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Nevin Manimala Statistics

The Influence of Local Cold Application and Resistance Exercise on the mRNA Response of Skeletal Muscle

J Strength Cond Res. 2025 Jul 30. doi: 10.1519/JSC.0000000000005209. Online ahead of print.

ABSTRACT

McGlynn, ML, Rosales, AM, Collins, CW, and Slivka, DR. The influence of local cold application and resistance exercise on the mRNA response of skeletal muscle. J Strength Cond Res XX(X): 000-000, 2025-Cold application post exercise is common practice despite empirical evidence suggesting it impairs muscle growth signaling. Our purpose was to determine the effects of local cold application and resistance exercise on muscle growth/breakdown gene expression. Twelve subjects completed a bilateral resistance exercise bout to volitional fatigue (leg press, leg extension) while wearing a thermal wrap on 1 limb (10° C fluid, EX + COLD) and no wrap contralaterally (EX). Bilateral vastus lateralis biopsies, skin temperature, and intramuscular temperature were collected pre intervention, post resistance exercise (temperatures only), and 4 hours post exercise. Statistical significance was set at p < 0.05. After 4 hours of cooling, skin (p < 0.001) and intramuscular temperatures (p < 0.001) were lower in the EX + COLD (20.4 ± 0.6, 26.1 ± 0.9° C) than in the EX limb (31.7 ± 0.6, 35.1 ± 0.3° C). Despite these temperature decreases, local cooling did not differentially influence myogenic and proteolytic gene expression (p > 0.05). Resistance exercise was the primary influence on gene expression change. Favorable myogenic gene expression changes were exhibited by Myogenin (increase, p = 0.007), Myogenic Factor 6 (increase, p = 0.002), and Myostatin (decrease, p < 0.001). However, myogenic gene Myogenic Factor 5 decreased (p < 0.001). All other myogenic genes went unchanged (Myogenic Differentiation 1, p = 0.665; Myocyte Enhance Factor 2a, p = 0.074; Ribosomal Protein S3, p = 0.773; Ribosomal Protein L3-Like, p = 0.118). Proteolytic gene expression changes were exhibited by Muscle Unique Ring Finger 1 (increase, p = 0.002) and Atrogin-1 (decrease, p = 0.020). However, F-box protein 32 went unchanged (p = 0.980). Local cooling may be paired with a resistance exercise bout because of minimal influence after 4 hours of cooling on skeletal muscle growth/breakdown mRNA signaling.

PMID:40729474 | DOI:10.1519/JSC.0000000000005209

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Nevin Manimala Statistics

Navigating the Hardship Together: Factors Associated With Couple Relationship Functioning in Parents With Cancer Who Have Dependent Children

Psychooncology. 2025 Aug;34(8):e70245. doi: 10.1002/pon.70245.

ABSTRACT

BACKGROUND: When a parent is diagnosed with cancer, it often affects both family life and the couple relationship significantly. However, research on factors that influence relationship functioning over time in this population is limited.

AIMS: To investigate the development of relationship functioning and factors associated with relationship functioning over a 1-year period among parents with cancer.

METHODS: In this longitudinal study, 180 parents with cancer, aged 24-60 years, with dependent children completed online surveys at 2 time-points: at inclusion (T1) and 1 year later (T2). Data included self-reported sociodemographic, physical health and psychological factors, and relationship functioning. The outcome was relationship functioning at T2 assessed using 4 subscales (Dyadic cohesion, Dyadic satisfaction, Sensuality, and Sexuality) of the validated self-assessment scale Quality of Dyadic Relationship Scale-36 (QDR). Linear regression analyses were conducted to identify factors associated with the outcome.

RESULTS: All aspects of relationship functioning statistically declined over time, except sexuality. After adjusting for multiple T1 factors, completion of cancer treatment predicted higher Dyadic cohesion; poor self-rated health predicted lower Dyadic satisfaction; higher age, being a mother and attachment-related anxiety predicted lower Sensuality; and lower age of youngest child, anxiety and attachment-related anxiety predicted lower Sexuality.

CONCLUSIONS: Cancer significantly impacts relationship functioning among parents with cancer who have dependent children, with significant declines in Dyadic cohesion, Dyadic satisfaction, and Sensuality over time. A number of sociodemographic, physical health and psychological factors were shown to predict lower relationship functioning. Addressing these factors may help identify and support parents with cancer who are at risk of, or who perceive, difficulties in their couple relationship.

PMID:40729468 | DOI:10.1002/pon.70245

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Nevin Manimala Statistics

Cross-Sectional Survey of Haemophilia Treatment Centres (HTCs) in India: Towards a Context‑Sensitive Stratification Model

Haemophilia. 2025 Jul 29. doi: 10.1111/hae.70095. Online ahead of print.

ABSTRACT

INTRODUCTION: Haemophilia treatment centres (HTCs) coordinate multidisciplinary care, yet the European HTC standards on which global accreditation systems really do not reflect the wide resource gradient found in India.

AIM: To assess HTC capacities across India and explore a tiered stratification model suited to diverse settings.

METHODS: A nationwide, self‑administered survey (February 2021-April 2022) was e‑mailed to all 291 HTCs registered with the Indian Association of Haemophilia and Allied Disorders. It captured infrastructure, laboratory capability and clinical services. Descriptive statistics and Spearman correlation were applied.

RESULTS: Ninety centres (30%) responded from 24 states/UTs. Only 34% fulfilled European HTC (EHTC) criteria and 11% met comprehensive‑care (EHCCC) criteria; 55% were unclassified despite providing haemophilia care. Laboratory‑to‑clinical functionality showed a moderate correlation (r = 0.61, p < 0.001). Twenty‑seven percent of centres operated without an onsite coagulation laboratory, whereas 40% lacked full‑time nurses and 60% lacked multidisciplinary teams. Factor VIII/IX supplies were uninterrupted at 31% of sites; 38% offered prophylaxis to at least one patient.

CONCLUSION: Rigid European categories mask the stepwise growth of Indian HTCs. A four‑tier model-anchored in predefined criteria for clinical and laboratory services could guide incremental upgrading while preserving patient safety.

PMID:40729467 | DOI:10.1111/hae.70095

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Nevin Manimala Statistics

Quality of Patient-Reported Outcomes in Multiple Myeloma Randomized Controlled Trial Protocols and Publications According to the SPIRIT-PRO and CONSORT-PRO guidelines: A Systematic Review

Eur J Haematol. 2025 Jul 29. doi: 10.1111/ejh.70002. Online ahead of print.

ABSTRACT

BACKGROUND: Patient-reported outcomes (PROs) are now frequently incorporated into multiple myeloma (MM) randomized controlled trials (RCTs) to help inform clinical decision making. Although the quality of PRO components in cancer RCT protocols is generally recognized as suboptimal, there are limited data on adherence to international quality standards in MM RCT protocols.

METHODS: We performed a systematic review to identify MM RCTs published between January 2014 and June 2023 that utilized the EORTC QLQ-C30 questionnaire. The quality of PRO-specific protocol content was evaluated using the SPIRIT-PRO guidelines, which establish key requirements for PRO inclusion in protocols. The framework consists of 16 items: 5 elaborations of the existing SPIRIT checklist and 11 PRO-specific extensions items. The quality of PRO reporting was evaluated using CONSORT-PRO Extension, which comprises 14 items to improve the reporting of PRO data in clinical trials.

RESULTS: Our systematic review identified 35 RCTs encompassing 20,612 patients, with 24 trials (69%) having publicly accessible protocols. The median protocol compliance was 7.5 SPIRIT-PRO items. Analysis of 24 protocols showed strong compliance in assessment schedules (96%), PRO domains/instrument justification (79%), and PRO objectives (71%). Intervention deviation procedures were described in 62% of protocols. Half included comprehensive data collection plans, while 58% addressed missing data methods and 42% outlined PRO research questions or multiplicity controls. Notably weak areas included strategies for preventing missing data (38%), and only 8% of protocols detailed PRO monitoring plans, personnel specifications, or eligibility criteria. CONSORT-PRO scores varied across all 35 RCTs (median 11, range 0.5-14). Among the 35 RCTs, while trials showed strong reporting of statistical elements (94% precision estimates, 91% subgroup analyses, 89% intention-to-treat, 86% timepoint completion) and results (80% hypothesized domains, 71% PRO validity, 69% clinical implications, 66% limitations), key PRO-specific components were reported by less than two-thirds of RCTs: only 11% stated PRO hypotheses, 31% specified administration mode, 43% identified domains, 60% addressed missing data, and 63% provided PRO rationale. Two factors were associated with higher reporting quality, both potentially reflecting publication bias: having a secondary PRO-focused paper (p < 0.001) and finding statistically significant EORTC QLQ-C30 differences (p = 0.024). Our multivariable analysis showed no significant association between SPIRIT-PRO scores and CONSORT-PRO scores.

CONCLUSION: Despite some foundational strengths of existing MM RCT protocols, gaps exist in PRO methodological specifications, statistical analysis, and clinical interpretation. Our findings may help to better inform PRO implementation in future MM RCT protocols. For example, since missing PRO data can be due to informative censoring, there should be increased attention on considering how to minimize missing data, already at the stage of protocol writing. Our findings regarding predictors of higher reporting quality suggest that trials with significant PRO differences receive systematically better reporting, possibly introducing bias in the available evidence base.

PMID:40729465 | DOI:10.1111/ejh.70002

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Nevin Manimala Statistics

Frequency and Number of B-Lines Using a Point-of-Care Thoracic Ultrasound Examination in Pet Rabbits (Oryctolagus cuniculus) Without Pulmonary Disease

J Vet Emerg Crit Care (San Antonio). 2025 Jul 29:e70000. doi: 10.1111/vec.70000. Online ahead of print.

ABSTRACT

OBJECTIVE: To assess the accuracy of a point-of-care thoracic ultrasound examination for the evaluation of the pulmonary parenchyma in rabbits without lower respiratory signs using thoracic radiography or computed tomography (CT) as the reference standard. An additional objective was to establish a baseline frequency and number of B-lines in rabbits without pulmonary disease.

DESIGN: Prospective, multicenter, clinical study from December 2021 to July 2023.

SETTING: University teaching hospital and an emergency and specialty referral center.

ANIMALS: Sixty-three pet rabbits (Oryctolagus cuniculus) without lower respiratory signs and with lungs verified to be healthy with radiography or CT.

INTERVENTIONS: Rabbits were screened for signs of respiratory disease. A modified point-of-care thoracic ultrasound examination was performed on each conscious rabbit, followed by a thoracic radiography or CT study. The frequency and number of B-lines were statistically compared based on signalment, body condition score, and health status.

MEASUREMENTS AND MAIN RESULTS: The overall frequency of B-lines was 33.3% (21/63) in rabbits without pulmonary disease. Most B-lines were categorized as single discrete artifacts. A single region was positive for B-lines in 17 of 21 rabbits, with 14 of them having a single B-line, two having two B-lines, and one having three B-lines. Two and three regions were positive in three and one rabbit, respectively. Cranial thoracic ultrasound revealed mediastinal tissue rather than pulmonary parenchyma in 61 of 63 rabbits.

CONCLUSIONS: This study evaluated a modified point-of-care thoracic ultrasound, including B-line frequency and distribution, and described what can be expected as a normal thoracic ultrasound in rabbits without pulmonary disease. Findings indicate that isolated B-line artifacts can be detected within the lungs of rabbits without pulmonary disease. Additional studies are needed to describe the pulmonary ultrasonographic features in rabbits with respiratory conditions and to determine the clinical use of this diagnostic technique in those cases.

PMID:40729450 | DOI:10.1111/vec.70000

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Nevin Manimala Statistics

Absence of Evidence of Beneficial Effects of Human Milk-Based Fortifier: A Bayesian Model-Averaged Meta-Analysis

Acta Paediatr. 2025 Jul 29. doi: 10.1111/apa.70260. Online ahead of print.

ABSTRACT

AIM: Human milk-based fortifiers (HMBFs) have been adopted in neonatal care despite limited efficacy data. Our objective was to conduct a Bayesian re-analysis of the current evidence on the protective effect of HMBF against necrotising enterocolitis (NEC, stage II-III).

METHODS: We searched for randomised controlled trials (RCTs) comparing HMBF versus bovine milk-based fortifier (BMBF) in infants with gestational age < 32 weeks or birthweight < 1500 g. Bayesian model-averaged (BMA) meta-analysis was used to calculate Bayes factors (BFs). The BF10 is the ratio of the probability of the data under the alternative hypothesis (H1, presence of effect) over the probability of the data under the null hypothesis (H0, absence of effect).

RESULTS: We included 3 RCTs (405 infants). The BMA analysis did not show conclusive evidence in favour of H1 (BF10 > 3) or in favour of H0 (BF10 < 1/3) for NEC (BF10 = 0.86), mortality (BF10 = 1.07), late onset sepsis (BF10 = 0.69), bronchopulmonary dysplasia (BPD, BF10 = 0.92), or severe retinopathy of prematurity (ROP, BF10 = 0.75).

CONCLUSIONS: The extant corpus of RCTs does not provide sufficient evidence to either confirm or exclude a potential effect of HMBF compared with BMBF on the risk of NEC, mortality, sepsis, BPD, or severe ROP.

PMID:40729426 | DOI:10.1111/apa.70260

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Connectomic and behavioural alterations in creatine transporter deficiency are partially normalized by gene therapy

Brain. 2025 Jul 29:awaf275. doi: 10.1093/brain/awaf275. Online ahead of print.

ABSTRACT

Creatine Transporter Deficiency (CTD) is an X-linked disorder due to the loss of SLC6A8 gene and presenting with low brain creatine, intellectual disability, autistic-like behavior and seizures. No treatments are available yet for CTD, and little is known about the brain circuit alterations underlying its pathological endophenotypes. Here, we tracked brain network and behavioral dysfunction in a murine model of CTD at two stages of disease progression. fMRI mapping revealed widespread disruption of brain connectivity in Slc6a8-KO mice, with robust somatomotor hypoconnectivity in juvenile animals, and weaker and more focal alterations of cortical and subcortical connectivity in adulthood. Notably, perinatal AAV-mediated expression of human SLC6A8 in Slc6a8-KO mice robustly prevented juvenile fMRI hypoconnectivity, an effect accompanied by the regression of multiple translationally relevant phenotypes, including reduced stereotyped movements, improved declarative memory and increased body weight, all of which persisted into adulthood. However, early cognitive deficits, impairments in working memory and residual fMRI hypoconnectivity in adult mice were not ameliorated by gene therapy. Furthermore, significant cognitive impairments were observed in WT mice receiving gene therapy, highlighting a potential detrimental effect of ectopic expression of SLC6A8 in healthy brain circuits. Finally, multivariate modeling in adult mice revealed a basal forebrain network whose activity was associated with behavioral performance and modulated by brain creatine levels. This brain-behavior relationship was disrupted in Slc6a8-KO mice. Our results document robust network disruption in CTD and demonstrate that CTD pathology can be partially alleviated by perinatal genetic expression of SLC6A8, providing a foundation for the future development of experimental therapies for this genetic disorder.

PMID:40729420 | DOI:10.1093/brain/awaf275

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A Bayesian hierarchical model of trial-to-trial fluctuations in decision criterion

PLoS Comput Biol. 2025 Jul 29;21(7):e1013291. doi: 10.1371/journal.pcbi.1013291. Online ahead of print.

ABSTRACT

Classical decision models assume that the parameters giving rise to choice behavior are stable, yet emerging research suggests these parameters may fluctuate over time. Such fluctuations, observed in neural activity and behavioral strategies, have significant implications for understanding decision-making processes. However, empirical studies on fluctuating human decision-making strategies have been limited due to the extensive data requirements for estimating these fluctuations. Here, we introduce hMFC (Hierarchical Model for Fluctuations in Criterion), a Bayesian framework designed to estimate slow fluctuations in the decision criterion from limited data. We first showcase the importance of considering fluctuations in decision criterion: incorrectly assuming a stable criterion gives rise to apparent history effects and underestimates perceptual sensitivity. We then present a hierarchical estimation procedure capable of reliably recovering the underlying state of the fluctuating decision criterion with as few as 500 trials per participant, offering a robust tool for researchers with typical human datasets. Critically, hMFC does not only accurately recover the state of the underlying decision criterion, it also effectively deals with the confounds caused by criterion fluctuations. Lastly, we provide code and a comprehensive demo to enable widespread application of hMFC in decision-making research.

PMID:40729408 | DOI:10.1371/journal.pcbi.1013291

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Nevin Manimala Statistics

PoweREST: Statistical power estimation for spatial transcriptomics experiments to detect differentially expressed genes between two conditions

PLoS Comput Biol. 2025 Jul 29;21(7):e1013293. doi: 10.1371/journal.pcbi.1013293. Online ahead of print.

ABSTRACT

Recent advancements in spatial transcriptomics (ST) have significantly enhanced biological research in various domains. However, the high cost for current ST data generation techniques restricts the large-scale application of ST. Consequently, maximization of the use of available resources to achieve robust statistical power for ST data is a pressing need. One fundamental question in ST analysis is detection of differentially expressed genes (DEGs) under different conditions using ST data. Such DEG analyses are performed frequently, but their power calculations are rarely discussed in the literature. To address this gap, we developed PoweREST, a power estimation tool designed to support the power calculation for DEG detection with 10X Genomics Visium data. PoweREST enables power estimation both before any ST experiments and after preliminary data are collected, making it suitable for a wide variety of power analyses in ST studies. We also provide a user-friendly, program-free web application that allows users to interactively calculate and visualize study power along with relevant parameters.

PMID:40729405 | DOI:10.1371/journal.pcbi.1013293

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Nevin Manimala Statistics

Difficulties in Nonadjacent Dependency Learning in French-Learning Toddlers

J Speech Lang Hear Res. 2025 Jul 29:1-10. doi: 10.1044/2025_JSLHR-23-00608. Online ahead of print.

ABSTRACT

PURPOSE: In the past three decades, statistical learning, that is, the capacity to detect patterns and regularities in the environment, has been shown to have an important role in language development. In particular, the ability to detect nonadjacent dependencies (NADs) between linguistic elements that are separated by intervening material seems to be linked to morphosyntactic development. However, there are few studies with French-speaking children, and none using artificial language learning methodologies.

METHOD: We investigated the acquisition of NADs in 18-month-old (n = 30) and 27-month-old (n = 32) monolingual French-learning children in an adaptation of Gómez (2002) artificial grammar learning study to a central fixation eye-tracking paradigm. After a 2-min familiarization with three element strings (e.g., /na sokɛ fib/), we monitored looking times for grammatical versus ungrammatical strings in two blocks of four test trials each, expecting a novelty effect at 18 months and exploring the behavior at 27 months.

RESULTS: No significant effect of grammaticality was found at either 18 or 27 months for the overall task. However, at 27 months, we observed a significant decrease in gaze duration for ungrammatical test trials between the first and the second blocks, together with a tendency to look longer at grammatical stimuli in the second block, a pattern of results that, if confirmed in future studies, might indicate the start of novel NAD learning.

CONCLUSIONS: Given the failure to clearly replicate effects observed in the studies with English-learning children, we propose several theoretical hypotheses to account for our results and discuss the importance of differences in age and language background as well as methodological parameters, a well-known challenge in research with young children. Further research is needed to develop robust tasks and to better understand the developmental trajectory of NAD processing abilities.

SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.29565149.

PMID:40728878 | DOI:10.1044/2025_JSLHR-23-00608