Miracle-dz/UniFAR-FTUs huggingface dataset:
Development of Electronic Health Record–Based Prediction Models for 30-Day Readmission Risk Among Patients Hospitalized for Acute Myocardial Infarction

Key Points Question Can machine learning deployed in electronic health records be used to improve readmission risk estimation for patients following acute myocardial infarction? Findings In this cohort study examining externally validated machine learning risk models for 30-day readmission of 10 187 patients following hospitalization for acute myocardial infarction, good discrimination performance was noted at the development site, but the best discrimination did not result in the best calibration. External validation yielded significant declines in discrimination and calibration. Meaning The findings of this study highlight that robust calibration assessments are a necessary complement to discrimination when machine learning models are used to predict post–acute myocardial infarction readmission; challenges with data availability across sites, even in the presence of a common data model, limit external validation performance.
Single‐particle motions in liquid water. II. The hydrodynamic model

A compilation is made of available data on the self‐diffusion coefficient, the dielectric relaxation time, and the NMR orientational time constant for liquid water under 1 atm pressure at temperatures between 273 and 333 K. The data then are examined in a self‐consistent manner for their adherence to a simple hydrodynamic model of single‐particle motions. In this model, a water molecule is treated as a rigid sphere with the van der Waals radius which carries out diffusive translations and rotations while surrounded by a viscous continuum. Arbitrary boundary conditions on the velocity field in the surrounding liquid are permitted at the sphere–liquid interface. It is found that the measured coefficient of self‐diffusion in liquid water is in quantitative agreement with the predictions of the hydrodynamic model under near‐slip boundary conditions, whereas the experimental values of the two orientational time constants are described well by the model under stick boundary conditions. Physical arguments are pr.
Childhood poverty and psychological well-being: The mediating role of cumulative risk exposure

Abstract The current study assessed whether the proportion of childhood (age 0–9 years) in poverty altered the developmental trajectories (ages 9–24) of multimethodological indicators of psychological well-being. In addition, we tested whether exposure to cumulative risk over time mediated the association between poverty exposure and psychological well-being. Measures of psychological well-being included internalizing and externalizing symptoms, a behavioral index of learned helplessness (task persistence), and chronic physiological stress (allostatic load). Exposure to poverty during childhood predicted the trajectory of each development outcome: individuals with more poverty exposure during childhood showed (a) relatively high levels of internalizing symptoms that diminished more slowly with maturation, (b) relatively high levels of externalizing symptoms that increased faster over time, (c) less task persistence indicative of greater learned helplessness, and (d) higher levels of chronic physiological stress which increased faster over time relative to persons with less childhood poverty exposure. Trajectories of cumulative risk exposure from physical and psychosocial surroundings from 9–24 years accounted for the association between childhood poverty and the growth curves of internalizing and externalizing symptoms but not for learned helplessness or chronic physiological stress. Additional sensitivity analyses indicate that early childhood disadvantage is particularly problematic for each outcome, except for internalizing symptoms which seem sensitive to the combination of early and lifetime poverty exposure. We also explored whether domains of cumulative risk as well as two alternatives, maternal sensitivity or family cohesion, functioned as mediators. Little evidence emerged for any of these alternative mediating constructs.
Activation of Nrf2 decreases bile acid concentrations in livers of female mice

Abstract 1. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a master regulator of oxidative/electrophilic stress. Studies suggest a role of Nrf2 in regulating bile acid (BA) metabolism in male mice. However, whether Nrf2 is important for BA homeostasis in female mice remains undefined. In this study, we systematically investigated the effect of Nrf2 activation, either through CDDO-imidazolide (CDDO-Im) treatment or genetic modulation of Kelch-like ECH associating protein 1 (Keap1), on BA homeostasis in female mice. 2. Both pharmacological and genetic Nrf2 activation increased mRNA levels of multidrug resistance‐associated protein 2 and 3 (Mrp2 and Mrp3), two Nrf2 target genes, in livers and ilea of female mice. Both pharmacological and genetic activation of Nrf2 decreased BA concentrations in the liver, which did not appear to be due to increased biliary BA excretion or decreased ileal BA absorption. Importantly, both pharmacological and genetic activation of Nrf2 downregulated hepatic Cyp7a1 mRNA, which might be attributable to the upregulation of the Fxr-Fgf15 signalling in the ileum. 3. To conclude, Nrf2 activation lowers BA concentrations in livers of female mice, which appears to be attributable to the decreased hepatic BA synthesis.
SYNTHESIS AND REACTIONS OF SOME THIENOPYRIDINE DERIVATIVES

Abstract Substituted thieno[2,3-b]pyridines (VIII-XII) were prepared by ring closure of the corresponding S-alkylated derivatives (II-VI). Thieno[2,3-b]pyridine-2-carbohydrazide XIII was interacted with some reagents afforded the expected pyridothienopyrirnidines (XIV-XVI). Also, the carboazide XVII undergo Curtius rearrangement giving imidazolothienopyridine (XVIII). The carboxarnide derivatives (X-XII) interacted with CS2 giving pyridothienopyrirnidines (XX-XXII), while interaction with nitrous acid, pyridothienotriazines (XXIII-XXV) were produced.
Etude structurale d'un hydrate 10 Å instable de kaolinite

The treatment of KGa-1 kaolinite with dimethyl sulfoxide and ammonium fluoride heated at 383 K provides an unstable hydrated phase characterized by a 10 A basal distance. When air-dried, this hydrate gives a dehydrated phase at 7.15 A. The aim of this work is to determine the structural characteristics of this hydrate. The method used to characterize this hydrate is based on the comparison between experimental and calculated X-ray diffraction profiles. This study is achieved in two steps: the study of 00l reflections enabled the determination of the number of intercalated water molecules, their positions and the stacking mode along the normal to the (a, b) plane; and the study of the hkl reflections with h and/or k ≠ 0 enabled the determination of the stacking mode and the positions of water molecules in the (a, b) plane. The unstable hydrate is characterized by two water molecules per Al2Si2O5(OH)4 unit situated at z1 = z2 = 7.57 A. Two adjacent layers are translated with respect to each other with TI = −0.155a + 0.13b + 10n.
Area-specific thalamocortical synchronization underlies the transition from motor planning to execution

Significance Thalamocortical interactions are a key component of normal brain functions both in sensory and motor areas. The fact that TC connectivity is excitatory has led to the suggestion that its main role is positively driving motor cortical activity. Here we show that the motor thalamus has contrasting, area-dependent interactions with cortical sites, such that it can either enhance or suppress motor cortical variability. The TC interactions with the primary motor vs. the premotor cortex put the motor thalamus in an ideal position to promote the transition from a motor plan to motor action and serve as an important driver of movement initiation. We studied correlated firing between motor thalamic and cortical cells in monkeys performing a delayed-response reaching task. Simultaneous recording of thalamocortical activity revealed that around movement onset, thalamic cells were positively correlated with cell activity in the primary motor cortex but negatively correlated with the activity of the premotor cortex. The differences in the correlation contrasted with the average neural responses, which were similar in all three areas. Neuronal correlations reveal functional cooperation and opposition between the motor thalamus and distinct motor cortical areas with specific roles in planning vs. performing movements. Thus, by enhancing and suppressing motor and premotor firing, the motor thalamus can facilitate the transition from a motor plan to execution.
Robustness of the microtubule network self-organization in epithelia

Robustness of biological systems is crucial for their survival, however, for many systems its origin is an open question. Here, we analyze one subcellular level system, the microtubule cytoskeleton. Microtubules self-organize into a network, along which cellular components are delivered to their biologically relevant locations. While the dynamics of individual microtubules is sensitive to the organism’s environment and genetics, a similar sensitivity of the overall network would result in pathologies. Our large-scale stochastic simulations show that the self-organization of microtubule networks is robust in a wide parameter range in individual cells. We confirm this robustness in vivo on the tissue-scale using genetic manipulations of Drosophila epithelial cells. Finally, our minimal mathematical model shows that the origin of robustness is the separation of time-scales in microtubule dynamics rates. Altogether, we demonstrate that the tissue-scale self-organization of a microtubule network depends only on cell geometry and the distribution of the microtubule minus-ends.
Effective Prediction of Prostate Cancer Recurrence through the IQGAP1 Network

Simple Summary Prostate cancer (PC) is a leading cause of cancer death in men in the developed countries. PC mortality is related to tumor relapse following curative therapy to primary tumors. It is thus essential to effectively assess the recurrence risk for personalized patient management. However, the current assessment capacity remains insufficient. We examined tumors produced in animals and samples derived from more than 1100 patients. A unique set of gene expression was observed following PC progression and a multigene panel consisting of 27 genes (Sig27gene) was constructed. Sig27gene is novel and robustly predicts PC relapse in two independent patient populations (n = 492 and n = 140) at p < 2 × 10−16. Sig27gene remains an independent risk factor of PC recurrence after adjusting for multiple clinical features. The novel and robust nature of Sig27gene support its translational potential to evaluate the risk of PC relapse in patients with primary PC. Abstract IQGAP1 expression was analyzed in: (1) primary prostate cancer, (2) xenografts produced from LNCaP, DU145, and PC3 cells, (3) tumor of PTEN−/− and TRAMP mice, and (4) castration resistant PC (CRPC) produced by LNCaP xenografts and PTEN−/− mice. IQGAP1 downregulations occurred in CRPC and advanced PCs. The downregulations were associated with rapid PC recurrence in the TCGA PanCancer (n = 492, p = 0.01) and MSKCC (n = 140, p = 4 × 10−6) cohorts. Differentially expressed genes (n = 598) relative to IQGAP1 downregulation were identified with enrichment in chemotaxis, cytokine signaling, and others along with reductions in immune responses. A novel 27-gene signature (Sig27gene) was constructed from these DEGs through random division of the TCGA cohort into a Training and Testing population. The panel was validated using an independent MSKCC cohort. Sig27gene robustly predicts PC recurrence at (hazard ratio) HR 2.72 and p < 2 × 10−16 in two independent PC cohorts. The prediction remains significant after adjusting for multiple clinical features. The novel and robust nature of Sig27gene underlie its great translational potential as a prognostic biomarker to predict PC relapse risk in patients with primary PC.
Sexual dimorphism in cancer: insights from transcriptional signatures in kidney tissue and renal cell carcinoma

Abstract Sexual dimorphism in cancer incidence and outcome is widespread. Understanding the underlying mechanisms is fundamental to improve cancer prevention and clinical management. Sex disparities are particularly striking in kidney cancer: across diverse populations, men consistently show unexplained 2-fold increased incidence and worse prognosis. We have characterized genome-wide expression and regulatory networks of 609 renal tumors and 256 non-tumor renal tissues. Normal kidney displayed sex-specific transcriptional signatures, including higher expression of X-linked tumor suppressor genes in women. Sex-dependent genotype–phenotype associations unraveled women-specific immune regulation. Sex differences were markedly expanded in tumors, with male-biased expression of key genes implicated in metabolism, non-malignant diseases with male predominance and carcinogenesis, including markers of tumor infiltrating leukocytes. Analysis of sex-dependent RCC progression and survival uncovered prognostic markers involved in immune response and oxygen homeostasis. In summary, human kidney tissues display remarkable sexual dimorphism at the molecular level. Sex-specific transcriptional signatures further shape renal cancer, with relevance for clinical management.
Safety, Immunogenicity, and Protective Efficacy of a Chimeric A/B Live Attenuated Influenza Vaccine in a Mouse Model

Influenza A and B viruses cause significant morbidity and mortality worldwide. Current influenza vaccines are composed of three or four strains: A/H1N1, A/H3N2, and B (Victoria and Yamagata lineages). It is of great interest if immunization against both type A and B influenza viruses can be combined in a single vaccine strain, thus reducing the cost of vaccine production and the possibility of strain interference within the multicomponent vaccine. In the current study, we developed an experimental live cold-adapted influenza intertype reassortant (influenza A and B) vaccine on the live attenuated influenza vaccine (LAIV) A/Leningrad/134/17/57 backbone. Hemagglutinin (HA) and neuraminidase (NA) functional domains were inherited from the influenza B/Brisbane/60/2008 strain, whereas their packaging signals were substituted with appropriate fragments of influenza A virus genes. The recombinant A/B virus efficiently replicated in eggs and Madin–Darby Canine Kidney (MDCK) cells under optimal conditions, temperature-sensitive phenotype was maintained, and its antigenic properties matched the influenza B parental virus. The chimeric vaccine was attenuated in mice: after intranasal immunization, viral replication was seen only in nasal turbinates but not in the lungs. Immunological studies demonstrated the induction of IgG antibody responses against the influenza A and B virus, whereas hemagglutination inhibition (HAI) and neutralizing antibodies were detected only against the influenza B virus, resulting in significant protection of immunized animals against influenza B virus challenge. IFNγ-secreting CD8 effector memory T cells (CD44+CD62L−) were detected in mouse splenocytes after stimulation with the specific influenza A peptide (NP366); however, the T-cell response was not sufficient to protect animals against infection with a high-dose mouse-adapted A/California/07/2009 (H1N1pdm09) virus, most probably due to the mismatch of key T-cell epitopes of the H1N1 virus and the LAIV backbone. Overall, generation of the chimeric A/B LAIV virus on a licensed LAIV backbone demonstrated prospects for the development of safe and efficacious vaccine candidates that afford combined protection against both type A and type B influenza viruses; however, further optimization of the T-cell epitope content within the LAIV backbone may be required.
Transcriptomic Signature of Asthma-Chronic Obstructive Pulmonary Disease Overlap in Whole Blood.

There is a subset of patients who present clinically with features of both asthma and chronic obstructive pulmonary disease (COPD), known as asthma–COPD overlap (ACO). Because asthma and COPD may be composed of multiple endotypes (1), characterization of ACO using molecular phenotypes may result in a more specific categorization. Because bronchoscopy is not part of the routine management of COPD, it will be important to identify more easily accessible biomarkers. Therefore, we quantified whole-blood gene expression by RNA sequencing and measured total IgE levels in ACO to identify a transcriptomic profile characteristic of the phenotype and to refine our understanding of molecular mechanisms underlying the disease. The Genetic Epidemiology of COPD (COPDGene) study is a multicenter observational study including 10,192 smokerswith andwithout COPD (2). Complete blood counts and blood for RNA sequencing were collected at the second visit,z5 years after initial recruitment. COPD was defined by a postbronchodilator ratio of forced expiratory volume in 1 second (FEV1) to forced vital capacity,0.7 with FEV1,80% predicted (Global Initiative for Chronic Obstructive Lung Disease stages 2–4). ACO was defined as COPD with self-report of physician-diagnosed asthma before the age of 40, as previously described (3, 4). Gene expression was measured in 1,199 current and 1,456 former smokers including 793 individuals with COPD, 120 subjects with ACO, 79
Cognition-oriented treatments for older adults: A systematic review of the influence of depression and self-efficacy individual differences factors

ABSTRACT The increasing prevalence of cognitive decline, mild cognitive impairment (MCI), and dementia with the aging population has led to scrutiny of the efficacy of cognition-oriented treatments (COTs) aiming to maintain functioning, and delay or prevent further cognitive decline. However, little is known regarding the role of individual differences patient-variables (such as depression, self-efficacy, and motivation) in moderating the efficacy of COTs. This systematic review aimed to identify and analyze COT trials which investigated the relationship between differences in these patient-variables and intervention outcomes for older adults across healthy, MCI, and dementia populations. Of the 4854 studies extracted from the systematic search, 14 were included for analysis. While results were mixed across interventions and populations, on balance, greater depression severity predicted poorer cognitive functioning, and improvement in depressive symptom severity may account for at least part of the cognitive benefits seen at post-intervention. These findings were strongest for studies of MCI populations, with there being limited evidence of a relationship for healthy older adults or those with dementia. Overall, this review demonstrates the need for further investigation into the role of individual differences and clinical variables – particularly depression symptom severity – in attenuating COT outcomes through larger sample, high-quality randomized controlled trials.
A meta‐analysis of functional outcomes in rat sciatic nerve injury models

Rat sciatic nerve injury (PNR) is the most utilized model in studies on peripheral nerve regeneration. However, large animal models are increasingly favored based on the assumption that nerve regeneration in rodents achieves more favorable outcomes than in humans. The purpose of this meta‐analysis was to investigate which rat PNR models are more stringent and should be used before utilizing large animal experimentation.
INTENTIONAL CONTROL OF GENE EXPRESSION BY TEMPERATURE USING THE REPRESSOR-PROMOTER SYSTEM OF BACTERIOPHAGE LAMBDA

Abstract We investigated a gene expression system which could be regulated by temperature manipulation to develop a biological tool for intentional control of microbial processes. For this purpose we used a plasmid, pSY100-5, harbouring the β-galactosidase gene (lacZ) whose expression was directed by a tandem promoter-operator, PROR-PLOL, of bacteriophage lambda along with a temperature sensitive repressor, cI857. β-Galactosidase was produced at a rate depending on the cultivation temperature between 36°C and 42°C. The induction and repression of the β-galactosidase gene could be regulated by shifting up and down the cultivation temperature, respectively. Measurement of the amount of mRNA specific for β-galactosidase revealed that the switching on and off of the production was directed at the transcriptional level. We designed a new cultivation system consisting of a conventional stirred fermentor controlled at 30°C and a plate heat exchanger type (PHE) fermentor controlled at 42°C. By controlling the res.
Biodegradable Polyurethane Elastomers for Biomedical Applications – Synthesis Methods and Properties

Biodegradable polyurethane elastomers (BioEPUR) are becoming increasingly important as biomaterials because they have excellent chemical, physico-mechanical and biological properties. This review presents the recent developments on BioEPUR and their potential applications in the biomedical and pharmaceutical fields. The aim of this work is to present an overview of the various methods of synthesis and properties of biomedical BioEPUR. Polyurethanes-based aliphatic or cycloaliphatic diisocyanates and polyesters, poly(ester-carbonate)s or copolymers of heterocyclic monomers were discussed. GRAPHICAL ABSTRACT
Microscopical Investigations of PEDOT:PSS Thin Films

Electron microscopy studies are used to explore the morphology of thin poly(3,4‐ethylenedioxythiophene) and polystyrene sulfonate acid (PEDOT:PSS) films. The figures show that the films are composed of grains with diameters in the range of about 50 nm. Energy dispersive X‐ray spectroscopy analysis reveals that individual grains have a PEDOT‐rich core and a PSS‐rich shell with a thickness of about 5–10 nm. Atomic force microscopy (AFM) is then used to analyze the topography of fracture surfaces of ruptured PEDOT:PSS tensile specimens. These AFM scans also show that the films are composed of grains dispersed in a matrix. The investigations presented herein yield a picture of PEDOT:PSS morphology with unprecedented clarity.
Single Crystal X-Ray Analyses of a Series of Hexamethylphosphoramide-Coordinated Complexes of Rare Earth Triflates: Existence of Tetrad Effects in the Coordinate Bonds

The molecular structures of [M(OTf)2(hmpa)4]OTf·CHCl3(OTf = OSO2CF3; M = Y, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, Lu), [Sc(OTf)2(hmpa)4]OTf, and [La(η2-OTf)(OTf)(hmpa)4]OTf·CHCl3 were accurately determined by single crystal X-ray analyses. Tetrad effects are manifested in the series of the coordinate bond lengths.