Tag: statistics

J Chem Inf Model. 2026 Jul 21. doi: 10.1021/acs.jcim.6c01901. Online ahead of print.

ABSTRACT

Clinical attrition in drug development is frequently driven by suboptimal pharmacokinetic and toxicological (ADMET) properties rather than inadequate target efficacy. Accordingly, early-stage ADMET assessment has become an increasingly important component of Structure-Based Drug Design (SBDD). Here, we present empirically derived chemical navigability guidelines based on an analysis of ADMET-related properties predicted by admetSAR 3.0 across approved drugs curated from DrugBank. These parameters were integrated into an intuitive color-coded visualization framework for rapid compound assessment. The proposed guidelines are intended as context-dependent heuristics derived from statistical trends within the predicted chemical space of approved drugs rather than as universal decision rules. The utility of the ADMET-first strategy was further evaluated using an external and independent library of 1,756 KEAP1/NRF2 modulator compounds from ChEMBL, employing experimentally determined biological activity (pChEMBL) instead of docking-derived metrics. Enrichment analysis demonstrated that ranking compounds according to the ADMET-score identified true active compounds substantially earlier than random selection, achieving an enrichment factor (EF) of 1.29 in the top 5% of the library and recovering approximately 80% of active compounds within a limited fraction of the evaluated chemical space. We provide a freely accessible (https//admetSAR.umh.es), curated database of more than two million ADMET-annotated commercially available compounds from the MolPort library, prefiltered according to the proposed chemical navigability guidelines.

PMID:42478342 | DOI:10.1021/acs.jcim.6c01901

Mediators Inflamm. 2026;2026(1):e7778073. doi: 10.1155/mi/7778073.

ABSTRACT

BACKGROUND: Patients receiving massive transfusion after acute hemorrhage are at risk for transfusion-related acute lung injury (TRALI), a severe complication. Neutrophil extracellular traps (NETs) play a key role in acute lung injury. This study aimed to explore the link between NETs and TRALI and to develop a risk-prediction model using machine learning for early detection and intervention.

METHODS: In this multicenter prospective study, 513 patients with acute massive hemorrhage who underwent transfusion therapy (March 2020-February 2025) were consecutively recruited. All biomarker assays, sampling time points, and the statistical analysis plan were prespecified and ethically approved before study initiation. Based on TRALI occurrence after transfusion, they were divided into an injured group (n = 42) and a uninjured group (n = 471). Clinical features and NET-related markers were compared. LASSO regression was used for variable selection, followed by random forest for importance ranking. Multivariate logistic regression identified independent predictors, and a nomogram model was built and evaluated using ROC analysis, calibration, and decision curve analysis.

RESULTS: The injured group had significantly higher rates of smoking history, total infusion volume, perioperative transfusion volume, and transfusion frequency (all p < 0.05). Levels of citrullinated histone H3 (citH3), myeloperoxidase (MPO), neutrophil elastase (NE), interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and interleukin-8 (IL-8) were also elevated (all p < 0.05). LASSO identified seven key variables, with citH3 and MPO showing high importance. Multivariate analysis confirmed citH3 (OR = 1.142), MPO (OR = 5.017), and NE (OR = 1.014) as independent predictors of TRALI (all p < 0.05). The combined model achieved an AUC of 0.85 (95% CI: 0.78-0.92), indicating strong predictive performance.

CONCLUSION: TRALI risk in acute massive hemorrhage patients is associated with NET-related markers, particularly citH3, MPO, and NE. A model integrating these indicators provides valuable early identification of TRALI, aiding clinical decision-making.

PMID:42478331 | DOI:10.1155/mi/7778073

Pain Res Manag. 2026;2026(1):e6121920. doi: 10.1155/prm/6121920.

ABSTRACT

INTRODUCTION: Transcranial alternating current stimulation (tACS), which can noninvasively entrain oscillatory brain activity, has attracted scientific attention as a possible technique to control pain. However, there is a scarcity of studies investigating the preventive effect of tACS on postoperative pain.

METHODS: This double-blind, randomized, sham-controlled trial enrolled 72 patients undergoing elective video-assisted thoracoscopic surgery (VATS). Patients were randomly allocated (1:1) to receive a single 20-min session of α-tACS on the primary somatosensory cortex (S1) or sham stimulation postoperatively. The primary outcomes were postoperative numerical rating scale pain scores and opioid consumption at 24 h postoperatively. Secondary outcomes included cumulative opioid consumption within 48 h and Quality of Recovery-15 (QoR-15) score. Adverse events were also assessed.

RESULTS: The tACS group exhibited significantly lower resting pain scores versus the sham group (β = -0.49, 95% confidence interval [CI], -0.78 to -0.20, p = 0.001) and lower movement pain scores versus the sham group (β = -0.45, 95% CI, -0.84 to -0.06, p = 0.025), though cumulative opioid consumption showed no difference at 24 h (median difference [MD] = 1.0 mg; 95% CI, -2.3 to 2.5; p = 0.76) and 48 h (MD = 3.3 mg; 95% CI, -0.6 to 9.1; p = 0.10) postoperatively. Additionally, the area under the curve for resting pain over 2-24 h (AUC_{2-24 h}) and 2-48 h (AUC_{2-48 h}), as well as the AUC_{2-48 h} of movement pain scores, were significantly lower in the tACS group. Moreover, QoR-15 scores and adverse events were also comparable.

CONCLUSION: For patients undergoing VATS, a single α-tACS treatment targeting the bilateral S1 regions yielded a statistically significant yet modest reduction in postoperative pain. However, no significant decrease in postoperative opioid consumption was observed, and further research is warranted.

TRIAL REGISTRATION: Chinese Registry of Clinical Trials: ChiCTR2300078723.

PMID:42478315 | DOI:10.1155/prm/6121920

Riv Psichiatr. 2026 Jul-Aug;61(4):181-192. doi: 10.1708/4747.47645.

ABSTRACT

The history of the transition from Kraepelin’s concept of manic-depressive psychosis and endogenous depression to the current model of major depression is traced. In particular, the changes that have characterized the transition from the narrative psychopathology of the positivist era to the operational psychiatry of the DSM-III and its successors over the last century are critically reviewed. The birth of psychopharmacology, with the consequent entry of market interests into psychiatry and de-institutionalization, have shifted psychiatric patients from mental hospitals to outpatient clinics, resulting in enormous changes in both quantity and quality of samples. The changing composition of psychiatric population, with an ever-increasing prevalence of non-psychotic cases, and the progressive abandonment of the phenomenological cultural substratum in favor of more empirical paradigms, has rendered old classifications based on narrative criteria inadequate. Hence the need for more ‘scientific’ models, driven mainly by the need for reproducibility, was necessary for the application of scientific empirical methods. This article focuses on the changes that the concept of depressive illness has undergone in the transition from descriptive psychopathology to the current operational diagnoses. The various forms of depression described prior to DSM-III (endogenous depression, neurotic depression, reactive depression, atypical depression, seasonal depression, masked depression, involutional depression, depressive pseudodementia), examined in the frame do DSM-5, are either excluded because of the lack of evident depression (masked depression, depressive pseudodementia) or all absorbed into the single broad category of major depressive disorder, which thus becomes a broad container which is likely to lack homogeneity, as has been repeatedly pointed out over the years. On the other hand, what the authors of DSM (the latest edition in particular) have proposed as a remedy, the sub-categorization of the disorder through the description of specific typer (the specifiers), is in fact ignored both in research and in clinical practice.

PMID:42478310 | DOI:10.1708/4747.47645

Riv Psichiatr. 2026 Jul-Aug;61(4):166-171. doi: 10.1708/4747.47643.

ABSTRACT

BACKGROUND: Violent behaviours continue to be a significant problem worldwide. The introduction of Motion Rooms, particularly within acute psychiatric settings, can provide a safe and therapeutic intervention that, by promoting emotional self-regulation, reduces emotional distress and aggressive behaviors.

AIM: To assess the effects of a therapeutic intervention through the use of the Motion Room on the risk of violent behavior and the use of physical restraint.

MATERIALS AND METHODS: A longitudinal design was used to evaluate the effectiveness of the Motion Room in an acute psychiatric unit. The Italian version of the Broset Violence Checklist (BVC-ita) was used for the assessment of the risk of aggression before (T0) and 2 hours after intervention (T1).

RESULTS: 102 patients were enrolled, 96 (94.12%) completed the intervention. The number of subjects at moderate/high risk decreased significantly at T1 (p=0.01). In the two hours following the intervention, one patient was subjected to physical restraint.

CONCLUSIONS: Our results suggest that sensory rooms can be a strong support for nursing staff in preventing aggressive behavior in an acute psychiatric ward. Further research with broader sampling and randomized studies is needed.

PMID:42478308 | DOI:10.1708/4747.47643

Riv Psichiatr. 2026 Jul-Aug;61(4):156-165. doi: 10.1708/4747.47642.

ABSTRACT

BACKGROUND: This survey aimed to investigate how physicians in Italy recognize, diagnose, and manage tardive dyskinesia (TD), as well as to assess and identify gaps in the current treatment approaches.

METHODS: A non-interventional cross-sectional online survey was conducted among Italian physicians who had managed patients with TD in the 1 year prior to the survey. The questionnaire explored physicians’ demographics, clinical experience, diagnostic methods, treatment strategies, perceptions of TD impact, and health care resource utilization related to TD. Data were summarized descriptively.

RESULTS: The survey included 70 psychiatrists and 30 movement disorder neurologists. Most patients presented with mild (49%) or moderate (35%) TD. Treatment strategies varied by TD severity; antipsychotic dose modification or switching was common, particularly to clozapine, quetiapine, and aripiprazole, whereas TD-specific add-on treatments such as tetrabenazine were rarely used (12% to 21% of physicians prescribed the treatment). Movement impairment was primarily assessed through patient or caregiver reports on quality-of-life impact, while standardized scales like the Abnormal Involuntary Movement Scale were underused, especially by psychiatrists. Physicians acknowledged significant challenges including a lack of highly effective treatments and an absence of specific Italian or European guidelines. TD was perceived as significantly affecting patients’ physical and psychosocial functioning and increasing health care resource utilization.

CONCLUSIONS: This study highlights variability and unmet needs in TD diagnosis and management among Italian specialists. Add-on treatments such as tetrabenazine are not considered standard of care in Italy due to lack of clinical practice guidelines, concerns around drug efficacy, adverse events, and overall treatment satisfaction.

PMID:42478307 | DOI:10.1708/4747.47642

Aust Endod J. 2026 Jul 21. doi: 10.1111/aej.70110. Online ahead of print.

ABSTRACT

This study evaluated the effects of kinematics (reciprocating vs. continuous rotation) and rotational speed (350 vs. 1200 rpm) on filling removal, canal transportation, and apical extrusion during retreatment of curved root canals. Vertucci type II mesial roots of mandibular molars were prepared, filled, and scanned by micro-computed tomography (micro-CT). After 30 days, specimens were assigned to four groups (n = 15): WOrec, WOctn, PF350, and PF1200. Retreatment time was recorded, and micro-CT was used to assess filling removal, canal transportation, and apical extrusion. Data were statistically evaluated and revealed that all systems significantly reduced the amount of filling material (p < 0.05). PF1200 and WOctn showed superior removal compared with PF350 and WOrec, respectively (p < 0.05). No differences were observed in extrusion (p > 0.05). Increased canal transportation occurred only in the mesiolingual canal with WOctn and PF1200 (p < 0.05). Higher speed and continuous rotation improved efficiency without increasing extrusion but resulted in greater transportation.

PMID:42478289 | DOI:10.1111/aej.70110

J Eur Acad Dermatol Venereol. 2026 Jul 21. doi: 10.1111/jdv.70594. Online ahead of print.

ABSTRACT

BACKGROUND: We report the first study of anumigilimab, a novel anti-G-CSFR antibody, in patients with neutrophil-driven skin diseases [hidradenitis suppurativa (HS) and palmoplantar pustulosis (PPP)].

METHODS: This phase 1b, open-label, repeat-dose study (NCT03972280) comprised 15-week treatment and 9-week follow-up periods. Enrolled patients had International HS Severity Score System (IHS4) score ≥4 or PPP Area and Severity Index (ppPASI) score ≥12. After ≥10 patients completed anumigilimab 0.3 mg/kg IV at 21-day intervals (Cohort 1), pharmacokinetic/pharmacodynamic modelling determined the Cohort 2 dose (0.6 mg/kg). Primary endpoints were treatment-emergent adverse events (TEAEs). Secondary endpoints were pharmacokinetics and immunogenicity. Exploratory endpoints were pharmacodynamics and clinical response.

RESULTS: Of 39 patients (HS, n = 22; PPP, n = 17), 33 patients (84.6%) experienced 198 TEAEs. Sixteen patients (41.0%) experienced 70 anumigilimab-related TEAEs; the most common were fatigue and neutropenia (both n = 7), which resolved spontaneously, and no association between neutropenia and infections was observed. No deaths or serious treatment-related TEAEs occurred. Presence of antidrug antibodies was negligible. Anumigilimab exposure and absolute neutrophil count reduction (pharmacodynamic endpoint) were dose dependent. In signal-finding exploratory analyses, 57.9% of patients with HS (n = 11/19 with data at Week 15) achieved ≥50% HS Clinical Response, IHS4 score decreased by 40.3%, and patients with PPP experienced a 40.4% reduction in ppPASI score. These clinical responses were not dose dependent, possibly due to imbalanced baseline characteristics and small sample size.

CONCLUSIONS: Anumigilimab was generally well tolerated in patients with HS or PPP, with no serious treatment-related safety concerns, and demonstrated dose-dependent pharmacology. While clinical responses in HS and PPP were observed, it should be noted that these observations were exploratory and signal-finding in nature. Importantly, the study was not powered to statistically confirm efficacy and lacked a placebo control, underscoring the need for future randomized, placebo-controlled trials to validate these preliminary signal-finding observations.

PMID:42478283 | DOI:10.1111/jdv.70594

Breastfeed Med. 2026 Jul 21:15568253261468535. doi: 10.1177/15568253261468535. Online ahead of print.

ABSTRACT

BACKGROUND: Prenatal intention to exclusively breastfeed is a proximal determinant of later infant-feeding behavior and may be shaped by breastfeeding self-efficacy, depressive symptoms, and perceived social support.

MATERIALS AND METHODS: Baseline prenatal data were analyzed from 516 third-trimester pregnant women enrolled in an ongoing prospective cohort at a tertiary university hospital in Istanbul, Türkiye. Exclusive breastfeeding intention was measured with the Infant Feeding Intentions (IFI) scale. Breastfeeding self-efficacy and depressive symptoms were assessed with the Prenatal Breastfeeding Self-Efficacy Scale-Short Form (PBSES-SF) and Edinburgh Postnatal Depression Scale (EPDS), respectively. Social support was evaluated as aggregate spouse/partner or close-family support and further characterized by emotional, informational, and practical/domestic support indicators.

RESULTS: Mean IFI, PBSES-SF, and EPDS scores were 13.12 ± 2.34, 32.23 ± 3.62, and 5.88 ± 2.05, respectively. Aggregate social support was reported by 495 participants (95.9%). Emotional, informational, and practical/domestic support were reported by 488 (94.6%), 446 (86.4%), and 465 (90.1%) participants, respectively, and were associated with higher IFI scores in bivariate analyses. In multivariable regression, PBSES-SF, EPDS, planned pregnancy, prior breastfeeding experience, and employment were independently associated with IFI; aggregate social support was not. The PBSES-SF × EPDS interaction was statistically significant.

CONCLUSION: Exclusive breastfeeding intention was associated with breastfeeding self-efficacy, depressive symptoms, selected experiential factors, and functional support indicators. Integrated antenatal counseling should address breastfeeding confidence, maternal mental health, and the quality of support available during late pregnancy.

PMID:42478261 | DOI:10.1177/15568253261468535

Disaster Med Public Health Prep. 2026 Jul 21;20:e85. doi: 10.1017/dmp.2026.10348.

ABSTRACT

BACKGROUND: Floods are increasing with climate change, and evacuating medically vulnerable people receiving home healthcare remains challenging. Patients dependent on medical devices and long-term care face complex challenges throughout the evacuation process. However, key factors influencing successful evacuation and effective support strategies remain underexamined. This study aimed to identify such factors and essential support measures across evacuation phases.

METHODS: Semi-structured interviews were conducted with 13 participants-family caregivers, healthcare providers, and municipal officials-from July 2022 to March 2023 in 3 Japanese regions. Snowball sampling was used via medical administrative institutions. Thematic analysis followed COREQ guidelines, focusing on three phases: preparation, evacuation, and post-evacuation. Ethics approval was obtained (MG2022-01).

RESULTS: Preparation showed heterogeneous readiness: some services had hazard maps and manuals/BCPs, whereas household engagement was limited and operationalization was constrained by resources. During evacuation, participants described transport and staffing limitations, difficulty in moving medical equipment, and uncertainty about feasible options, with occasional consideration of vertical evacuation. Post-evacuation challenges centered on shelter sanitation and supplies, continuity of medical support, and coordination of support systems.

CONCLUSIONS: A three-phase, multi-stakeholder perspective clarifies how constraints accumulate and informs coordinated planning among municipalities, home-care teams, and families. Limitations include a small, region-specific sample and no direct patient interviews.

PMID:42478258 | DOI:10.1017/dmp.2026.10348