Drexel University

To evaluate the efficacy and safety of conservative (oxygen saturation [Sp o2 ] 88-94% or Pa o2 < 80 mm Hg) vs. liberal oxygen targets (Sp o2 ≥ 94% or Pa o2 ≥ 90 mm Hg) in mechanically ventilated critically ill adults. PubMed, Cochrane CENTRAL, Embase, and ClinicalTrials.gov . We conducted the OXY-BREATHES, a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing conservative vs. liberal oxygen targets in mechanically ventilated ICU patients. Primary outcomes were 90-day mortality and ICU length of stay. Secondary outcomes included ventilator- and vasopressor-free days, renal replacement therapy, nosocomial pneumonia, and cardiac or cerebral ischemic events. Subgroup analyses included patients with sepsis/septic shock and post-cardiac arrest. Data were collected according to study selection criteria. Certainty of evidence was appraised with Grading of Recommendations, Assessment, Development, and Evaluation, and risk of bias with the Cochrane tool. Data were analyzed using a random-effects model. Nine RCTs enrolling 20,447 patients were included. Conservative and liberal targets showed no substantial differences in 90-day (risk ratio [RR], 1.01; 95% CI, 0.94-1.09) or ICU length of stay (mean difference [MD], -0.17; 95% CI, -0.41 to 0.06). Secondary outcomes, including organ support-free days and the incidence of adverse events, were comparable between groups. In subgroup analyses, conservative targets yielded more vasopressor-free days in septic patients (MD, 2.0; p = 0.008) and a potential survival benefit in post-cardiac arrest patients (RR, 0.89; p = 0.05). Certainty of evidence was rated moderate for 90-day mortality, ICU length of stay, vasopressor-free days, and ventilator-free days; low for renal replacement therapy and nosocomial pneumonia; and very low for cerebral and cardiac ischemia due to imprecision and open-label trial designs. Conservative oxygenation is comparable to liberal oxygen targets in mechanically ventilated critically ill patients, with possible advantages in sepsis and post-cardiac arrest. Future condition-specific RCTs are warranted to define optimal ICU oxygen strategies.

Intracranial calcifications are commonly found in adults and may represent either benign or pathological lesions. Conventional imaging modalities detect static macrocalcifications but do not capture molecular microcalcification. In this study, we used 18 F-sodium fluoride (NaF) PET/computed tomography (CT) to idetect intracranial molecular microcalcification. A total of 127 subjects underwent 18 F-NaF PET/CT 90 min following radiotracer injection. Artificial intelligence-based quantification was performed to obtain regions of interest for the brainstem, basal ganglia (caudate and lentiform nuclei), insula, thalamus, and ventricles. Linear regression models were used to correlate NaF mean standardized uptake value (SUV mean ) with various clinical factors. NaF SUV mean was highest in the insula (0.8 ± 0.4) and brainstem (0.8 ± 0.3), while uptake was lowest in the caudate nucleus (0.1 ± 0.1). No differences were found in NaF SUV mean between healthy volunteers and at-risk patients. On multivariate regression, NaF SUV mean directly correlated with age in the brainstem ( β = 0.01, P = 0.01), lentiform nucleus ( β < 0.01, P = 0.02), and ventricles ( β < 0.01, P < 0.01). Male sex inversely correlated with NaF SUV mean in the insula ( β = -0.30, P < 0.01). There was an association between NaF SUV mean and BMI in the brainstem, caudate nucleus, lentiform nucleus, thalamus, and ventricles ( β ≤ 0.01, P < 0.01 in all regions). Thalamic and ventricular NaF SUV mean directly correlated with hypertension on univariate but not multivariate analysis. NaF PET/CT detects intracranial molecular microcalcification that is not visible on conventional CT and may provide insight into pathology associated with this biological process.

Purpose This study aims to address the lack of emphasis within forensic mental health assessment (FMHA) on formal appraisal of race- and ethnicity-related experiences, despite their profound impact on minoritized groups. It provides theoretical and ethical justification for integrating explicit appraisal of race and ethnicity into FMHA. Design/methodology/approach The study conducted a scoping review of 108 existing race- and ethnicity-focused (REF) psychological measures to identify those that are psychometrically sound (i.e. reliable, valid), recent and sufficiently documented for potential use in forensic contexts. Measures were evaluated against these criteria and narrowed down to a final set of 16. Findings Only one measure, the UConn racial/ethnic stress and trauma survey, was deemed currently appropriate for use in FMHA without revision. The remaining 15 require further development or adaptation to meet the standards for forensic application. The study outlines considerations for revising these tools for such use. Research limitations/implications The authors view this publication as a starting point for the further empirical work that will be required to validate revised or newly developed measures for forensic use and to understand how these assessments may influence FMHA outcomes. Social implications Formal inclusion of race and ethnicity appraisals in FMHA may reduce bias, enhance fairness and improve the relevance of forensic evaluations for minoritized individuals. Originality/value To the best of the authors’ knowledge, this is the first study to systematically evaluate race- and ethnicity-related psychological measures for their applicability in FMHA, filling a critical gap in the literature and advancing the discussion of equity and cultural competence in forensic practice.

Bulk tissue rhythms arise from the coordination of thousands of individual cellular oscillations. Bulk rhythm amplitude differences may reflect changes in the amplitude of the underlying cellular oscillators or changes in their temporal coherence. To resolve this fundamental ambiguity, we developed ORPHEUS ( O scillatory R hythm P hase H eterogeneity E stimated U sing S tatistical-moments), an analytical method that quantifies cellular desynchrony by leveraging the unique 12hr rhythmic signature it imparts on intercellular expression variance. After validating ORPHEUS in silico and on data from the mouse suprachiasmatic nucleus (SCN), we applied it to data from the mouse liver and human brain to uncover disease- and pathway-related differences in intercellular synchrony. In both tissues, we found that circadian synchrony is higher in cells and samples with higher MTORC activity. Most critically, we observed a dramatic loss of cellular synchrony in excitatory neurons from subjects with Alzheimer's Disease (AD) dementia. By decoupling the influence of cellular amplitude and synchrony, ORPHEUS introduces a new, interpretable tool for analyzing circadian coordination in time-course single-cell data.

Cocrystallization can be used to tune key drug properties, such as aqueous solubility, without altering molecular structure; however, the space of possible coformers is enormous and design rules are empirical. We present a Bayesian optimization framework that couples Gaussian process (GP) classification and regression that can accelerate cocrystal discovery and solubility enhancement. Starting from 6338 literature-derived binary coformer pairs, vector fingerprints that combine 2D structural information (fragment and MQN fingerprints) with low-cost shape and polarity descriptors were engineered for cocrystal prediction. A GP classifier, trained on an actively constructed training set of ∼1000 coformer pairs selected by uncertainty sampling achieves up to 94% accuracy and Matthews correlation coefficient of 0.79 on a test set of >5000 unseen pairs. Property-driven coformer selection was formulated as a Bayesian optimization problem, using a machine learning model as a surrogate for aqueous solubility and Tanimoto-similarity to guide campaigns across several discovery scenarios. In simulations, the framework rapidly identifies highly soluble cocrystals, typically recovering top-5 candidates after fewer than 10 evaluations. Finally, we validate the workflow experimentally with 12 pharmaceutical and pharmaceutical-like compounds, discovering two new cocrystals, resveratrol + praziquantel and purin-6-amine + thiazole-4-carboxylic acid, with markedly enhanced aqueous solubility. These results demonstrate a practical, data-efficient route to Bayesian optimization for cocrystal design.