Exploratory Analysis Research Articles

A Longitudinal Study of Head Circumference Trajectories in Autism and Autistic Traits.

Increased head circumference is an established finding in autism spectrum disorder (ASD); however, it is unclear when this increase occurs, if it persists and whether it manifests across the whole ASD spectrum. Head circumference is a strong predictor of brain size and can therefore provide key insights into brain development in ASD. We used data from the Avon Longitudinal Study of Parents and Children to compare head circumference trajectories from birth to 15 years in children with an ASD diagnosis (N = 78, controls = 6,404) or elevated autistic traits as measured using the Social Communication Disorder Checklist (N = 639, controls = 6,230). Exploratory analyses were conducted in those with ASD and co-morbid cognitive learning needs (CLN). Children with an ASD diagnosis had larger head circumference from birth across childhood and adolescence compared to controls in univariable (B = 0.69, 95% confidence interval [CI]: 0.28-1.09, p = 0.001) and multivariable models (B = 0.38, 95% CI: 0.003-0.75, p = 0.048). Differences were more marked in those with co-morbid CLN. Children with elevated autistic traits had significantly smaller head circumference compared to controls. There was weak evidence of group differences when height was included as a covariate. Head circumference trajectories in ASD deviate from control children and persist until adolescence. Autistic traits were associated with smaller head circumference, suggesting distinct growth trajectories between clinical cases from those with non-clinical traits.

A comparative analysis of face and object perception in 2D laboratory and virtual reality settings: insights from induced oscillatory responses.

In psychophysiological research, the use of Virtual Reality (VR) for stimulus presentation allows for the investigation of how perceptual processing adapts to varying degrees of realism. Previous time-domain studies have shown that perceptual processing involves modality-specific neural mechanisms, as evidenced by distinct stimulus-locked components. Analyzing induced oscillations across different frequency bands can provide further insights into neural processes that are not strictly phase-locked to stimulus onset. This study uses a simple perceptual paradigm presenting images of faces and cars on both a standard 2D monitor and in an immersive VR environment. To investigate potential modality-dependent differences in attention, cognitive load, and task-related post-movement processing, the induced alpha, theta and beta band responses are compared between the two modalities. No evidence was found for differences in stimulus-dependent attention or task-related post-movement processing between the 2D conditions and the realistic virtual conditions in electrode space, as posterior alpha suppression and re-synchronization of centro-parietal beta did not differ between conditions. However, source analysis revealed differences in the attention networks engaged during 2D and 3D perception. Midfrontal theta was significantly stronger in laboratory conditions, indicating higher cognitive load than in the VR environment. Exploratory analysis of posterior theta showed stronger responses in VR, possibly reflecting the processing of depth information provided only by the 3D material. In addition, the theta response seems to be generated by distinct neuronal sources under realistic virtual conditions indicating enhanced involvement of semantic information processing and social cognition.

Adjuvant Nivolumab in High-Risk Muscle-Invasive Urothelial Carcinoma: Expanded Efficacy From CheckMate 274.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.CheckMate 274 is a phase III, randomized, double-blind trial of adjuvant nivolumab versus placebo for muscle-invasive urothelial carcinoma (MIUC) at high risk of recurrence after radical resection. The primary end points of disease-free survival (DFS) in intent-to-treat (ITT) and tumor PD-L1 expression ≥1% populations were met. We report results at an extended median follow-up of 36.1 months in the ITT population. In addition, we report interim overall survival (OS) data for the first time and an exploratory analysis among patients with bladder primary tumors (muscle-invasive bladder cancer [MIBC]). Consistent DFS benefit with nivolumab versus placebo was observed in both the ITT (hazard ratio [HR], 0.71 [95% CI, 0.58 to 0.86]) and PD-L1 ≥1% (HR, 0.52 [95% CI, 0.37 to 0.72]) patients. The HR for OS with nivolumab versus placebo was 0.76 (95% CI, 0.61 to 0.96) in the ITT population and 0.56 (95% CI, 0.36 to 0.86) in the PD-L1 ≥1 population. Continuous benefit in nonurothelial tract recurrence-free survival and distant metastasis-free survival was also observed in both patient populations. The exploratory analysis of patients with MIBC also showed continued efficacy benefits, irrespective of PD-L1 status. No new safety signals were reported. Overall, these results further support adjuvant nivolumab as a standard of care for high-risk MIUC after radical resection.

Deciphering Cathepsin K inhibitors: a combined QSAR, docking and MD simulation based machine learning approaches for drug design

ABSTRACT Cathepsin K (CatK), a lysosomal cysteine protease, contributes to skeletal abnormalities, heart diseases, lung inflammation, and central nervous system and immune disorders. Currently, CatK inhibitors are associated with severe adverse effects, therefore limiting their clinical utility. This study focuses on exploring quantitative structure–activity relationships (QSAR) on a dataset of CatK inhibitors (1804) compiled from the ChEMBL database to predict the inhibitory activities. After data cleaning and pre-processing, a total of 1568 structures were selected for exploratory data analysis which revealed physicochemical properties, distributions and statistical significance between the two groups of inhibitors. PubChem fingerprinting with 11 different machine-learning classification models was computed. The comparative analysis showed the ET model performed well with accuracy values for the training set (0.999), cross-validation (0.970) and test set (0.977) in line with OECD guidelines. Moreover, to gain structural insights on the origin of CatK inhibition, 15 diverse molecules were selected for molecular docking. The CatK inhibitors (1 and 2) exhibited strong binding energies of −8.3 and −7.2 kcal/mol, respectively. MD simulation (300 ns) showed strong structural stability, flexibility and interactions in selected complexes. This synergy between QSAR, docking, MD simulation and machine learning models strengthen our evidence for developing novel and resilient CatK inhibitors.

Enter the matrix: Examining the psychosocial determinants of support for a technocracy of artificial intelligence

AbstractArtificial Intelligence (AI) stands as the most transformative technology since the Industrial Revolution. As AI is integrated into different domains of life, it is likely to also permeate politics. In fact, some voices already advocate for AI to make political decisions. This paper emphasizes the necessity to delve into the psychosocial determinants shaping support for supporting a technocracy of AI (TecAI). The research aims to ascertain whether anomie, moderated by NCC and SDO, predicts support for TecAI across three studies involving Spanish participants (Ntotal = 754). The findings confirm anomie's predictive power on support of TecAI, albeit without establishing causality consistently, as anomie's condition failed to alter support for TecAI in experiments 2 and 3. However, an exploratory analysis showed a small effect of the subdimension of “breakdown of leadership” on support for TecAI in a directional test, informing future research. Moreover, NCC and SDO did not significantly moderate the anomie‐support‐for‐TecAI link. Ideology also emerged as a consistent predictor, with conservatives consistently showing more support, a finding that ought to be re‐examined and clarified. This study marks an initial empirical exploration into AI's political perceptions, hinting at the need for further investigation into this critical domain.

The efficacy of socially assistive robots in improving children’s pain and negative affectivity during needle-based invasive treatment: A systematic review and meta-analysis

BackgroundThe ability of socially assistive robots (SARs) to treat dementia and Alzheimer’s disease has been verified. Currently, to increase the range of their application, there is an increasing amount of interest in using SARs to relieve pain and negative emotions among children in routine medical settings. However, there is little consensus regarding the use of these robots.ObjectiveThis study aimed to evaluate the effect of SARs on pain and negative affectivity among children undergoing invasive needle-based procedures.DesignThis study was a systematic review and meta-analysis of randomized controlled trials that was conducted in accordance with the Cochrane Handbook guidelines.MethodsThe PubMed, CINAHL, Web of Science, Cochrane Library, Embase, CNKI, and WanFang databases were searched from inception to January 2024 to identify relevant randomized controlled trials (RCTs). We used the Cochrane Risk of Bias tool 2.0 (RoB2.0) to assess the risk of bias among the included studies, and we used RevMan 5.4 software to conduct the meta-analysis. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework was used to assess the quality of the evidence.ResultsTen RCTs involving 815 pediatric subjects were selected for this review and reported outcomes related to pain and emotions during IV placement, port needle insertion, flu vaccination, blood sampling, and dental treatment. Children undergoing needle-related procedures with SARs reported less anxiety (SMD= -0.36; 95% CI= -0.64, -0.09) and fewer distressed avoidance behaviors (SMD= -0.67; 95% CI= -1.04, -0.30) than did those receiving typical care. There were nonsignificant differences between these groups in terms of in pain (SMD = -0.02; 95% CI = − 0.81, 0.78) and fear (SMD = 0.38; 95% CI= -0.06, 0.82). The results of exploratory subgroup analyses revealed no statistically significant differences based on the intervention type of robots or anesthetic use.ConclusionsThe use of SARs is a promising intervention method for alleviating anxiety and distress among children undergoing needle-related procedures. However, additional high-quality randomized controlled trials are needed to further validate these conclusions.Trial registrationThe protocol of this study has been registered in the database PROSPERO (registration ID: CRD42023413279).

Effectiveness of community-based Baduanjin exercise intervention for older adults with varying frailty status: a randomized controlled trial

BackgroundDue to poorer exercise tolerance, it may be challenging for frail older adults to engage in moderate- or vigorous-intensity exercise. While low-intensity exercise interventions may be more feasible, its effectiveness for such population group remains unclear. We examined the effectiveness and implementation of community-based Baduanjin Qigong, a low-intensity exercise program in older adults with varying frailty status.MethodsA two-arm, multicenter assessor-blind parallel group randomized controlled trial was conducted at three local senior activity centers. Fifty-six community-dwelling older adults with low handgrip strength were randomly allocated to either the intervention (IG) or wait-list control (CG) group. The IG underwent a supervised 16-week Baduanjin exercise program at a frequency of 2–3 × 60 min sessions/week. The CG was instructed to maintain their usual activity and received a monthly health education talk. The primary outcome measures were knee extension strength, vital exhaustion, and fear of falling. Secondary outcome measures include physiological falls risk, handgrip strength, gait speed, timed up and go test, 30-second sit-to-stand, quality of life, depression, and frailty. All outcome measures were assessed at baseline and 4-month follow-up.ResultsOverall, there were no statistically significant differences in all outcome measures between CG and IG at 4-month follow-up. However, in exploratory compliance analysis, a statistically significant group x time interaction was found for vital exhaustion (B = -3.65, 95% CI [-7.13, -0.16], p = .047) among participants with at least 75% attendance. In post-hoc within-group comparisons, IG showed improved vital exhaustion by 4.31 points (95% CI [1.41, 7.20], d = 0.60). The average participant attendance rate was 81.3%. No major adverse events occurred, and all participants reported positive experiences with the exercise intervention.ConclusionsOur study demonstrated that Baduanjin is a safe, feasible, and acceptable exercise program that can be successfully implemented in community settings for older adults with varying frailty status. With good adherence, Baduanjin exercise could potentially be effective in alleviating vital exhaustion. However, the effectiveness of Baduanjin on physical performance, psychological measures and frailty in community-dwelling older adults remains equivocal.Trial registrationClinicalTrials.gov NCT04549103. Registered September 16, 2020.

“When my teacher quits, I’ll quit too.” – A mixed methods study on trust and (dis-)continuation in adult basic education

ABSTRACT Democratic values and social cohesion face challenges globally, affecting education access and participation. Global education policies aim to reduce barriers, particularly in literacy and adult basic education (ABE). Low literacy levels correlate with decreased social trust and stigmatisation, hindering further education enrolment due to associated shame. Trust emerges as a pivotal need among learners, facilitating enrolment bridged by trusted individuals, and enhancing the emotional value of participation. This study investigates the role of interpersonal trust in course (dis)continuation in the field of literacy and ABE. It explores clusters of learners based on generalised and particularised trust, examining how trust influences course continuation. Survey data was collected from 79 ABE learners in Germany and an exploratory cluster analysis was conducted. In-depth interviews with 8 active learners were matched with the results of the cluster analysis and were further qualitatively analysed. The analysis revealed two distinct learner clusters determined by trust levels. Findings underline the relevance of trust in drop-out decisions, both intra-individually and interpersonally. This study seeks to contribute to the discourse on the role of trust in drop-out and retention, thus aligning with the goal of enhancing social participation through basic education.

Nucleus reuniens: Modulating emotional overgeneralization in peri-adolescents with anxiety.

Anxiety affects 4.4-million children in the USA with an onset between childhood and adolescence, a period marked by neural changes that impact emotions and memory. Negative overgeneralization - or responding similarly to innocuous events that share features with past aversive experiences - is common in anxiety but remains mechanistically underspecified. The nucleus reuniens (RE) has been considered a crucial candidate in the modulation of memory specificity. Our study investigated its activation and functional connectivity with the medial prefrontal cortex (mPFC) and hippocampus (HPC) as neurobiological mechanisms of negative overgeneralization in anxious youth. As part of a secondary data analysis, we examined data from 34 participants between 9 and 14years of age (mean age ± SD, 11.4 ± 2.0years; 16 females) with varying degrees of anxiety severity. During the Study session participants rated images as negative, neutral, and positive. After 12h, participants returned for a Test session, where they performed a memory recognition test with repeated (targets) and similar (lures) images. Labeling negative relative to neutral lures as "old" (false alarms) was our operational definition of negative overgeneralization. Negative relative to neutral false alarmed stimuli displayed elevated RE activation (at Study and Test) and increased functional connectivity with the Cornu Ammonis (CA) 1 (at Test). Elevated anxiety severity was associated with reductions in the RE-mPFC functional coupling for neutral relative to negative stimuli. Exploratory analyses revealed similar patterns in activation and functional connectivity with positive stimuli. Our findings demonstrate the importance of the RE in negative overgeneralization and anxiety.

“Warning: ultra-processed”: an online experiment examining the impact of ultra-processed warning labels on consumers’ product perceptions and behavioral intentions

BackgroundNutrient content and degree of processing are complementary but distinct concepts, and a growing body of evidence shows that ultra-processed foods (UPFs) can have detrimental health effects independently from nutrient content. 10 + countries currently mandate front-of-package labels (FOPL) to inform consumers when products are high in added sugars, saturated fat, and/or sodium. Public health advocates have been calling for the addition of ultra-processed warning labels to these FOPLs, but the extent to which consumers would understand and be influenced by such labels remains unknown. We examined whether the addition of ultra-processed warning labels to existing nutrient warning labels could influence consumers’ product perceptions and purchase intentions.MethodsIn 2023, a sample of adults in Brazil (n = 1,004) answered an open-ended question about the meaning of the term “ultra-processed,” followed by an online experiment where they saw four ultra-processed products carrying warning labels. Participants were randomly assigned to view either only nutrient warning labels or nutrient plus ultra-processed warning labels. Participants then answered questions about their intentions to purchase the products, product perceptions, and perceived label effectiveness.ResultsMost participants (69%) exhibited a moderate understanding of the term “ultra-processed” prior to the experiment. The addition of an ultra-processed warning label led to a higher share of participants who correctly identified the products as UPFs compared to nutrient warning labels alone (Cohen’s d = 0.16, p = 0.02). However, the addition of the ultra-processed warning label did not significantly influence purchase intentions, product healthfulness perceptions, or perceived label effectiveness compared to nutrient warning labels alone (all p > 0.05). In exploratory analyses, demographic characteristics and prior understanding of the concept of UPF did not moderate the effect of ultra-processed warning labels.ConclusionsUltra-processed warning labels may help consumers better identify UPFs, although they do not seem to influence behavioral intentions and product perceptions beyond the influence already exerted by nutrient warning labels. Future research should examine how ultra-processed warning labels would work for products that do and do not require nutrient warnings, as well as examine the benefits of labeling approaches that signal the health effects of UPFs.Trial registrationClinicalTrials.gov, NCT05842460. Prospectively registered March 15th, 2023.

Urban Flooding Disaster Risk Assessment Utilizing the MaxEnt Model and Game Theory: A Case Study of Changchun, China

This research employs the maximum entropy (MaxEnt) model alongside game theory, integrated with an extensive framework of natural disaster risk management theory, to conduct a thorough analysis of the indicator factors related to urban flooding. This study conducts an assessment of the risks associated with urban flooding disasters using Changchun city as a case study. The validation outcomes pertaining to urban flooding hotspots reveal that 88.66% of the identified flooding sites are situated within areas classified as high-risk and very high-risk. This finding is considered to be more reliable and justifiable when contrasted with the 77.73% assessment results derived from the MaxEnt model. Utilizing the methodology of exploratory spatial data analysis (ESDA), this study applies both global and local spatial autocorrelation to investigate the disparities in the spatial patterns of flood risk within Changchun. This study concludes that urban flooding occurs primarily in the city center of Changchun and shows a significant agglomeration effect. The region is economically developed, with a high concentration of buildings and a high percentage of impervious surfaces. The Receiver Operating Characteristic (ROC) curve demonstrates that the MaxEnt model achieves an accuracy of 90.3%. On this basis, the contribution of each indicator is analyzed and ranked using the MaxEnt model. The primary determinants affecting urban flooding in Changchun are identified as impervious surfaces, population density, drainage density, maximum daily precipitation, and the Normalized Difference Vegetation Index (NDVI), with respective contributions of 20.6%, 18.1%, 13.1%, 9.6%, and 8.5%. This research offers a scientific basis for solving the urban flooding problem in Changchun city, as well as a theoretical reference for early warnings for urban disaster, and is conducive to the realization of sustainable urban development.

Prognostic and predictive factors in advanced upper gastrointestinal cancer treated with immune checkpoint inhibitors: a systematic review and meta-analysis of the current evidence

BackgroundImmune checkpoint inhibitors (ICIs) have shown encouraging treatment efficacy for upper gastrointestinal cancers (UGICs). However, durable clinical responses only existed in a minority of patients. We evaluated evidence predicting survival benefits to identify the optimal population followed by ICI-based therapy.MethodsA comprehensive search was performed using PubMed, Embase, Cochrane Library, and Web of Science to identify clinical trials for UGICs with ICI-based therapy. The outcomes were objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). The quality of evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation System (GRADE).ResultsThirty-six studies comprising 12,440 patients were included for quantitative synthesis. Patients with PD-L1-positive (OR = 2.08, p < 0.00001), EBV+ (OR = 8.47, p = 0.003) tumors were more likely to respond to ICI treatment. Moreover, OS was significantly improved with the statistical subgroup difference concerning sex (p = 0.02) and region (p = 0.02). An exploratory subgroup analysis showed significantly improved OS with ICI plus chemotherapy in patients with CPS ≥ 10 (HR = 0.66, p = 0.001) and CPS ≥ 1 (HR = 0.75, p < 0.00001).ConclusionUGIC patients with PD-L1-positive, EBV + status are associated with a better therapeutic response to ICI-based therapy. The male patients and Asian patients could derive more survival benefits following ICI treatment than female and non-Asian ones. A combination of prognostic and predictive factors was suggested to help guide immunotherapy decision-making in UGIC patients.

The association between novel negative pressure ureteroscopic lithotripsy combined with flexible ureteroscopy versus percutaneous nephrolithotomy on stone-free rates: implications for clinical practice and policy

The correlation between novel negative pressure ureteroscopic lithotripsy (NP-URL) combined with flexible ureteroscopy (FU) and percutaneous nephrolithotomy (PCNL) on stone-free rates (SFR) remains unclear. There is a lack of evidence from Chinese populations regarding the relationship between SFR and NP-URL combined with FU (NP-URL-FU) versus PCNL. We aimed to assess the association between NP-URL-FU and PCNL on SFR. We conducted a cohort study involving 166 participants with 2–4 cm kidney stones. Data on SFR (7 days and 2 months) were collected from all participants. Logistic regression analysis was used to substantiate the research objectives. NP-URL-FU versus PCNL showed an 86% decrease in the 7-day SFR (OR = 0.14, 95% CI 0.07–0.29). The results remained stable even after adjusting for potential confounders. However, no statistically significant association was found between the surgical method and the 2-month SFR. Further exploratory subgroup analyses showed no significant interactions, with all P values > 0.05. Among patients with 2–4 cm kidney stones, NP-URL-FU was associated with a lower risk of incident 7-day SFR than PCNL. However, no statistically significant difference was found in the long-term stone removal rate. Therefore, NP-URL-FU may be a viable alternative surgical option for patients seeking minimally invasive procedures.

Association of Cannabis Use Reduction With Improved Functional Outcomes: An Exploratory Aggregated Analysis From Seven Cannabis Use Disorder Treatment Trials to Extract Data-Driven Cannabis Reduction Metrics.

This exploratory analysis sought to determine whether decreases in cannabis use are associated with improvements in cannabis-related problems and functional outcomes, and if so, what percentage decrease is associated with improvement. Data were aggregated from seven cannabis use disorder treatment trials conducted in the United States (N=920; ages 13 years and older; mean age, 25 years; 30% female, 7% Black, 11% Hispanic/Latinx). Outcome measures included the patient-reported Marijuana Problems Scale (MPS), Health-Related Quality of Life scale (HRQOL), and Pittsburgh Sleep Quality Index and the clinician-rated Clinical Global Impressions (CGI) severity and improvement scales (CGI-S and CGI-I). Generalized estimating equations tested the association between changes in 4-week cannabis use and improvements in functional outcomes. Classification and regression tree (CART) models were developed to determine what reductions in cannabis use could be used as classifiers of improvement. Decreases in the amount and frequency of cannabis use were significantly associated with improvements in MPS severity and total scores as well as improvements on the CGI-I and in sleep quality, but not improvements on the HRQOL. CART models performed best for CGI-I scores (72%-75% correct classification), while other outcome measures did not perform as well (40%-62% correct classification). CART models showed improvements on the CGI at 74% reduction in use amounts and 47% reduction in use days. Reductions in cannabis use (∼50% reduction in use days and ∼75% reduction in use amounts) were associated with clinician-assessed improvement, which suggests that cannabis use reduction may yield benefit among individuals with cannabis use disorder. These exploratory results extract a data-driven metric to inform future studies, clinicians, patients, and policy recommendations.

Dietary modulation of human milk bioactives is associated with maternal FUT2 secretor phenotype: an exploratory analysis of carotenoids and polyphenol metabolites

IntroductionMaternal diet modifies profiles of human milk oligosaccharides (HMOs), carotenoids, and polyphenols in human milk (HM). However, substantial variability in profiles exists between women, highlighting the complexity of non-dietary factors modulating these profiles. The objective of this study was to carry out a secondary analysis exploring the effect of maternal diet on HM carotenoids and polyphenols and relationships between dietary modulation of HM bioactives (carotenoids, polyphenols, and oligosaccharides) and maternal α1,2-fucosyltransferase 2 (FUT2) secretor phenotype.MethodsIn this pilot study, 16 exclusively breastfeeding women with obesity were enrolled between 4 and 5 months postpartum. The women were provided a 4-week meal plan consistent with the 2020 Dietary Guidelines for Americans (DGA). HM was collected for 24 h at baseline and post-intervention. Maternal FUT2 secretor phenotype was determined by 2′-fucosyllactose concentration in HM (non-secretor: &amp;lt; 100 nmol/ml; secretor: ≥100 nmol/ml). Concentrations of carotenoids and HMOs were determined by LC and polyphenol metabolites by UPLC–MS/MS.ResultsThirteen women completed the study (6 secretors, 7 non-secretors). The change in HM concentrations of the HMOs lacto-N-tetraose (LNT, p = 0.007), lacto-N-fucopentaose II (LNFP II, p = 0.02), difucosyllacto-N-tetraose (DFLNT, p = 0.003), and disialyllacto-N-tetraose (DSLNT, p = 0.003) and polyphenol metabolites 4-hydroxybenzoic acid (4-HBA, p = 0.08) and ferulic acid (p = 0.02) over the intervention time frame was differentially associated with maternal secretor status. 4-HBA and ferulic acid positively correlated with HMOs LNT and DSLNT (rrm = 0.82–0.90, p = 0.03–0.06) for secretors but not for non-secretors. Only secretors demonstrated a negative correlation between 4-HBA and DFLNT (rrm = −0.94, p = 0.001).DiscussionThe influence of maternal diet on composition of HMOs and polyphenol metabolites in HM differs based on maternal secretor status. Consideration of non-dietary factors is needed to evaluate differences in response of HM bioactives to dietary modulation.

Cluster analysis identifies long COVID subtypes in belgian patients

Abstract SARS CoV-2 infection presents complications known as long COVID, a multisystemic organ disease which allow multidimensional analysis. Objectives This study aims to uncover clusters of long COVID cases and establish their correlation with the clinical classification developed at the Clinical Research Unit of Brugmann University Hospital, Brussels. Such an endeavour is instrumental in customizing patient management strategies tailored to the unique needs of each distinct group. Method A two-stage multidimensional exploratory analysis was performed on a retrospective cohort of 205 Long COVID patients, involving a Factorial Analysis of Mixed Data (FAMD), and then Hierarchical Clustering Post Component Analysis (HCPC). Results The study's sample comprised 76% women, with an average age of 44.5 years. Three clinical forms were identified: long, persistent, and post-viral syndrome. Multidimensional analysis using demographic, clinical and biological variables identified three clusters of patients. Biological data did not provide sufficient differentiation between clusters. This emphasizes the importance of identifying or classifying long COVID patients according to their predominant clinical syndrome. Conclusion long COVID phenotypes, as well as clinical forms, appear to be associated with distinct pathophysiological mechanisms or genetic predispositions. This underscores the need for further research.

Pembrolizumab Plus Chemotherapy for Advanced and Recurrent Cervical Cancer: Final Analysis According to Bevacizumab Use in the Randomized KEYNOTE-826 Study

In KEYNOTE-826 (NCT03635567), pembrolizumab plus chemotherapy (± bevacizumab) significantly improved overall survival (OS) and progression-free survival (PFS) in patients with persistent, recurrent, or metastatic cervical cancer. This exploratory analysis examined outcomes in patient subgroups defined by bevacizumab use. Eligible adult patients had persistent, recurrent, or metastatic squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix not previously treated with chemotherapy and not amenable to curative treatment; measurable disease per RECIST v1.1; and an Eastern Cooperative Oncology Group performance status ≤1. Patients were randomized 1:1 to pembrolizumab 200 mg every 3 weeks or placebo for up to 35 cycles plus chemotherapy (± bevacizumab 15 mg/kg). Dual primary endpoints were OS and PFS per RECIST v1.1 by investigator assessment. Outcomes were assessed in subgroups defined by bevacizumab use. Hazard ratios (HRs) and 95% CIs were based on a stratified Cox regression model. 617 patients were randomized (pembrolizumab arm, n=308 [63.6% with bevacizumab]; placebo arm, n=309 [62.5% with bevacizumab]). The most common reason for bevacizumab exclusion was medical contraindication (75.9%). Among patients who received bevacizumab, HRs (95% CIs) for PFS favored the pembrolizumab arm in the PD-L1 combined positive score (CPS) ≥1 (0.56 [0.43-0.73]) and all-comer (0.57 [0.45-0.73]) populations; OS results were 0.60 (0.45-0.79) and 0.61 (0.47-0.80), respectively. Among patients who did not receive bevacizumab, HRs (95% CIs) for PFS also favored the pembrolizumab arm in the PD-L1 CPS≥1 (0.61 [0.44-0.85]) and all-comer (0.69 [0.50-0.94]) populations; OS results were 0.61 (0.44-0.85) and 0.67 (0.49-0.91), respectively. Among patients who received bevacizumab, grade ≥3 treatment-related adverse events occurred in 74.0% of patients in the pembrolizumab arm and 66.8% in the placebo arm. Pembrolizumab plus chemotherapy prolonged PFS and OS and had manageable safety compared with placebo plus chemotherapy in patient subgroups defined by bevacizumab use.

The Antecedents of the Entrepreneurial Intention of Cooperative Founders: The Case of the Province of Larache

This paper aims to identify the antecedents of entrepreneurial intention among the founders of cooperatives in the Larache province of Morocco. The theoretical model used is Ajzen's Theory of Planned Behavior, which explains intention based on attitudes toward behavior, social norms, and perceived behavioral control. Our analysis adopts a quantitative approach for 57 founders of cooperatives. The data underwent exploratory analysis using Principal Component Analysis (PCA) and confirmatory analysis through linear regression using the SPSS software. Our findings suggest a relationship between attitude toward behavior and intention while rejecting the link between social norms and intention, as well as perceived behavioral control and intention. Our findings also underscore the role of ancestral solidarity practices in empowering indigenous peoples. In this regard, the Georgist political economy approach provides a suitable perspective to promote cooperative entrepreneurship in Africa.

Apixaban dosing in hemodialysis - can drug level monitoring mitigate controversies?

BackgroundInconsistent study results and contradictory recommendations from health authorities regarding the use of apixaban in patients on hemodialysis have generated considerable uncertainty among clinicians, making investigations of appropriate dosing an unmet need.MethodsWe analyzed pre-dialysis apixaban drug levels from a tertiary care dialysis unit, comparing 2.5 mg once versus twice daily dosing. We applied mixed-effects models including dialysis modality, adjusted standard Kt/V, ultrafiltration, and dialyzer characteristics. We included an exploratory analysis of bleeding events and compared the drug levels of our dialysis patients to those from non-CKD reference populations taking the standard dose of 5 mg twice daily.ResultsWe analyzed 143 drug levels from 24 patients. Mean (SD) age at first drug level measurement was 64.7 (15.9) years (50 % female), median (IQR) follow-up was 12.5 (5.5 – 21) months. For the apixaban 2.5 mg once and twice daily groups, median (IQR) drug levels were 54.4 (< 40 – 72.1) and 71.3 (48.8 – 104.1) ng/mL respectively (P < 0.001). Levels were below the detection limit in 30 % (with 2.5 mg once daily) and 14 % (with 2.5 mg twice daily) respectively. Only dosing group (twice versus once daily) was independently associated with higher drug levels (P = 0.002). Follow-up did not suggest accumulation. The 95th percentile of drug levels did not exceed those of non-CKD populations taking 5 mg twice daily. Median (IQR) drug levels before a bleeding (8 episodes) were higher than those without a subsequent bleeding: 111.6 (83.1 – 129.3) versus 54.8 (< 40 – 77.1) ng/mL (P < 0.001). Concomitant antiplatelet therapy was used in 86% of those with bleeding events versus 6% without bleeding events (P < 0.001).ConclusionsDrug monitoring may be a contributory tool to increase patient safety. Despite non-existing target ranges, drug levels on both edges of the spectrum (e.g. below detectability or beyond the 95th percentiles of reference populations) may improve decision-making in highly individualized risk-benefit analyses.

Development of Prediction Models to Detect the Presence of MGMT Promoter Methylation for Prognosis of Brain Tumor

Methylation of the MGMT promoter is a molecular marker of predictive relevance in brain tumors. Methylation of the MGMT promoter is related to an improved prognosis and may influence therapy decisions. According to the most recent Malaysian National Cancer Registry Report (MNCRR) for 2012–2016, there were 2097 cases of brain tumors in Malaysia overall, with 1117 cases involving men and 908 cases involving women. This research aims to create prediction models for detecting MGMT promoter methylation in brain tumors. So, a dataset from the BraTS (Brain Tumor Segmentation) challenge, which included MRI scans and clinical data for patients with brain tumors, was utilized and explored using Exploratory Data Analysis (EDA) and data visualization techniques. The dataset has 306 methylation cases identified as “1” and 276 unmethylated cases identified as “0”. The average number of scans of train data for modality per patient is between 127 and 171, which provides a wealth of information for pattern learning while the average number of scans of test data for modality per patient is between 124 and 165. In both sets, FLAIR has the least number of files while T2w has the highest number of files among them. Two models of deep learning approaches, ResNet50 and EfficientNetV2, were used to construct and form the prediction models. Various criteria were employed to evaluate the performance of the models. The T2w modality consistently achieved the highest validation accuracy, precision, recall, and F1-score for both the ResNet50 and EfficientNetV2 models. Specifically, the T2w modality achieved a validation accuracy of 0.9453 and a validation loss of 0.2417 for ResNet50. Furthermore, the brain tumor diagnosis interface utilized DICOM images from MRI scans to identify MGMTp methylation status, aiding in therapy effectiveness prediction. Pre-trained ResNet50 model on T2w images was used for classification. The interface displayed the original MRI image, predicted state, and treatment effectiveness indication, while promptly notifying users of invalid or inadequate data for accurate analysis.