Small Sample Size Research Articles

Diagnostic and prognostic value of time to positivity in blood cultures. An opinion paper

Time to positivity (TTP) refers to the duration required for a microbiological culture test to indicate a positive result, marking the onset of detectable bacterial or fungal growth in the sample. Numerous variables, including patient characteristics, infection source, former antimicrobial therapy, blood sample volume, and sample transportation time can influence the value of TTP. Several studies have been conducted on bloodstream infections, whereas studies on the clinical significance of yeast TTP are quite limited in the literature. Furthermore, many studies are retrospective and have a small sample size. In this opinion paper, we have formulated some questions and attempted to provide answers based on the available literature and our perspective. The objective of this opinion paper is to summarise current knowledge based on the literature, aiming to offer a critical perspective, particularly on aspects with weaker evidence, which could guide future studies in this area. We believe that TTP of blood cultures appears to exhibit considerable potential and may prove to be a valuable tool in clinical practice for estimating patient mortality risk and guiding antimicrobial therapy choices. Topics discussed include the diagnostic and prognostic role of TTP in Gram-positive and Gram-negative bacteremias and in candidemias, and the significance of differential time to positivity (DTTP). In summary, our opinion is that, based on the available literature, it is not possible to determine whether TTP provides prognostic information, particularly concerning candidemia. Therefore, clinical decisions cannot be systematically based on this parameter.

Pilot study utilizing short contact protocols for treatment of actinic keratoses (AK) with ALA gel-red light photodynamic therapy (PDT)

Background: Red light photodynamic therapy (PDT) is an effective option for actinic keratosis (AK) lesions. However, stinging pain during illumination limits utility. Objective: To compare three modified red-light PDT regimens (short incubation, whole-face application, no occlusion) and to determine whether these can reduce pain yet still provide significant AK lesion clearance. Methods: Patients in this randomized clinical trial (n = 30) were randomized into one of three groups [incubation with 10% ALA gel, illumination with red-light]: Group A: 10 min, 20 min (75 J/cm2); Group B: 20 min, 10 min (37 J/cm2); Group C: 1 hour, 10 min (37 J/cm2). Two PDT treatments were administered 8 weeks apart. Lesions were counted at each visit, and pain was recorded on a scale from 0 – 10. Results: Patients Groups A and B (shorter incubations) experienced significantly less pain during illumination than Group C. After one treatment, the AK lesion reduction in Group A (59%) was statistically non-inferior to Group C (43%), with a noninferiority margin of ±15%. Final lesion counts after two PDT treatments showed a reduction from baseline by 82% in Group C, 76% in Group A, and 74% in Group B. Groups A and B did not meet the statistical non-inferiority endpoint relative to Group C after two treatments. Limitations: Small sample size, which limited the ability to reach statistical significance after 2 PDT treatments. Conclusion: Two short/modified red light PDT regimens were essentially painless, and all three provided AK lesion clearances comparable to conventional regimens.

The effect of ischemic preconditioning on the cardiac autonomic nervous system after exercise: A systematic review and meta-analysis

Aims: The objective of this study is to comprehensively evaluate the influence of ischemic preconditioning intervention on the autonomic control nerves of athletes during the post-exercise period. Methods: Randomized controlled trials (RCTs) were sourced from PubMed, Web of Science, Embase, Wipo, CNKI, and Cochrane databases, covering the period from inception to December 2023. The quality of the included RCTs was evaluated using the Cochrane Risk Assessment Tool, and a systematic assessment was conducted using RevMan 5.3. Results: Seven randomized controlled trials (RCTs) involving 88 subjects were included in the analysis. The meta-analysis indicated that ischemic preconditioning significantly improved heart rate during both short-term recoveries (mean difference [MD] = -3.99, 95% confidence interval [CI]: -5.93 to -2.05, p < 0.00001) and long-term recovery post-exercise (MD = -9.73, 95% CI: -12.74 to -6.73, p < 0.00001). However, there was no significant effect observed on resting state heart rate variability (HRV) or peak heart rate (HR peak) at the end of exercise (MD = -0.16, 95% CI: -2.46 to 2.14, p = 0.89). Conclusion: Ischemic preconditioning facilitates the prompt reactivation of cardiac parasympathetic nerves following exercise and enhances both short-term and long-term heart rate recovery. The extent of this recovery effect may be influenced by factors such as the dosage of the intervention, the individual’s training level, and the intensity of the exercise performed. Limitation: Given the limited number of included studies, the small sample size, and the unclear definition of some experimental procedures, it is essential to design more rigorous and comprehensive high-quality randomized controlled trials (RCTs) in the future to investigate the effects of ischemic preconditioning on cardiac autonomic control nerves following exercise. Registration: INPLASY202440069

Aromatic Serenity: How Lavender Eases Stress and Anxiety - A Literature Review

In today's fast-paced society, rising stress levels necessitate effective management strategies. While pharmacological treatments are common, their side effects have spurred interest in alternative therapies, particularly those rooted in natural remedies. Lavender (Lavandula angustifolia), long esteemed for its calming properties, has emerged as a promising non-pharmacological option. Historical use in herbal medicine for anxiety and stress-related disorders has inspired modern scientific research to explore its potential. This review synthesizes recent studies on lavender essential oil, examining its mechanisms—such as neurotransmitter modulation—and its effectiveness in diverse settings, from reducing stress among healthcare professionals to improving sleep quality. Despite promising results, limitations like small sample sizes and variability in application methods highlight the need for more rigorous research to establish lavender's efficacy and optimize its therapeutic use in stress management and mental health care.

Successful colonization of the testicular germinal epithelium by bone marrow stem cells producing spermatozoa of donor genotype is rare

AbstractBackgroundIt is not known whether bone marrow stem cells when injected intravenously for a bone marrow transplant colonize the human testicular epithelium. No previous studies of sperm genotype after bone marrow transplantation are reported.ObjectivesTo differentiate host from donor genotype in spermatozoa of men who have undergone successful bone marrow transplants.Materials and methodsTriplet DNA samples (spermatozoa, blood, and hair) obtained from men who had recovered sperm production after bone marrow transplant were genotyped using 44 autosomal and three sex‐related single nucleotide polymorphisms to determine the tissue genotype in pairwise comparisons of DNA profiles.ResultsParticipants were 14 men at a median of 5.5 years after allogeneic bone marrow transplant who had a median sperm output of 77 million spermatozoa/ejaculate. In 14/14 the donor (leukocyte) DNA genotype differed significantly from the spermatozoa and hair genotypes whereas hair and sperm genotypes showed no variations.DiscussionThese data suggest that paternity after a successful bone marrow transplant is likely to be of the host and not the donor's genetic origins. The study's small sample size reflects the paucity of eligible man with recovered spermatogenesis after bone marrow transplant and represents preliminary evidence. A large‐scale epidemiological analysis to estimate the frequency of bone marrow donor stem cell colonization of the testicular germinal epithelium based on progeny sex ratio and frequency of female donors is proposed.ConclusionSuccessful colonization of the testicular germinal and hair follicle epithelia by allogeneic bone marrow transplant donor stem cells is rare or does not occur.

A Comparative Study of Discussions, Debates, and Oral Presentations in Enhancing EFL Learners’ Oral Proficiency

This case study investigated the effects of different speaking activities (oral presentations, discussions, debates) on the speaking performance of 11 young adult EFL learners at a university in central Mexico. Data was collected through semi-structured interviews and an online survey and analyzed using thematic analysis. The findings revealed that combining socialization with varied speaking activities and incorporating popular culture topics relevant to students increased motivation, reduced the affective filter, boosted confidence, and improved fluency and accuracy. The integration of student interests and fostering of personal relationships promoted a holistic understanding of cognitive and metacognitive strategies, enhancing overall speaking skills. However, limitations include a small sample size from the same sociocultural context. Further research with a larger, more diverse sample is recommended for unbiased results. The study highlights the benefits of tailoring speaking activities to students' interests and encourages developing interpersonal relationships to facilitate language learning.

Psychometric properties of the Specific Phobia Dimensional Scale in an Australian adult community sample

ABSTRACT Objective The Specific Phobia Dimensional Scale (SP-D) is a 10-item scale developed by the Diagnostic and Statistical Manual (Fifth Edition) Anxiety, Obsessive-Compulsive Spectrum, Posttraumatic and Dissociative Disorder work group to supplement current categorical approaches to Specific Phobia (SP) assessment. The aim of the current study was to examine the psychometric properties of the SP-D in an Australian community sample. Method A total of 285 participants (74% female) aged 18–76 years (M = 28.15; SD = 12.01) completed the study. A smaller subsample (n = 18) completed the measures of interest a second time to examine test–retest reliability. Results Confirmatory factor analysis indicated a unidimensional factor structure of the SP-D (root mean square error of approximation [RMSE] = 0.13; comparative fit index [CFI] = 0.94). Internal consistency and test–retest reliability was high (a = 0.95 and Intraclass Correlation Coefficient [ICC] = 0.95, respectively). The measure demonstrated adequate convergent validity with the Specific Phobia Questionnaire (SPQ; r s = 0.54), and unsatisfactory divergent validity with the Fear Questionnaire – Agoraphobia subscale (FQ-Ag; r s = 0.45). Conclusions Overall, the findings suggest that the SP-D can reliably and briefly measure SP symptoms within an Australian community sample. Further research is required to investigate divergent validity. Replication of the test–retest results are required due to small sample size. Overall, this study is limited in its female-biased convenience sample and recruitment methodologies.

Impact of Multidisciplinary Team Management on Survival and Recurrence in Stage I–III Colorectal Cancer: A Population-Based Study in Northern Italy

This study aimed to assess whether multidisciplinary team (MDT) management improves outcomes in patients with stage I–III colorectal cancer (CRC) compared to non-MDT care. This study included 460 CRC patients diagnosed from 2017 to 2018 in a northern Italian province, of whom 300 (65%) were managed by MDT. MDT patients were younger, more frequently had rectal cancers, were diagnosed at earlier stages, and were more likely to undergo surgery and chemotherapy. Disease-free survival (DFS) and overall survival (OS) were significantly better in the MDT group. The recurrence rate was 8.5%, with no significant differences between MDT and non-MDT patients, although MDT patients exhibited lower recurrence rates for early-stage tumors. A multivariable analysis showed that DFS and OS were adversely affected by older age, advanced stage, and lack of MDT management. Kaplan–Meier estimates demonstrated a 3-year DFS of 78% in the MDT group versus 65% in the non-MDT group, as well as an OS of 83% versus 69%, respectively. The MDT approach was associated with improved treatment adherence and better management of recurrences. While limited by a small sample size, this population-based study highlights the beneficial impact of MDT care on CRC outcomes. Further research with extended follow-up is warranted to confirm these findings.

English Language Competence, Communicative Competence, and Public Speaking Anxiety of Pre-service Teachers

This research sought to investigate the pre-service teachers' English language competence, communication competence, and public speaking anxiety. These competencies are vital skills in delivering adequate instructions. The study utilized a quantitative method through survey questionnaires. The result provides significant insights on the pre-service teachers as follows: some pre-service teachers are confident about their ability to communicate in English; however, many still suffer from speaking anxiety. The PSCAS revealed that anxiety happens in specific situations, such as when pre-service teachers are called to speak without preparation. Physiological effects like increased heart rate and sweaty palms are common symptoms of public speaking anxiety that affect their speaking presentation. Lastly, pre-service teachers fail to retain information learned and remain calm while delivering public speech despite the long academic exposure. However, this study faced limitations, including a relatively small sample size and only relying on self-reported data, which introduced bias. Despite this limitation, the researchers recommend structured intervention to enhance the pre-service teachers' English, communicative, and public speaking competence, particularly in light of the evolving educational trend.

Individual and community level determinants of minimum meal frequency among breastfeeding children aged 6–23 months in Ethiopia: a multilevel analysis of 2019 Ethiopian Demographic Health Survey data

BackgroundMinimum meal frequency (MMF) is a vital indicator of whether a child’s energy needs are being met. Previous studies in Ethiopia on MMF have primarily focused on individual factors, often using basic logistic regression models with limited scope and small sample sizes. In contrast, this study aims to identify the key determinants of MMF among breastfed children aged 6–23 months in Ethiopia, examining both individual and community-level factors through multilevel logistic regression analysis, utilizing nationally representative data.MethodThe study utilized a community-based cross-sectional design with a sample of 1,245 6–23 month breastfed children in Ethiopia, using data from the 2019 Ethiopian Mini Demographic Health Survey. Mixed effect logistic regression was used to identify factors associated with MMF. Adjusted odds ratios (AOR) with 95% confidence intervals were used to assess variable associations, while Intra-cluster correlation (ICC), median odds ratio (MOR), and proportional change in variance (PCV) were employed to gauge random variation.ResultThe proportion of 6–23-month breastfeeding children with MMF was found to be 55.9% (95% CI: 53.2, 58.6). In mixed effect logistic regression; breastfeeding initiation time within days after birth [AOR = 0.44; 95%CI: (0.24, 0.80)], maternal primary educational level [AOR = 1.46; 95%CI: (1.03, 2.05)], maternal higher level education [AOR = 2.43; 95%CI: (1.22, 4.81)] and children from wealthiest household wealth index [AOR = 2.13; 95%CI: (1.04, 4.33)] were individual-level factors and children from city-based regions [AOR = 1.75; 95%CI: (1.10, 2.77)] was community level factors significantly associated with MMF. The final model indicates that 50.8% of the variation in MMF was explained by combined factors at both individual and community levels and also the variation across clusters remained statistically significant (ICC = 8.1% and variance = 0.29 with p < 0.001).ConclusionMinimum meal frequency is a proxy for meeting energy requirements and it is a key indicator of infant and young child feeding (IYCF) practice. According to this study finding, the prevalence of MMF among 6–23-month children in Ethiopia was found to be low. The study also suggest that time of breastfeeding initiation, women’s educational level, household wealth index, and contextual region were factors significantly associated with MMF. It is recommended that IYCF strategies should be implemented widely through women’s education and empowerment and promoting early initiation of breast feeding to increase the proportion of children to be fed with MMF appropriate for their age.

Comparison of Occupational Performance in Immersive Virtual and Real Environments Among Patients With Stroke: Observational Randomized Crossover Pilot Study.

Conventional rehabilitation approaches involve therapists simulating various occupational tasks in health care settings or recreating real-life situations to assess and train patients in instrumental activities of daily living (IADLs). As an alternative, immersive virtual reality (IVR) has been widely used in stroke rehabilitation for years, but research comparing occupational performance between virtual and real environments is limited. This study aims to introduce a novel IVR shopping system designed for patients with stroke and to investigate the correlation of occupational performance in virtual and real environments among patients with stroke. Ten patients with stroke were recruited from the Department of Rehabilitation Medicine, Shenzhen Hospital, Southern Medical University, who met the inclusion and exclusion criteria for this observational, randomized crossover study; the patients were predominantly male (n=7), had experienced ischemic stroke (n=9), were aged 14 to 73 years, and had a time since stroke of 1 to 42 months. All patients attempted shopping tasks in virtual and real environments. The Mini-Mental State Examination (MMSE), Timed Up and Go Test (TUGT), modified Barthel index (MBI), and Lawton index (LI) were used to assess cognition, ambulation, and activities of daily living. Memory capacity and duration in the virtual and real environments were recorded as the primary parameters of occupational performance. The Wilcoxon test and Spearman correlation coefficients were used to analyze the differences and correlations between the 2 environments. The Wilcoxon test showed no significant differences between the virtual and real environments in memory capacity and duration of task completion (P>.99 and P=.99), and memory capacity in both environments correlated with the LI (ρ=0.81; P=.005). Memory duration had a relationship with the TUGT in the virtual environment (ρ=0.68; P=.03) and a borderline negative correlation with MMSE in the real environment (ρ=-0.58; P=.08). Considering the small sample size used in this study and the study's limitations, despite the significant correlation between shopping performance in IVR and the real world, it is still too early to conclude that IVR is a noninferior approach, but it presents the potential to be an alternative for assessment and training in IADLs when resources are limited. However, further research is needed to investigate the psychometric properties, clinical effects, and impact of virtual training on real-world performance. The implications for practice might include the following: (1) occupational performance in virtual shopping might be the same as real-world shopping, and more virtual IADLs could thus be developed; (2) virtual IADL assessment and training systems could be used in remote locations or locations with limited resources; and (3) more objective parameters of IADLs could be extracted from virtual environments.

Perifoveal Exudative Vascular Anomalous Complex (PEVAC): Retinal Vascular Density Findings

Objectives: This study aimed to describe the clinical, optical coherence tomography (OCT) and OCT angiography (OCTA) findings and characteristics in patients with perifoveal exudative vascular anomalous complex (PEVAC) and compare the macular vascular density with the age-matched control group. Methods: We conducted a case–control study to compare demographic information, clinical observations, and OCT/OCTA findings in eyes with PEVAC (n = 5 eyes in 5 patients) and a control group of subjects matched for age (n = 9). The Advanced Retina Imaging (ARI) network algorithms were utilized to evaluate OCTA observations. Statistical analysis was performed by the nonparametric Mann–Whitney U test. Results: Patients with PEVAC had a mean (±SD) age at presentation of 70 ± 12.6 years, the mean follow-up period was 7.8 ± 5.2 months, and unilateral disease was observed. Four out of the five patients in our cohort had a history of systemically treated hypertension and dyslipidemia. Three eyes had lesions in the inner temporal retinal zone, while the remaining two eyes had lesions in the inner inferior or central zone. Retina slab analysis using OCTA showed no significant difference in vascular density parameters between the PEVAC and control groups. Conclusions: Although limited by a small sample size, our study suggests that macular vessel density shows no significant difference between PEVAC cases and control eyes.

A retrospective clinico epidemiological study of pattern of dermatosis involving trigeminal distribution in a tertiary care center

Trigeminal nerve is the principal sensory nerve of face. Many dermatological conditions known occur in relation to trigeminal nerve distribution clinically presenting as unilateral facial lesions with strict midline demarcation. To study the clinical pattern and epidemiological determinants of dermatoses along trigeminal nerve among the patients of both the sexes, involving all the age groups. Thirty two patients presenting with skin lesions along trigeminal nerve presenting to Dermatology department of a tertiary care center, Bangalore, Karnataka, are selected for the study. Study design is retrospective hospital record based study conducted from January 2023 to January 2024. In this study, out of 32 patients most common dermatoses along trigeminal nerve were infection of which herpes zoster was seen thirteen (40.62%) patients, followed by nevi (n=6, 18.75%), pigmentary disorders (n=5, 15.62%), vascular disorder (n=4, 12.5%) and auto inflammatory disorder (n=4, 12.5%) was seen. Most common branch affected was ophthalmic followed maxillary branch .Females were more common and mean age was 24 years. Small sample size and rare clinical cases are included Studies focusing on the pattern of dermatoses involving the trigeminal nerve contribute to the advancement of medical knowledge and facilitate the development of novel diagnostic techniques and therapeutic modalities. By elucidating the underlying pathophysiological mechanisms and identifying potential risk factors, research in this field can lead to the development of more effective treatment strategies tailored to the specific needs of patients.

Differences in 6-Minute Walk Distance Across Heart Disease Recurrence Risk Levels in Cardiac Rehab Patients

Background/Objectives: Cardiac rehabilitation (CR) programs are multi-component interventions comprising structured strength and cardiovascular exercise training, psychological support, education, and therapies to promote positive lifestyle changes. This study aimed to determine if there are differences in the 6-minute walk distance (6MWD) across risk groups for recurrent heart disease. Methods: This retrospective cohort study used existing data collected from electronic medical records. The 6-minute walk distance was measured at baseline (pre-6MWD) and upon the completion of the CR program (post-6MWD). Short-term cardiac event recurrence risk was determined using a two-year recurrent coronary heart disease (2yRCHD) risk percentage, calculated according to the Framingham 2yRCHD calculator. Risk was then stratified into (1) low, (2) moderate, and (3) high-risk groups. Demographic variables (e.g., age, sex, racial/ethnic group) and clinical variables (e.g., BMI, lipid panels, fasting glucose levels, comorbidities) were collected to describe the study participants and identify potential confounders. An ANOVA and ANCOVA were performed to examine the differences in 6MWD across the 2yRCHD risk groups. Results: A total of 394 CR participants’ data were included in this analysis. Ninety-nine percent of the female participants were classified as low risk for recurrent heart disease, resulting in an extremely small sample size in the moderate-risk (n = 1) and no representation (n = 0) in the high-risk group. This lack of representation made it impossible to conduct comparative analyses across all the participants or to analyze female participants separately by risk category. Consequently, only male participant data were included in the final analysis. The study showed that pre- and post-6MWD measurements were significantly different across the three 2yRCHD risk groups (p = 0.006 for pre-6MWD; p = 0.002 for post-6MWD). The ANCOVA indicated that these differences were independent of the selected covariates. Post hoc analyses revealed significant differences in 6MWDs between the low- and high-risk groups and between the moderate- and high-risk groups, but not between the low- and moderate-risk groups, for both pre- and post-6MWD measurements. Compared to the CR participants in the high-risk group, those in the low- and moderate-risk groups achieved significantly longer distances in the 6-minute walk tests. Conclusions: The observed differences in the 6MWD across short-term cardiac recurrence risk levels suggest its potential as a simple, accessible tool for assessing cardiac recurrence risk levels in community settings. Further research is needed to generalize these findings to more diverse populations and to support aging in place for older adults living with heart disease.

Bayesian optimization for personalized dose-finding trials with combination therapies

Abstract Identification of optimal dose combinations in early-phase dose-finding trials is challenging, due to the trade-off between precisely estimating the many parameters required to flexibly model the possibly nonmonotonic dose-response surface, and the small sample sizes in early-phase trials. This difficulty is even more pertinent in the context of personalized dose-finding, where patient characteristics are used to identify tailored optimal dose combinations. To overcome these challenges, we propose the use of Bayesian optimization for finding optimal dose combinations in standard (one size fits all) and personalized multi-agent dose-finding trials. Bayesian optimization is a method for estimating the global optima of expensive-to-evaluate objective functions. The objective function is approximated by a surrogate model, commonly a Gaussian process, paired with a sequential design strategy to select the next point via an acquisition function. This work is motivated by an industry-sponsored problem, where the focus is on optimizing a dual-agent therapy in a setting featuring minimal toxicity. To compare the performance of the standard and personalized methods under this setting, simulation studies are performed for a variety of scenarios. Our study concludes that taking a personalized approach is highly beneficial in the presence of heterogeneity.

Brain-wide alterations revealed by spatial transcriptomics and proteomics in COVID-19 infection.

Understanding the pathophysiology of neurological symptoms observed after severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection is essential to optimizing outcomes and therapeutics. To date, small sample sizes and narrow molecular profiling have limited the generalizability of findings. In this study, we profiled multiple cortical and subcortical regions in postmortem brains of patients with coronavirus disease 2019 (COVID-19) and controls with matched pulmonary pathology (total n = 42) using spatial transcriptomics, bulk gene expression and proteomics. We observed a multi-regional antiviral response without direct active SARS-CoV2 infection. We identified dysregulation of mitochondrial and synaptic pathways in deep-layer excitatory neurons and upregulation of neuroinflammation in glia, consistent across both mRNA and protein. Remarkably, these alterations overlapped substantially with changes in age-related neurodegenerative diseases, including Parkinson's disease and Alzheimer's disease. Our work, combining multiple experimental and analytical methods, demonstrates the brain-wide impact of severe acute/subacute COVID-19, involving both cortical and subcortical regions, shedding light on potential therapeutic targets within pathways typically associated with pathological aging and neurodegeneration.

Spanish Translation, Adaptation and Psychometric Analysis of a Short Version of the Intercultural Sensitivity Scale in Chilean Public Workers.

Chile has been facing socio-cognitive, affective and cultural tensions and changes due to the constant increase of the migrant population in Chile over the last two decades. This means that local public policy workers must interact and achieve effective communication with migrant users living in their territories. Intercultural sensitivity is understood as the affective dimension of intercultural communication. This dimension facilitates the awareness that people differ in their behaviors, perceptions and feelings during intercultural communication processes, promoting acceptance and respect towards these differences. The aim of this paper was to analyze the factor structure, psychometric properties and invariance of the Intercultural Sensitivity scale (Chen & Starosta, 2000) in a sample of Chilean workers. The sample consists of 337 workers from five municipalities in two regions of Chile. The sample has a mean age of 42.8years (SD = 10.4), and 62.9% report being female. To determine the factor structure, an unweighted least squares (ULS) parameter estimation method was used, which is recommended for relatively small sample sizes, as is the case in this study. The overall structure of the original scale, although showing adequate indicators in a confirmatory factor analysis, presented serious conflicts in the covariance matrix used. Therefore, the 5-factor structure seen in other studies is disconfirmed. Because of this, it was decided to construct an abbreviated version, but reducing the limitations encountered during the validation process. The final result is a 4-dimensional structure, corresponding to four of the original dimensions, with a total of 13 items. The goodness-of-fit indices (CFI, TLI, RMSEA and SRMR) had optimal levels. The Manifest and Subtle Prejudice scale was used for its divergent validity, presenting all the dimensions of the instrument, and its total score, inverse and significant correlations with manifest prejudice, subtle prejudice, and total prejudice, as expected.

Addressing statistical challenges in the analysis of proteomics data with extremely small sample size: a simulation study.

One of the most promising approaches for early and more precise disease prediction and diagnosis is through the inclusion of proteomics data augmented with clinical data. Clinical proteomics data is often characterized by its high dimensionality and extremely limited sample size, posing a significant challenge when employing machine learning techniques for extracting only the most relevant information. Although there is a wide array of statistical techniques and numerous analysis pipelines employed in proteomics data analysis, it is unclear which of these methods produce the most efficient, reproducible, and clinically meaningful results. In this study, we compared 9 unique analysis schemes comprised of different machine learning and dimensionality reduction methods for the analysis of simulated proteomics data consisting of 1317 proteins measured in 26 subjects (i.e., 13 controls and 13 cases). In scenarios where the sample size is extremely small (i.e., n < 30), all schemes resulted in an exceptionally high level of performance metrics, indicating potential overfitting. While performance metrics did not exhibit significant differences across schemes, the set of proteins selected to be discriminatory between groups demonstrated a substantial level of heterogeneity. However, despite heterogeneity in the selected proteins, their biological pathways and genetic diseases exhibited similarities. A sensitivity analysis conducted using varying sample sizes indicated that the stability of a set of selected biomarkers improves with larger sample sizes within a scheme. When the aim of the study is to identify a statistical model that best distinguishes between cohort groups using proteomics data and to uncover the biological pathways and disorders common among the selected proteins, the majority of widely used analysis pipelines perform similarly. However, if the main objective is to pinpoint a set of selected proteins that wield significant influence in discriminating cohort groups and utilize them for subsequent investigations, meticulous consideration is necessary when opting for statistical models, due to the possibility of heterogeneity in the sets of selected proteins.

Using a Pre-Radiation Window to Identify Potentially Active Cytotoxic Agents in Adults with Newly Diagnosed Glioblastoma.

Therapies shown to improve outcomes in patients with recurrent cancers are commonly used in the neoadjuvant setting to optimize surgery, reduce radiation fields, and treat micro-metastatic disease. While pre-radiation chemotherapy (PRC) use has flourished in systemic cancers, it has not in glioblastomas. This review documents these trajectories and highlights the potential of PRC to rapidly and safely screen cytotoxic drugs for efficacy in patients with newly diagnosed glioblastoma. Prospective trials of adults with newly diagnosed systemic and brain cancers treated with PRC published between 1980 and 2023 were identified in PubMed. NCCN guidelines were used to document the standard use of PRC in patients with systemic and brain cancers. Over 5,000 prospective PRC trials in solid tumors were identified. These accrued >1 million patients and resulted in neoadjuvant therapies being standard-of-care in ~28 systemic cancers. Only 50 similar trials (2,206 patients) were identified in high grade gliomas. In 13 trials containing PRC temozolomide (n=846), radiographic responses ranged from 6-53% with a median survival of ~13 months. Glioblastoma PRC trials were not associated with unexpected toxicities or major negative impacts on survival. PRC in patients with glioblastoma appears safe and feasible. The pre-radiation window is ideally suited to rapidly screen cytotoxic agents for efficacy. It permits radiographic response as a primary outcome, small sample sizes, and initiation of standard therapies a few months after diagnosis. PRC may be most appropriate in patients with glioblastoma who are unlikely to benefit from temozolomide.

BN SO19 - Evaluating Wrap Pressure Augmentation Ratio and Physiological Transit Time for Post-Fundoplication Dysphagia

Abstract Background Post-fundoplication dysphagia affects many patients that can often lead to significant weight loss and reduced quality of life, and prompt some to seek surgical reversal. Current diagnostic methods may not fully explain the dysphagia which may necessitate repeat oesophageal physiology testing. This study retrospectively evaluates two novel markers, Wrap Pressure Augmentation Ratio (WPAR) and Physiological Transit Time (PTT), to better understand and manage the post-fundoplication dysphagia. Method The study retrospectively reviewed 54 post-Nissen’s fundoplication patients from January 2020 to May 2024. WPAR was calculated as the ratio of the augmented wrap basal pressure to the median integrated relaxation pressure found during high-resolution manometry following the Chicago Classification guideline [1]. PTT was measured from controlled measurements of antegrade bolus movement [2] during multichannel impedance-pH studies [3]. Patients completed HODQ forms to assess dysphagia [4]. Optimal WPAR and PTT thresholds were determined using Youden’s J index from receiver operating characteristic curves. This study was ethically approved (REC 18/NW/0120, IRAS 333800). Results Out of 54 cases (female=28:26, mean age 50.6), 75.9% reported clinical dysphagia post-fundoplication. Significant correlations were found with WPAR (&amp;lt;1.49, p=0.017) and PTT (&amp;gt;0.83 minutes, p=0.028)(see Table 1). These findings suggest WPAR and PTT as effective markers for post-fundoplication dysphagia. The analysis revealed a moderate correlation between WPAR and PTT (r =-0.45, p&amp;lt;0.05), suggesting that lower WPAR values tend to be associated with longer PTT. SensitivityPositive Predictive Valueχ2p-valueWPAR &amp;lt;1.490.610.895.680.017PTT &amp;gt;0.83 minutes0.780.844.820.028 Table 1 showing predictive DR and PTT values for clinical dysphasia post fundoplication. Conclusion This pilot study identifies PAR and PTT as promising physiological markers for diagnosing post-fundoplication dysphagia. The moderate correlation between PAR and PTT suggests a potential link, indicating that lower pressure augmentation might be associated with slower oesophageal transit times. These markers could enhance management strategies for affected patients. However, the study's small sample size and lack of a control group limit generalizability. Larger, controlled studies are necessary to validate these findings and further explore the relationship between PAR and PTT.