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Effects of cinnamon supplementation combined with exercise training on anthropometric indices and reproductive hormones in overweight and obese women.

BACKGROUND: The prevalence of obesity and increased fat in the chest and abdomen in women and hormonal changes, can affect female fertility. The present study aims to investigate the effect of exercise training combined with cinnamon supplementation on chest and abdominal circumference, as well as sex hormones, in overweight and obese women. METHODS: Twenty-six inactive overweight and obese women were randomly allocated to an exercise (E; n = 13) and exercise plus cinnamon supplementation (E+S; n = 13) group. Both groups completed a 4-week exercise program three times weekly, while the E+S group additionally received cinnamon supplementation three times weekly. Chest and abdominal circumferences and serum concentrations of estradiol, progesterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) were assessed before and after the intervention. RESULTS: Significant pre-to-post reductions in chest and abdominal circumference were observed in both groups (all p ≤ 0.005). Estradiol, progesterone, and FSH concentrations increased, whereas LH concentrations decreased significantly in both groups (all p ≤ 0.005). However, between-group comparisons revealed a significant difference only for chest circumference (p = 0.003), with no significant group differences in abdominal circumference or any reproductive hormone concentration (all p > 0.05). CONCLUSION: Both groups showed favorable changes in anthropometric and reproductive hormone measures following the 4-week study period. However, the significant between-group difference was limited to chest circumference, providing no clear evidence that cinnamon supplementation conferred additional benefits for abdominal circumference or reproductive hormone profiles beyond those observed with exercise. These findings highlight the potential relevance of exercise-based interventions while warranting confirmation in larger, adequately powered trials.

Humans

Therapeutic approaches for the treatment of bovine metritis: a systematic review of clinical, reproductive and productive outcomes.

Bovine metritis is a complex multifactorial disease associated with substantial clinical and economic impact due to reduced milk production, subfertility, and increased culling rates. Considerable uncertainty remains regarding the comparative efficacy of the many therapeutic strategies used to manage it. This systematic review aimed to summarize and critically evaluate the available evidence on therapeutic approaches for bovine metritis, with respect to clinical cure, reproductive performance, productive performance, and culling. A literature search conducted in PubMed, Web of Science and CABI Digital Library (2010-2025) identified 18 randomized controlled clinical trials eligible for inclusion. Risk of bias was assessed independently by two reviewers using the Cochrane RoB 2 tool. Given substantial clinical and methodological heterogeneity across studies, findings were synthesized narratively by outcome, without meta-analytic pooling, and the certainty of evidence was assessed using GRADE for the comparisons supported by more than one study. Overall, systemic antimicrobial therapies consistently improved short-term clinical cure rates, although their effects on long-term reproductive and productive performance remained inconsistent. In selected cases, nonsteroidal anti-inflammatory drugs (NSAIDs) showed clinical outcomes comparable to antimicrobial treatments, allowing reductions in antimicrobial use ranging from 50% to 92%. Alternative approaches, such as intrauterine flavonoid, chitosan or dextrose-based therapies, produced inconsistent results that appeared to correlate with disease severity and treatment protocol. The evidence base is limited by substantial heterogeneity in disease definitions, postpartum timing of diagnosis, and cure criteria across studies, and by the near-universal absence of allocation concealment in the primary literature; these limitations restrict the certainty of most conclusions to low or moderate. Therefore, effective metritis control should move beyond symptom resolution and incorporate integrated and preventive strategies targeting inflammatory and metabolic dysregulation during the transition period.

Animals

Influence of Repeated-Sprint Bout Duration in Sprint Interval Training Intervention on Physical Performance Adaptations of Young Volleyball Players.

The objective of this study was to examine the effects of repeated-sprint training (RST) with varying bout durations on the physical fitness adaptations of young male volleyball players. Forty athletes were randomly allocated to one of three intervention groups performing RST with varying bout durations and similar repetition volumes, all executed at maximal effort. The 3-sec group (n = 10) completed two sets of 30 bouts, the 6-sec group (n = 10) performed two sets of 15 bouts, and the 9-sec group (n = 10) carried out two sets of 10 bouts, each adhering to a 1:3 work to rest ratio. An active control group (n = 10) engaged solely in regular volleyball training without the RST intervention. Physical fitness measures-including countermovement vertical jump (CMVJ), 10-m and 20-m linear sprints, T-test change-of-direction speed (T-CODS), reactive strength index (RSI), and the Wingate anaerobic power test-were assessed pre- and post-a 6-week training intervention (i.e., 18 sessions). All RST groups showed significant post-intervention improvements in physical fitness (main effect of time, p = 0.001), with greater adaptations compared with the control group and effect sizes ranging from small to very large. The 3-sec bout group demonstrated greater gains in CMVJ, 10-m and 20-m sprint performance, RSI, and peak power output compared with the 9-sec group (all, p < 0.05). Conversely, the 9-sec group exhibited superior adaptations in T-CODS and mean power output relative to the 3-sec group (all, p < 0.05). In conclusion, the 3-sec group experienced greater enhancements in explosive and sprint performances, while the 9-sec group showed superior gains in change of direction and mean power output. These findings indicate that manipulation of sprint-bout duration in RST can be used to optimize distinct performance adaptations in young volleyball players.

Humans

Effects of blood flow restriction training combined with resistance training on lower-limb strength and sport-specific performance in athletes: a systematic review and meta-analysis.

BACKGROUND: In contemporary sports science, athletes and coaches continuously explore strategies to reduce training load and injury risk while increasing muscular strength and sport-specific performance. This meta-analysis evaluated the effects of blood flow restriction training (BFRT) combined with resistance training (RT) on lower-limb muscle strength and sport-specific performance in athletes. METHODS: Relevant randomized controlled trials (RCTs) were systematically searched across major databases (e.g. PubMed, Web of Science, Cochrane, CNKI, Wanfang Data, and Embase) from inception until November 2024. Two independent reviewers carefully assessed the studies. Data analysis was carried out using RevMan 5.4 software, which included heterogeneity testing, meta-analysis, subgroup analysis, and assessment of publication bias. RESULTS: Ten RCTs (181 athletes; 91 in the BFRT and RT group, 90 in the control group) were included. Outcomes determined BFRT combined with RT yielded notable enhancements in lower-limb muscle strength (SMD = 1.09, 95% CI [0.52, 1.66], p&#x2009;<&#x2009;0.05) and muscle hypertrophy (MD = 1.09, 95% CI [0.10, 2.09], p&#x2009;<&#x2009;0.05) compared to control training. However, no significant improvement in sport-specific performance was found (SMD = 0.11, 95% CI [-0.18, 0.40], p&#x2009;=&#x2009;0.46). Substantial heterogeneity was observed for strength outcomes (I2 = 75%), whereas low heterogeneity was observed for sport-specific performance and hypertrophy outcomes (I2 = 0%). No evidence of significant publication bias was detected. CONCLUSION: BFRT combined with RT appears to provide effective augmentation of lower-limb muscle strength and hypertrophy in athletes compared to RT or conventional training alone. It may be prudent to integrate this approach systematically into training cycles to optimize physiological muscle stimulation and training outcomes, despite not directly improving sport-specific performance.

Humans

Health Literacy and Capecitabine Adherence in a Remote Monitoring Pilot Trial for Breast Cancer: Post Hoc Exploratory Analysis.

BACKGROUND: Oral anticancer therapy enables convenient, home-based cancer care but can introduce adherence challenges, particularly with complex dosing schedules. Capecitabine is commonly used in breast cancer, often as adjuvant therapy or in advanced disease, and typically requires twice-daily dosing on cyclical schedules, increasing the risk of missed or incorrect doses. Low health literacy may exacerbate these difficulties, and emerging remote monitoring tools may help close this gap. OBJECTIVE: In this post hoc exploratory analysis, we evaluated whether health literacy (1) was associated with capecitabine adherence and (2) modified a remote monitoring intervention's effectiveness. METHODS: We conducted post hoc analyses of a 2-arm pilot trial that randomized women with breast cancer treated with capecitabine to enhanced usual care (EUC) or remote patient monitoring (RPM). Adherence was captured with a smart pill bottle, Nomi by SMRxT, that recorded dose timing and quantity. Participants in the RPM group received messages for missed or incorrect doses and weekly symptom assessments. Incorrect or missed doses and severe symptoms triggered alerts to the oncologist. Health literacy was assessed at enrollment. To evaluate moderation, we used linear regression with an interaction term (health literacy &#xd7; intervention arm) predicting adherence (proportion of days). Marginal effects quantified differences in adherence by study arm and health literacy. RESULTS: Among 28 participants (EUC, n=15 and RPM, n=13), 9 (32.1%) had lower health literacy, 16 (57.1%) identified as Black, 10 (35.7%) identified as White, and 15 (53.6%) had income below 200% of the federal poverty level. In the regression model, the health literacy &#xd7; randomized group interaction did not reach statistical significance (-16.3 percentage points, 95% CI -35.5 to 2.9; P=.09). Predicted adherence among lower health literacy participants was 87.5% in the RPM group and 65.5% in the EUC group (difference: +22.1 percentage points, 95% CI 6.2-37.9; P=.008). Among participants with higher health literacy, adherence was 89.9% in the RPM group and 84.1% in the EUC group (difference: +5.7 percentage points, 95% CI -5.2 to 16.7; P=.29). Within the EUC group, predicted adherence was 18.6 percentage points lower among those with lower versus higher health literacy (95% CI -32.4 to -4.9; P=.01); within the RPM group, this difference was 2.3 percentage points lower among those with lower versus higher health literacy (95% CI -15.8 to 11.1; P=.73). CONCLUSIONS: In this post hoc exploratory analysis, the estimated difference in capecitabine adherence between the RPM and EUC groups was larger among participants with lower health literacy. Although the formal interaction test was not statistically significant, the magnitude and direction of the observed difference support further investigation of RPM as a potential approach to improve adherence among patients facing health literacy-related adherence barriers. Larger, prospectively powered studies are needed to confirm these findings and evaluate downstream clinical outcomes.

Humans

Superficial Cervical Plexus Block and Quality of Recovery after Thyroidectomy: A Randomized Clinical Trial.

BACKGROUND: Whether adding a bilateral superficial cervical plexus block to a thyroidectomy enhanced recovery pathway improves postoperative quality of recovery remains uncertain. METHODS: In a single-center prospective, randomized, double-blind, placebo-controlled trial in adults undergoing thyroidectomy with general anesthesia, participants were randomized to bilateral superficial cervical plexus blocks with 0.25% bupivacaine or saline. All participants received multimodal analgesia with dexamethasone, acetaminophen, nonsteroidal anti-inflammatory drugs, and incisional local anesthetic. The primary outcome was quality of recovery, measured by the QoR-40 survey, on postoperative day 1. Secondary outcomes included the need for rescue opioid, total opioid consumption, nausea, vomiting, antiemetic administration, length of stay in the postanesthesia care unit (PACU), and opioid use on postoperative day 1. RESULTS: A total of 160 participants were randomized to receive a superficial cervical plexus block with bupivacaine 0.25% (n = 78) or saline (n = 82). On postoperative day 1, mean QoR-40 scores were 174 (95% CI, 170 to 178) for bupivacaine and 173 (95% CI, 169 to 177) for saline. The adjusted mean difference between bupivacaine versus saline was 0.91 (95% CI, -3.57 to 5.40; P = 0.688). There were no significant between-group differences in the need for opioids in the PACU or on postoperative day 1, nausea, vomiting, or PACU length of stay. However, the total amount of opioid administered in the PACU was lower in the bupivacaine group (median [interquartile range], 0 [0 to 8]) compared with the saline group (2 [0 to 20]; Hodges-Lehmann location shift, 0 morphine milligram equivalents; 95% CI, -4 to 0; P = 0.017), and fewer participants in the bupivacaine group received rescue antiemetics (3 [3.8%] vs . 13 [16%]; difference, -12%; 95% CI, -22% to -1.8%; P = 0.011). CONCLUSIONS: Bilateral superficial cervical plexus blocks did not improve quality of recovery after thyroidectomy when added to a multimodal analgesic regimen including dexamethasone, acetaminophen, nonsteroidal anti-inflammatory drugs, and incisional local anesthetic but were associated with lower total PACU opioid consumption.

Humans

Effect of self-activating phthalocyanine gel on palatal donor site healing, inflammatory biomarkers, somatosensory and patient-centered outcomes: a randomized split-mouth clinical trial.

OBJECTIVES: To evaluate effects of self-activating phthalocyanine (PHY) gel on palatal donor site after subepithelial connective tissue graft (SCTG) harvesting, considering clinical outcomes, inflammatory biomarkers, patient-centered outcomes, and quantitative somatosensory changes. MATERIALS AND METHODS: Twenty participants were included in this randomized, crossover, split-mouth clinical trial. Donor sites received topical PHY gel (PHY group-PHYG) and placebo gel (control group-CG). Clinical parameters (residual wound area-RWA, wound epithelialization-WE, residual remodeling area-RRA and tissue thickness-TM) were assessed at baseline, 7, 14, 30, and 60 days. Patient-centered outcomes were recorded during 14 postoperative days and inflammatory biomarkers at 3 and 7 days postoperatively. Mechanical detection threshold (MDT) and mechanical pain threshold (MPT) were evaluated at baseline, 2 months, and 6 months. RESULTS: PHYG and CG exhibited similar clinical outcomes, but PHYG demonstrated superior performance in reducing RRA. Both groups presented positive postoperative progression of patient-centered outcomes. IL-10 levels showed a significant increase in PHYG, suggesting a more favorable anti-inflammatory response. MDT remained stable but, donor sites exhibited transient hypersensitivity (MPT) at 2 months. CONCLUSIONS: PHYG and CG protocols promoted satisfactory healing of palatal donor sites. Most clinical parameters and patient-centered outcomes were similar between groups. The PHYG presented reduced RRA and increased IL-10 levels. Donor sites exhibited transient hypersensitivity, which tended to resolve over time. CLINICAL RELEVANCE: Both postoperative protocols resulted in favorable healing of palatal donor sites following SCTG harvesting, with comparable clinical and patient-centered outcomes. Quantitative sensory testing indicates that hypersensitivity may occur during healing, but sensory function tends to recover progressively.

Humans

Ultrashort vs Standard-Duration Dual Antiplatelet Therapy in Acute Coronary Syndrome Patients Undergoing PCI: A Meta-Analysis.

BACKGROUND: The efficacy and safety of ultrashort (&#x2264;1-month) dual antiplatelet therapy (DAPT) followed by antiplatelet monotherapy remain uncertain in acute coronary syndrome (ACS) patients. OBJECTIVES: This study sought to compare ultrashort vs standard-duration DAPT in patients with ACS undergoing percutaneous coronary intervention (PCI). METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials until February 15, 2026. Primary outcomes were major adverse cardiac and cerebrovascular events (MACCE), major bleeding, and net adverse clinical event (NACE). Prespecified subgroup analyses examined by ethnicity (East Asian vs non-East Asian) and abbreviation strategy (intensive: &#x2264;1-week DAPT or clopidogrel/aspirin monotherapy vs moderate: &#x2265;2-week DAPT, followed by ticagrelor/prasugrel monotherapy). RESULTS: Across 10 trials (n = 29,232), ultrashort DAPT did not increase MACCE risk (HR: 1.06; 95% CI: 0.93-1.20; P = 0.38; I2 = 24%), with higher MACCE risk observed in ST-segment elevation myocardial infarction (STEMI) but not non-ST-segment elevation ACS (NSTE-ACS), and significantly reduced major bleeding (HR: 0.47; 95% CI: 0.35-0.64; P < 0.00001; I2 = 44%), resulting in a net clinical benefit (HR: 0.83; 95% CI: 0.72-0.97; P = 0.02; I2 = 61%). Bleeding reduction was more pronounced in East Asians (HR: 0.35; 95% CI: 0.25-0.49; P < 0.00001; I2 = 0%) than non-East Asians (HR: 0.63; 95% CI: 0.43-0.93; P = 0.02; I2 = 44%), with a significant interaction (P = 0.02). The abbreviation strategy significantly modified outcomes (P for interaction = 0.003): intensive abbreviation raised MACCE risk (HR: 1.37; 95% CI: 1.11-1.69; P = 0.003; I2 = 0%), while moderate abbreviation had no statistically significant difference (HR: 0.96; 95% CI: 0.85-1.08; P = 0.47; I2 = 0%). CONCLUSIONS: In patients with ACS undergoing PCI, ultrashort DAPT reduced bleeding without increasing ischemic events overall, although a signal of increased MACCE was observed in STEMI but not in NSTE-ACS. Bleeding reduction was greater in East Asians, while &#x2264;1-week DAPT or clopidogrel/aspirin monotherapy may increase ischemic risk.

Humans

Treatment preference for once-weekly versus once-daily DPP-4 inhibitors in patients with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND/OBJECTIVE: Although once-weekly and once-daily DPP-4 inhibitors have gained widespread market recognition, patient preference differences remain a key focus. This meta-analysis compares treatment preferences for once-weekly versus once-daily DPP-4 inhibitors in T2DM, offering evidence to guide clinical decisions and healthcare policies. METHODS: PubMed, OVID, EBSCO, Web of Science, CNKI, Wanfang, and clinical trial registries were searched up to June 30, 2025. After screening literature against predefined criteria, a systematic review was conducted to compare the effects of once-weekly and once-daily DPP-4 inhibitors on the treatment preferences of patients with T2DM. RESULTS: 8 RCTs with 1,575 participants were analyzed. No significant difference in medication adherence and DTSQ total score between the once-weekly and once-daily groups (p > 0.05). HbA1c percentage (MD = -0.21, 95% CI [-0.42, -0.01], p < 0.05) decreased significantly with once-weekly dosing, while GA and FPG showed no change (p > 0.05), this suggests greater improvement in HbA1c percentage levels following a switch to once-weekly DPP-4 inhibitors. Once-weekly DPP-4 inhibitors showed higher musculoskeletal/connective tissue disorder risk (RR = 2.63; 95% CI [1.18, 5.83]), but no significant differences in other adverse events (p > 0.05). No significant differences in treatment burden between both groups (p > 0.05). CONCLUSION: No statistically significant association between treatment preferences for once-weekly versus once-daily DPP-4 inhibitors among T2DM patients and medication adherence, treatment satisfaction, glycemic level changes, safety, or treatment burden for these two dosing regimens. Further research is needed to elucidate the influence of physician prescribing behavior on these preferences.

Humans

Determinants of Nonspecific Response to Treatment in Randomized Controlled Trials of Major Depressive Disorder: A Narrative Review.

The design, conduct, and interpretation of double-blind randomized placebo-controlled clinical trials in major depressive disorder (MDD) are complicated by determinants of nonspecific response to treatment (NSRT). This narrative review provides a comprehensive overview of the determinants of NSRT in randomized controlled trials (RCTs) for MDD, including the placebo effect, factors related to measurement of the primary endpoint, the inclusion of misdiagnosed patients, the relapsing-remitting course of MDD, and factors related to functional unblinding. Potential strategies to reduce the impact of the determinants of NSRT and to improve the interpretation of RCT outcomes in MDD are also summarized. These strategies include use of centralized rating and standardized rater training, independent diagnostic confirmation, optimized site selection, minimizing financial incentives, exclusion of subjects participating in multiple clinical trials, exclusion of patients with unstable major depressive episode trajectories, and use of active placebo and alternative trial designs. Uniformity among experts in the definitions of determinants of NSRT and related concepts, as well as in strategies to address them, may facilitate progress in the development of novel treatments for MDD.

Humans

Early-stage trajectories of social-occupational functioning and long-term functional outcome prediction in early psychosis: A 12-year follow-up of the randomized controlled trial on extended early intervention.

BACKGROUND: Functional impairment in psychosis often persists despite symptomatic remission. There is a paucity of research examining early-course psychosocial functioning trajectories, and none has been conducted to examine relationship between the trajectories and prospective long-term functional outcomes in early psychosis sample. METHODS: We conducted 12-year follow-up of a randomized controlled trial on extended early intervention for first-episode psychosis to identify early-course social-occupational functioning trajectories and their baseline predictors and associations with 12-year outcomes. Participants who completed Social and Occupational Functioning Scale (SOFAS) scores at three or more timepoints between baseline and 3-year follow-up were included in the study. Premorbid adjustment, illness characteristics, symptom severity, functioning, and treatment profiles were assessed. Latent growth mixture modeling was employed to derive early-course social-occupational functioning trajectories based on SOFAS scores over 3-year follow-up. RESULTS: A total of 148 participants were included in this study, with 106 patients having completed the 12-year follow-up. Our results identified four distinct trajectories, including persistently-good class, gradually-improved class, suboptimal-stable class, and persistently-poor class. Patients in persistently-poor class had more severe negative symptoms at baseline compared to patients in persistently-good class. Patients with persistently-poor trajectory had worse long-term outcomes than those with other classes in the majority of functional measures at 12-year follow-up. CONCLUSIONS: The majority of patients were classified in early-stage suboptimal or poor functional trajectories. Above one-fourth of the participants exhibited persistently-poor social-occupational functioning trajectory, which predicted worse functional outcomes at 12-year follow-up. These findings highlighted the importance of tracking functional changes during the initial years of illness.

Humans

Branded packaging raises likelihood of cigarette purchasing in an experimental retail setting by increasing craving.

INTRODUCTION: Exposure to branded cigarette packaging in retail settings has been shown to be associated with purchasing behavior, but the mechanisms underlying this effect are unclear. This study tested whether cigarette craving and perceived health harms mediate the effect of branded packaging on cigarette purchasing in a simulated retail environment. METHODS: Young adults aged 21-34 who currently smoke cigarettes (n&#x2009;=&#x2009;290) completed an experimental shopping task in the RAND StoreLab, a life-sized replica of a convenience store. Participants were randomly assigned to one of two conditions: (1) branding present, in which branded cigarette packages were displayed; and (2) branding absent condition, in which branded elements were removed and packages were standardized in a brown-green color and uniform text. Cigarette purchases were recorded, and participants completed post-shopping measures of cigarette craving and perceived health harms. Causal effect decomposition analyses were used to assess whether these variables mediated the effect of study condition on the likelihood of purchasing cigarettes. RESULTS: Craving, but not perceived health harms, partially mediated the effect of branded packaging on cigarette purchasing. Exposure to branded packs increased the likelihood of purchasing by elevating craving (average mediated effect = 2.4%, 95% CI 0.2% - 5.0%, p&#x2009;=&#x2009;.03). CONCLUSIONS: Branded cigarette packaging appears to increase cigarette purchasing at least in part by increasing cigarette craving at point of sale. Interventions that address craving management in retail settings (e.g., just-in-time interventions, prn nicotine replacement therapy) may help mitigate the impact of branding on young adults' cigarette purchasing.

Humans

Molecular evaluation of residual disease following neoadjuvant chemotherapy in triple-negative breast cancer CALGB 40603 (Alliance).

BACKGROUNDDespite therapeutic advances in early-stage triple-negative breast cancer (TNBC), residual disease (RD) following neoadjuvant therapy remains a key predictor of a worse prognosis and obstacle to improving patient outcomes.METHODSTo better characterize RD and identify survival-associated features, we performed comprehensive transcriptomic profiling of 340 pretreatment stage II/III TNBCs and 70 matched posttreatment RD samples from the randomized CALGB 40603 (Alliance) phase II clinical trial. To explore preclinical treatment strategies for RD, patient-derived xenograft (PDX) mouse models mimicking RD were treated with antibody-drug conjugates (ADCs).RESULTSOur study shows prognostic genomic features measured pretreatment may differ from prognostic features measured posttreatment from RD specimens. Patients with a genomic PAM50 subtype of basal-like in RD specimens had a poor survival outcome, and their matching pretreatment tumors were characterized by elevated chromosomal amplifications of oncogenic drivers and significantly reduced B and T cell expression features. Paired analyses of basal-like RD and matched pretreatment tumors revealed further lymphocyte depletion in RD, along with lower expression of MHC class I and interferon signaling, indicating an immune-cold RD microenvironment. Treatment of a basal-like and conventional chemotherapy-resistant PDX model, resembling basal-like RD, with sacituzumab govitecan or trastuzumab deruxtecan produced a marked antitumor response.CONCLUSIONRD biology differs from pretreatment tumors, with basal-like subtype RD following neoadjuvant chemotherapy being immune cold and associated with poor survival. Preclinical modeling suggests this high-risk group may benefit from adjuvant ADC therapy.TRIAL REGISTRATIONClinicalTrials.gov NCT00861705.FUNDINGNIH NCI U10CA180821 (Alliance for Clinical Trials in Oncology), NCI U24CA176171 (Alliance for Clinical Trials in Oncology), NCI UG1CA233373 (Alliance for Clinical Trials in Oncology), NCI Breast SPORE program P50-CA058223; Susan G. Komen SAC-160074; Breast Cancer Research Foundation BCRF-23-127; NIH NCI R01-CA229409; UNC LCCC Triple Negative Breast Cancer Center.

Humans

Potential Links Between Physiological and Perceptual Strain in High Heat Stress.

The physiological strain index (PhSI) is widely used to quantify thermoregulatory and cardiovascular strain during heat stress. However, direct physiological measurements may not always be feasible in occupational or athletic settings. Therefore, this study aimed to examine the relationship and agreement between perceptual strain and integrated physiological strain indices during high heat stress. Ten healthy, physically active, non-heat-acclimated males (29 (7) yr; 1.79 (0.11) m; 77.4 (9.3) kg) completed two randomized crossover exercise trials in hot-dry (HD) and warm-humid (WH) environments with equivalent wet-bulb globe temperatures. Heart rate, rectal temperature, skin temperature, rating of perceived exertion, and thermal sensation were measured at baseline and every 15&#xa0;minutes during 60&#xa0;minutes of cycling. Physiological strain index (PhSI), adaptive physiological strain index (aPhSI), and perceptual strain index (PeSI) were calculated using validated equations. Repeated-measures correlation analyses demonstrated very strong associations between PeSI and both PhSI and aPhSI under HD (Rrm&#xa0;=&#xa0;0.940-0.943) and WH (Rrm&#xa0;=&#xa0;0.980-0.982; all p&#xa0;<&#xa0;0.001). Receiver operating characteristic analyses demonstrated good-to-excellent discrimination of physiological strain by PeSI (AUC&#xa0;=&#xa0;0.895-0.969). Mixed-effects analyses showed that higher PeSI values were associated with increased PhSI (&#x3b2;&#xa0;=&#xa0;1.325, p&#xa0;<&#xa0;0.001) and aPhSI (&#x3b2;&#xa0;=&#xa0;1.459, p&#xa0;<&#xa0;0.001). However, Bland-Altman analyses demonstrated relatively small mean biases (0.4-0.9 AU) but wide limits of agreement (-2.8 to 4.2 AU), indicating that PeSI and physiological strain indices are not interchangeable. These findings suggest that PeSI may serve as a practical adjunctive or screening indicator of physiological strain when direct physiological measurements are unavailable.

Humans

Comparative transcriptome analysis reveals ncRNA-mediated regulatory networks associated with muscle crispiness in grass carp.

Non-coding RNAs (ncRNAs) have been demonstrated to be involved in muscle development and to function as key regulators. However, the molecular mechanism underlying muscle crispiness in grass carp (GC) remains poorly understood, and whether these ncRNAs are involved in its regulation is still unknown. In the current investigation, differentially expressed (DE) RNAs (including lncRNAs, circRNAs, miRNAs, and mRNAs) were identified; concomitantly, target genes prediction was conducted, and functional and signaling pathway enrichment analyses were performed. Pathways related to muscle crispiness were identified, and the competitive endogenous RNA (ceRNA) (lncRNA/circRNA-miRNA-mRNA) regulatory network was further constructed. The results showed that a total of 126 DE-lncRNAs, 17 DE-circRNAs, 329 DE-miRNAs, and 442 DE-mRNAs were identified in muscle tissues of both the GC and crisp grass carp (CGC). GO and KEGG enrichment analyses revealed that target genes of DE-ncRNAs were significantly enriched in signaling pathways, including structural constituents of muscle, apoptosis, oxidative phosphorylation, and regulation of actin cytoskeleton, suggesting that these pathways may be involved in muscle texture remodeling. Subsequently, DE-RNAs enriched in related pathways were identified, and a core ceRNA regulation network comprising 3 lncRNAs, 4 circRNAs, 3 miRNAs, and 17 mRNAs was constructed. Additionally, 10 DE-RNAs from randomly selected groups were validated by qRT-PCR. Our findings not only provide scientific evidence elucidating the molecular mechanisms underlying muscle crispiness in GC but also establish a foundation for studying changes in muscle textural qualities across other fish species.

Animals

Frontline therapies for adult patients with newly diagnosed Philadelphia chromosome-negative B-cell acute lymphoblastic leukemia: a systematic literature review.

OBJECTIVES: Philadelphia (Ph) chromosome-negative B-cell acute lymphoblastic leukemia (B-ALL) is the most common ALL in adults. Overall survival (OS) with frontline chemotherapy remains poor. Blinatumomab is currently the only targeted agent approved for frontline treatment. METHODS: We systematically reviewed 96 studies (43 interventional, 53 observational) between 2012-2026 evaluating frontline pharmacologic therapy in adults with Ph- B-ALL. RESULTS: Across chemotherapy studies, nearly half of patients relapsed within 3 years, and only 49%-69% survived beyond 3 years. Blinatumomab demonstrated robust and consistent efficacy in first complete response (CR1), supported by 2 randomized controlled trials (RCT) and 16 single-arm trials (SAT). In one RCT, blinatumomab reduced the risk of death by 59% versus chemotherapy alone (HR 0.41) when added to frontline consolidation in minimal residual disease (MRD) negative patients. Median OS reached 41.2 months in a SAT where blinatumomab monotherapy was administered to patients in MRD-positive CR1. SATs showed consistent efficacy outcomes regardless of age, MRD status, or chemotherapy backbone. DISCUSSION: Additional targeted therapies still under investigation have shown mixed results. CONCLUSION: Frontline inotuzumab (&#xb1;blinatumomab) plus chemotherapy showed promise in older populations, while the efficacy benefit of rituximab was inconclusive. No new safety signals were identified in the frontline setting for targeted therapies.

Humans

Effectiveness of grief interventions in underrepresented regions: a systematic review and exploratory meta-analysis.

Background: Most evidence on grief and bereavement interventions originates from Western, Educated, Industrialized, Rich, and Democratic (WEIRD) populations, raising concerns about the generalizability and cultural relevance of existing findings in diverse global contexts. Individuals confronted with the death of a close person, particularly in cases of sudden or potentially traumatic loss, may be at increased risk of adverse psychological and physical health outcomes, highlighting the importance of effective interventions. This study aimed to synthesize evidence on the effectiveness of grief interventions in underrepresented regions.Method: A systematic search of Web of Science, APA PsycInfo, and Scopus, supplemented by manual reference checks, identified randomized controlled trials (RCTs) targeting bereaved individuals in underrepresented regions. Meta-analyses were conducted to estimate overall and subgroup effects based on control type, loss type, and intervention characteristics.Results: Fourteen RCTs comprising 1122 participants were included. Grief interventions demonstrated a significant moderate-to-large effect compared to control conditions (SMD&#x2009;=&#x2009;-0.74, 95% CI [-1.01, -0.47]). Substantial heterogeneity was observed (I&#xb2;&#x2009;=&#x2009;77%). No significant subgroup differences were identified.Conclusion: Grief interventions show promising effectiveness across diverse cultural and geographical contexts. However, the limited and heterogeneous evidence base highlights the need for more high-quality RCTs and for the development of culturally sensitive and contextually grounded approaches to mental health care in underrepresented regions.

Humans

Comparative Transcriptomics Reveals Shared Downstream Pathways in Craniofacial Pathology.

Treacher Collins syndrome and Nager syndrome are craniofacial developmental disorders caused by defects in ribosome biogenesis and RNA splicing, respectively, yet they exhibit overlapping abnormalities affecting neural crest cell-derived craniofacial structures. To investigate shared downstream pathogenic mechanisms, we performed a comparative transcriptomic analysis of zebrafish polr1c and sf3b4 mutant models from our previous studies. Comparative analysis identified 17 shared differentially expressed genes (DEGs) between polr1c and sf3b4 mutants, with the majority of shared genes dysregulated in the same direction, indicating a coordinated rather than random transcriptional response. Gene ontology analysis identified ATP-dependent protein folding chaperone activity as the only shared molecular function, driven in part by upregulation of hsp90aa1.2, indicating a common proteostasis response. Because chaperone activity is linked to extracellular matrix (ECM) protein processing, we cross-referenced DEGs from both mutants against the curated zebrafish matrisome. Three of the 17 shared DEGs (serpinh1b, il11a, and lepa) were matrisome-associated and upregulated in both mutants. Serpinh1b, a collagen-specific chaperone, was strongly expressed in craniofacial cartilage and mesenchymal populations during pharyngeal arch development and exhibited nearly identical fold changes in both mutants. Il11a is of particular interest because its receptor, IL11RA, is known to be associated with human craniosynostosis, suggesting potential relevance to craniofacial development. Together, it is possible to hypothesize that shared chaperone-associated transcriptional changes, together with altered ECM-related gene expression, may contribute to polr1c- and sf3b4-associated craniofacial disorders, warranting further functional validation.

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