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ObjectivesThis study aimed to evaluate hematological inflammatory indices in patients with knee osteoarthritis and to investigate their association with radiographic disease severity. It also assessed whether these indices may have adjunctive value in distinguishing early-stage from late-stage osteoarthritis.MethodsThis retrospective study included 2176 patients diagnosed with knee osteoarthritis between January 1, 2023, and July 1, 2025. Patients aged 50-90 years with primary knee osteoarthritis and an available complete blood count (CBC) were included. Age, gender, Kellgren-Lawrence (KL) stage, neutrophil, lymphocyte, monocyte, and platelet counts were recorded. Neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), monocyte to lymphocyte ratio (MLR), systemic immune inflammation index (SII), systemic inflammation response index (SIRI), and pan-immune inflammation value (PIV) were calculated. Receiver operating characteristic (ROC) analysis and multivariable binary logistic regression adjusted for age and gender were performed.ResultsNLR (p < 0.001), MLR (p < 0.001), SII (p < 0.001), SIRI (p < 0.001), and PIV (p < 0.001) were significantly higher in patients with late-stage osteoarthritis, whereas PLR did not differ significantly between groups (p = 0.061). ROC analysis showed that NLR, MLR, SII, SIRI, and PIV had statistically significant but poor to modest discriminatory ability for late-stage osteoarthritis. Although SIRI showed the highest AUC among the evaluated indices, its performance remained within the modest range, and none of the markers demonstrated clinically meaningful discriminatory ability. In multivariable binary logistic regression analysis adjusted for age and gender, NLR, MLR, SII, SIRI, and PIV remained associated after adjustment for age and gender with late-stage osteoarthritis.ConclusionNLR, MLR, SII, SIRI, and PIV were associated with greater radiographic severity in knee osteoarthritis. Among the investigated biomarkers, SIRI, PIV, and SII showed relatively better discriminatory performance than the other indices; however, the overall ability of all markers to distinguish early-stage from late-stage osteoarthritis was limited. These findings suggest that CBC-derived inflammatory indices may serve as inexpensive adjunctive markers of radiographic severity, but they should not be used as stand-alone tools in clinical decision-making.

Reduced responsiveness to hearing one's own name is a core early behavioral predictor of autism spectrum disorder (ASD). This behavioral maker reflects atypicalities in self-related and social auditory processing, that are foundational to the development of social communication. To better understand the underlying neural mechanism of this alteration, the current study investigated neural correlates of auditory own-name processing in a sample of toddlers with ASD and typically developing (TD) controls using an auditory novelty oddball paradigm. Participants included 54 toddlers (30 ASD, 24 TD; 2-4 years) who passively listened to five auditory stimuli consisted of pure tones (500Hz and 1000Hz) and name types (self, familiar and stranger names). An auditory novelty oddball paradigm was utilized to assess neural response to standard and deviant stimuli, as well as to the different name types. Event-related potentials (ERPs) were recorded to measure neural activity during the stimulus processing. Compared to TD controls, autistic toddlers showed reduced late MMN to deviant tones that was infrequently presented relative to standard tones; Analysis of ERP components during own-name processing revealed atypical neural response pattern: autistic toddlers exhibited enhanced central P3a coupled with decreased LDN amplitudes to one's own-name relative to other names, and lack of parietal LPP effect typically observed in response to one's own-name. Our findings provide insight into the neural mechanisms underlying altered own-name processing in toddlers with ASD. These results suggest preserved early attentional capture of self-relevant salience, but atypical higher-order cognitive functioning during self-related and social auditory processing in toddlers with ASD.

Hip arthroscopy is increasingly used in the management of femoroacetabular impingement syndrome (FAIS), yet the definition of treatment failure remains unsettled. In response to the recent study by Mygind-Klavsen et al., we argue that conversion to total hip arthroplasty (THA), although clinically important, is a late and highly selective endpoint that does not capture the broader spectrum of unsuccessful hip preservation. Patients who remain symptomatic, fail to achieve clinically meaningful improvement, or undergo revision without THA are not represented by arthroplasty conversion alone. We further question whether conventional radiographic variables such as alpha angle, lateral joint-space width, and T&#xf6;nnis grade are sufficient to explain failure in a condition as structurally and biologically heterogeneous as femoroacetabular impingement syndrome. Recent evidence suggests that cartilage status, composite risk stratification, and technique-related factors may be more informative for long-term survivorship than conventional morphology alone. Finally, the long registry period analysed in the target article spans different technical eras, raising the possibility that treatment-era effects were conflated with patient-related risk. In our view, the study provides a useful registry-based estimate of THA conversion after hip arthroscopy, but its findings should not be interpreted as establishing the dominant determinants of failure in contemporary hip-preservation practice.

In advanced estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer, the combination of cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) with endocrine therapy (ET) is the standard of care for treatment in the first-line setting. While CDK4/6i were initially developed to induce cell cycle arrest, it is evident that CDK4/6i also have the potential to regulate the tumor immune microenvironment. Here, we characterize the baseline immune landscape and the immunomodulatory effects of abemaciclib and ET in advanced breast cancer tumors. We used single-cell RNA-sequencing of CD45-enriched cells to investigate the impact of the CDK4/6i, abemaciclib, and ET on the transcriptome of immune cell populations in 13 matched-pair advanced and metastatic ER+/HER2- breast tumor biopsies. We tested the association of immune cell population gene signatures with survival in publicly available datasets. We profiled 170,798 cells from bone, breast, lymph node, and liver biopsies. We find that expression of genes associated with interferon response are downregulated in many T cell populations. Expression of genes associated with antigen presentation were upregulated in tumor-associated macrophages (TAMs) and dendritic cells following treatment. The relative proportion of TREM2+ TAMs decreases following treatment with abemaciclib and ET in late progressors and lower expression of the TREM2+ TAM signature is associated with improved overall survival in breast cancer patients. Our data reveal heterogeneous lymphoid and myeloid subpopulations in advanced and metastatic breast tumors that are associated with late progression on abemaciclib and ET and overall survival in breast cancer patients.

Elderly patients exhibit heightened susceptibility to postoperative complications following general anesthesia and surgery, yet the molecular mechanisms driving this age-dependent vulnerability remain poorly defined. We performed RNA sequencing on olfactory bulb (OB), hippocampus (HI), lung, and spleen from young (3-month, m), late middle-aged (17&#xa0;m), and geriatric (27&#xa0;m) male C57BL/6 mice 24&#xa0;h after 2&#xa0;h of exposure to isoflurane anesthesia and laparotomy (ISO/OP). Short-term ISO/OP elicited pronounced, age-dependent transcriptional remodeling across tissues. Late middle-aged mice exhibited robust activation of stress- and metabolism-associated pathways in the OB and HI, accompanied by suppression of lipid, synaptic, and structural maintenance programs. In contrast, young adults displayed limited responses, characterized by modest and adaptive synaptic remodeling in the HI. Peripheral organs showed a parallel age-dependent divergence. Late middle-aged mice exhibited amplified immune and inflammatory signaling in the lung and spleen alongside suppression of structural, regulatory, and metabolic homeostatic programs, whereas young adults demonstrated attenuated, metabolically adaptive transcriptional responses. Circulating extracellular vesicles (EVs) mirrored tissue-level shifts, indicating a systemic transition from adaptive plasticity in 3&#xa0;m to stress and immune dominant signaling by 17&#xa0;m. Geriatric mice displayed a distinct response pattern, characterized by activation of stress and detoxification programs in brain tissues, altered circadian gene expression in lung and spleen, and extensive remodeling of EV protein cargo enriched for inflammatory and growth factor-related signatures. Together, these findings indicate that late middle-age is associated with amplified peri-anesthetic biological reactivity across central and peripheral systems, suggesting an under-recognized window for perioperative risk stratification and preventative intervention.

African swine fever (ASF) is a highly contagious and lethal disease caused by African swine fever virus (ASFV), with a mortality rate approaching up to 100%. At present, the functions of multiple genes of ASFV remain to be elucidated. In this study, we demonstrate that pD345L is a late-expressed viral protein and localizes to the viral factory. The recombinant strain JX23-02&#x394;D345L was obtained from the genotype &#x2160;/&#x2161; strain JX23-02. In vitro assays demonstrated that the deletion of D345L remarkably impairs viral replication. Further analyses revealed that JX23-02&#x394;D345L significantly upregulated pro-inflammatory cytokines (IL-1&#x3b2;, TNF-&#x3b1;) and IFN pathway components in PAMs, induced pyroptosis, apoptosis, and interferon responses. In vivo animal experiments demonstrated that the JX23-02&#x394;D345L strain was completely attenuated in pigs, failing to induce any typical clinical signs of ASF even with a high-dose inoculation. Moreover, a single immunization with JX23-02&#x394;D345L can elicit specific humoral and cellular immune responses against ASFV, conferring 80% protection against intramuscular challenge with the homologous strain JX23-02 and 60% protection against heterologous strain SY18. These results reveal D345L as a crucial virulence-related gene for ASFV pathogenesis, which is highly correlated with viral replication and the host antiviral response. Furthermore, JX23-02&#x394;D345L represented a candidate for the development of effective and safe ASFV vaccines. This finding provides a foundation for the research on ASFV and offers an important target and evidence for vaccine development.

Prenatal care starting in the first trimester is widely accepted as a best practice for improving maternal health. However, evidence is limited on the association between early prenatal care and maternal and infant health outcomes. This study evaluated maternal and infant health outcomes among nulliparous mothers to evaluate associations between late (&#x2265;4 months) prenatal care or no prenatal care compared with early (months 1-3) prenatal care. We used birth record data from the National Center for Health Statistics for this analysis. The study population consisted of singleton, nulliparous live births to mothers who gave birth in the United States from January 1, 2014, through December 31, 2022. Compared with early prenatal care, late initiation of prenatal care was associated with an increased risk of preterm birth (risk ratio [RR]&#x2009;=&#x2009;1.21; 99% CI, 1.15-1.28), insufficient gestational weight gain (RR&#x2009;=&#x2009;1.23; 99% CI, 1.17-1.30), and no reported breastfeeding at discharge (RR&#x2009;=&#x2009;1.09; 99% CI, 1.06-1.13). Compared with early prenatal care, no prenatal care was associated with substantially greater risk across nearly every measured outcome, including preterm birth (RR&#x2009;=&#x2009;2.26; 99% CI, 1.82-2.80), low birth weight (RR&#x2009;=&#x2009;2.03; 99% CI, 1.72-2.40), neonatal intensive care unit admission (RR&#x2009;=&#x2009;1.88; 99% CI, 1.48-2.39), abnormal conditions of the newborn (RR&#x2009;=&#x2009;1.87; 99% CI, 1.73-2.02), and no reported breastfeeding at discharge (RR&#x2009;=&#x2009;1.90; 99% CI, 1.53-2.35). Prenatal care timing was not significantly associated with maternal morbidity. These findings highlight that although early prenatal care results in the best outcomes, late prenatal care still has important benefits relative to no prenatal care.

This experimental study aimed to evaluate the effects of crocin on wound healing and fibrosis in vocal fold injury. Thirty-six male Wistar Albino rats were randomly divided into 3 groups: a sham group, a local crocin treatment group, and a systemic crocin treatment group. In the study, all rats underwent injury to their right vocal folds. Six rats from each group were randomly sacrificed on the 5th and 30th days after surgery. Tissue samples were evaluated for lamina propria thickness, inflammation severity, epithelial regeneration, edema, hyaluronic acid, collagen, elastin, and the cytokines TGF-&#x3b2;1, FGF2, and HGF. In the early phase, less inflammation, more epithelial regeneration, and lamina propria were observed in the systemic treatment group compared to the sham group. In the late phase, Compared to the sham group, both the systemic and local treatment groups showed higher values in lamina propria thickness, elastin, and HGF measurements, while collagen levels were significantly decreased. Furthermore, in the systemic group, TGF-&#x3b2;1 decreased in the late period, while hyaluronic acid and FGF2 levels remained high. When the groups were evaluated within themselves, inflammation and edema were observed to decrease more significantly in the late period in all groups. Hyaluronic acid decreased significantly in the sham and local treatment groups, while this decrease was limited in the systemic treatment group. Lamina propria thickness increased significantly in the treatment groups on day 30 compared to day 5. Crocin treatment applied using different methods has shown positive effects on various parameters, wound healing, and fibrosis reduction in the early and late periods after vocal fold injury. However, more extensive preclinical and clinical studies are needed to determine the efficacy and applicability of this treatment.

Smartphone-based cognitive behavioral therapy (CBT) programs offer accessible interventions for subthreshold depression, yet engagement needed for meaningful benefit remains unclear. We examined how lesson and worksheet engagement relate to depressive symptom improvements in a behavioral activation (BA) intervention, accounting for time-varying confounders. This secondary analysis included 298 adults assigned to the BA arm of the RESiLIENT trial, a randomized controlled trial in Japan. Lesson and worksheet completion were treated as time-varying exposures, each yielding four engagement patterns: minimal (Few-Few), early (Many-Few), late (Few-Many), and consistently high (Many-Many). Outcomes were depressive symptom changes measured by the Patient Health Questionnaire-9 (PHQ-9) at weeks 6 and 26. We applied the parametric g-formula to estimate counterfactual PHQ-9 changes under each pattern, adjusting for baseline and time-varying confounders. Early lesson engagement during weeks 0-3 was associated with larger PHQ-9 reductions at both weeks 6 and 26, even when later engagement declined (Many-Few vs. Few-Few: week 6: -1.47 [95% CI -2.52 to -0.53]; week 26: -1.27 [-2.53 to -0.17]). In contrast, higher worksheet engagement was linked to improved PHQ-9 at week 6, with maximal benefit among consistently high engagers (Many-Many vs. Few-Few: -1.25 [-2.17 to -0.44]) and late engagers (Few-Many vs. Few-Few: -1.18 [-2.20 to -0.08]), but not persist to week 26. Greater engagement with smartphone-delivered BA is associated with larger symptom reductions. Early lesson engagement drives sustained benefit, whereas worksheet engagement did not persist. These findings may guide digital CBT design by emphasizing early lesson completion alongside concurrent skill practice.

Surgical treatment of recurrent posterior shoulder instability gives good results in cases of isolated posterior labral lesion and relies on arthroscopic capsulo-labral repair. In cases of associated posterior glenoid bony lesions or for revision surgery, iliac crest bone block procedures seem to yield good short-term results, but there might be a concern for long-term results with resorption of the bone block, recurrence, and late arthritis. The Kouvalchouk technique, described in 1993, is using a bone block harvested from the posterior acromion and pedicled to a band of posterior deltoid muscle with presumed sling and vascularization effects. The primary objective of the study was to assess the mid-term results of a slightly modified Kouvalchouk procedure (open or arthroscopic-assisted) for recurrent posterior shoulder instability. The secondary objectives were to describe the results in subgroups determined by the origin of the instability (traumatic or nontraumatic), surgical history (primary surgery or revision surgery), or surgical technique (open or arthroscopic-assisted surgery) and to evaluate the bone healing of the bone block, its position on the glenoid in the axial and sagittal planes, and the influence of bone loss and glenoid version on pre-operative and post-operative clinical data. Thirty-one procedures were followed over an average period of 4.8 years, and at the last evaluation, 77% of shoulders were stable. All bone blocks were healed. The stability rate was higher in cases of post-traumatic instability (87% vs. 66% for nontraumatic cases). Similarly, Walch-Duplay scores and patient satisfaction were better in traumatic cases (80 vs. 57 and 81% of satisfied patients vs. 40%, respectively). Previous surgery was an unfavorable condition regarding clinical results. As for clinical results or bone block positioning, arthroscopic assistance did not prove better than open surgery.Revision surgery was mostly related to recurrence and was more frequent in atraumatic cases or in previously operated patients. There were as many removals of screws for pain reasons in traumatic and atraumatic cases. Higher glenoid retroversion was associated with lower pre-operative Walch-Duplay and Rowe scores. Glenoid version lower than - 10&#xb0; was associated with a higher Walch-Duplay postoperative score. Glenoid bone loss had no influence on clinical results. The modified Kouvalchouk procedure provides good results in the stabilization of recurrent posterior unstable shoulders in traumatic cases and patients without previous surgery, with the advantage of local harvesting of a bone block and a potential sling effect.