Miracle-dz/UniFAR-FTUs huggingface dataset:
Physiologically‐Based Pharmacokinetic Modeling for the Prediction of CYP2D6‐Mediated Gene–Drug–Drug Interactions

The aim of this work was to predict the extent of Cytochrome P450 2D6 (CYP2D6)‐mediated drug–drug interactions (DDIs) in different CYP2D6 genotypes using physiologically‐based pharmacokinetic (PBPK) modeling. Following the development of a new duloxetine model and optimization of a paroxetine model, the effect of genetic polymorphisms on CYP2D6‐mediated intrinsic clearances of dextromethorphan, duloxetine, and paroxetine was estimated from rich pharmacokinetic profiles in activity score (AS)1 and AS2 subjects. We obtained good predictions for the dextromethorphan–duloxetine interaction (Ratio of predicted over observed area under the curve (AUC) ratio (Rpred/obs) 1.38–1.43). Similarly, the effect of genotype was well predicted, with an increase of area under the curve ratio of 28% in AS2 subjects when compared with AS1 (observed, 33%). Despite an approximately twofold underprediction of the dextromethorphan–paroxetine interaction, an Rpred/obs of 0.71 was obtained for the effect of genotype on the area under the curve ratio. Therefore, PBPK modeling can be successfully used to predict gene–drug–drug interactions (GDDIs). Based on these promising results, a workflow is suggested for the generic evaluation of GDDIs and DDIs that can be applied in other situations.
Effects of Auditory Training on Electrophysiological Measures in Individuals with Autism Spectrum Disorder

Abstract Background: Identifying objective changes following an auditory training program is central to the assessment of the program’s efficacy. Purpose: This study aimed (1) to objectively determine the efficacy of a 12-week auditory processing training (APT) program in individuals with autism spectrum disorder using auditory evoked potentials (AEPs) and (2) to identify the top central AEP predictors of the overall score on the Test of Auditory Processing Skills-3 (TAPS-3), the primary behavioral outcome measure of the APT program published in our earlier article. Research Design: A one-group pretraining, posttraining design was used. Study Sample: The sample included 15 children and young adults diagnosed with autism spectrum disorder. Participants underwent the APT program consisting of computerized dichotic training, one-on-one therapist-directed auditory training, and the use of remote microphone technology at home and in the classroom. Data Collection and Analysis: All participants underwent pre- and posttraining auditory brain stem responses (ABRs), complex auditory brain stem responses (cABRs), and auditory late responses (ALRs). Test results from ABRs and ALRs were grouped based on scores obtained in their dominant and nondominant ears. Paired t-tests were used to assess the efficacy of the training program, and least absolute shrinkage and selection operator regression was used to assess the relationship between ALRs and the TAPS-3 overall summed raw score reported in our earlier article. Results and Conclusions: When compared with pretraining results, posttraining results showed shorter ABR latencies and larger amplitudes. The cABRs showed decreased latencies of the frequency following waves, a reduction in pitch error, and enhancement of pitch strength and phase shift. ALR results indicated shorter latencies and larger amplitudes. Our earlier article showed that the TAPS-3 overall score was significantly higher after training. This study showed that the top three ALR predictors of TAPS-3 outcomes were P1 amplitude in the dominant ear, and N1 amplitude in the dominant and nondominant ears.
Young Women’s Sexuality in Black and White: Racial Differences in Appraisals of Sexually Active Young Women

Evidence suggests that U.S. attitudes are increasingly accepting of young women’s rights to sexual self-expression and activity. However, such support may not be unequivocal or uniformly offered and received. It is especially unclear how the endorsement of young women’s sexuality varies by race, both in who holds these supportive views and in who benefits from them. We examined whether appraisals of a hypothetical sexually active young woman would vary by her race (Black or White) and/or a participant’s (Black or White). Analyzing a sample of 416 U.S. adults (aged 18–40) comprised of equivalent numbers of Black women, Black men, White women, and White men, we found that across vignette subject and participant race, a sexually active young woman was rated as more competent than likable and that Black participants’ appraisals of a sexually active woman (Black or White) were less favorable than White participants’. Against our hypothesis, we found no quantitative evidence of bias against a Black sexually active young woman; however, post-hoc qualitative analysis of participants’ comments cast doubt on this apparent racial symmetry. We consider these findings in the context of ongoing racial/misogynist sexual stigmatization of Black women and the consequent attitudes held by – and about – them.
Factors Associated with Dental Fear and Anxiety in Children Aged 7 to 9 Years

The aim was to investigate changes in dental fear and anxiety (DFA) and verify factors associated with DFA in children. A longitudinal cohort study that included 160 children aged 7 years was carried out. A questionnaire was completed by parents at two time points and evaluated the immigrant background, maternal education, whether the child had ever had toothache, and whether the parents had dental fear. The oral clinical examination evaluated decayed, extracted, and filled primary teeth (deft). The children’s fear survey schedule dental subscale (CFSS-DS) was used to assess the dental fear of the children. Multilevel mixed-effects logistic regressions analyses were used. The CFSS-DS found that 7% of the children had dental fear at age 7 and mean CFSS-DS was 22.9. At 9 years of age, 8% reported dental fear and the mean increased to 25.4. Parental dental fear, experience of toothache, and report of painful dental treatment and caries development between 7 and 9 years of age were factors that were significantly related to development of DFA. There was a change in DFA between 7 and 9 years of age. Dental fear and anxiety is a dynamic process in growing individuals and is significantly related to painful symptoms and experiences of dental care as well as parental dental fear.
Apathy in Obsessive-Compulsive Disorder and Its Psychological Correlates: Comparison With Individuals With Schizophrenia.

OBJECTIVE Apathy, defined as reduced goal-directed behavior, is a frequent symptom in mental and neurological disorders but has been poorly studied in individuals with obsessive-compulsive disorder (OCD). The primary aim of this study was to examine levels of apathy between individuals with OCD, healthy control subjects, and individuals with schizophrenia, a mental disorder with high levels of apathy. The second aim was to assess whether the psychological factors that have been previously shown as underlying apathy in other mental disorders were associated with apathy in patients with OCD. METHODS This exploratory study included 25 individuals with OCD, 24 individuals with schizophrenia, and 24 healthy control subjects. Apathy was assessed using the Lille Apathy Rating Scale. Measures of depression, sensibility to punishment and reward, defeatist performance beliefs, and cognitive functioning were also assessed. RESULTS Individuals diagnosed with OCD and schizophrenia scored significantly higher than healthy control subjects on the apathy total score. Levels of apathy among OCD patients were mainly associated with depression but also dysexecutive functioning and defeatist beliefs. CONCLUSIONS These findings suggest that motivational deficits could play a central role in disability caused by OCD. Similar to other mental disorders, various psychological factors, including depression, defeatist beliefs, and dysexecutive functioning, are involved in apathetic manifestations. However, the fact that depression is the variable most associated with apathy indicates that apathetic symptoms in patients with OCD must be considered mainly as secondary rather than primary symptoms.
ARQ schemes with adaptive modulation/TDMA/TDD systems for wireless multimedia communication services

This paper proposes automatic repeat request (ARQ) protocols combined with an adaptive modulation system (AMS) (ARQ/AMS) to achieve high throughput data transmission for wireless multimedia communication services. First, it analyses the cause of the throughput limitation of the conventional fixed modulation ARQ system, and discusses basic strategies to improve the throughput performance by effectively combining ARQ and AMS. Next, it proposes a selective repeat ARQ (SR-ARQ) with AMS (SR-ARQ/AMS), and shows its throughput performance improvement effect. Finally, this paper proposes a type-II hybrid ARQ with a punctured convolutional coding combined with the AMS (type-II hybrid ARQ/AMS) to further improve the throughput performance. Computer simulation confirms that the proposed type-II hybrid ARQ/AMS can achieve higher throughput performance than the conventional selective repeat ARQ with QPSK under any channel conditions.
A comparison of constant and variable amplitude command shaping techniques for vibration reduction

Investigates the characteristics of constant-amplitude input shapers for robust time-optimal maneuvers of flexible structures. Trends in the timing of the shaper impulses are shown as a function of the system damping constant and move distance. The insensitivity to modeling errors, time-optimality, amount of vibration caused during maneuvers, and high frequency excitation of these shapers are then discussed and compared with some variable-amplitude input shapers.
The Zinc Transporter Zip7 Is Downregulated in Skeletal Muscle of Insulin-Resistant Cells and in Mice Fed a High-Fat Diet

Background: The zinc transporter Zip7 modulates zinc flux and controls cell signaling molecules associated with glucose metabolism in skeletal muscle. The present study evaluated the role of Zip7 in cell signaling pathways involved in insulin-resistant skeletal muscle and mice fed a high-fat diet. Methods: Insulin-resistant skeletal muscle cells were prepared by treatment with an inhibitor of the insulin receptor, HNMPA-(AM)3 or palmitate, and Zip7 was analyzed along with pAkt, pTyrosine and Glut4. Similarly, mice fed normal chow (NC) or a high-fat diet (HFD) were also analyzed for protein expression of Glut4 and Zip7. An overexpression system for Zip7 was utilized to determine the action of this zinc transporter on several genes implicated in insulin signaling and glucose control. Results: We identified that Zip7 is upregulated by glucose in normal skeletal muscle cells and downregulated in insulin-resistant skeletal muscle. We also observed (as expected) a decrease in pAkt and Glut4 in the insulin-resistant skeletal muscle cells. The overexpression of Zip7 in skeletal muscle cells led to the modulation of key genes involved in the insulin signaling axis and glucose metabolism including Akt3, Dok2, Fos, Hras, Kras, Nos2, Pck2, and Pparg. In an in vivo mouse model, we identified a reduction in Glut4 and Zip7 in the skeletal muscle of mice fed a HFD compared to NC controls. Conclusions: These data suggest that Zip7 plays a role in skeletal muscle insulin signaling and is downregulated in an insulin-resistant, and HFD state. Understanding the molecular mechanisms of Zip7 action will provide novel opportunities to target this transporter therapeutically for the treatment of insulin resistance and type 2 diabetes.
A new field test to estimate the aerobic and anaerobic thresholds and maximum parameters

Abstract Evaluation of cardiorespiratory parameters is important in athletic population in order to monitor the training status and define training intensities. The aim of this study was to validate an easy-to-perform running test called RABIT® (Running Advisor Billat Training) for detecting aerobic (AerT) and anaerobic (AnT) threshold and maximum parameters. Fifteen trained runners completed a graded (GRAD) and RABIT test (four self-selected pace steps: (i) 10 minutes at free warm-up pace, (ii) 5 minutes at medium pace, (iii) 3 minutes at hard pace, (iv) 10 minutes at easy pace). We compared the cardiorespiratory parameters and running speed of the RABIT with those corresponding to AerT, AnT or maximum parameters obtained by the GRAD. The ⩒O2max, HRmax, RERmax and running speed max measured during the 3-minute hard pace of the RABIT were not statistically different from the maximum parameters measured during GRAD (p > 0.05). The ⩒O2, HR and RER measured during the medium and easy pace of the RABIT were not significantly different from the AnT and AerT parameters measured during GRAD. In conclusion, RABIT was validated for all the maximum parameters and for most of Ant- and AerT-related parameters and then it might be used for detecting training zones in athletes.
Benzene and leukemia: from scientific evidence to regulations. A historical example

Background: Benzene is a highly flammable, highly volatile liquid aromatic hydrocarbon. It has been used in many industrial processes as a solvent or a starting material. At the beginning of the twentieth century, it was very widely used in the workplace, especially in printing and in the shoe manufacturing and rubber industries. Although benzene was first recognized to cause aplastic anemia, its association with leukemia has been investigated only since the 1930s. In 1963, Italy was one of the first countries in the world to adopt a law to ban benzene as a solvent in work activities. Objectives: This study analyzed the contribution of the Clinica del Lavoro in Milan, Italy, to studies of the relationship between exposure to benzene and leukemia. Methods: Scientific literature and historical sources on benzene and leukemia in the twentieth century were reviewed, and interviews with a first-hand witness of that period were conducted. Results: By 1928, several scholars had reported anecdotal cases of leukemia among workers exposed to benzene. Enrico Vigliani was the first to collect all of these cases and to try to conduct statistical analysis on these data, in order to support the association between benzene and leukemia. In the 1960s, Vigliani and Alessandra Forni showed that benzene could cause chromosome aberrations in the bone marrow that could produce leukemic clones. Conclusions: As a result of these studies and the subsequent regulations which banned benzene, exposure conditions changed in the workplace in the last few decades. The resulting low concentrations have prompted researchers to investigate new exposure biomarkers and to study any related health problems.
Processes of Care Associated With Risk of Mortality and Recurrent Stroke Among Patients With Transient Ischemic Attack and Nonsevere Ischemic Stroke

Key Points Question Which processes of care are associated with reduced risk of mortality or recurrent stroke after transient ischemic attack or nonsevere ischemic stroke? Findings In this cohort study of 8076 patients with transient ischemic attack or nonsevere ischemic stroke, only 1216 (15.3%) received without-fail care, defined as receiving all guideline-concordant processes of care for which they were eligible (ie, brain imaging, carotid artery imaging, antihypertensive intensification, high- or moderate-potency statin therapy, antithrombotics, and anticoagulation for atrial fibrillation). Receiving all 6 processes was associated with lower risk of death (31.2% reduction at 1 year) but not lower risk of recurrent stroke. Meaning Clinicians should ensure that patients with transient ischemic attack and nonsevere ischemic stroke receive all guideline-concordant processes of care for which they are eligible.
Screening and offering online programs for eating disorders: Reach, pathology, and differences across eating disorder status groups at 28 U.S. universities.

OBJECTIVE The Internet-based Healthy Body Image (HBI) Program, which uses online screening to identify individuals at low risk of, high risk of, or with an eating disorder (ED) and then directs users to tailored, evidence-based online or in-person interventions to address individuals' risk or clinical status, was deployed at 28 U.S. universities as part of a randomized controlled trial. The purpose of this study is to report on: (a) reach of HBI, (b) screen results, and (c) differences across ED status groups. METHOD All students on participating campuses ages 18 years or older were eligible, although recruitment primarily targeted undergraduate females. RESULTS The screen was completed 4,894 times, with an average of 1.9% of the undergraduate female student body on each campus taking the screen. ED risk in participating students was high-nearly 60% of students screened were identified as being at high risk for ED onset or having an ED. Key differences emerged across ED status groups on demographics, recruitment method, ED pathology, psychiatric comorbidity, and ED risk factors, highlighting increasing pathology and impairment in the high-risk group. DISCUSSION Findings suggest efforts are needed to increase reach of programs like HBI. Results also highlight the increasing pathology and impairment in the high-risk group and the importance of programs such as HBI, which provide access to timely screening and intervention to prevent onset of clinical EDs.
Fatigue and Discomfort During Spatially Distributed Sequential Stimulation of Tibialis Anterior

Neuromuscular electrical stimulation is conventionally applied through a single pair of electrodes over the muscle belly, denominated single electrode stimulation (SES). SES is limited by discomfort and incomplete motor-unit recruitment, restricting electrically-evoked torque and promoting premature fatigue-induced torque-decline. Sequential stimulation involving rotation of pulses between multiple pairs of electrodes has been proposed as an alternative, denominated spatially distributed sequential stimulation (SDSS). The present aim was to compare discomfort, maximal-tolerated torque, and fatigue-related outcomes between SES and SDSS of tibialis anterior. Ten healthy participants completed two experimental sessions. The self-reported discomfort at sub-maximal torque, the maximal-tolerated torque, fatigue-induced torque-decline during, and doublet-twitch torque at 10- and 100-Hz before and after, 300 intermittent (0.6-s-ON-0.6-s-OFF) isokinetic contractions were compared between SES and SDSS. SDSS stimulation improved fatigue-related outcomes, whereas increased discomfort and reduced maximal-tolerated torque. SDSS holds promise for reducing fatigue. However, limited torque production and associated discomfort may limit its utility for rehabilitation/training.
Lymphoproliferative tumors involving the lacrimal drainage system: a major review

ABSTRACT Purpose To provide a literature review on lymphoproliferative lesions involving the lacrimal drainage system. Methods The authors performed a pubmed search of all articles published in English on lymphoma/leukemia of lacrimal sac and the nasolacrimal duct. Data analyzed include prevalence, demographics, clinical presentations, treatment outcomes of primary versus secondary lacrimal involvement, and recurrence rates. Results Lymphoma/leukemia of lacrimal sac presented at a mean age of 55 years. The majority of the tumors (63%) were primary involvement of lacrimal sac, bilateral involvement being more common in secondary than primary lacrimal sac lymphoma. Epiphora (96%, 98/102), swelling in the lacrimal sac region (75%, 77/102), and acute dacryocystitis (31%) were the most frequent presenting features. Thirty-six percent of the lesions were diagnosed incidentally while performing a dacryocystorhinostomy (DCR). Among primary sac lymphomas, diffuse large B-cell lymphoma (DLBCL) (43%) was the most common sub-type followed by MALToma (24%), unclassified B-cell lymphoma (21%), lymphoid hyperplasia (5%) and 3% each small lymphocytic lymphoma (SLL) and NK/T cell lymphoma. Management usually involves chemotherapy and/ or radiotherapy with or without surgical resection. Successful outcomes in terms of local disease control could be achieved in all the cases; however, 15% died of the systemic disease after a mean 18 months from the time of sac involvement. Aggressive lymphomas like NK/T-cell have the worst prognosis. Conclusion Lymphoproliferative involvement of lacrimal sac has a high incidence of acute dacryocystitis with a good response to chemotherapy. Epiphora in patients with leukemia/lymphoma should arouse suspicion of a lacrimal drainage involvement.
Effect of Vitamin D Supplementation on Lipid Profile in Vitamin D-Deficient Children with Type 1 Diabetes and Dyslipidemia

Background: Vitamin D (VD) was suggested to have both direct and indirect effects on modifying lipid profile in patients with diabetes through its regulatory action that increases the activity of lipoprotein lipase in adiposity. Objectives: To detect the relationship between serum 25-hydroxyvitamin D (25OHD) and lipid profiles in dyslipidemic T1D patients and study the effect of VD supplementation on lipid profiles of VD-deficient T1D patients. Methods: Fifty patients with T1D (for >2 years) and dyslipidemia were included. 25OHD was assessed and patients were divided accordingly into 2 groups: VD sufficiency (>30 ng/mL) and VD deficiency (VDD) or insufficiency (<29 ng/mL) who were allocated to VD3 supplementation for 4 months, then lipid profile was reevaluated in both groups. Results: Thirty patients had VDD, while 20 patients had VD sufficiency. There was no significant correlation between 25OHD and different study parameters (p > 0.05). A significant difference was found among both groups in the family history of coronary heart disease (p = 0.036) and free tetraiodothyronine 4 (p = 0.035). After 4 months of VD supplementation in VDD group, the mean difference (at 0 and 4 months) in low-density lipoproteins (LDL) and hemoglobin A1c (HbA1c) was statistically significant (p = 0.02 and 0.04 respectively) between both groups. The mean basal LDL was 126.91 mg/dL in VDD group that improved to 117.13 mg/dL after 4 months of VD therapy with a mean difference of –9.7 mg/dL compared to a mean difference of –2 mg/dL in VD sufficiency group. Conclusions: VDD was highly prevalent in patients with T1D. There was no significant correlation between 25OHD levels and lipid profile in patients with T1D. VD supplementation for 4 months had a significant lowering effect on LDL and HbA1c.
Investigating the evolution and development of biological complexity under the framework of epigenetics

Biological complexity is a key component of evolvability, yet its study has been hampered by a focus on evolutionary trends of complexification and inconsistent definitions. Here, we demonstrate the utility of bringing complexity into the framework of epigenetics to better investigate its utility as a concept in evolutionary biology. We first analyze the existing metrics of complexity and explore the link between complexity and adaptation. Although recently developed metrics allow for a unified framework, they omit developmental mechanisms. We argue that a better approach to the empirical study of complexity and its evolution includes developmental mechanisms. We then consider epigenetic mechanisms and their role in shaping developmental and evolutionary trajectories, as well as the development and organization of complexity. We argue that epigenetics itself could have emerged from complexity because of a need to self‐regulate. Finally, we explore hybridization complexes and hybrid organisms as potential models for studying the association between epigenetics and complexity. Our goal is not to explain trends in biological complexity but to help develop and elucidate novel questions in the investigation of biological complexity and its evolution.