Miracle-dz/UniFAR-FTUs huggingface dataset:
Fatty acid synthase knockout impairs early embryonic development via induction of endoplasmic reticulum stress in pigs

Fatty acid synthase (FAS) is an important enzyme involved in the de novo synthesis of long‐chain fatty acids. During development, the function of FAS in growth is greater than that in energy storage pathways; therefore, we hypothesized that knockout of FAS would affect early embryonic development owing to the induction of endoplasmic reticulum (ER) stress. In the present study, the function of FAS was studied using the CRISPR (clustered regularly interspaced short palindromic repeats)/ CRISPR‐associated protein 9 (Cas9) system. Cas9 and single‐guide RNA (sgRNA) were injected into parthenotes to decrease the number of FAS‐positive embryos. The efficiency of knockout was assayed by DNA sequencing. We found that FAS knockout caused excessive production of reactive oxygen species (ROS). Excess ROS induced ER stress, resulting in activation of the adaptive unfolded protein response (UPR). FAS knockout caused splicing of the X‐box binding protein 1 gene (XBP1) and expression of spliced XBP1 mRNA. In addition, FAS knockout caused phosphorylation of PKR‐like ER kinase (PERK), and an increase in the mRNA expression of the ER stress‐regulated genes, activating transcription factor 4 (ATF4), and C/EBP homologous protein (CHOP). Finally, Ca2+ was released from the ER and taken up by the mitochondria. As the ER stress became intolerable, apoptosis was initiated. These results demonstrate that FAS knockout induced ROS generation, which mediated the activation of UPR via the ER stress, ultimately leading to apoptosis induction.
Changes in Upper Airway Volume in Edentulous Obstructive Sleep Apnea Patients Treated with Modified Mandibular Advancement Device.

PURPOSE This study was an attempt to verify the utility of complete dentures modified as a mandibular advancement device (MAD) in effecting expansion in pharyngeal volume to treat obstructive sleep apnea (OSA) in edentulous patients. MATERIALS AND METHODS The sample consisted of 17 patients (12 male, 5 female, average age 61 ± 4 years; BMI, 22 ± 5; apnea hypopnea index [AHI] 15 to 30). All patients had worn complete dentures for at least 1 year; all patients had the dentures modified to a MAD. Five variables were assessed preoperatively and 6 months after wearing the modified MADs. These variables were: sleep efficiency, AHI, oxygen desaturation events/hr. , mean oxygen saturation, snoring index, and airway volume. This assessment was done by subjecting the patients to all-night polysomnography. RESULTS Without any prosthesis or device in the edentulous patients, the mean velopharyngeal volume was 8.05 ± 0.58 cm(3) , oropharyngeal volume was 2.14 ± 0.38 cm(3) , and hypopharyngeal volume was 3.26 ± 0.78 cm(3) . With complete dentures (unaltered) in the edentulous patients, the mean velopharyngeal, oropharyngeal, and hypopharyngeal volumes were 10.73 ± 0.98 cm(3) , 2.60 ± 0.48 cm(3) , and 4.31 ± 0.89 cm(3) , respectively. There was a statistically significant change in the airway volume following insertion of the complete dentures modified as MADs with velopharyngeal, oropharyngeal, and hypopharyngeal volume recorded as 11.76 ± 1.07 cm(3) , 3.33 ± 0.51 cm(3) , and 4.94 ± 0.83 cm(3) , respectively. CONCLUSION From the results obtained in this limited small sample study, it was inferred that the pharyngeal expansion induced by complete dentures modified as MADs effectively reduced symptoms of OSA. Increased volume was most pronounced in the velopharynx region followed by hypopharynx and oropharynx.
Teens’ self-efficacy to deal with dating violence as victim, perpetrator or bystander

Multiple studies have demonstrated that adolescent dating violence is highly prevalent and is associated with internalizing and externalizing problems. A number of prevention initiatives are being implemented in North American high schools. Such initiatives aim to raise awareness among potential victims and offenders, and also among peer bystanders. As teenagers mainly reach out to their peers when experiencing adversity, it is important to address adolescents’ efficacy in dealing with witnessing dating violence or with friends disclosing dating abuse, in addition to increasing their ability to deal with experienced dating violence victimization or perpetration. The aim of this study is to explore adolescents’ self-efficacy to deal with dating violence victimization and perpetration in their relationships and those of their peers. A paper-and-pencil questionnaire was completed by 259 14−18-year-olds in Quebec, Canada. The data allow building insight into adolescents’ confidence to reach out for help or to help others in a situation of dating violence victimization and perpetration. We also considered the impact of gender and dating victimization history. Results suggest that dating violence prevention can build on teens’ self-efficacy to deal with dating violence and offer them tools to do so efficiently.
Where are the Behavioral Sleep Medicine Providers and Where are They Needed? A Geographic Assessment

Although it is widely acknowledged that there are not enough clinicians trained in either Behavioral Sleep Medicine (BSM) in general or in Cognitive Behavioral Therapy for Insomnia (CBT-I) in specific, what is unclear is whether this problem is more acute in some regions relative to others. Accordingly, a geographic approach was taken to assess this issue. Using national directories as well as e-mail listservs (Behavioral Sleep Medicine group and Behavioral Treatment for Insomnia Roster), the present study evaluated geographic patterning of CBSM and BSM providers by city, state, and country. Overall, 88% of 752 BSM providers worldwide live in the United States (n = 659). Of these, 58% reside in 12 states with ≥ 20 providers (CA, NY, PA, IL, MA, TX, FL, OH, MI, MN, WA, and CO), and 19% reside in just 2 states (NY and CA). There were 4 states with no BSM providers (NH, HI, SD, and WY). Of the 167 U.S. cities with a population of > 150,000, 105 cities have no BSM providers. These results clearly suggest that a targeted effort is needed to train individuals in both the unserved and underserved areas.
Distinctive Neuropsychological Patterns in Frontotemporal Dementia, Semantic Dementia, And Alzheimer Disease

ObjectiveTo assess the ability of a brief neuropsychological bedside screening battery to discriminate between Alzheimer disease, frontotemporal dementia, and semantic dementia. MethodsSubjects were 21 patients with frontotemporal dementia, 14 patients with semantic dementia, and 30 patients with Alzheimer disease comparable in terms of Mini Mental Status Examination score, age, and education. Frontotemporal dementia and semantic dementia diagnoses were made clinically using the consensus criteria of Neary et al. 1 Subjects were administered a brief neuropsychological screening assessing episodic memory, working memory, executive function, naming, spatial ability, abstract reasoning, and calculations. ResultsBoth the Alzheimer disease and semantic dementia groups were significantly impaired relative to the frontotemporal dementia group on verbal memory, whereas only the Alzheimer disease group was impaired on visual memory. Frontotemporal dementia patients performed significantly worse on backward digit span and made significantly more executive errors than Alzheimer disease and semantic dementia patients. Semantic dementia patients were more impaired than Alzheimer disease and frontotemporal dementia patients on confrontation naming. Discriminant function analyses identified the 5 most discriminating variables that correctly classified 89.2% of cases. ConclusionsFrontotemporal dementia, semantic dementia, and Alzheimer disease are associated with distinct neuropsychological profiles that classify these dementia syndromes with considerable success. The neuropsychological profiles highlight the distinctiveness between the 3 syndromes, are consistent with the known loci of neuropathology in these conditions, and can potentially serve as an adjunct to the current clinical criteria.
MALDI-TOF MS analysis of bovine and zoonotic Trichophyton verrucosum isolates reveals a distinct peak and cluster formation of a subgroup with Trichophyton benhamiae

The zoophilic dermatophyte Trichophyton verrucosum is the most important causative agent of bovine dermatophytosis. Additionally, it causes profound and poorly healing skin infections in humans indicating the high zoonotic potential. The objective of this study was to establish differentiation of T. verrucosum from other dermatophytes by mass spectrometry and to identify distinct features of the mass spectra. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was successful for identification of this pathogen only after extension of the database of the manufacturer with spectra from T. verrucosum strains, which were identified as such by sequencing of the internal transcribed spacer (ITS) region. MALDI-TOF MS analysis was conducted with 46 field isolates from cattle, two live vaccine strains, and 10 isolates from humans identified as T. verrucosum by sequence analysis of the ITS region. The results suggest a very good agreement of both methods. Comparison with the mass spectra of 68 strains of other keratinophilic fungi revealed that most T. verrucosum wild-type isolates showed a characteristic peak at 7950-7954 m/z, which was missing in the spectra of other keratinophilic fungi and the live vaccine strains. The spectra of T. verrucosum were most similar to the spectra of T. benhamiae, an emerging zoophilic dermatophyte. In summary, MALDI-TOF MS is a powerful and reliable tool to identify T. verrucosum.
Predicted contributions of cytochrome P450s to drug metabolism in human liver microsomes using relative activity factor were dependent on probes

Abstract Contributions of cytochrome P450 (CYP450) isoforms to drug metabolism are often predicted using relative activity factor (RAF) method, assuming RAF values were independent of probe. We aimed to report probe-dependent characteristic of RAF values using CYP3A4 or CYP2C9 probes. Metabolism of four CYP3A4 probes (testosterone, midazolam, verapamil and atorvastatin) and three CYP2C9 probes (tolbutamide, diclofenac and S-warfarin) in human liver microsomes (HLM) and cDNA-expressed recombinant CYP450 (Rec-CYP450) systems were characterized and RAFCL value was estimated as ratio of probe intrinsic clearance in HLM to that in Rec-CYP450. CYP450i contributions to metabolic reaction of a probe were predicted using other probes and compared with data from specific inhibitions. Contributions of CYP3A4 and CYP2C9 to metabolism of deoxypodophyllotoxin and nateglinide were also predicted. RAF values were dependent on probes, leading to probe-dependently predicted contributions. Predicted contributions of CYP3A4 to formations of 6β-hydroxytestosterone, 1′-hydroxymidazolam, norverapamil, ortho-hydroxyatorvastatin and para-hydroxyatorvastatin using other probes were 47.46–219.46%, 21.62–98.87%, 186.49–462.44%, 21.87–101.15% and 53.62–247.97%, respectively. Predicted contributions of CYP3A4 and CYP2C9 to nateglinide metabolism were 8.18–37.84% and 36.08–94.04%, separately. In conclusion, CYP450i contribution to drug metabolism in HLM estimated using RAF approach were probe-dependent. Therefore, contribution of each isoform must be confirmed by multiple probes.
University of Birmingham Dilated Cardiomyopathy

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An Incentivized, Workplace Physical Activity Intervention Preferentially Increases Daily Steps in Inactive Employees

Although physical activity (PA) is associated with decreased risk of chronic diseases, fewer than half of American adults meet the recommendations for daily PA, in part, due to large amounts of sedentary time in the workplace. Purpose: To determine the efficacy of an incentivized workplace PA intervention. Design: Retrospective cohort design. Setting: Large southeastern university. Participants: Of the 16 588 eligible employees working ≥8 h/wk, 6246 (37.6%) participated and 2206 (13.3%) were included in data analysis. Intervention: Six-week PA intervention with tiered incentives (value: $10.50-$29.00). Measures: Steps/day measured via consumer-grade PA monitors for 1-week pre-, 6-weeks during, and 1-week postintervention. Analysis: Participants were grouped by preintervention PA into 4 groups: <6000 (I); 6000 to 7999 (II); 8000 to 9999 (III); and ≥10 000 (IV) steps/d (n = 481, 540, 485, and 700, respectively) in accordance with the tiered incentive schedule. Statistical comparisons were made by repeated-measures analysis of variance. Results: During the intervention, participants achieving ≥10 000 steps/d increased by 60%. Groups I, II, and III significantly increased steps/day during the intervention (46%, 24%, and 11%, respectively), which was partially maintained in groups I and II 1-week postintervention. Group IV did not increase steps/day during the intervention and significantly decreased steps/day 1-week postintervention. The estimated cost per participant of this intervention increased with from group I ($55.41) to IV ($71.90). Conclusion: An incentivized, workplace PA intervention preferentially increases PA and is most cost-effective among university employees with low initial PA who may benefit substantially from increased levels of PA.
Influence of Food with High Moisture Content on Oxygen Barrier Property of Polyvinyl Alcohol (PVA)/Vermiculite Nanocomposite Coated Multilayer Packaging Film.

This study investigates the potential complications in applying nanoclay-based waterborne coating to packaging films for food with high moisture content. Multilayer packaging films were prepared by dry laminating commercially available polyvinyl alcohol (PVA)/vermiculite nanocomposite coating films and linear low-density polyethylene film, and the changes in oxygen barrier properties were investigated according to different relative humidity using 3 types of food simulants. When the relative humidity was above 60%, the oxygen permeability increased sharply, but this was reversible. Deionized water and 3% acetic acid did not cause any large structural change in the PVA/vermiculite nanocomposite but caused a reversible deterioration of the oxygen barrier properties. In contrast, 50% ethanol, a simulant for the semifatty food, induced irreversible structural changes with deterioration of the oxygen barrier property. These changes are due to the characteristics of PVA rather than vermiculite. PRACTICAL APPLICATION We believe this manuscript would be of interest to the wide group of researchers, organizations, and companies in the field of developing nanoclay-based gas barrier packaging for foods with high moisture content. Hence, we wish to diffuse our knowledge to the scientific community.
Breathing, Pausing and Reading

Abstract An analysis of the breathing patterns of speakers in a variable-rate reading task shows that the duration and frequency of breathing pauses are dependent both on the rate of speaking and the syntactic nature of the pause location. Non-breathing pauses follow the same pattern of occurrence as breathing pauses, but are always shorter and tend to occur primarily at minor constituent breaks. At slow and normal rates, speakers accommodate their need to inhale to the preplanned pause patterns. At fast rates, however, the physiological need to breathe is the sole determinant of pausing.
What Are Our AIMs? Interdisciplinary Perspectives on the Use of Ancestry Estimation in Disease Research

Background: Ancestry estimation serves as a tool to identify genetic contributions to disease but may contribute to racial discrimination and stigmatization. We sought to understand user perspectives on the benefits and harms of ancestry estimation to inform research practice and contribute to debates about the use of race and ancestry in genetics. Methods: Key informant interviews with 22 scientists were conducted to examine scientists’ understandings of the benefits and harms of ancestry estimation. Results: Three main perspectives were observed among key informant scientists who use ancestry estimation in genetic epidemiology research. Population geneticists self-identified as educators who controlled the meaning and application of ancestry estimation in research. Clinician-researchers were optimistic about the application of ancestry estimation to individualized risk assessment and personalized medicine. Epidemiologists remained ambivalent toward ancestry estimation and suggested a continued role for race in their research. Conclusions: We observed an imbalance of control over the meaning and application of ancestry estimation among disciplines that may result in unwarranted or premature translation of ancestry estimation into medicine and public health. Differences in disciplinary perspectives need to be addressed if translational benefits of genetic ancestry estimation are to be realized.
Treatment-Resistant Depression and Axis II Comorbidity

Background: Researchers of unipolar depression have speculated that personality disturbance is a contributing factor in the development of treatment resistance. The purpose of this study was to compare the prevalence of Axis II disorders between a sample of rigorously defined, treatment-resistant depressed outpatients and a sample of depressed outpatients not having experienced treatment resistance. Methods: 53 patients with treatment-resistant depression (TRD) and 105 patients with non-treatment-resistant depression (non-TRD) were recruited through respective outpatient clinical trials at the Massachusetts General Hospital’s Depression Clinical and Research Program. Diagnosis of Major Depressive Disorder was made using the Structured Clinical Interview for the DSM-III-R, personality disorders were assessed using the Structured Clinical Interview for DSM-III-R Personality Disorders, and antidepressant treatment resistance was defined using the McLean Hospital Antidepressant Treatment Record. Participants from both studies were matched for baseline HAM-D-17 total score and gender. Multiple chi-square analysis was used to compare frequencies of Axis II disorders between TRD and non-TRD patients as well as to compare categorical baseline demographic variables. Unpaired t tests were used to compare baseline demographic and clinical variables measured in a continuous manner. Results: Non-TRD patients had a higher rate of obsessive-compulsive personality disorder than TRD patients, but this difference was not statistically significant after adjusting for multiple comparisons. No other differences were found to be statistically significant. Range of Axis II comorbidity was 0.0–30.2% for TRD patients and 2.9–37.1% for non-TRD patients. Conclusions: In this sample, treatment resistance in a current major depressive episode was not associated with an increased rate of Axis II disorders. Strengths of this study include the use of structured interview instruments to assess Axis I and II conditions, and having the two study groups matched for gender and baseline severity of depression. Limitations of this study include a modest sample size and reliance on DSM personality constructs.
Low RMRratio as a Surrogate Marker for Energy Deficiency, the Choice of Predictive Equation Vital for Correctly Identifying Male and Female Ballet Dancers at Risk.

Ballet dancers are reported to have an increased risk for energy deficiency with or without disordered eating behavior. A low ratio between measured (m) and predicted (p) resting metabolic rate (RMRratio < 0.90) is a recognized surrogate marker for energy deficiency. We aimed to evaluate the prevalence of suppressed RMR using different methods to calculate pRMR and to explore associations with additional markers of energy deficiency. Female (n = 20) and male (n = 20) professional ballet dancers, 19-35 years of age, were enrolled. mRMR was assessed by respiratory calorimetry (ventilated open hood). pRMR was determined using the Cunningham and Harris-Benedict equations, and different tissue compartments derived from whole-body dual-energy X-ray absorptiometry assessment. The protocol further included assessment of body composition and bone mineral density, blood pressure, disordered eating (Eating Disorder Inventory-3), and for females, the Low Energy Availability in Females Questionnaire. The prevalence of suppressed RMR was generally high but also clearly dependent on the method used to calculate pRMR, ranging from 25% to 80% in males and 35% to 100% in females. Five percent had low bone mineral density, whereas 10% had disordered eating and 25% had hypotension. Forty percent of females had elevated Low Energy Availability in Females Questionnaire score and 50% were underweight. Suppressed RMR was associated with elevated Low Energy Availability in Females Questionnaire score in females and with higher training volume in males. In conclusion, professional ballet dancers are at risk for energy deficiency. The number of identified dancers at risk varies greatly depending on the method used to predict RMR when using RMRratio as a marker for energy deficiency.
The fibrinolytic enzyme system in acute and chronic liver injury.

Components of the fibrinolytic enzyme system were measured in patients with liver disease. Patients with hepatic cirrhosis and chronic active hepatitis had a trend towards increased plasminogen activator activity and decreased plasminogen levels. Patients with non-cirrhotic alcoholic liver damage had decreased activator activity with elevated fibrinogen and α1-antitrypsin levels. Primary biliary cirrhosis was associated with reduced activator activity and high levels of fibrinogen, α1-antitrypsin and α2-macroglobulin.
Novel combination for the treatment of acne differentiated based on gender: a new step towards personalized treatment.

BACKGROUND The aim of this study is to evaluate efficacy and tolerability of a complete skin care line consisting of an oral supplement in two distinct formulations for males and females, and a topical cream device in the treatment of mild and moderate acne. Oral supplements contain biotin, probiotic, vitamin E, zinc, nicotinamide; in the formulation for males beta sitosterol and Boswellia serrata were added, the oral supplement for females contains myo-inositol and folic acid. The topical cream device is represented by the association between active plant agents (verbascoside, Ocimum gratissimum) and keratolytic molecules (salicylic acid, gluconolactone, complex alpha-hydroxy acids). METHODS An equal number of male and female patients with mild to moderate acne were enrolled in a double-blinded clinical trial. Efficacy and tolerability evaluations were performed at week 4 (T1) and week 12 (T2) by Global acne Grading System (GAGs). RESULTS Most of patients had satisfactory therapeutic response, in terms of GAGs reduction. All the four groups presented a statistically significant improvement of the mean GAGs at T2 but those assuming the oral supplement improved more, as expected. CONCLUSIONS Our data suggest that this association can be considered a new effective option for mild and moderate acne. This therapeutic line differs from others in the gender matched oral treatment.