Correction For Multiple Comparisons Research Articles

Search for molecular markers of joint hypermobility

Background: Joint hypermobility (JH) is a condition that can be either benign or accompanied by pain and early development of osteoarthritis. For early verification of the risk of complications, it is necessary to study the molecular pathogenesis of various JH variants. The aim of the study: The aim of this study was to search for candidate genes involved in connective tissue metabolism and causing joint hypermobility in a form isolated or combined with connective tissue dysplasia (CTD). Materials and methods: The study involved young (21,86±0,22 y.o.) people (n=181). A clinical study was conducted for the presence of signs of JH (Beighton scale) and CTD (tables Kadurina T.I.). Further, a molecular genetic study was carried out and the search for associations of polymorphic variants of genes (vitamin D receptor (VDR), lumican (LUM), tenascin (TNXB), growth/differentiation factor 5 (GDF5), magnesium ion channel TRPM6), bone morphogenetic protein type 5 (BMP5)) and JH, CTD in isolated and combined forms. Statistical data processing was carried out by comparing qualitative features using the χ2 test, Fisher's exact test, and the χ2 test with Yates' correction for contingency tables 2x2. The strength of associations was assessed in terms of the odds ratio (Odds Ratio, OR, at p<0.05), the correction for multiple comparisons was carried out using the FDR method (Benjamin- Hochberg). Quantitative data were evaluated in pairs using the Student's t-test, the normality of distribution according to the Kolmogorov-Smirnov test. Results: Associations of the G allele and the GG genotype of the rs3734444 locus of the BMP5 gene with the presence of JH (OR=3.70 and OR=5.10), the A allele of the rs1470527 locus of the BMP5 gene and the presence of JH+CTD- (OR=8.00), the T allele and the TT genotype of the rs11144134 locus of the TRPM6 gene with JH in isolated (OR=3.00 and OR =10.19) and in the forms combined with CTD (OR=3.17 and OR=11.28), the TT genotype was also associated with the isolated form of CTD (OR=3.74). The GT genotype of the rs73611720 locus of the GDF5 gene was associated with isolated CTD (OR=4.15). No statistically significant associations were found for polymorphic variants rs11540149 (VDR), rs2268578 and rs3759222 (LUM), rs3130342 (TNXB). Conclusion: The G allele of locus rs3734444 of the BMP5 gene is a potential risk marker for JH in general, the A allele of locus rs1470527 is an isolated JH, the GT genotype of locus rs73611720 of the GDF5 gene is a marker for isolated CTD, the T allele of locus rs11144134 of the TRPM6 gene is a marker for JH combined with CTD.

Exposure to Volatile Organic Compounds May Contribute to Atopic Dermatitis in Adults.

Volatile organic compounds (VOC) are major indoor air pollutants. Previous studies reported an association between VOC exposure and allergic diseases. Here, we aimed to explore the relationship between VOC exposure and atopic dermatitis (AD) in adults. We prospectively enrolled 31 adult AD patients and 11 healthy subjects as controls. Urine metabolite levels of VOCs, including 1.3-butadiene, acrylamide, benzene, toluene, and xylene, were all determined with liquid chromatography-mass spectrometry. The relationship between AD and log-transformed urine levels of VOC metabolites were examined using a multivariate linear regression model adjusted for age and sex. We also treated mouse bone marrow-derived cells (BMMCs) with 1,3-butadiene and toluene and measured the release of β-hexosaminidase. Our results demonstrated that creatinine-corrected urine levels of N-Acetyl-S- (3,4-dihydroxybutyl)-L-cysteine (DHBMA), N-Acetyl-S-(2-carbamoyl-2-hydroxyethyl)-L-cysteine (GAMA), and N-Acetyl-S-(benzyl)-L-cysteine (BMA) were all elevated in AD patients compared with controls. In a multivariate linear regression model, creatinine-corrected urine levels of BMA (a toluene metabolite) and DHBMA (a 1,3-butadiene metabolite) appeared elevated in AD patients, although statistical significance was not reached after correction for multiple comparisons. In addition, 1,3-butadiene and toluene could stimulate BMMCs to degranulate as much as compound 48/80. Some VOCs, such as 1,3-butadiene and toluene, might be associated with AD pathogenesis in adults.

Exudative Age-Related Macular Degeneration: Association between Treatment Efficacy and Single-Nucleotide Variants in RAD51B, TRIB1, COL8A1, COL10A1, IL-9, IL-10, and VEGFA Genes.

Age-related macular degeneration (AMD) is a progressive neurodegenerative condition leading to vision loss and eventual blindness, with exudative AMD posing a heightened risk due to choroidal neovascularization and localized edema. Therapies targeting the VEGF pathway aim to address this mechanism for treatment effectiveness. Our study aimed to evaluate associations between specific genetic variants (RAD51B rs8017304, rs2588809; TRIB1 rs6987702, rs4351379; COL8A1 rs13095226; COL10A1 rs1064583; IL-9 rs1859430, rs2069870, rs11741137, rs2069885, rs2069884; IL-10 rs1800871, rs1800872, rs1800896; VEGFA rs1570360, rs699947, rs3025033, rs2146323) and the response to anti-VEGF treatment for exudative AMD. We enrolled 119 patients with exudative AMD categorized as responders or non-responders based on their response to anti-VEGF treatment. Statistical analysis revealed that RAD51B rs8017304 heterozygous and homozygous minor allele carriers had increased CMT before treatment compared to wild-type genotype carriers (p = 0.004). Additionally, TRIB1 rs4351379 heterozygous and homozygous minor allele carriers exhibited a greater decrease in central macular thickness (CMT) after 6 months of treatment than wild-type genotype carriers (p = 0.030). IL-9 rs1859430, rs2069870, and rs2069884 heterozygous and homozygous minor allele carriers had worse BCVA before treatment than wild-type genotype carriers (p = 0.018, p = 0.012, p = 0.041, respectively). Conversely, IL-9 rs2069885 heterozygous and homozygous minor allele carriers showed greater improvement in BCVA after 6 months compared to wild-type genotype carriers (p = 0.032). Furthermore, VEGFA rs699947 heterozygous and homozygous minor allele carriers had better BCVA before treatment and after 3 and 6 months of treatment than wild-type genotype carriers (p = 0.003, p = 0.022, respectively), with these carriers also exhibiting higher CMT after 6 months of anti-VEGF treatment (p = 0.032). Not all results remained statistically significant under this stringent correction for multiple comparisons. The comparisons of the serum concentrations of IL-10, VEGF-A, and VEGF-R2/KDR between non-responders and responders did not yield statistically significant differences. Our study identified significant associations between genetic variants, including RAD51B rs8017304, TRIB1 rs4351379, IL-9 rs1859430, rs2069870, rs2069884, rs2069885, and VEGFA rs699947, and parameters related to the efficacy of exudative AMD treatment, such as BCVA and CMT.

Assessing causal associations of bile acids with obesity indicators: A Mendelian randomization study.

Maintaining a balanced bile acids (BAs) metabolism is essential for lipid and cholesterol metabolism, as well as fat intake and absorption. The development of obesity may be intricately linked to BAs and their conjugated compounds. Our study aims to assess how BAs influence the obesity indicators by Mendelian randomization (MR) analysis. Instrumental variables of 5 BAs were obtained from public genome-wide association study databases, and 8 genome-wide association studies related to obesity indicators were used as outcomes. Causal inference analysis utilized inverse-variance weighted (IVW), weighted median, and MR-Egger methods. Sensitivity analysis involved MR-PRESSO and leave-one-out techniques to detect pleiotropy and outliers. Horizontal pleiotropy and heterogeneity were assessed using the MR-Egger intercept and Cochran Q statistic, respectively. The IVW analysis revealed an odds ratio of 0.94 (95% confidence interval: 0.88, 1.00; P = .05) for the association between glycolithocholate (GLCA) and obesity, indicating a marginal negative causal association. Consistent direction of the estimates obtained from the weighted median and MR-Egger methods was observed in the analysis of the association between GLCA and obesity. Furthermore, the IVW analysis demonstrated a suggestive association between GLCA and trunk fat percentage, with a beta value of -0.014 (95% confidence interval: -0.027, -0.0004; P = .04). Our findings suggest a potential negative causal relationship between GLCA and both obesity and trunk fat percentage, although no association survived corrections for multiple comparisons. These results indicate a trend towards a possible association between BAs and obesity, emphasizing the need for future studies.

Effects of exercise or metformin on myokine concentrations in patients with breast and colorectal cancer: A phase II multi-centre factorial randomized trial.

Physical activity and metformin pharmacotherapy are associated with improved clinical outcomes in breast and colorectal cancer survivors. Myokines are cytokines secreted from skeletal muscle that may mediate these associations. This hypothesis-generating analysis used biospecimens collected from a multi-centre 2×2 factorial randomized design of 116 patients with stage I-III breast and colorectal cancer who were randomized to 12weeks of (1) aerobic exercise (moderate intensity titrated to 220min/week); (2) metformin (850mg daily for 2weeks and then titrated to 850mg twice per day); (3) aerobic exercise and metformin; or (4) control. Fourteen myokines were quantified using a multiplex panel. Myokine concentrations were log-transformed, and main effects analyses were conducted using linear mixed-effects regression models. The type I error rate was controlled with the Holm sequential testing procedure. Randomization to exercise increased leukaemia inhibitory factor (1.26pg/mL, 95% confidence interval [CI]: 0.69, 1.84; adjusted P=0.001) and interleukin-15 (2.23pg/mL, 95% CI: 0.87, 3.60; adjusted P=0.013) compared with randomization to no exercise. Randomization to metformin decreased apelin (-2.69pg/mL, 95% CI: -4.31, -1.07; adjusted P=0.014) and interleukin-15 (-1.74pg/mL, 95% CI: -2.79, -0.69; adjusted P=0.013) compared with randomization to no metformin. Metformin decreased myostatin, irisin, oncostatin M, fibroblast growth factor 21 and osteocrin; however, these changes were not statistically significant after correction for multiple comparisons. This pilot study demonstrates that randomization to exercise and metformin elicit unique effects on myokine concentrations in cancer patients. This hypothesis-generating observation warrants further basic, translational and clinical investigation and replication.

Serum bile acid profiles are associated with heart failure with preserved ejection fraction in patients with metabolic dysfunction-associated fatty liver disease: An exploratory study.

To analyse the association between serum bile acid (BA) profile and heart failure (HF) with preserved ejection fraction (HFpEF) in patients with metabolic dysfunction-associated fatty liver disease (MAFLD). We enrolled 163 individuals with biopsy-proven MAFLD undergoing transthoracic echocardiography for any indication. HFpEF was defined as left ventricular ejection fraction >50% with at least one echocardiographic feature of HF (left ventricular diastolic dysfunction, abnormal left atrial size) and at least one HF sign or symptom. Serum levels of 38 BAs were analysed using ultra-performance liquid chromatography coupled with tandem mass spectrometry. Among the 163 patients enrolled (mean age 47.0 ± 12.8 years, 39.3% female), 52 (31.9%) and 43 (26.4%) met the HFpEF and pre-HFpEF criteria, and 38 serum BAs were detected. Serum ursodeoxycholic acid (UDCA) and hyocholic acid (HCA) species were lower in patients with HFpEF and achieved statistical significance after correction for multiple comparisons. Furthermore, decreases in glycoursodeoxycholic acid and tauroursodeoxycholic acid were associated with HF status. In this exploratory study, specific UDCA and HCA species were associated with HFpEF status in adults with biopsy-confirmed MAFLD.

Perivascular Adipose Tissue Density and Stenosis Plaque Degree in Lower Limb Peripheral Arteries in CT

Background: Perivascular adipose tissue (PVAT) attenuation has emerged as a novel biomarker for identifying high-risk arterial plaques due to its association with inflammation. Recognizing the systemic nature of atherosclerosis and its link with major cardiovascular events in coronary disease, this study evaluated PVAT attenuation in the peripheral arteries using CT imaging to expand the understanding of its diagnostic and prognostic potential. Methods: a retrospective analysis of 53 consecutive patients who underwent CT angiography, examining PVAT density across five primary peripheral arterial segments. A 5 mm region of interest adjacent to the vascular wall was analyzed by two blinded readers, with reproducibility coefficients calculated to determine the reliability of the measurements. For the statistical analyses, mean values were derived from these measurements. The patients were stratified into four groups based on the degree of arterial stenosis: <25%, 25–50%, 50–70%, and >70%. PVAT density comparisons between these groups were performed using the Kruskal–Wallis test and the pairwise Mann–Whitney U test with Holm–Bonferroni correction for multiple comparisons. Results: the Kruskal–Wallis test revealed statistically significant disparities in PVAT density across the categorically differentiated stenosis groups (p < 0.001), indicating an association between PVAT density and arterial stenosis severity. This association was especially pronounced in the external iliac, common femoral, superficial femoral, and popliteal arteries, where the p-values were consistently below 0.05. Subsequent pairwise analyses utilizing the Mann–Whitney U test with Holm–Bonferroni correction affirmed these findings, in particular for the external iliac, common femoral, superficial femoral and popliteal arteries (p < 0.05). Conclusions: our findings reinforce the correlation between increased PVAT density and the degree of arterial stenosis, supporting the clinical value of PVAT as a non-invasive biomarker for cardiovascular risk stratification and potentially guiding therapeutic interventions.

Head movements induced by voluntary neck flexion stabilize sensorimotor synchronization of the finger to syncopated auditory rhythms.

Head movements that are synchronized with musical rhythms often emerge during musical activities, such as hip hop dance. Although such movements are known to affect the meter and pulse perception of complex auditory rhythms, no studies have investigated their contribution to the performance of sensorimotor synchronization (SMS). In the present study, participants listened to syncopated auditory rhythms and flexed their dominant hand index finger in time with the perceived pulses (4/4 meters). In the first experiment (Exp. 1), the participants moved their heads via voluntary neck flexion to the pulses in parallel with finger SMS (Nodding condition, ND). This performance was compared with finger SMS without nodding (Without Nodding condition, WN). In the second experiment (Exp. 2), we investigated the specificity of the effect of head SMS on finger SMS confirmed in Exp. 1 by asking participants to flex their bilateral index fingers to the pulses (Bimanual condition, BM). We compared the performance of dominant hand finger SMS between the BM and ND conditions. In Exp. 1, we found that dominant hand finger SMS was significantly more stable (smaller standard deviation of asynchrony) in the ND versus WN condition (p < 0.001). In Exp. 2, dominant hand finger SMS was significantly more accurate (smaller absolute value of asynchrony) in the ND versus BM condition (p = 0.037). In addition, the stability of dominant hand finger SMS was significantly correlated with the index of phase locking between the pulses and head SMS across participants in the ND condition (r = -0.85, p < 0.001). In contrast, the stability of dominant hand finger SMS was not significantly correlated with the index of phase locking between pulses and non-dominant hand finger SMS in the BM condition (r = -0.25, p = 0.86 after multiple comparison correction). These findings suggest that SMS modulation depends on the motor effectors simultaneously involved in synchronization: simultaneous head SMS stabilizes the timing of dominant hand finger SMS, while simultaneous non-dominant hand finger SMS deteriorates the timing accuracy of dominant hand finger SMS. The present study emphasizes the unique and crucial role of head movements in rhythmic behavior.

Transdiagnostic markers across the psychosis continuum: a systematic review and meta-analysis of resting state fMRI studies.

https://osf.io/, identifier (ycqpz).

Assessing the Role of Locus Coeruleus Degeneration in Essential Tremor and Parkinson's Disease with Sleep Disorders.

Previous studies have demonstrated the importance of the locus coeruleus (LC) in sleep-wake regulation. Both essential tremor (ET) and Parkinson's disease (PD) share common sleep disorders, such as poor quality of sleep (QoS). LC pathology is a feature of both diseases. A question arises regarding the contribution of LC degeneration to the occurrence of poor QoS. To evaluate the association between LC impairment and sleep disorders in ET and PD patients. A total of 83 patients with ET, 124 with PD, and 83 healthy individuals were recruited and divided into ET/PD with/without poor QoS (Sle/NorET and Sle/NorPD) subgroups according to individual Pittsburgh Sleep Quality Index (PSQI) score. Neuromelanin-sensitive magnetic resonance imaging (NM-MRI) and free-water imaging derived from diffusion MRI were performed. Subsequently, we evaluated the association between contrast-to-noise ratio of LC (CNRLC) and free-water value of LC (FWLC) with PSQI scores in ET and PD groups. CNRLC was significantly lower in ET (p = 0.047) and PD (p = 0.018) than in healthy individuals, whereas no significant difference was found in FWLC among the groups. No significant differences were observed in CNR/FWLC between patients with/without sleep disorders after multiple comparison correction. No correlation was identified between CNR/FWLC and PSQI in ET and PD patients. LC degeneration was observed in both ET and PD patients, implicating its involvement in the pathophysiology of both diseases. Additionally, no significant association was observed between LC integrity and PSQI, suggesting that LC impairment might not directly relate to overall QoS.

Statistical Considerations for the Design and Analysis of Pragmatic Trials in Aging Research.

Pragmatic trials aim to assess intervention efficacy in usual patient care settings, contrasting with explanatory trials conducted under controlled conditions. In aging research, pragmatic trials are important designs for obtaining real-world evidence in elderly populations, which are often underrepresented in trials. In this review, we discuss statistical considerations from a frequentist approach for the design and analysis of pragmatic trials. When choosing the dependent variable, it is essential to use an outcome that is highly relevant to usual medical care while also providing sufficient statistical power. Besides traditionally used binary outcomes, ordinal outcomes can provide pragmatic answers with gains in statistical power. Cluster randomization requires careful consideration of sample size calculation and analysis methods, especially regarding missing data and outcome variables. Mixed effects models and generalized estimating equations (GEEs) are recommended for analysis to account for center effects, with tools available for sample size estimation. Multi-arm studies pose challenges in sample size calculation, requiring adjustment for design effects and consideration of multiple comparison correction methods. Secondary analyses are common but require caution due to the risk of reduced statistical power and false-discovery rates. Safety data collection methods should balance pragmatism and data quality. Overall, understanding statistical considerations is crucial for designing rigorous pragmatic trials that evaluate interventions in elderly populations under real-world conditions. In conclusion, this review focuses on various statistical topics of interest to those designing a pragmatic clinical trial, with consideration of aspects of relevance in the aging research field.

Comprehensive whole genome and transcriptome analysis of patients with advanced solid tumor treated with immune checkpoint inhibitor therapy in the pan-cancer cohorts from the Marathon of Hope Cancer Centres Network Study (MOHCCN).

2645 Background: Immune checkpoint inhibitors (ICI) improve survival in multiple advanced solid tumors but many patients do not benefit. We conducted a comprehensive whole genome transcriptome sequencing (WGTS) analysis to identify predictors of immune sensitivity. Methods: Clinical and molecular data from archival or pre-treatment FFPE tumor tissue were available for analysis from The Marathon of Hope Cancer Centres Network Study (MOHCCN). It includes patients (Pts) with advanced solid tumors and ECOG PS 0 or 1 treated with ICIs targeting PD-1, PD-L1, or CTLA-4 in the INSPIRE (NCT02644369) and OCTANE (NCT02906943) cohorts. Response (R) to ICI was defined as radiological and clinical response without PFS event at 6 months; versus non-response (NR) as radiological or clinical progression within 6 months. Responders without evidence of progression for &gt;12 months were categorized as durable responders (DR). Nucleic acids were sequenced using Illumina NovaSeq 6000 system targeting minimum coverage of 80X and 30X for tumour and normal WGS, respectively and 80M reads for tumour RNA-seq. WGTS data were integrated with clinical data to identify associations with response to ICIs. Also, an analysis of immune cell types was conducted using multiplexed IHC and RNA-Seq deconvolution (CIBERSORT). Results: 59 Pts were included in this analysis: 28 (R) and 31 (NR). The most common tumor types were head and neck (n = 19) and melanoma (n = 7). Median age was 62 years (range 24-81); male 58% and median follow-up was 58 months (range 11-280). The most frequent ICI was pembrolizumab 76%, with 90% of all pts receiving ICI monotherapy and 10% combination. 75% of pts received chemotherapy prior to ICI. Higher tumor mutation burden (TMB) was observed in R vs NR (median 13 vs 5 coding mut/Mb, p=0.001), with the highest TMB in patients with DR (median 14 mut/Mb ). Differential RNA gene expression analysis showed NR had increased expression of several oncogenic pathway signatures, including MYC targets, G2M checkpoint, and E2F targets. Differential abundance analysis of immune cell types did not yield any differences of immune cell populations amongst R versus NR after correction for multiple comparisons. Responders had significant enrichment in mutations in WNT/β-catenin pathway genes in both coding (APC, AMER1, LZTR1, TCF7L2) and promoter regions (CTNNB1). Notably, the 6 Pts with CTNNB1 promoter mutations had significantly increased CTNNB1 gene expression (p = 0.005). Conclusions: ICI responders showed enrichment in coding mutations of several negative regulators of the Wnt/β-catenin pathway and non-coding promoter mutations in CTNNB1 compared with non-responders. Further investigation is ongoing to biologically validate how these mutations in the Wnt/β-catenin pathway may lead to improved response to ICI.

Reported Personality Traits and Histories of Childhood Maltreatment in Borderline Personality Disorder and Bipolar 2 Disorder: A Comparative Study

This study compared borderline personality disorder (BPD) and bipolar 2 disorder (BP 2 disorder) with respect to reported childhood trauma and Five-Factor personality traits using the Childhood Trauma Questionnaire (CTQ) and the NEO Five-Factor Inventory (NEO-FFI). Participants were 50 men and women, aged 18-45, with DSM-5-diagnosed BPD and 50 men and women in the same age group with DSM-5-diagnosed BP 2 disorder. Participants could not meet criteria for both BPD and BP 2 disorder. Borderline participants had significantly higher scores on the neuroticism subscale and significantly lower scores on the agreeableness subscale of the NEO-FFI. After correction for multiple comparisons, there were no between-group differences on CTQ scores. Study results suggest that BPD and BP 2 disorder differ primarily with respect to underlying temperament/genetic architecture and that environmental factors have only a limited role in the differential etiologies of the two disorders.

Resident-as-Teacher: Can It Be Done With an E-Learning Module?

Background Resident-as-teacher initiatives are traditionally specialty-specific and performed in-person, limiting ability to disseminate essential teaching skills to all residents. Objective The aim of this study was to develop, implement, and evaluate a resident-as-teacher interactive e-learning module on growth mindset and coaching. Methods The module was designed and implemented between August 2022 and March 2023. It was distributed to postgraduate year (PGY) 1 residents in all specialties at a large academic institution. Completion rates, Likert ratings, and answers to 2 open-ended questions were used for assessment. Descriptive statistics and 1-way analysis of variance with Sîdák correction for multiple comparisons were performed on Likert ratings. Responses to open-ended questions were evaluated using content analysis. Results The module was completed by all 277 PGY-1 residents (100%), with the evaluation completed by 276 of 277 (99.6%) residents. Mean rating of the module's relevance to the role of resident teacher was 4.06±0.90 (5-point Likert scale), with general surgery residents rating the module less favorably compared to all specialties (3.28±1.06; P<.01; 95% CI 0.26-1.30). Open-ended comments revealed that residents most liked the delivery of relevant teaching strategies and the interactive design of the module. The most common area for suggested improvement was the addition of content such as teaching in challenging situations. Time needed for design, implementation, and evaluation was 80 hours total. Conclusions An e-learning module offers an interactive platform for teaching skills and was found to be an acceptable method of instruction for residents.

Sensory-motor training with virtual reality as a complementary intervention to manual therapy for persistent non-specific neck pain: a randomized controlled trial.

Persistent non-specific neck pain (NP) is a widespread condition described as a complex biopsychosocial disorder, characterized by physical and psychological symptoms. Virtual reality (VR) shows promise in NP treatment, potentially reducing pain, kinesiophobia, and improving range of motion (ROM) and motor control. The primary aim of the study was to assess the effectiveness of VR sensorimotor training, combined with manual therapy, in reducing the level of disability in persistent non-specific NP individuals. The secondary aim was to determine if this VR-enhanced approach also contributes to improvement in overall function, pain perception and kinesiophobia. Monocentric, single-blind, randomized controlled trial. We conducted this trial at San Raffaele Scientific Institute, Department of Rehabilitation and Functional Recovery, Milan, Italy. Forty NP participants were enrolled in the study and randomly allocated into two groups. The study involved a 6-week rehabilitation program, comprising 12 sessions of 45 minutes each, twice weekly. Both intervention groups underwent manual therapy as a consistent component of their treatment. The Experimental Group (VRT) was additionally engaged in sensorimotor rehabilitation exercises using Virtual Reality, whereas the Control Group (CT) performed the same exercises without VR. We assessed subjects at baseline (T0) and after six weeks of rehabilitation (T1). The primary outcome was the disability (Neck Disability Index) while the secondary outcomes were: pain perception (Numeric Rating Scale, NP and Disability Scale, Central Sensitization Inventory) function (Cervical Kinematics) and kinesiophobia (Tampa Scale of Kinesiophobia). Both groups demonstrated significant reduction in level of disability, pain perception, and kinesiophobia. Significant advancements in kinematics were observed: VRT group showed enhanced ROM during craniocervical rotation (P=0.039), lateral bending (P=0.001), flexion-extension (P=0.009), and mean velocity across movements (P<0.001), whereas CT group improved in maximal ROM during lateral bending rotation (P=0.001). Between-group analysis, after Bonferroni's correction for multiple comparisons, revealed that VRT group had significantly better outcomes in ROM during rotation (P=0.040), ratio of the primary over the secondary movement while performing rotation (P=0.021), and mean velocity during lateral bending (P=0.031). Sensorimotor training, combined with manual therapy, could enhance kinematic outcomes for NP patients, supporting the potential of VR in rehabilitation. This study highlighted that both groups demonstrated significant reduction in level of disability, pain perception, and kinesiophobia after sensorimotor training combined with manual therapy. It is important to underscore that in terms of reducing the level of neck disability, both interventions proved to be equally effective. This parity in efficacy is a critical finding, reaffirming the robustness of our therapeutic approaches for this specific outcome.

Changes in Compression Pressure of Elastic Stockings for the Lower Limbs During Cesarean Section: A Prospective Observational Study.

Background Postpartum peripheral nerve injuries can impact recovery. Elastic stockings are recommended for thromboembolism prevention, although concerns about entrapment neuropathy exist. In this prospective observational study, we investigated the differential compressions caused by wearing elastic stockings before and after anesthesia, as well as changes in the diameters of the lower leg and ankle in parturient women undergoing spinal anesthesia for elective cesarean section (CS). Methods Eighteen pregnant women, classified by the American Society of Anesthesiologists as having physical status 2, underwent lower leg measurements taken before a CS. Elastic stockings were applied, and compression pressure was measured at pre-anesthesia, post-surgery, and six hours post-return to a hospital room. Fluid, blood loss, urine output, and neuropathy presence were recorded. For all parameters, changes at the three time points were compared for the primary analysis. For secondary analysis, participants were categorized as having intraoperative blood loss greater than (group P) or less than 1,000 g (group N), and factors were compared with pre-anesthesia and six hours post-return to a room. Data were analyzed and presented using a one-way analysis of variance with Bonferroni correction for multiple comparisons or unpaired two-tailed t-tests for pairwise comparison. Results None of the women had postoperative entrapment neuropathy. Six patients had >1,000 g of blood loss. Compression significantly increased from pre-anesthesia (left 13.6 ± 2.4, 95% CI: 12.18 to 14.52; right 13.4 ± 2.4, 95% CI: 12.41 to 14.69) to post-surgery (left, 17.4 ± 2.6, 95% CI: 15.68 to 18.12; right, 16.9 ± 2.6, 95% CI: 16.20 to 18.70) (p < 0.01). Compression pressure at post-surgery differed significantly between group P (left, 15.3 ± 1.3; right, 14.7 ± 1.8; 95% CI: -4.98 to -0.32) and group N (left, 18.1 ± 2.9; right, 17.8 ± 2.4; 95% CI: -5.38 to -0.26) (p < 0.05). The results are expressed as mean ± standard deviation, with P-values <0.05 indicating statistical significance. Conclusions In this study, no neuropathy occurred; however, over-compression risk with elastic stockings, especially when exceeding recommended pressure levels, was highlighted. Balancing thromboembolism prevention and over-compression risks is crucial for patients undergoing CSs with spinal anesthesia.

Association of human interpretable features derived from pancreatic ductal adenocarcinoma pathology slides with disease-free survival.

e16368 Background: Pancreatic ductal adenocarcinoma (PDAC) is predicted to be the second cause of cancer death in the US by 2040. For the minority of patients who are candidates for curative-intent surgical resection, a neoadjuvant approach with chemotherapy or chemotherapy followed by chemoradiotherapy (chemoRT) has become the standard of care. The tumor microenvironment (TME) has been recognized as a key factor in therapeutic resistance and disease progression. This study aims to explore the prognostic value of human-interpretable machine learning image features (HIFs) derived from whole-slide H&amp;E images. Methods: Consecutive PDAC patients who underwent neoadjuvant therapy followed by surgical resection were studied in this single-institution retrospective study. Clinical variables collected include tumor site (head/body/tail), surgery extent, histology, sex, age at diagnosis, grade, treatment response (4-point scale), LVI, PNI, resection margin status, pathological TNM staging, number of lymph nodes removed/positive, neoadjuvant strategy (chemotherapy vs chemoRT), and number of neoadjuvant chemo cycles. These factors were analyzed with a multivariable Cox proportional hazards model for disease-free survival (DFS) after surgery. Additionally, 420 human-interpretable image features (HIFs) derived from a commercial machine learning software were analyzed with a univariable Cox model on a binary outcome of 1-yr DFS, applying a Bonferroni correction for multiple comparisons to identify significant predictors. Results: Increased neoadjuvant chemotherapy cycles (HR = 0.62, p = 0.001, [median: 8, IQR: 6-12]) and receipt of combination neoadjuvant therapy (HR = 0.15, p = 0.020, [29% chemo, 71% +chemoRT]) exhibited a protective effect in the multivariable DFS model. 3 HIFs quantifying immune cells and macrophages within the cancerous tissue and its stroma were associated with an improved probability of 1-year DFS. Conclusions: In addition to clinical factors, HIFs may offer valuable insights into the tumor microenvironment's influence on PDAC progression, paving the way for improved prognostic models and therapeutic strategies. Future work will integrate clinical predictors with HIFs in a combined model.

Association of ESR1 Germline Variants with TP53 Somatic Variants in Breast Tumors in a Genome-wide Study.

Emerging data show ancestry-specific differences in TP53 and PIK3CA mutation frequency in breast tumors suggesting that germline variants may influence somatic mutational processes. This study identified variants near ESR1 associated with TP53 mutation status and identified additional loci with suggestive association which may provide biological insight into observed differences.

Brain structural and functional abnormalities associated with acute post-traumatic headache: iron deposition and functional connectivity

BackgroundThe purpose of this study was to interrogate brain iron accumulation in participants with acute post-traumatic headache (PTH) due to mild traumatic brain injury (mTBI), and to determine if functional connectivity is affected in areas with iron accumulation. We aimed to examine the correlations between iron accumulation and headache frequency, post-concussion symptom severity, number of mTBIs, and time since most recent TBI.MethodsSixty participants with acute PTH and 60 age-matched healthy controls (HC) underwent 3T magnetic resonance imaging including quantitative T2* maps and resting-state functional connectivity imaging. Between group T2* differences were determined using T-tests (p < 0.005, cluster size threshold of 90 voxels). For regions with T2* differences, two analyses were conducted. First, the correlations with clinical variables including headache frequency, number of lifetime mTBIs, time since most recent mTBI, and Sport Concussion Assessment Tool (SCAT) symptom severity scale scores were investigated using linear regression. Second, the functional connectivity of these regions with the rest of the brain was examined (significance of p < 0.05 with family wise error correction for multiple comparisons).ResultsThe acute PTH group consisted of 60 participants (22 male, 38 female) with average age of 42 ± 14 years. The HC group consisted of 60 age-matched controls (17 male, 43 female, average age of 42 ± 13). PTH participants had lower T2* values compared to HC in the left posterior cingulate and the bilateral cuneus. Stronger functional connectivity was observed between bilateral cuneus and right cerebellar areas in PTH compared to HC. Within the PTH group, linear regression showed negative associations of T2* in the left posterior cingulate with SCAT symptom severity score (p = 0.05) and T2* in the left cuneus with headache frequency (p = 0.04).ConclusionsIron accumulation in posterior cingulate and cuneus was observed in those with acute PTH relative to HC; stronger functional connectivity was detected between the bilateral cuneus and the right cerebellum. The correlations of decreased T2* (suggesting higher iron content) with headache frequency and post mTBI symptom severity suggest that the iron accumulation that results from mTBI might reflect the severity of underlying mTBI pathophysiology and associate with post-mTBI symptom severity including PTH.

A machine-learning approach for differentiating borderline personality disorder from community participants with brain-wide functional connectivity

BackgroundFunctional connectivity has garnered interest as a potential biomarker of psychiatric disorders including borderline personality disorder (BPD). However, small sample sizes and lack of within-study replications have led to divergent findings with no clear spatial foci. AimsEvaluate discriminative performance and generalizability of functional connectivity markers for BPD. MethodWhole-brain fMRI resting state functional connectivity in matched subsamples of 116 BPD and 72 control individuals defined by three grouping strategies. We predicted BPD status using classifiers with repeated cross-validation based on multiscale functional connectivity within and between regions of interest (ROIs) covering the whole brain—global ROI-based network, seed-based ROI-connectivity, functional consistency, and voxel-to-voxel connectivity—and evaluated the generalizability of the classification in the left-out portion of non-matched data. ResultsFull-brain connectivity allowed classification (∼70 %) of BPD patients vs. controls in matched inner cross-validation. The classification remained significant when applied to unmatched out-of-sample data (∼61–70 %). Highest seed-based accuracies were in a similar range to global accuracies (∼70–75 %), but spatially more specific. The most discriminative seed regions included midline, temporal and somatomotor regions. Univariate connectivity values were not predictive of BPD after multiple comparison corrections, but weak local effects coincided with the most discriminative seed-ROIs. Highest accuracies were achieved with a full clinical interview while self-report results remained at chance level. LimitationsThe accuracies vary considerably between random sub-samples of the population, global signal and covariates limiting the practical applicability. ConclusionsSpatially distributed functional connectivity patterns are moderately predictive of BPD despite heterogeneity of the patient population.