Miracle-dz/UniFAR-FTUs huggingface dataset:
Autism spectrum in patients with schizophrenia: correlations with real-life functioning, resilience, and coping styles

Abstract Background Previous researches highlighted among patients with schizophrenia spectrum disorders (SSD) a significant presence of autistic traits, which seem to influence clinical and functional outcomes. The aim of this study was to further deepen the investigation, evaluating how patients with SSD with or without autistic traits may differ with respect to levels of functioning, self-esteem, resilience, and coping profiles. Methods As part of the add-on autism spectrum study of the Italian Network for Research on Psychoses, 164 outpatients with schizophrenia (SCZ) were recruited at eight Italian University psychiatric clinics. Subjects were grouped depending on the presence of significant autistic traits according to the Adult Autism Subthreshold Spectrum (AdAS Spectrum) instrument (“AT group” vs “No AT group”). Other instruments employed were: Autism Spectrum Quotient (AQ), Specific Levels of Functioning (SLOF), Self-Esteem Rating scale (SERS), Resilience Scale for Adults (RSA), and brief-COPE. Results The “AT group” reported significantly higher scores than the “No AT group” on SLOF activities of community living but significantly lower scores on work skills subscale. The same group scored significantly lower also on SERS total score and RSA perception of the self subscale. Higher scores were reported on COPE self-blame, use of emotional support and humor domains in the AT group. Several correlations were found between specific dimensions of the instruments. Conclusion Our findings suggest the presence of specific patterns of functioning, resilience, and coping abilities among SSD patients with autistic traits.
A study on the feasibility of delivering a psychologically-informed ward-based intervention on an acute mental health ward.

Acute mental health inpatient wards have been criticised for being non-therapeutic. The study aimed to test the feasibility of delivering a psychologically-informed intervention in these settings. This single-arm study evaluated the feasibility of clinical psychologists delivering a ward-based psychological service model over a 6-month period on two acute mental health wards. Data were gathered to assess trial design parameters and the feasibility of gathering patient/staff outcome data. Psychologists were able to deliver key elements of the intervention. Baseline staff and patient participant recruitment targets were met. However, there was significant patient attrition at follow-up, with incorrect contact details on discharge being the primary reason. Implementation of a ward-based psychological intervention appears feasible when implemented flexibly. It is feasible to recruit staff and patient participants and to collect staff outcome measures over a six-month period. However, greater efforts need to be taken to trace patient movement following discharge.
Computational evaluation of interactions between olfactory receptor OR2W1 and its ligands

Mammalian olfactory receptors are a family of G protein‒coupled receptors (GPCRs) that occupy a large part of the genome. In human genes, olfactory receptors account for more than 40% of all GPCRs. Several types of GPCR structures have been identified, but there is no single olfactory receptor whose structure has been determined experimentally to date. The aim of this study was to model the interactions between an olfactory receptor and its ligands at the molecular level to provide hints on the binding modes between the OR2W1 olfactory receptor and its agonists and inverse agonists. The results demonstrated the modes of ligand binding in a three-dimensional model of OR2W1 and showed a statistically significant difference in binding affinity to the olfactory receptor between agonists and inverse agonists.
Directed Evolution of Stabilized Monomeric CD19 for Monovalent CAR Interaction Studies and Monitoring of CAR-T Cell Patients

CD19 is among the most relevant targets in cancer immunotherapy. However, its extracellular domain (ECD) is prone to aggregation and misfolding, representing a major obstacle for the development and analysis of CD19-targeted therapeutics. Here, we engineered stabilized CD19-ECD (termed SuperFolder) variants, which also showed improved expression rates and, in contrast to the wild type protein, they could be efficiently purified in their monomeric forms. Despite being considerably more stable, these engineered mutants largely preserved the wild type sequence (>98.8%). We demonstrate that the variant SF05 enabled the determination of the monovalent affinity between CD19 and a clinically approved FMC63-based CAR, as well as monitoring and phenotypic characterization of CD19-directed CAR-T cells in the blood of lymphoma patients. We anticipate that the SuperFolder mutants generated in this study will be highly valuable tools for a range of applications in basic immunology and CD19-targeted cancer immunotherapy.
Effects of long‐term ethanol storage on muscle architecture

Muscle excursion and force potential can be estimated from architectural variables, including mass, volume, fascicle length, and density. These have been collected from fresh specimens, preserved specimens, and sometimes mixed samples of both. However, preservation alters the gross morphology of muscles. This study aims to quantify the effects of long‐term storage on myological properties across a sample of fresh and ethanol preserved Mus musculus specimens ranging in storage time from 16 to 130 years. Masses, volumes, and densities of biceps femoris, quadriceps femoris, and triceps surae were measured, and histological cross‐sections of some specimens were used to evaluate the microscale effects of long‐term fluid preservation. For the remainder of the sample, chemically dissected fascicle lengths were measured to evaluate the fixation effects on the linear dimensions of muscle architecture. Relative muscle mass, volume, fascicle length, average fiber area, and density, and percent fiber area were regressed against years stored in ethanol. Muscle size dropped steeply between fresh and stored samples, ultimately decreasing by 62 and 60%, respectively. These losses correlate with histologically measured shrinking of average muscle fiber area. Density of stored specimens plateaued 5% below that of fresh ones. Although muscles lost mass and volume during ethanol storage, fascicle lengths did not shorten significantly (presumably because they were preserved attached on either end to bone). This study demonstrates that muscle mass, volume, and density of specimens stored long‐term in ethanol should be corrected by factors of 2.64, 2.49, and 1.054 respectively for comparability to fresh specimens.
Obesity Primer for the Practicing Gastroenterologist

With worsening of the obesity pandemic, gastroenterologists will see more patients with this chronic disease. Given the association between obesity and several gastrointestinal conditions and the interplay between obesity pathophysiology and gut hormones, gastroenterologists can play an important role in the management of this disease. Furthermore, because more patients undergo bariatric surgery, an understanding of postsurgical anatomy and medical and endoscopic management of bariatric surgical complications is essential. This article provides clinical tools for the assessment and management of obesity for the general gastroenterologist. Tables containing high-yield practical information are also provided for quick reference.
High‐throughput identification of conditional MHCI ligands and scaled‐up production of conditional MHCI complexes

Despite the need to monitor the impact of Cancer Immunotherapy (CI)/Immuno‐Oncology (IO) therapeutics on neoantigen‐specific T‐cell responses, very few clinical programs incorporate this aspect of immune monitoring due to the challenges in high‐throughput (HTP) generation of Major Histocompatibility Complex Class I (MHCI) tetramers across a wide range of HLA alleles. This limitation was recently addressed through the development of MHCI complexes with peptides containing a nonnatural UV cleavable amino acid (conditional MHCI ligands) that enabled HTP peptide exchange upon UV exposure. Despite this advancement, the number of alleles with known conditional MHCI ligands is limited. We developed a novel workflow to enable identification and validation of conditional MHCI ligands across a range of HLA alleles. First, known peptide binders were screened via an enzyme‐linked immunosorbent assay (ELISA) assay. Conditional MHCI ligands were designed using the highest‐performing peptides and evaluated in the same ELISA assay. The top performers were then selected for scale‐up production. Next‐generation analytical techniques (LC/MS, SEC‐MALS, and 2D LC/MS) were used to characterize the complex after refolding with the conditional MHCI ligands. Finally, we used 2D LC/MS to evaluate peptide exchange with these scaled‐up conditional MHCI complexes after UV exposure with validated peptide binders. Successful peptide exchange was observed for all conditional MHCI ligands upon UV exposure, validating our screening approach. This approach has the potential to be broadly applied and enable HTP generation of MHCI monomers and tetramers across a wider range of HLA alleles, which could be critical to enabling the use of MHCI tetramers to monitor neoantigen‐specific T‐cells in the clinic.
Ultrasonic investigations in ternary liquid mixtures of substituted benzenes with acetophenone at different temperatures

The ultrasonic velocity, density and viscosity have been measured for the ternary mixtures of substituted benzenes such as chlorobenzene, bromobenzene and nitrobenzene with acetophenone in 1-butanol at 303, 308 and 313 K. The experimental data have been used to calculate the acoustical parameters namely adiabatic compressibility (β), free length (L f ), free volume (V f ), internal pressure (π i ), acoustic impedance (Z) and molar volume (V m ). Some of the above excess parameters have been evaluated and fitted to Redlich-Kister polynomials. It is eventually observed that molecular association between acetophenone and 1-butanol is through hydrogen bonding and substituted benzenes through strong dipole-dipole interactions. The formation of donor-acceptor complexes also observed in the present study.
Functional analysis of XRCC4 mutations in reported microcephaly and growth defect patients in terms of radiosensitivity

Abstract Non-homologous end joining is one of the main pathways for DNA double-strand break (DSB) repair and is also implicated in V(D)J recombination in immune system. Therefore, mutations in non-homologous end-joining (NHEJ) proteins were found to be associated with immunodeficiency in human as well as in model animals. Several human patients with mutations in XRCC4 were reported to exhibit microcephaly and growth defects, but unexpectedly showed normal immune function. Here, to evaluate the functionality of these disease-associated mutations of XRCC4 in terms of radiosensitivity, we generated stable transfectants expressing these mutants in XRCC4-deficient murine M10 cells and measured their radiosensitivity by colony formation assay. V83_S105del, R225X and D254Mfs*68 were expressed at a similar level to wild-type XRCC4, while W43R, R161Q and R275X were expressed at even higher level than wild-type XRCC4. The expression levels of DNA ligase IV in the transfectants with these mutants were comparable to that in the wild-type XRCC4 transfectant. The V83S_S105del transfectant and, to a lesser extent, D254Mfs*68 transfectant, showed substantially increased radiosensitivity compared to the wild-type XRCC4 transfectant. The W43R, R161Q, R225X and R275X transfectants showed a slight but statistically significant increase in radiosensitivity compared to the wild-type XRCC4 transfectant. When expressed as fusion proteins with Green fluorescent protein (GFP), R225X, R275X and D254Mfs*68 localized to the cytoplasm, whereas other mutants localized to the nucleus. These results collectively indicated that the defects of XRCC4 in patients might be mainly due to insufficiency in protein quantity and impaired functionality, underscoring the importance of XRCC4’s DSB repair function in normal development.
A multi-center survey on the postpartum mental health of mothers and attachment to their neonates during COVID-19 in Hubei Province of China

Background There is an emerging literature on the mental health of both pre- and post-partum mothers during the coronavirus disease 2019 (COVID-19) pandemic. Methods As of April 1, 2020, 23 mothers confirmed with COVID-19, 15 mothers suspected with COVID-19 but with negative polymerase chain reaction tests, and 33 mothers without COVID-19 (Control Group) were recruited for a study from Hubei Province in China. The Maternal Postnatal Attachment Scale (MPAS), the Zung Self-rating Anxiety Scale, and the Zung Self-rating Depression Scale were applied to investigate the attachment of mothers to their neonates and the postpartum mental health of mothers within the first 3 months after delivery (between 20 to 89 days). Results The period of mother-child separation among the confirmed group (33.9±20.9 days) was significantly longer than that of suspected group (16.7±12.2 days) and control group (10.7±8.4 days). The total score of the MPAS in mothers confirmed with COVID-19 (45.5±4.2) was significantly lower (indicating less mother-child attachment) than that in the suspected (50.5±4.7) and control (48.8±4.6) groups. A negative correlation was noted between the mother-child separation time and the MPAS scores, including the subscale scores of attachment (MPAS acore: Spearman’s ρ =−0.33, 95% CI: −0.095 to −0.538, P=0.005; Subscale score of attachment: Spearman’s ρ =−0.40, 95% CI: −0.163 to −0.592, P=0.001). The incidence of postpartum anxiety in the confirmed, suspected and control groups was 4.3%, 6.7% and 12.1%, respectively; and the incidence of postpartum depression was 39.1%, 33.3% and 30.3%, respectively. No significant difference was found with regards to maternal postpartum anxiety and depression among the three groups. Conclusions Decreased mother-child attachment found among mothers confirmed with COVID-19, indicates that further intervention is needed to ensure mother-child interaction to appropriately develop attachment. Mother-child attachment experienced disruption due to prolonged mother-child separation necessitated by the COVID-19 management protocol, which needs to be revised to reduce prolonged mother-child separation. Additionally, mothers with and without COVID-19 suffered a high incidence of depression, which warrants further mental health investment for pregnant mothers during the COVID-19 pandemic.
Nurse Faculty Experiences Teaching Chronic Illness Self-Management Concepts: An Exploratory Study

Supplemental digital content is available in the text. Abstract AIM The aim of the study was to explore how nurse faculty prepare students to teach chronic disease self-management. BACKGROUND Self-management addresses patient activities in response to a change in baseline health. Evidence suggests nurses may not be educated on how to engage patients in chronic disease self-management. METHOD This qualitative study used semistructured interviews to explore experiences of 13 nurse faculty across three universities in preparing nursing students to address self-management concepts for adults living with chronic disease. RESULTS Three themes emerged from 104 identified significant statements: conceptualizing and valuing chronic disease self-management in nursing education, making chronic disease self-management fit, and sharing the impact of health care reform on chronic disease care. CONCLUSION Self-management is regarded as highly complex and evolving. As such, nursing education curricula must also evolve to emphasize successful approaches to preventing chronic disease and incorporating chronic disease self-management and behavior modification in the curriculum.
Detecting and Reporting Deceptive Prescription Drug Promotion: Differences Across Consumer and Physician Audiences and by Number and Type of Deceptive Claims and Tactics

ABSTRACT The U.S. Food and Drug Administration’s (FDA) Bad Ad program provides an avenue for healthcare providers to report false or misleading prescription drug promotion. Yet, whether healthcare providers can detect such promotion, and whether they believe it should be reported to FDA, remain open questions. Consumer audiences may also be capable of detecting such promotion and believe it should be reported, but even less is known about capability and belief in this population. Across two experiments using mock pharmaceutical websites, this research investigated capability to detect and inclination to report deceptive prescription drug promotion among a sample of primary care physicians and consumers. Study 1 varied the number of deceptive claims and tactics on a website for a chronic pain medication, operationalized as none, two, or five. Study 2 varied the type of deceptive content on a website for a weight loss medication, operationalized as none, implicit, or explicit. Findings reveal that, in line with expectations from FDA’s Bad Ad program, physicians can detect deceptive promotion and tend to believe it should be reported. Consumers are also capable of detecting deceptive promotion and tend to believe it should be reported, but their capabilities and beliefs regarding reporting are generally lower.
Genome-wide analysis in Escherichia coli unravels a high level of genetic homoplasy associated with cefotaxime resistance

Cefotaxime (CTX) is a third-generation cephalosporin (3GC) commonly used to treat infections caused by Escherichia coli . Two genetic mechanisms have been associated with 3GC resistance in E. coli . The first is the conjugative transfer of a plasmid harbouring antibiotic-resistance genes. The second is the introduction of mutations in the promoter region of the ampC β-lactamase gene that cause chromosome-encoded β-lactamase hyperproduction. A wide variety of promoter mutations related to AmpC hyperproduction have been described. However, their link to CTX resistance has not been reported. We recultured 172 cefoxitin-resistant E. coli isolates with known CTX minimum inhibitory concentrations and performed genome-wide analysis of homoplastic mutations associated with CTX resistance by comparing Illumina whole-genome sequencing data of all isolates to a PacBio sequenced reference chromosome. We mapped the mutations on the reference chromosome and determined their occurrence in the phylogeny, revealing extreme homoplasy at the −42 position of the ampC promoter. The 24 occurrences of a T at the −42 position rather than the wild-type C, resulted from 18 independent C>T mutations in five phylogroups. The −42 C>T mutation was only observed in E. coli lacking a plasmid-encoded ampC gene. The association of the −42 C>T mutation with CTX resistance was confirmed to be significant (false discovery rate <0.05). To conclude, genome-wide analysis of homoplasy in combination with CTX resistance identifies the −42 C>T mutation of the ampC promotor as significantly associated with CTX resistance and underlines the role of recurrent mutations in the spread of antibiotic resistance.
Depression in patients with epilepsy during the COVID‐19 pandemic based on longitudinal self‐reporting

Abstract Objective. The current study screened major depression in people with epilepsy (PWE) during the epidemic of the novel coronavirus‐related disease COVID‐19, in order to identify whether the outbreak generated negative psychological impact on PWE. Methods. A Chinese version of the Neurological Disorders Depression Inventory for Epilepsy (C‐NDDI‐E), a self‐reporting depression inventory, was applied for rapid detection of major depression. Assessment was carried out online during three different periods (prior to, during, and after the outbreak of COVID‐19), with the aim of identifying changes in prevalence of depression and associated risk factors. Results. A total of 158 PWE were recruited into the study (48.7% female). The questionnaire completion rates were 94.3% and 70.9% during and after the outbreak, respectively. The prevalence of depression prior to the epidemic, as the baseline, was 34.8% and increased to 42.3% during the period of the epidemic. Towards the end of the outbreak, the prevalence declined towards the baseline (36.6%). Factors such as living alone (OR = 4.022, 95% CI: 1.158‐13.971, P = 0.028) and active seizures before the epidemic (OR = 2.993, 95% CI: 1.197‐7.486, P = 0.019) were associated with depression during the epidemic. Monotherapy appeared to be protective against depression (OR = 0. 105, 95% CI: 0.047‐0.235, P <0.001). Significance. Our results suggest that the pandemic exerts negative influence on PWE's mental health. Depression is one of the common psychological disorders that needs greater attention during this extraordinary period.
Varenicline for the Treatment of Cocaine Dependence

Objectives: Varenicline is a partial agonist at the α2β4 and α6β2 nAChR receptors and a full agonist at α7 receptors. Both α7 and α6β2 receptors are implicated in the neural reward circuitry activated by cocaine use. A preliminary clinical trial suggested that varenicline treatment reduced cocaine use. This trial was intended to replicate and extend the findings of the previous trial. Methods: This was a 12-week, double-blind, placebo-controlled clinical trial involving 156 subjects with DSM IV cocaine dependence. Subjects received up to 2 mg of varenicline or identical placebo daily along with weekly relapse prevention psychotherapy. The primary outcome measure was cocaine use measured by thrice-weekly urine drug screens. Additional outcome measures included end of study cocaine abstinence, cocaine craving, cocaine withdrawal symptom severity, cigarette use, and global improvement measure by the Clinical Global Improvement Scale. Results: End of study cocaine abstinence, measured by urine drug screens during the last 3 weeks of the trial, was not different between groups (8% in the varenicline treated subjects and versus 9% in placebo-treated subjects). Generalized estimating equations analysis of urine drug screen results showed no significant difference between groups in cocaine abstinence over the 12 weeks of the trial. There were no significant differences between the 2 groups in cocaine craving or cocaine withdrawal symptom severity. Varenicline was well-tolerated. There were no medication-associated serious adverse events. Conclusions: Varenicline plus cognitive-behavioral therapy does not seem to be an efficacious treatment for cocaine dependence.