Miracle-dz/UniFAR-FTUs huggingface dataset:
Real-World Experience with Bezlotoxumab for Prevention of Recurrence of Clostridioides difficile Infection

Bezlotoxumab is marketed for the prevention of recurrent Clostridioides difficile infection (rCDI). Its high cost could be determining its prescription to a different population than that represented in clinical trials. The objective of the study was to verify the effectiveness and safety of bezlotoxumab in preventing rCDI and to investigate factors related to bezlotoxumab failure in the real world. A retrospective, multicentre cohort study of patients treated with bezlotoxumab in Spain was conducted. We compared the characteristics of cohort patients with those of patients treated with bezlotoxumab in the pivotal MODIFY trials. We assessed recurrence rates 12 weeks after completion of treatment against C. difficile, and we analysed the factors associated with bezlotoxumab failure. Ninety-one patients were included in the study. The cohort presented with more risk factors for rCDI than the patients included in the MODIFY trials. Thirteen (14.2%) developed rCDI at 12 weeks of follow-up, and rCDI rates were numerically higher in patients with two or more previous episodes (25%) than in those who had fewer than two previous episodes of C. difficile infection (CDI) (10.4%); p = 0.09. There were no adverse effects attributable to bezlotoxumab. Despite being used in a more compromised population than that represented in clinical trials, we confirm the effectiveness of bezlotoxumab for the prevention of rCDI.
Perceived Factors of Stress and Its Outcomes among Hotel Housekeepers in the Balearic Islands: A Qualitative Approach from a Gender Perspective

Tourism is the main economic sector in the Balearic Islands (Spain) and hotel housekeepers (HHs) are a large occupational group, in which stress is becoming a major issue. This study aims at exploring in-depth factors perceived as stressors by HHs and key-informants, and their effects on work-life balance (WLB). A qualitative design with phenomenological approach was used, conducting six focus groups with 34 HHs and 10 individual interviews with key-informants. Results were analyzed adopting the job demands-resources model and a gender perspective. High demands, e.g., work overload, time pressure, physical burden…, lack of enough resources and little control, derived from role conflict, unexpected events…, were the most important factors explaining HHs’ stress. Additionally, this imbalance was perceived as leading to health problems, mainly musculoskeletal disorders. Working schedule was mentioned as a facilitator to WLB, whereas an imbalance between job demands and resources led to work-home conflict, preventing them from enjoying leisure time. Multiple roles at work and at home increased their stress. HHs experienced their job as invisible and unrecognised. Regarding practical implications, our recommendations for hotel organization include reducing workload and increasing resources, which would improve the job demands-resource balance, diminish negative mental and physical outcomes and improve WLB.
Population pharmacokinetic modelling of intravenous immunoglobulin in patients with predominantly antibody deficiencies

There is considerable interpatient variability in the pharmacokinetics (PK) of intravenous immunoglobulin G (IVIG), causing difficulty in optimizing individual dosage regimen. This study aims to estimate the population PK parameters of IVIG and to investigate the impact of genetic polymorphism of the FcRn gene and clinical variability on the PK of IVIG in patients with predominantly antibody deficiencies.
Hybrid Inhibitors of DNA Gyrase A and B: Design, Synthesis and Evaluation

The discovery of multi-targeting ligands of bacterial enzymes is an important strategy to combat rapidly spreading antimicrobial resistance. Bacterial DNA gyrase and topoisomerase IV are validated targets for the development of antibiotics. They can be inhibited at their catalytic sites or at their ATP binding sites. Here we present the design of new hybrids between the catalytic inhibitor ciprofloxacin and ATP-competitive inhibitors that show low nanomolar inhibition of DNA gyrase and antibacterial activity against Gram-negative pathogens. The most potent hybrid 3a has MICs of 0.5 µg/mL against Klebsiella pneumoniae, 4 µg/mL against Enterobacter cloacae, and 2 µg/mL against Escherichia coli. In addition, inhibition of mutant E. coli strains shows that these hybrid inhibitors interact with both subunits of DNA gyrase (GyrA, GyrB), and that binding to both of these sites contributes to their antibacterial activity.
Is There an Association between Herpetic Infections and Giant Cell Arteritis? A Population-Based Study

Recent data suggests that herpes zoster (HZ) and herpes simplex virus (HSV) may be one of the underlying immunological triggers for giant cell arteritis (GCA). However, there is limited population-based data to support this. Our goal was to determine if herpetic infections increase the likelihood of GCA in the British Columbia (BC) population. The background prevalence of GCA was compared to the prevalence of GCA in subjects with HZ and HSV using diagnostic billing code data from an online BC database (BC Data ScoutTM). BC residents ≥30 years old at the time of diagnosis from January 2000 to January 2019 were included. The relevant International Classification of Disease codes was used to identify patients with GCA, HZ, and HSV. Comparisons were made using two-sample Z tests. There were 4315 GCA diagnoses, from a total population of 3,026,005 subjects. The prevalence of GCA was 143 per 100,000 people. In terms of herpetic infections, 850 GCA cases were identified in 249,900 subjects with HZ versus 310 diagnoses of GCA in 163,170 subjects with HSV. The prevalence of GCA in subjects with HZ (0.340%) was significantly higher than the prevalence of GCA (0.143%) in the general population (p < 0.00001). The prevalence of GCA in HSV subjects (0.190%) was also significantly higher (p < 0.00001) than the population prevalence but lower than (p < 0.00001) the GCA with HZ prevalence. The likelihood of GCA appears to increase with herpetic infections, more significantly with HZ.
Use of cognitive techniques is associated with change in positive compensatory skills in the treatment of major depressive disorder in a community mental health setting

Abstract Objective: To examine the association between adherence and competence in cognitive therapy (CT) techniques and change in positive compensatory skills and depressive symptoms within a community mental health setting. Method: Adherence ratings were available for 97 individuals receiving CT for major depressive disorder. Assessments of adherence and competence were rated on one early session of CT. Compensatory skills were measured using the Ways of Responding Community Version at baseline and months 1, 2, and 5. Symptom severity was evaluated using the Hamilton Rating Scale for Depression at baseline and months 1, 2, 4, and 5. Results: In mixed effects models, adherence was significantly associated with linear change in positive compensatory skills from baseline to month 5 (F [1, 76] = 8.05, p=.006, r=.31). Competence was also significantly associated with change in positive compensatory skills from baseline to month 5 (F [1, 78] = 5.1, p=.027, r=.25). High adherence was associated with improvements in HAM-D scores from baseline to month 5 (F [1, 78] = 5.1, p=.027, r=.25). Conclusions: Results support the hypothesis that use of CT techniques is associated with change in compensatory skills in a community mental health setting.
Endoglin Targeting: Lessons Learned and Questions That Remain

Approximately 30 years ago, endoglin was identified as a transforming growth factor (TGF)-β coreceptor with a crucial role in developmental biology and tumor angiogenesis. Its selectively high expression on tumor vessels and its correlation with poor survival in cancer patients led to the exploration of endoglin as a therapeutic target for cancer. The endoglin neutralizing antibody TRC105 (Carotuximab®, Tracon Pharmaceuticals (San Diego, CA, USA) was subsequently tested in a wide variety of preclinical cancer models before being tested in phase I-III clinical studies in cancer patients as both a monotherapy and in combination with other chemotherapeutic and anti-angiogenic therapies. The combined data of these studies have revealed new insights into the role of endoglin in angiogenesis and its expression and functional role on other cells in the tumor microenvironment. In this review, we will summarize the preclinical work, clinical trials and biomarker studies of TRC105 and explore what these studies have enabled us to learn and what questions remain unanswered.
The DNA repair protein ATM as a target in autism spectrum disorder

Impairment of the GABAergic system has been reported in epilepsy, autism, attention deficit hyperactivity disorder, and schizophrenia. We recently demonstrated that ataxia telangiectasia mutated (ATM) directly shapes the development of the GABAergic system. Here, we show for the first time to our knowledge how the abnormal expression of ATM affects the pathological condition of autism. We exploited 2 different animal models of autism, the methyl CpG binding protein 2–null (Mecp2y/–) mouse model of Rett syndrome and mice prenatally exposed to valproic acid, and found increased ATM levels. Accordingly, treatment with the specific ATM kinase inhibitor KU55933 (KU) normalized molecular, functional, and behavioral defects in these mouse models, such as (a) delayed GABAergic development, (b) hippocampal hyperexcitability, (c) low cognitive performances, and (d) social impairments. Mechanistically, we demonstrate that KU administration to WT hippocampal neurons leads to (a) higher early growth response 4 activity on Kcc2b promoter, (b) increased expression of Mecp2, and (c) potentiated GABA transmission. These results provide evidence and molecular substrates for the pharmacological development of ATM inhibition in autism spectrum disorders.
Intermittent Fasting Ameliorated High-Fat Diet-Induced Memory Impairment in Rats via Reducing Oxidative Stress and Glial Fibrillary Acidic Protein Expression in Brain

Intermittent fasting (IF) plays an important role in the protection against metabolic syndrome-induced memory defects. This study aimed to assess the protective effects of both prophylactic and curative IF against high-fat diet (HFD)-induced memory defects in rats. The control group received a normal diet; the second group received a HFD; the third group was fed a HFD for 12 weeks and subjected to IF during the last four weeks (curative IF); the fourth group was fed a HFD and subjected to IF simultaneously (prophylactic IF). A high-fat diet significantly increased body weight, serum lipids levels, malondialdehyde (MDA) concentration, glial fibrillary acidic protein (GFAP) and H score in brain tissue and altered memory performance. In addition, it significantly decreased reduced glutathione (GSH) concentration in brain tissue and viability and thickness of pyramidal and hippocampus granular cell layers. However, both types of IF significantly decreased body weight, serum lipids, GFAP protein expression and H score and MDA concentration in brain tissue, and improved memory performance, while it significantly increased GSH concentration in brain tissue, viability, and thickness of pyramidal and granular cell layers of the hippocampus. This study indicated that IF ameliorated HFD-induced memory disturbance and brain tissue damage and the prophylactic IF was more potent than curative IF.
On the Optical Activity of Poly(l-lactic acid) (PLLA) Oligomers and Polymer: Detection of Multiple Cotton Effect on Thin PLLA Solid Film Loaded with Two Dyes

Optical rotatory dispersion (ORD) is a beautiful analytical technique for the study of chiral molecules and polymers. In this study, ORD was applied successfully to follow the degree of polycondensation of l-(+)-lactic acid toward the formation of poly(lactic acid) oligomers (PLAO) and high molecular weight poly(l-lactic acid) (PLLA) in a simple esterification reaction equipment. PLLA is a biodegradable polymer obtainable from renewable raw materials. The racemization of the intrinsically isotactic PLLA through thermal treatment can be easily followed through the use of ORD spectroscopy. Organic or molecular electronics is a hot topic dealing with the combination of π-conjugated organic compounds and polymers with specific properties (e.g., chirality) which can be exploited to construct optoelectronic devices, such as organic light-emitting diodes (OLEDs), organic photovoltaic (OPV) high efficiency cells, switchable chirality devices, organic field-effect transistors (OFETs), and so on. ORD spectroscopy was applied to study either the gigantic optical rotation of PLLA films, as well as to detect successfully the excitonic coupling, occurring in thin solid PLLA green film loaded with a combination of two dyes: SY96 (a pyrazolone dye) and PB16 (the metal-free phthalocyanine pigment). The latter compound PLLA loaded with SY96 and PB16 shows a really gigantic optical activity in addition to typical ORD signal due to exciton coupling and may be considered as a simple and easily accessible model composite of a chiral polymer matrix combined with π-conjugated dyes for molecular electronics studies.
Modification of lignin and its application as char agent in intumescent flame‐retardant poly(lactic acid)

Urea-modified lignin was prepared according to the Mannich reaction and well characterized by Fourier transform infrared spectrometer, elemental ananlyses, and scanning electron microscopy (SEM). Ammonium polyphosphate (APP) and urea-modified lignin were added into poly(lactic acid) (PLA) as a novel intumescent flame-retardant (IFR) system to improve flame retardancy of PLA. The flammability of IFR–PLA composites was studied using limiting oxygen index, UL-94 vertical burning method and cone calorimeter test, and their thermal stability was evaluated by thermogravimetric analysis. The results showed that the urea-modified lignin combined with APP exhibited much better flame retardancy and thermal stability than that of the combination of virgin lignin and APP. The improvement may be attributed to the better char morphology with more phosphoric char evidenced by SEM and X-ray photoelectron spectroscopy. POLYM. ENG. SCI., 2012. © 2012 Society of Plastics Engineers
Training Preferences of School Food Service Staff Vary by Role in the School Nutrition Program

Professional development has been identified as a critical component for school nutrition professionals (SNPs) to successfully implement school meal standards in the United States. However, training needs may vary based on different factors. This study examined (1) the topics of highest priority for SNPs; (2) preferred learning methods; (3) where and when trainings should be conducted; and (4) whether responses differ according to important factors including position type, school locale (urban vs. rural), or job experience. Participants completed surveys that included questions on demographics and preferences for learning methods and training topics (n = 492). Descriptive statistics characterized survey responses. Chi square tests assessed differences in learning method and training topic preferences by participant role, locale, and job experience; Cramer’s V assessed the strength of association for each chi square result. Qualitative responses to open-ended questions were analyzed using an inductive thematic analysis method. Nearly all training topic preferences were significantly different (p < 0.001 using Bonferroni method) when stratified by role. Significant differences were also observed for school locale and years of experience, but to a lesser degree. There was less variation in learning method preferences across staff role. Qualitative results (n = 93) identified three key themes related to training needs: role-specific trainings, innovative learning methods, and geographic access. The combination of quantitative and qualitative analysis indicate that professional development for SNPs should mostly be conducted in-person, be easily accessible, and include hands-on activities. Further, training should be tailored by job role and address situational barriers unique to the geographic area.
Measurements of human tolerance to horizontal rotation within an MRI scanner: Towards gantry‐free radiation therapy

Recent advances in image guidance and adaptive radiotherapy could enable gantry‐free radiotherapy using patient rotation. Gantry‐free radiotherapy could substantially reduce the cost of radiotherapy systems and facilities. MRI guidance complements a gantry‐free approach because of its ability to visualise soft tissue deformation during rotation. A potential barrier to gantry‐free radiotherapy is patient acceptability, especially when combined with MRI. This study investigates human experiences of horizontal rotation within an MRI scanner.
Trait-Based Dimensions Discriminating Adults with Attention Deficit Hyperactivity Disorder (ADHD), Autism Spectrum Disorder (ASD) and, Co-occurring ADHD/ASD

This study assessed the co-occurrence of attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) in newly diagnosed adults of normal intelligence and the contribution of trait-based dimensions deriving from the Barkley Adult ADHD Rating Scale-IV (BAARS-IV), the Autism-Spectrum Quotient (AQ), and the Empathy Quotient (EQ) to the differentiation of patients with ADHD, ASD, and ADHD/ASD. A total of 16.1% of patients with ADHD received a co-occurring ASD diagnosis, while 33.3% of patients with ASD received an ADHD diagnosis. Subjects with ADHD or ADHD/ASD had higher scores in all ADHD traits compared to ASD subjects. Compared to the ADHD group, the ASD group had AQ scores that were significantly greater, except for attention to detail. ADHD/ASD co-occurrence significantly increased the score of attention to detail. The total EQ score was greater in the ADHD group. In the stepwise logistic regression analyses, past hyperactivity, current inattention and impulsivity, attention switching, communication, imagination, and total EQ score discriminated ADHD patients from ASD patients. Attention to detail, imagination, and total EQ score discriminated ADHD cases from ADHD/ASD cases, while past hyperactivity and current impulsivity discriminated ASD subjects from ADHD/ASD subjects. Our findings highlight the importance of particular trait-based dimensions when discriminating adults with ADHD, ASD, and co-occurring ADHD/ASD.
Combining the Integrated-Change Model with Self-Determination Theory: Application in Physical Activity

Background: Critically testing and integrating theoretical models can aid health promotion research and intervention planning. This study aimed to critically compare and integrate Self-Determination Theory (SDT) and Integrated-Change Model (ICM) for explaining physical activity behaviour. Methods: A dataset was used with Dutch adults, consisting of information on demographics and socio–cognitive and behavioural determinants. There were three measurements over a period of six months, with the baseline sample consisting of 1867 participants. Confirmatory factor analysis was conducted to assess the reliability of the items and their corresponding scales. To examine cognitive pathways, we applied Structural Equation Modelling (SEM). Results: For SDT, none of the pathways were significant but the model fit was decent (R2 = 0.20; RMSEA = 0.07; CFI = 0.91). For ICM, the model fit was similar (R2 = 0.19; RMSEA = 0.07; CFI = 0.73), with many significant pathways, as stipulated by the theory. The integration of STD and ICM constructs revealed similar explained behavioural variance (R2 = 21%), with no significantly different model fit. Conclusion: The integration of SDT and ICM added no value as a prediction model. However, the integrated model explains the underlying mechanism of STD constructs, as well as the determinants of attitude, social influences, and self-efficacy. In the context of intervention design, ICM or the integrated model seem most useful as it reveals the stages and pathways to behaviour change.
Histologic progression of acne inversa/hidradenitis suppurativa: Implications for future investigations and therapeutic intervention

Since first recognized in 1839, the pathogenesis of acne inversa (AI) has undergone repeated revisions. Although there is agreement that AI involves occlusion of hair follicles with subsequent inflammation and the formation of tracts, the histologic progression of this disease still requires refinement. The objective of this study was to examine the histologic progression of AI based on the examination of a large cohort of punch biopsies and excisional samples that were examined first by hematoxylin and eosin staining. The most informative of these samples were step‐sectioned and stained by immunohistochemistry for epithelial and inflammatory markers. Based on this examination, the following observations were made: 1) AI arises from the epithelium of the infundibulum of terminal and vellus hairs; 2) These form cysts and epithelial tendrils that extend into soft tissue; 3) Immunohistochemical staining demonstrates the epithelium of AI is disordered with infundibular and isthmic differentiation and de novo expression of stem cell markers; 4) The inflammatory response in AI is heterogeneous and largely due to cyst rupture. The conclusions of this investigation were that AI is an epithelial‐driven disease caused by infiltrative, cyst forming tendrils and most of the inflammation is due to cyst rupture and release of cornified debris and bacteria. Cyst rupture often occurs below the depths of punch biopsy samples indicating their use for analysis may give an incomplete picture of the disease. Finally, our data suggest that unless therapies inhibit tendril development, it is unlikely they will cause prolonged treatment‐induced remission in AI.
Entrepreneurs’ Capacity for Mentalizing: Its Influence on Burnout Syndrome

Burnout is a mental disorder that leads to difficulties for the entrepreneur in controlling his or her personal and professional life. The most common consequences of entrepreneurial burnout include the subject experiencing low motivation, low organizational commitment, loss of energy, demoralization in connection with their work, poor quality of work, feeling of failure, and the perception that his or her company is performing poorly. We used a sample of 157 Spanish entrepreneurs selected at random from the Iberian Balance Sheet Analysis System database. We employed the Spanish version of the Reflective Functioning Questionnaire to measure mentalizing and the Spanish version of the Maslach-Burnout Inventory-General Survey (MBI-GS) to measure burnout. This research showed that entrepreneurial burnout could be avoided in part if the entrepreneur achieved a good capacity for mentalizing. Hypomentalizing contributed to explaining entrepreneurs’ levels of professional efficacy, cynicism, and emotional exhaustion. In contrast, the explanatory power of hypermentalizing was not significant for any of the dimensions of burnout. This study provides new evidence of burnout in entrepreneurs; a professional group with an important economic, politic, and social role has been little studied.