed medical therapy, and higher all-cause mortality risk. Current assessment strategies include physical performance measures, multidimensional frailty instruments, and comprehensive geriatric assessment. The recently developed Heart Failure Frailty Score (HFFS) represents the first HF-specific multidimensional frailty instrument. Management strategies include exercise rehabilitation, nutritional optimisation, structured medication review, and integration of frailty assessment into advanced HF decision-making. Future research should prioritise prospective validation of HF-specific frailty tools and randomised trials evaluating frailty-targeted interventions in HF populations.
This study aimed to examine the frequency of long head of the biceps tendon (LHBT) pathologies in anterosuperior rotator cuff tears (RCT) involving the LHBT pulley system and investigate the relationship between RCT types and LHBT pathology subtypes. A retrospective review was conducted of 555 shoulder arthroscopies performed for rotator cuff tears between 2017 and 2023. Patients were classified into 3 groups: isolated subscapularis (SSC) tears (n=74), isolated supraspinatus (SSP) tears (n=177), and combined SSC+SSP tears (n=304). The severity of the subscapularis tear was graded using the Lafosse classification. The LHBT pathologies were categorized as tendinitis, subluxation, dislocation, partial rupture, and full-thickness rupture. The LHBT pathology was present in 86.1% of cases. The most common pathologies were tendinitis (44.7%), complete rupture (13.5%), partial rupture (12.1%), subluxation (8.5%), and dislocation (7.4%). The SSC+SSP group had the highest LHBT pathology rate (99.0%) compared to isolated SSC (70.3%) and SSP (70.6%) groups (P < .001). The SSC+SSP group had a 36.04 times higher risk of LHBT pathology than the SSP group (P < .001). Dislocation and complete rupture were most frequent in the SSC+SSP group (P < .001). The LHBT pathology prevalence increased with Lafosse grade (P < .001), and higher grades were strongly associated with dislocation and rupture. Anterosuperior rotator cuff tears are strongly associated with LHBT pathologies, and the severity of LHBT pathologies increases in parallel with the Lafosse grade. Combined SSC+SSP tears significantly increase the risk of LHBT pathology, particularly dislocation and complete rupture, highlighting the need for thorough LHBT evaluation in anterosuperior RCT cases. Level III, Prognostic Study. Cite this article as: Kaya I, Yaş S, Bircan R, Ahmadov A, Sarikaya B, Kanatli U. Combined subscapularis and supraspinatus tears markedly increase the risk of long head of the biceps tendon pathology. Acta Orthop Traumatol Turc., 2026, 60(2), 0483, doi: 10.5152/j.aott.2026.25483.
G-quadruplexes (G4s) are four-stranded nucleic acid structures formed by guanine-rich sequences. Over the past two decades, G4s have emerged as key elements in genome organisation and transcription. Their remarkable structural diversity distinguishes G4s from other non-canonical DNA structures, including i-motifs and triplexes. Recent evidence suggests that G4s may serve as emerging regulatory hubs for transcriptional control, adding complexity to simple models in which G4s act solely as recruiters of transcription factors at gene promoters. Emerging data indicate that G4s can influence nucleosome occupancy, chromatin accessibility, and long-range chromatin interactions. Recent evidence also suggests a key role of G4s in modulating the formation of biomolecular condensate, which have been widely implicated in the regulation of transcription and chromatin organisation. Altogether, these findings highlight the potential of G4s to act as architectural elements of chromatin. In this review, we examine what makes G4s structurally unique compared to other alternative DNA structures, and discuss their potential involvement in genome architecture, nucleosome occupancy, and chromatin looping. We also highlight recent methodological advances, from small molecule stabilisers to CRISPR-based precision targeting, that enabled the manipulation of individual G4s in their native genomic context, revealing context-dependent G4 functions and highlighting their potential as therapeutic targets.