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Survival by Race and Ethnicity in Children and Adolescents/Young Adults With Relapsed/Refractory Hodgkin Lymphoma: A Pooled Analysis of Children's Oncology Group Trials.

PURPOSE: Despite 5-year survival rates of over 90% among children and adolescents/young adults (CAYAs) with classic Hodgkin lymphoma (cHL), 15%-20% relapse after frontline therapy. Prior analysis of frontline Children's Oncology Group (COG) clinical trials demonstrated that, despite similar rates of relapse, non-Hispanic Black (NHB) and Hispanic (vs. non-Hispanic White [NHW]) patients experienced higher post-relapse mortality. It is unknown whether post-relapse disparities persist when second-line treatment is delivered in a cooperative group trial setting. We examined overall survival (OS) by race and ethnicity in CAYAs enrolled in COG trials for relapsed/refractory (r/r) cHL. METHODS: A pooled analysis of individual-level data from CAYAs (≤ 29 years) receiving therapy for r/r cHL on COG clinical trials (2001-2016) was conducted. The Kaplan-Meier method estimated 3-year OS by racial and ethnic groups. Cox regression models examined associations of race and ethnicity and OS, adjusted for age, insurance, first versus ≥2 relapse, and time from initial diagnosis to relapse trial enrollment. RESULTS: Among 175 CAYAs treated on COG trials for r/r cHL (5.7% Asian or Pacific Islander, 14.9% Hispanic, 14.3% NHB, 61.7% NHW, 3.4% other), at median follow-up of 4.9 years, 3-year OS was 82.1% (95% confidence interval [CI], 75.3%-87.1%) and did not differ by race and ethnicity (p = 0.36). In multivariable analyses, shorter time from diagnosis to relapse trial enrollment (p = 0.01) and ≥2 relapses (vs. first, p = 0.004) conferred worse OS, with no significant effect of race and ethnicity (p = 0.43). CONCLUSION: Post-relapse survival did not differ by race and ethnicity among CAYAs enrolled in COG trials for r/r cHL, suggesting access to clinical trials may mitigate OS disparities.

Humans

Comparison of analgesic efficacy of pericapsular group of nerve block versus anterior quadratus lumborum block in adult patients undergoing unilateral hip arthroplasty: A comparative randomized controlled trial.

BACKGROUND: Total hip arthroplasty is a painful surgical procedure; therefore, it is a challenge to manage effective pain control during the perioperative period. STUDY OBJECTIVES: We compared the analgesic efficacy of the pericapsular nerve group block and the anterior quadratus lumborum block in patients undergoing unilateral hip arthroplasty. DESIGN: Randomized controlled trial. SETTINGS: Operating room of a tertiary care center. PATIENTS: 92 adult patients of >18 years who underwent elective, unilateral total hip arthroplasty under spinal anesthesia were randomized to either Group P (USG guided PENG block with 30 ml 0.25% ropivacaine +4 mg dexamethasone) or Group Q (USG guided QL block with 30 ml 0.25% ropivacaine +4 mg dexamethasone) 20 min before surgery. MEASUREMENTS: We compared the total perioperative fentanyl consumption between the two groups in the first 24 h as the primary outcome. Other outcomes included time to first rescue analgesia in the postoperative period, NRS scores at rest and on movement at 0, 2, 4, 6, 12, and 24 h, incidence of intraoperative hemodynamic changes, and incidence of postoperative PONV. MAIN RESULTS: There was no significant difference in the total fentanyl consumption between the two groups: 237.5 (150-450) μg in the P group and 250 (125-400) μg in the Q group; p = 0.617. The time to first rescue analgesia was similar in both groups: the P group (198 [123-268] minutes) and the Q group (241 [180-318] minutes); p = 0.120. There was also no difference in pain scores, intraoperative hemodynamic changes, or PONV. CONCLUSION: There was no difference in the perioperative opioid consumption, pain scores, and adverse event rates between the pericapsular nerve group block and anterior quadratus lumborum block in adult patients undergoing unilateral hip arthroplasty. TRIAL REGISTRATION: Clinical Trials Registry of India (CTRI number: CTRI/2023/08/057157).

Humans

Association of cancer antigen 15-3 with distant recurrence in immunohistochemically defined breast cancer subtypes in Canadian Cancer Trials Group MA.32.

BACKGROUND: Circulating levels of cancer antigen (CA) 15-3 have been associated with distant breast cancer recurrence; data on breast cancer subtypes are sparse. We examined associations of CA 15-3 with outcomes across immunohistochemically defined breast cancer subtypes in MA.32. METHODS: A total of 3649 participants with T1-3, N0-1, M0 breast cancer were randomly assigned; 2740 (75.1%) provided blood at entry (mean = 278&#x2009;days postdiagnosis) and 6&#x2009;months later. Prognostic associations of baseline and 6-month change in CA 15-3 with distant recurrence-free survival (RFS) were examined in luminal (estrogen receptor-positive and/or progesterone receptor-positive, HER2-negative), triple-negative (estrogen receptor, progesterone receptor, HER2 negative) and HER2-positive (any estrogen receptor, progesterone receptor) breast cancer using Cox proportional hazards models. RESULTS: Mean age was 52&#x2009;years. Breast cancer was luminal in 1589 (58.7%), triple negative in 655 (24.2%), and HER2 positive in 464 (17.1%) participants. Median follow-up was 96&#x2009;months. CA 15-3 at study entry was not associated with outcome in any subtype. Rising CA 15-3 at 6&#x2009;months was associated with poor distant RFS in luminal and triple-negative breast cancer (hazard ratio [HR] per 25% increase&#x2009;=&#x2009;1.41, P&#x2009;<&#x2009;.0001, and HR = 1.35, P&#x2009;<&#x2009;.0001, respectively). New elevations in CA 15-3 at 6&#x2009;months were adversely associated with distant RFS in those with luminal or triple-negative breast cancer (HR = 4.14, 95% CI = 2.69 to 6.38; P&#x2009;<&#x2009;.001; and HR = 3.57, 95% CI = 1.59 to 7.99; P&#x2009;=&#x2009;.002, respectively). In HER2-positive breast cancer, CA15-3 was not associated with distant RFS. CONCLUSION: Rising CA 15-3 was associated with reduced distant RFS in luminal and triple-negative breast cancer but not in HER2-positive breast cancer. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT01101438.

Humans

Context-dependent functional diversity of dorsomedial posterior parietal neurons revealed by single-unit fMRI mapping during naturalistic viewing.

The dorsomedial posterior parietal cortex (dmPPC) plays an important role in episodic processing by integrating sensory, cognitive, and motor information across distributed brain systems. However, how individual dmPPC neurons participate in large-scale functional organization during naturalistic experience remains poorly understood. To address this question, we combined single-unit electrophysiology and awake fMRI in five rhesus macaques of both sexes viewing identical naturalistic video stimuli. Using single-unit fMRI mapping, we generated whole-brain neuron-BOLD functional maps by correlating individual neuronal activity with voxel-wise fMRI signals across the brain. We found that neuron-BOLD functional maps exhibited strong context-dependent organization, with neurons recorded during the same video context showing substantially greater similarity than neurons recorded during different video conditions. Compared with neuronal spiking activity or critical fMRI frames alone, neuron-BOLD functional maps more robustly captured contextual structure. Despite this shared large-scale organization, a substantial subset of neighboring neurons recorded simultaneously from the same electrode displayed markedly distinct whole-brain association patterns, revealing substantial local functional heterogeneity within the dmPPC. This local heterogeneity was not readily explained by waveform-based putative cell class or by opposing neuronal firing dynamics. In addition, distributed cortical and medial temporal regions exhibited highly context-dependent neuron-BOLD association patterns during naturalistic viewing. Together, these findings demonstrate that dmPPC neurons participate in dynamic and heterogeneous large-scale functional organization during naturalistic episodic processing. More broadly, this study establishes single-unit fMRI mapping as a framework for linking single-neuron activity to distributed whole-brain dynamics across contextual conditions.Significance Statement Using single-unit fMRI mapping, this study examined how individual dorsomedial posterior parietal cortex (dmPPC) neurons relate to large-scale brain activity during naturalistic video viewing in macaque monkeys. We found that neuron-BOLD functional maps exhibit strong context-dependent organization and capture contextual structure more robustly than neuronal spiking activity or fMRI frames alone. Despite this shared organization, a substantial subset of neighboring dmPPC neurons displayed markedly distinct whole-brain association patterns, revealing local functional heterogeneity that was not readily explained by waveform-based putative cell class or opposing firing dynamics. These findings provide insight into how local neuronal populations participate in distributed brain-wide functional organization during naturalistic episodic processing.

Journal Article

Effect of demographic characteristics on the outcome of prostate cancer salvage radiotherapy: Analysis from a randomized controlled trial.

BACKGROUND: This study investigated the impact of advanced molecular imaging, race, socioeconomic status, and metabolic dysregulation on the outcome of salvage radiotherapy (sRT) for prostate cancer recurrence in a clinical trial setting. METHODS: The authors randomized post-prostatectomy men with detectable prostate-specific antigen to sRT guided by conventional imaging (arm A) or 18F-fluciclovine-positron emission tomography/computed tomography (arm B) and followed them up for up to 48 months to determine failure-free survival (FFS). The authors computed socioeconomic status (SES) and allostatic load (AL) scores to quantify socioeconomic status and level of metabolic dysregulation. They stratified patients by race as African American men (AAM) versus men of other races (MOR) and compared FFS between them using the z-test. RESULTS: Eighty-one (AAM&#xa0;=&#xa0;29, MOR&#xa0;=&#xa0;52) and 76 (AAM&#xa0;=&#xa0;26, MOR&#xa0;=&#xa0;50) men completed per-protocol sRT in arms A and B, respectively. Across study arms, AAM showed a higher FFS rate than MOR (72.8% [95% CI, 53.8%-85.0%] vs. 58.7% [95% CI, 46.6%-68.9%]; p&#xa0;=&#xa0;.002). In arm A, FFS rate was better for AAM than MOR, (64.0% [95% CI, 34.4%-82.9%] vs. 45.3% [95% CI, 28.8%-60.4%]; p&#xa0;=&#xa0;.008). In arm B, FFS improved for both groups but less so for AAM, (81.5% [95% CI, 57.2%-92.7%] vs. 73.0% [95% CI, 56.3%-84.1%]; p&#xa0;=&#xa0;.131). The authors found lower SES scores and higher AL scores for AAM in both study arms than MOR. CONCLUSION: Despite lower socioeconomic status and higher burden of metabolic dysregulation, in a clinical trial setting that controls for disparities in health care access, AAM have a more favorable sRT outcome than MOR.

Humans

Low-Dose Perineural Dexamethasone Enhances Analgesia After Pediatric Hand Surgery Without Elevating Systemic Stress Markers: A Randomized Controlled Trial.

BACKGROUND: Supraclavicular brachial plexus block is a widely used technique for upper limb surgery in children. Although perineural dexamethasone has demonstrated efficacy in prolonging analgesia in adults, data on its optimal dosing and systemic safety in pediatric patients are limited. This study aimed to evaluate whether low-dose perineural dexamethasone can prolong postoperative analgesia without increasing systemic stress markers in young children undergoing hand or wrist surgery. METHODS: In this triple-blinded, randomized controlled trial (ClinicalTrials.gov Identifier: NCT06086392), 90 children aged 3 months to 6 years undergoing elective upper extremity surgery were assigned to receive supraclavicular brachial plexus block with 0.2% ropivacaine combined with either normal saline (control), dexamethasone 0.05&#xa0;mg/kg, or dexamethasone 0.1&#xa0;mg/kg. The primary outcome was time from arrival in the postanesthesia care unit to first administration of rescue opioid analgesia. Secondary outcomes included total opioid consumption, postoperative pain intensity using the FLACC scale, blood glucose levels, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and time to motor recovery. RESULTS: Both dexamethasone groups demonstrated significantly prolonged time to first opioid use compared with the control group (mean&#xb1;SD: 19.4&#xb1;2.2&#xa0;h in the 0.1&#xa0;mg/kg group, 16.0&#xb1;1.9&#xa0;h in the 0.05&#xa0;mg/kg group, and 8.5&#xb1;1.3&#xa0;h in controls; P <0.0001). Total opioid consumption was significantly reduced in the dexamethasone groups. Postoperative pain scores were lower in both intervention groups, especially during the first 12 hours. No significant differences were found among groups in blood glucose, inflammatory markers, or incidence of nerve deficits. Motor recovery was delayed in the dexamethasone groups but did not interfere with early mobilization. CONCLUSIONS: Low-dose perineural dexamethasone (0.05 to 0.1&#xa0;mg/kg) safely and effectively prolongs postoperative analgesia and reduces opioid needs in children undergoing upper limb surgery, without causing systemic metabolic or inflammatory disturbances. The 0.05&#xa0;mg/kg dose may offer a more favorable balance between analgesic efficacy and motor recovery time. LEVEL OF EVIDENCE: Level I-randomized controlled trial.

Humans

Dexamethasone as an adjuvant to continuous erector spinae plane block for postoperative analgesia after video-assisted thoracoscopic surgery for pulmonary nodule surgery: a randomized controlled trial.

BACKGROUND: While dexamethasone is proven to enhance single-shot erector spinae plane block (ESPB), its role as an adjuvant in continuous ESPB catheters is unclear. This randomised controlled trial evaluated whether adding dexamethasone to ropivacaine improves analgesia after video-assisted thoracoscopic surgery (VATS). METHODS: 85 patients undergoing VATS with continuous ESPB were randomised to receive postoperative infusion of either 0.2% ropivacaine(C-ESPB group) or ropivacaine with 10&#x2009;mg dexamethasone(D&#x2009;+&#x2009;C-ESPB group). The primary outcome was resting pain visual analog scale (VAS)at 12&#x2009;h postoperatively, while secondary outcomes included QoR-15 scores, tramadol consumption, time to first analgesic requirement, postoperative adverse events, 3-month incidence of chronic pain, catheter-related complications, pain intensity at other times, and hospital stay. RESULTS: The D&#x2009;+&#x2009;C-ESPB group had significantly lower resting pain at 12&#x2009;h [2.56 (1.03) vs 3.24 (1.21), mean difference -0.680, p&#x2009;=&#x2009;0.006]; and lower coughing pain at 12&#x2009;h [4.60 (1.48) vs 5.69 (1.35), mean difference 1.086, p&#x2009;<&#x2009;0.001], with analgesic superiority sustained through 72&#x2009;h. Quality of Recovery-15 scores were higher at 12&#x2009;h [124.70 (12.48) vs 117.26 (12.24); mean difference -7.436, p&#x2009;=&#x2009;0.007] and 48&#x2009;h [141.60 (5.51) vs 138.98 (6.64); mean difference -2.628, p&#x2009;=&#x2009;0.050]; Total tramadol consumption over 72&#x2009;h was markedly reduce [0 (0,100) vs 100 (75,100), z&#xa0;=&#xa0;-3.807, p&#x2009;<&#x2009;0.001], and hospital stay was shorter [Mean (SD) 6.09 (1.34)&#xa0;d vs 6.93 (1.55)d, p&#x2009;<&#x2009;0.001]. The intervention did not, however, alter the 3-month incidence of chronic postsurgical pain (31% vs 34%, p&#x2009;=&#x2009;0.756). CONCLUSION: Dexamethasone significantly enhances the analgesic efficacy of continuous ESPB, improving early pain control, recovery quality, and opioid-sparing after VATS, but does not reduce the incidence of chronic persistent surgical pain.

Humans

Intravenous lidocaine reduces the propofol EC50 for loss of consciousness and intraoperative anesthetic consumption in gynecological laparoscopy: A randomized controlled trial.

BACKGROUND: Intravenous lidocaine reduces propofol requirements and procedure-related adverse events. OBJECTIVES: The study aimed to test whether intravenous lidocaine would reduce the effect-site concentration of propofol required to achieve loss of consciousness and decrease propofol consumption during total intravenous anesthesia in gynecological laparoscopy. METHODS: This was a prospective, randomized, double-blind, placebo-controlled trial. Sixty patients were randomly allocated to receive either intravenous lidocaine (1.5 mg&#xb7;kg-&#xb9; bolus) followed by continuous infusion or an equal volume of saline. Propofol was administered via target-controlled infusion starting at an effect-site concentration of 3.5 &#x3bc;g/mL. The concentration was then adjusted in steps of 0.5 &#x3bc;g/mLaccording to Dixon's up-and-down sequential method: decreased if loss of consciousness was achieved, or increased if not. Loss of consciousness was defined as loss of response to verbal commands. The median effective concentration (EC50) of propofol for inducing loss of consciousness was calculated using the Dixon's up-and-down method. General anesthesia was maintained with propofol and remifentanil, guided by state entropy (target 40-60) and surgical pleth index (target 20-50). Drug consumption was normalized to anesthesia duration and body weight. RESULTS: The estimated EC50 of propofol for inducing loss of consciousness was significantly lower in the lidocaine group than in the saline group (3.32 &#x3bc;g/mL, 95% Confidence Interval (CI): 3.04-3.59 vs. 3.89 &#x3bc;g/mL, 95% CI: 3.50-4.28). Under the study protocol, the lidocaine group also required less propofol (8.62 mg&#xb7;kg-1&#xb7;h-1, 95% CI: 8.10-9.15 vs. 9.89 mg&#xb7;kg-1&#xb7;h-1, 95% CI: 9.05-10.73) and less remifentanil (0.23 &#x3bc;g&#xb7;kg-1&#xb7;min-1, 95% CI: 0.21-0.24 vs. 0.27 &#x3bc;g&#xb7;kg-1&#xb7;min-1, 95% CI: 0.24-0.30) compared with the saline group. CONCLUSION: Intravenous lidocaine reduced the propofol EC50 for Loss of Consciousness (LOC) and decreased intraoperative propofol and remifentanil consumptions in patients undergoing gynecological laparoscopy. These findings suggest a propofol- and opioid-sparing effect of intravenous lidocaine in this setting, although confirmation in larger multicenter trials is needed.

Humans

Effectiveness of Topical Huzhang Sanhuang with Standard Nursing for Chemotherapy-Induced Phlebitis: Randomized Controlled Study.

Chemotherapy-induced phlebitis (CIP) is a common complication of peripheral intravenous chemotherapy that can cause pain, local inflammation, treatment interruption, and diminished quality of life. This randomized controlled trial evaluated the efficacy and safety of the topical Huzhang Sanhuang (HZSH) formula, combined with standard nursing care, in managing CIP. Ninety-four hospitalized patients with CIP (grade I or higher) were randomly assigned in a 1:1 ratio to receive either topical HZSH formula plus standard nursing care (experimental group, n = 47) or 50% magnesium sulfate wet dressing plus standard nursing care (control group, n = 47) for 14 days. Prespecified outcomes included phlebitis grade, visual analog scale (VAS) pain score, high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), symptom resolution time, and safety indicators. By Day 14, patients in the experimental group demonstrated significantly greater improvement in phlebitis severity than those in the control group (risk ratio for grade &#x2265; II, 0.42; 95% confidence interval, 0.20-0.87; P = 0.012). The experimental group also showed significantly larger reductions in VAS pain scores, hs-CRP levels, and IL-6 concentrations (all P < 0.01). Kaplan-Meier analysis further demonstrated faster resolution of multiple local symptoms in the experimental group. Treatment adherence was high in both groups, and no serious adverse events or major safety concerns were observed. These findings indicate that the topical HZSH formula, combined with standard nursing care, is a safe and effective integrative nursing intervention that accelerates clinical recovery, alleviates local symptoms, and reduces the inflammatory burden in patients with chemotherapy-induced phlebitis.

Humans

Evaluation of the clinical and mechanistic role of MCM2 expression in the prediction of meningioma recurrence after radiotherapy.

OBJECTIVE: Postoperative radiotherapy is an effective treatment for meningiomas; however, treatment response varies among patients. In addition, practical methods for predicting tumor recurrence after radiotherapy have not been well established. Minichromosome maintenance protein 2 (MCM2), a key regulator of DNA replication licensing, was recently implicated in highly proliferative molecular subtypes of meningioma. In this study, the authors evaluated whether MCM2 immunohistochemical expression predicts response to radiotherapy in patients with meningiomas. METHODS: The authors retrospectively analyzed the records of patients with WHO grade 1-3 meningiomas treated with resection followed by radiotherapy at a single institution between July 2003 and November 2023. The MCM2 labeling index was assessed immunohistochemically, and patients were stratified into MCM2-high and -low groups using a cutoff of 35%. Progression-free survival (PFS) was defined as the interval from the completion of radiation therapy to postoperative radiological tumor recurrence or regrowth. Patients who showed no progression were censored at their last follow-up. PFS was estimated using Kaplan-Meier analysis and subsequently evaluated with Cox proportional hazards models. To further investigate the biological mechanisms associated with MCM2 expression, comprehensive transcriptomic analyses, including gene set enrichment analysis, was performed to elucidate the molecular processes that occur within MCM2-high tumors. RESULTS: The study population included 15 men (42%) and 21 women (58%), with a mean age of 63 years. Ten tumors (28%) were classified as MCM2-high meningiomas and 26 (72%) as MCM2-low meningiomas. High MCM2 expression was significantly associated with WHO grades 2-3 histology and higher Ki-67 labeling indices. During a median follow-up of 2.52 years, tumor progression after radiotherapy occurred in 47% of the patients. High MCM2 expression (HR 8.34, p = 0.03) was significantly associated with shorter PFS and remained an independent predictor of recurrence after adjustment for WHO grade, tumor size, and Ki-67 labeling index. Transcriptomic analyses of MCM2-high tumors revealed upregulation of cell proliferation-related pathways, accompanied by increased signaling through the E2F8-CHEK1 axis associated with radiation resistance and suppression of the TNF-&#x3b1; signaling pathway implicated in radiosensitivity. CONCLUSIONS: In meningiomas, high MCM2 expression is associated with early recurrence following radiotherapy. The study findings suggest that this association is driven by diverse biological mechanisms related to cell cycle regulation and radioresistance. Immunohistochemical assessment of MCM2 expression may serve as a practical and accessible biomarker for risk stratification and may support the future development of individualized postoperative radiotherapy strategies.

Humans

Introgression shapes the genomic conflict landscape of Malus, providing evidence for a reticulate backbone in a woody crop lineage.

Phylogenomic discordance is widespread across plants, but its evolutionary significance is often obscured when conflict is treated primarily as analytical noise rather than as evidence of underlying processes. In woody lineages in particular, incomplete lineage sorting, introgression, and genome duplication can interact over long timescales to produce complex genomic histories that are not adequately summarized by a strictly bifurcating tree. Here, we use Malus as a model woody genus to investigate how these processes structure conflict across a genus-scale, accession-based phylogenomic framework. Using broad taxon sampling, hundreds of nuclear loci, plastid genomes, and genome-wide SNP summaries, we reconstruct a robust nuclear backbone for sampled Malus lineages and evaluate where discordance is concentrated and which processes best explain it. Nuclear analyses resolve eight major clades, whereas conflict is non-random and localized to recurrent hotspots rather than evenly distributed across the tree. Cytonuclear discordance is similarly concentrated, especially around Clade H, represented by sampled accessions of M. tschonoskii, where localized plastid-nuclear disagreement is consistent with candidate plastid capture or organellar introgression. Multiple complementary analyses further indicate that the strongest conflict is not explained by ILS alone, but instead reflects lineage-structured introgression, while polyploid complexes represent additional localized sources of evolutionary complexity. Together, these results provide evidence for a reticulate genomic backbone in Malus and show how integrating nuclear, plastid, and genome-wide conflict analyses can help distinguish background discordance from process-specific signals in woody plant radiations. Several lineage-level reticulation hypotheses identified here should now be tested with broader population-level sampling and curated reference accessions.

Malus

Spatial proximity or vector orientation? Re-evaluating ECG interpretation in anterior myocardial infarction using cardiac magnetic resonance.

BACKGROUND: The electrocardiogram (ECG) is widely used to infer infarct location and extent in anterior myocardial infarction (MI), based on either anatomical lead proximity or vectorial orientation of ST-segment deviation. However, the validity of these approaches against direct imaging of myocardial injury remains uncertain. METHODS: In this prospective study, 105 patients with anterior MI underwent cardiac magnetic resonance (CMR) imaging 3-7&#xa0;days after presentation. Admission ECGs were analyzed using (1) conventional ECG localization categories, and (2) simplified frontal and horizontal ST-axis orientation. CMR-defined injury distribution was assessed using late gadolinium enhancement and myocardial edema imaging. RESULTS: Conventional ECG localization categories demonstrated no significant association with CMR-defined infarct distribution (P&#xa0;=&#xa0;0.24), with poor agreement (&#x3ba;&#xa0;=&#xa0;0.122) and substantial overlap across categories. Simplified ST-axis orientation showed modest and inconsistent associations with infarct location and did not meaningfully explain infarct size. In contrast, global ST-segment burden was associated with CMR-defined infarct size (&#x3a3;STE: standardized &#x3b2;&#xa0;=&#xa0;0.307, P&#xa0;=&#xa0;0.002; lead count: standardized &#x3b2;&#xa0;=&#xa0;0.267, P&#xa0;=&#xa0;0.007). CONCLUSIONS: In this selected cohort of reperfused LAD-related anterior STEMI patients undergoing early CMR, conventional ECG localization categories and simplified ST-axis orientation showed poor or inconsistent correspondence with CMR-defined infarct distribution, whereas global ST-segment burden showed a modest association with infarct size. These findings suggest that, in this cohort, the ECG may be better suited to reflect the extent of myocardial injury rather than its precise anatomical location.

Humans

Regional genomic analysis of lineage distribution and transferable multidrug resistance among chicken-associated Salmonella Kentucky isolates in China.

Salmonella enterica serovar Kentucky is an important multidrug-resistant foodborne pathogen in the poultry meat supply chain. Although recent broader genomic studies have elucidated the population structure and epidemiological significance of major lineages in China (e.g., ST198 and ST314), the regional dynamics within local poultry supply chains remain insufficiently characterized. In this study, 31 chicken meat-derived isolates from Shanghai and 39 publicly available genomes from China were analyzed using antimicrobial susceptibility testing, whole-genome sequencing, phylogenetic analysis, conjugation experiments, and complete sequencing of representative plasmids. This enabled a systematic characterization of the molecular epidemiological features of the population and the mechanisms underlying resistance dissemination. Population genomic analysis revealed a lineage composition markedly different from the global epidemiological pattern: ST314 was the predominant sequence type among the Shanghai chicken-derived isolates (74.2%), whereas the internationally recognized high-risk clone ST198 accounted for only 25.8% of the local isolates. However, risk stratification analysis indicated that although ST198 was detected less frequently, it carried a significantly greater burden of acquired resistance genes and therefore represented a higher-risk resistant lineage. Functional and structural validation further elucidated the molecular basis of resistance dissemination within this high-risk lineage. Conjugation experiments confirmed the co-transfer of a multidrug resistance module carrying blaTEM-1 and blaCTX-M-267 to the recipient strain Escherichia coli J53. Complete plasmid analysis revealed that these two &#x3b2;-lactam resistance genes were co-localized on a 242-kb transferable plasmid flanked by Tn1331, Tn3, and multiple transposase-associated elements, thereby providing a structural basis for their horizontal transfer. This study provides important molecular epidemiological evidence for lineage-specific surveillance and risk-stratified control of resistant Salmonella in the poultry meat supply chain and further underscores the need for continuous monitoring of mobile genetic elements within a One Health framework.

Animals

A study on the differences in recovery effects of different types of nutritional supplements on competitive performance of esports athletes under mental fatigue.

BACKGROUND: To compare the effects of different nutritional supplements on the recovery of core competitive performance abilities in esports athletes following mental fatigue and to observe changes in the autonomic nervous system during recovery after nutritional supplementation by monitoring heart rate variability (HRV). METHODS: A randomized crossover within-subject controlled experimental design was adopted, including nutritional supplement type (caffeine, nitrate, Ginkgo biloba extract, catechins, placebo)&#x2009;&#xd7;&#x2009;mental fatigue state (initial, fatigued, post-supplementation). Twenty high-level first-person shooter (FPS) esports athletes were recruited. Mental fatigue was induced using a Stroop task. After ingesting the different supplements and resting for 60&#x2009;minutes, the participants completed assessments of shooting accuracy, shooting stability, spatial localization, and multitasking ability using the KovaaK's simulation trainer. HRV indices were also recorded to evaluate changes in autonomic regulation. RESULTS: For shooting accuracy, compared with the placebo condition, all four supplements significantly improved shooting accuracy scores following mental fatigue (all p&#x2009;<&#x2009;0.05); however, no significant differences were observed among the effects of the different supplements. For shooting stability, caffeine, nitrate, and catechins produced significant recovery effects on shooting stability (all p&#x2009; <&#x2009;0.05); however, no significant differences were observed among the effects of these three supplements. For spatial localization and multitasking ability, the improvements in these two abilities in the post-supplementation state may have resulted from natural recovery, and none of the four nutritional supplements demonstrated a significant recovery effect. The HRV results showed that indices including RMSSD and SDNN changed under some supplement conditions. CONCLUSIONS: Mental fatigue significantly reduced the competitive performance of esports athletes. Four types of nutritional supplements all promoted the recovery of shooting accuracy, while caffeine, nitrate, and catechins promoted the recovery of shooting stability. However, no additional recovery advantages of the nutritional supplements over placebo were identified for spatial localization or multitasking ability. Changes in HRV may reflect changes in autonomic regulation during recovery, but further research is still warranted.

Humans

LitCTL1: A novel C-type lectin involved in the mucosal and cellular immunity of the common periwinkle Littorinalittorea.

C-type lectins (CTLs) are vital pattern-recognition receptors (PRRs) that mediate innate immune responses in mollusks, yet their characterization in Caenogastropoda, the largest gastropod group, remains limited. This study characterizes LitCTL1, a novel secreted single-domain C-type lectin from the common periwinkle, Littorina littorea. The 199-amino acid polypeptide contains a conserved carbohydrate recognition domain with canonical QPD and WND motifs and is predicted to form a homodimer. Uniquely, LitCTL1 was localized in both circulating hemocytes and mucus-secreting epithelial cells of the foot, mantle, and hypobranchial gland - the first report of such dual localization for a molluscan lectin, linking systemic and mucosal defense. Expression analysis revealed that LitCTL1 is constitutively expressed in hemocytes. Functional assays with recombinant LitCTL1 demonstrated its role as a potent opsonin with hemagglutinating activity, significantly enhancing hemocyte spreading and the phagocytosis of zymosan. Genomic analysis reveals that LitCTL1 belongs to a rapidly diversifying, genus-specific expansion distinct from conserved perlucin-like lineages. These results identify LitCTL1 as a key effector molecule in both systemic and mucosal innate immunity, likely reflecting an evolutionary adaptation to the microbial challenges of the intertidal environment.

Animals

Functional characterization of the MdFLZ2 gene in drought and salt stress tolerance in apple.

Drought and salt stress are significant environmental limitations that severely constrain plant growth and productivity, therefore, enhancing stress tolerance is a key goal in crop improvement. The plant-specific FCS-like zinc finger (FLZ) proteins have been identified as important regulators of stress adaptation. In this study, we conducted a genome-wide characterization of the FLZ gene family in apple and functionally characterized MdFLZ2. qRT-PCR analysis revealed that MdFLZ2 was differentially expressed across various tissues and transcriptionally induced by both drought and salt stress. Subcellular localization assays demonstrated that the MdFLZ2 protein is localized to both the nucleus and the cytoplasm. The overexpression of MdFLZ2 in apple calli, Arabidopsis and tomato conferred increased resistance to drought and salt stress. In addition, yeast two-hybrid (Y2H) assays confirmed that MdFLZ2 interacted with MdSnRK1.1, and similar interactions were also detected between other MdFLZ family members and MdSnRK1.1. Collectively, our findings suggest MdFLZ2 as a positive regulator of drought and salt tolerance and highlight its potential to serve as a genetic resource for abiotic stress improvement.

Malus

Molecular mechanisms of neuroendocrine regulation of molting in the Chinese mitten crab (Eriocheir sinensis): A transcriptomic analysis based on eyestalk ablation model.

Molting disability severely restricts the sustainable aquaculture of the Chinese mitten crab, yet the neuroendocrine mechanisms coordinating physiological responses remain poorly understood. Using unilateral eyestalk ablation to remove the primary source of molt-inhibiting hormone (MIH), we performed time-resolved transcriptomic profiling of the thoracic ganglion at 24&#xa0;h (early premolt) and 48&#xa0;h (ecdysis) post-ablation. We identified 2825 differentially expressed genes and uncovered a biphasic molecular response. At 24&#xa0;h, the thoracic ganglion activates pathways associated with neuromuscular adaptation, oxidative stress, and cardiac muscle contraction. Notably, the arachidonic acid metabolism pathway is selectively rewired: cytochrome P450 &#x3c9;-hydroxylases (CYP2J2, CYP4V2) are upregulated, while competing branches (epoxide hydrolase, cyclooxygenase) are suppressed, promoting local synthesis of the potent vasoconstrictor 20-HETE within the thoracic ganglion. This enzymatic switch provides a mechanistic link between MIH withdrawal and the local generation of elevated hemolymph pressure required for molting. By 48&#xa0;h, the transcriptional program shifts toward chitin-based extracellular matrix remodeling, glycosphingolipid biosynthesis, and synaptic reorganization. Collectively, our findings redefine the thoracic ganglion as an active neuroendocrine integrator that translates reduced MIH signaling into phased physiological outputs, revealing a "neuro-endocrine-hemolymph pressure" regulatory axis. This study provides novel molecular targets (e.g., CYP2J2, CHS1, UGCG) for mitigating molting disability in E. sinensis aquaculture.

Animals

Integrative multi-omics reveals a fibroblast-centered, ZFHX3-prioritized regulatory framework linking sick sinus syndrome and atrial fibrillation.

OBJECTIVE: To define shared genetic and multi-scale mechanisms underlying comorbidity between sick sinus syndrome (SSS) and atrial fibrillation (AF). METHODS: We integrated genome-wide association study (GWAS) summary statistics for SSS and AF with Genotype-Tissue Expression (GTEx) expression and splicing quantitative trait loci (eQTL/sQTL), atrial single-cell and spatial transcriptomics, and epigenomics. We identified trait-relevant tissues and pathways, prioritized shared cell types, quantified genome-wide and local genetic sharing, detected joint loci by cross-trait meta-analysis, and linked loci to regulatory programs via colocalization and cell-prioritized co-expression networks. RESULTS: Both traits showed strongest enrichment in cardiac tissue, especially Heart Atrial Appendage. Fibroblasts from the left atrial appendage were consistently prioritized as the key shared cell population. SSS and AF displayed significant positive genome-wide genetic correlation, with multiple locally shared regions, including six major loci. Cross-trait meta-analysis identified eight joint-phenotype SNPs implicating four susceptibility genes. ZFHX3 was the leading tissue-cell-gene candidate, acting as a hub in fibroblast co-expression modules and colocalizing with cardiac regulatory signals. CONCLUSION: Shared liability for SSS and AF is highly tissue- and cell-specific, converging on regulatory networks in atrial appendage fibroblasts, with ZFHX3 serving as a central mechanistic and biomarker node.

Humans