Miracle-dz/UniFAR-FTUs huggingface dataset:
In silico QSAR modeling to predict the safe use of antibiotics during pregnancy

Abstract The use of medicines during pregnancy is a growing public health concern due to the risk of developmental toxicity. Healthcare providers heavily rely on the FDA pregnancy risk categories (A, B, C, D, and X). Antibiotics are among the most prescribed drugs during pregnancy and are often listed under category B or C. However, the risk-benefit assessment may be lacking due to challenges in the clinical toxicology studies on pregnant women, such as ethical concerns. The primary focus of this study is to generate a model that predicts the safe use of antibiotics during pregnancy by using in silico approaches. Thus, a QSAR model was created to assess the FDA pregnancy category (B or C) of antibiotics. The dataset consisted of 97 antibiotics obtained from the FDA. A total of 6420 molecular descriptors were determined via multiple software and various machine learning algorithms were utilized. The performance of the models was measured using internal and external validation. The accuracy (ACC) values of the most successful model were 83.82% for the internal and 94.11% for the external validation. Sensitivity (SE), specificity (SP), MCC, and ROC values were 0.878, 0.778, 0.68, and 0.892 for the internal validation and 0.9, 1, 0.887, and 0.936 for the external validation, respectively. Kappa statistics also indicate that there was a substantial agreement for internal validation with 0.6765 and an almost perfect agreement for external validation with 0.8811. In conclusion, our model can be used as an initial step before pre-clinical and clinical studies to predict the safe use of antibiotics in pregnancy.
The Spatial Distribution of Gamma-Ray Bursts Observed by BATSE

An improvement of a combination motor and auxiliary cleaning mechanism actuator is included in a manually operated, rotary cleaning machine. The actuator includes an elongated actuator member mounted on the handle of the machine for movement among at least three actuator positions. The actuator member extends alongside the handle grip portion of the machine handle between two handle grips. Springs bias the actuator member to the first actuator position. Movement of the actuator member to the second actuator position places a first switch in an energizing state for energizing the motor of the machine, and movement of the actuator member to the third actuator position places a second switch in an energizing state for energizing an auxiliary cleaning mechanism of the machine.
Relationships of pulsed frequency and anammox bacteria growth rate, at low temperatures

ABSTRACT This study explored pulsed frequency that could enhance the anammox bacteria growth rate and TN removal rate at low temperatures (16 ± 1°C). The results showed that the growth rate of anammox bacteria in R1 (1000 Hz) was significantly higher than in R2 (30 Hz) and R3 (106Hz). The relative abundance values of anammox bacteria R1 were higher by 52.21% and 172.41% than R2 and R3, while that of MLSS were as high as 241.07% and 471.36% than R2 and R3, with the nitrogen loading rate was 6.84 kg-N/m³/d. Besides, the dynamics also showed that the specific anammox activity (SAA) and the cellular yield of R1 were higher than R2 and R3. The intermediate frequency could enhance the cell division by stimulating the anammoxosome and reduce the ionic hydration layer to accelerate the ion migration rate, further improving the number of anammox bacteria even at low temperatures. The pulsed frequency could enhance the anammox growth rate and the doubling time is just 5 d. GRAPHICAL ABSTRACT
SPEACH_AF: Sampling protein ensembles and conformational heterogeneity with Alphafold2

The unprecedented performance of Deepmind’s Alphafold2 in predicting protein structure in CASP XIV and the creation of a database of structures for multiple proteomes and protein sequence repositories is reshaping structural biology. However, because this database returns a single structure, it brought into question Alphafold’s ability to capture the intrinsic conformational flexibility of proteins. Here we present a general approach to drive Alphafold2 to model alternate protein conformations through simple manipulation of the multiple sequence alignment via in silico mutagenesis. The approach is grounded in the hypothesis that the multiple sequence alignment must also encode for protein structural heterogeneity, thus its rational manipulation will enable Alphafold2 to sample alternate conformations. A systematic modeling pipeline is benchmarked against canonical examples of protein conformational flexibility and applied to interrogate the conformational landscape of membrane proteins. This work broadens the applicability of Alphafold2 by generating multiple protein conformations to be tested biologically, biochemically, biophysically, and for use in structure-based drug design.
Effects of Cimicifuga racemosa (L.) Nutt on sexual function in women receiving tamoxifen for breast cancer

Abstract To assess the effects of Cimicifuga racemosa (L.) Nutt on climacteric symptoms and sexual function in women receiving tamoxifen after breast cancer treatment. A prospective study of women treated at the Mastology Outpatient Clinic of the Department of Obstetrics and Gynecology of the Santa Casa de Sao Paulo School of Medical Science of the hospital was conducted between 2018 and 2021. Patients diagnosed with breast cancer that underwent surgical, radiotherapy and chemotherapy treatment more than one year prior, receiving tamoxifen, exhibited climacteric symptoms and were sexually active were selected. Total of 34 women were recruited and during outpatient visits completed sociodemographic questionnaire, Blatt-Kupperman Index (KI) and Female Sexual Function Index (FSFI). The group showed improvements in climacteric symptoms (p<.001) and sexual function (p=.011) after the 6-month follow-up. Cimicifuga racemosa (L.) Nutt promoted improvements in climacteric symptoms and sexual function in women surgically treated for breast cancer. Clinical Trials.gov ID: NCT02467686. Impact Statement What is already known on this subject? The medications used for the treatment of breast cancer can lead to important complaints of vasomotor manifestations with a negative impact on the success of their treatment, and cases have been described until their interruption. Cimicifuga racemosa (L.) Nutt. is described in several works as a therapy to alleviate these symptoms. Numerous works in the literature present climatic symptoms and sexual function with a selective approach to the themes. What do the results of this study add? Our study evaluated a group of women who were treated for breast cancer after menopause taking into account the following aspects: climacteric symptoms and sexual function. When we reviewed the literature, we did not find, so far, work similar to ours. What are the implications of these findings for clinical practice and/or further research? In clinical practice, assessing vasomotor symptoms and sexual response of breast cancer patients can contribute towards improving the lives of this patient group. Prescribing Cimicifuga racemosa (L.) Nutt in cases with climacteric complaints and poor sexual response can relieve distress and promote better health and life status for these women. Although the present investigation has generated important data on female breast cancer survivors, there are limitations regarding the number of participants. We recommend further clinical research with expansion of the sample studied and the results presented.
Dietary exposure to low-calorie sweeteners in a sample of Brazilian pregnant women

Abstract The dietary exposure to low-calorie sweeteners (LCS) was estimated in a sample of pregnant Brazilian women. Consumption data were obtained with a 24-h Dietary Recall interview. Because of the uncertainty in assessing foods with LCS, they were classified into three scenarios to ensure inclusion of the 15 LCS allowed for use in Brazil: ranging from a less to a more conservative scenario. The concentration of LCS was estimated using the amount declared on the label or the maximum permitted levels and analytical determination data for table-top sweeteners. The frequency of consumption was higher for acesulfame-K, aspartame, and cyclamate. The food groups contributing the most to the consumption of LCS were non-alcoholic beverages, table-top sweeteners, confectionary and desserts. The level of dietary exposure to LCS was within the safety limit. However, continued efforts to monitor their dietary exposure are necessary given the limitations highlighted in this study.
Association of the Maryland Medicaid Behavioral Health Home Program with Cancer Screening in People with Serious Mental Illness

Objective: Cancer is the second leading cause of death in people with serious mental illness (SMI), yet cancer screening rates are low. This study evaluated the association of the Maryland Medicaid behavioral health home (BHH) integrated care program on cancer screening. Methods: Using administrative claims data from October, 2012-September, 2016 among adults eligible for cervical (n=6,811), breast (n=1,658), and colorectal (n=3,430) cancer screening, 27% (n=3298) of the population had ever enrolled in a BHH and the remaining never enrolled. Marginal structural modeling was used to examine the association between BHH enrollment and receipt of annual cancer screening. Results: Relative to non-enrollment, BHH enrollment was associated with increased screening for cervical and breast cancer but not for colorectal cancer. Predicted annual rates remained low, even in BHHs. Conclusions: Despite potential improvements after BHH implementation, cancer screening rates remain suboptimal. Broader interventions are needed to improve cancer screening for people with SMI.
Deciding to Visit the Emergency Department for Non-Urgent Conditions: A Systematic Review of the Literature

Background— A large proportion of all emergency department (ED) visits in the U.S. are for non-urgent conditions. Use of the ED for non-urgent conditions may lead to excessive healthcare spending, unnecessary testing and treatment, and weaker patient-primary care provider relationships. Objectives— To understand the factors influencing an individual’s decision to visit an ED for a non-urgent condition Methods— We conducted a systematic literature review of the U.S. literature. Multiple databases were searched for studies published after 1990, conducted in the U.S., and which assessed factors associated with non-urgent ED use. Based on those results we developed a conceptual framework. Results— Twenty-six articles met inclusion criteria. No two articles used the same exact definition of non-urgent visits. Across the relevant articles, the average fraction of all ED visits that were judged to be non-urgent (whether prospectively at triage or retrospectively following ED evaluation) was 37% (range: 8–62%). Articles were very heterogeneous with respect to study design, population, comparison, group, and non-urgent definition. The limited evidence suggests that younger age, convenience of the ED compared to alternatives, referral to the ED by a physician, and negative perceptions about alternatives such as primary care providers all play a role in driving nonurgent ED use. Conclusion— Our structured overview of the literature and conceptual framework can help to inform future research and the development of evidence-based interventions to reduce non-urgent ED use.
Effects of Early-Life Stress on 5-HT 1A Receptors in Juvenile Rhesus Monkeys Measured by PET

Background— Traumatic experiences in early childhood are associated with increased risk for developing mood and anxiety disorders later in life. Low serotonin 1A receptor (5-HT 1A R) density during development has been proposed as a trait-like characteristic leading to increased vulnerability of stress-related neuropsychiatric disorders. Methods— To assess the relationship between early-life stress and alterations in the serotonin system during development, we used positron emission tomography (PET) to measure in vivo 5-HT 1A R density and apparent dissociation constant (K Dapp ) in the brain of juvenile rhesus monkeys exposed to the early-life stress of peer-rearing. Results— In general, 5-HT 1A R density and K Dapp were decreased in peer-reared compared with control mother-reared animals. However, increase in receptor density was found in the dorsomedial prefrontal cortex of peer-reared females. Conclusions— These findings suggest that exposure to an adverse early-life environment during infancy is associated with long-term alterations in the serotonin system and, support previous studies suggesting that reduced 5-HT 1A R density during development may be a factor increasing vulnerability to stress-related neuropsychiatric disorders. Further, alterations in the serotonin system appeared to be gender- and region-specific, providing a biological basis for the higher prevalence of affective disorders in women. Low 5-HT 1A R binding, measured by PET and in vitro binding assays of postmortem brain tissue, is found in individuals with several anxiety-related disorders, including depression, social anxiety and panic disorders (1–8). Moreover, a spontaneous variation in the HTR1A gene promoter that results in lower levels of HTR1A expression (9) is also associated with anxiety-related personality traits (10).
Neuroanatomical patterns of the ,u, 6, and Kc opioid receptors of rat brain as determined by quantitative in vitro autoradiography

Highly specific radioligands and quantitative autoradiography reveal strikingly different neuroanatomical patterns for the ,u, 8, and K opioid receptors of rat brain. The ,I receptors are most densely localized in patches in the striatum, layers I and III ofthe cortex, the pyramidal cell layer of the hippocampal formation, specific nuclei of the thalamus, the pars reticulata of the substantia nigra, the interpeduncular nucleus, and the locus coeruleus. In contrast, 8 receptors are highly confined, exhibiting selective localization in layers I, H, and VIa of the neocortex, a diffuse pattern in the striatum, and moderate concentration in the pars reticulata of the substantia nigra and in the interpeduncular nucleus. 8 receptors are absent in most other brain structures. This distribution is unexpected in that the enkephalins, the putative endogenous ligands of the 8 receptor, occur essentially throughout the brain. The K receptors of rat brain exhibit a third pattern distinct from that of the ,u and 8 receptors. K receptors occur at low density in patches in the striatum and at particularly high density in the nucleus accumbens, along the pyramidal and molecular layers of the hippocampus, in the granular cell layer of the dentate gyrus, specific midline nuclei of the thalamus, and hindbrain regions. K receptors appear to be uniformly distributed across regions in the neocortex with the exception of layer m, which revealed only trace levels of binding. An important conclusion of the present study is that 8 receptors occur at high density only in the forebrain and in two midbrain structures, whereas ,u and K receptors exhibit discrete
A Route to Well-being: Intelligence vs. Wise Reasoning

Laypeople and many social scientists assume that superior reasoning abilities lead to greater wellbeing. However, previous research has been inconclusive. This may be because prior investigators used operationalizations of reasoning that favored analytic as opposed to wise thinking. We assessed wisdom in terms of the degree to which people use various pragmatic schemas to deal with social conflicts. With a random sample of Americans we found that wise reasoning is associated with greater life satisfaction, less negative affect, better social relationships, less depressive rumination, more positive vs. negative words used in speech, and greater longevity. The relationship between wise reasoning and well-being held even when controlling for socioeconomic factors, verbal abilities, and several personality traits. As in prior work there was no association between intelligence and well-being. Further, wise reasoning mediated age-related differences in well-being, particularly among the middle-aged and older adults. Implications for research on reasoning, well-being and aging are discussed. age (B = .186, SE = .065, |t| = 2.87, p = .004). Simple slopes analyses (Aiken, et al., 1996) indicated that middle-aged participants who scored low (10th quantile) on wise reasoning showed similarly high mortality probability as their older counterparts (B = .022, SE = .037, |t| < 1, ns.). However, middle-aged participants who scored above average (50 th quantile) on wise reasoning showed significantly lower mortality probability than their older counterparts (B = 1.208, SE = .036, |t| = 3.33, p < .001). In addition, wise reasoning did not significantly contribute towards greater longevity among participants above 67 years of age (|B|< 2.299, SE = 1.644, |t| = 1.40, p = .16). Note, however, that the death numbers in the present study were fairly small, thus interaction results have to be interpreted with caution.
In-the-moment drinking characteristics: An examination across ADHD history and race

Background— Adults with a history of childhood attention-deficit/hyperactivity disorder (ADHD) and Black drinkers are at elevated risk for alcohol problems and alcohol use disorder. Processes that increase risk for these distinct populations have not focused on in-the-moment behaviors that occur while drinking. The present study examined in-the-moment drinking characteristics (i.e., location, social context, day, time, drink type, speed of consumption) that may differ for individuals with and without ADHD histories or for Black and White drinkers. We also examined the interplay among these in-the-moment drinking characteristics to further understanding of contexts when risk may be momentarily increased. Methods— As part of a larger study, 135 individuals (M age = 27.81, 69.6% male, 45.9% ADHD, 69.6% White) completed a 10-day ecological momentary assessment protocol that included self-initiated reports following consumption of an alcoholic drink. Hypotheses were tested using multilevel modeling. Results— Controlling for multiple demographic covariates, Black drinkers drank significantly more quickly than White drinkers and were more likely to consume hard liquor-containing beverages. Differences in drinking speed remained significant when adjusting for Black drinkers’ greater likelihood to consume liquor-containing beverages and momentary experience of discrimination; however, Black drinkers’ increased likelihood to consume liquor-containing beverages was no longer significant when adjusting for momentary experience of discrimination. Individuals with ADHD histories did not differ from those without ADHD histories in any in-the-moment drinking characteristics. ADHD and race did not interact to predict any drinking characteristic. Conclusions— Differences in speed of alcohol consumption and propensity to consume liquor containing beverages may contribute to increased risk for alcohol problems experienced by Black drinkers compared to White drinkers. potential outcome of occurring risk processes. We found no statistically significant interactions small effect in our A power simulation conducted in using for observed effect observed assessment cluster structure indicated . 38 to for of to test
“For how long are we going to take the tablets?” Kenyan stakeholders’ views on priority investments to tackle Soil-transmitted Helminths illuminate aid-dependency and sustainability

Recent global commitments to shift responsibility for Neglected Tropical Disease (NTD) control to affected countries reflect a renewed emphasis on sustainability, away from aid-dependency. This calls for a better understanding of how domestic stakeholders perceive investments in different strategies for NTD control. Soil transmitted helminths (STH) are among the NTDs targeted for elimination as a public health problem by international agencies through mass drug administration, provided periodically to at-risk population groups, often using drugs donated by pharmaceutical companies. This study was conducted in Kenya at a time when responsibilities for long running STH programmes were transitioning from external to national and sub-national agencies. Following an initial assessment in which we identified key domestic stakeholders and reviewed relevant scientific and government documents, the perspectives of stakeholders working in health, education, community engagement and sanitation were investigated through semi-structured interviews with national level policymakers, county level policymakers, and frontline implementers in one high-STH burden county, Kwale. Our conceptual framework on sustainability traced a progression in thinking, from ensuring financial stability through the technical ability to adapt to changing circumstances, and ultimately to a situation where a programme is prioritised by domestic policymakers because empowered communities demand it. It was clear from our interviews that most Kenyan stakeholders sought to be at the final stage in this progression. Interviewees criticised long-term investment in mass drug administration, the approach favoured predominantly by external agencies, for failing to address underlying causes of STH. Instead they identified three synergistic priority areas for investment: changes in institutional structures and culture to reduce working in silos; building community demand for and ownership; and increased policymaker engagement on underlying socioeconomic and environmental causes of STH. Although challenging to implement, the shift in responsibility from external agencies to domestic stakeholders may lead to emergence of new strategic directions.
th Risk , Diagnosis and Treatment of Cardiovascular Disease in Women

H ypertension (HTN) is recognized worldwide as the leading risk factor for death and disability in adults. It kills more people globally than does tobacco use (9 vs 6 million). Approximately 1 billion adults worldwide have high blood pressure (BP), and this number is expected to increase to 1.56 billion by 2025. The World Health Organization has reported a global HTN prevalence of 40%, which is compounded by genetic factors, lifestyle choices, salt-rich diets, and physical inactivity. According to the National Health and Nutrition Examination Survey, one third of adults >20 years old in the United States have HTN. Self-reported rates of HTN are similar (Fig. 1). In the U.S. population, 64.9% of adults older than age 60 years develop HTN, and only half have well-controlled BP. By age 50 years, isolated systolic HTN is the prevalent form of HTN, and systolic BP (SBP) is the main risk predictor for stroke, adverse coronary events, heart failure, and end-stage renal disease (ESRD). The control and treatment of HTN is associated with a reduced risk of cardiovascular (CV) disease, including stroke (by 35%–40%), myocardial infarction (MI) (by 15%–25%), and heart failure (by up to 50%). Although results of observational studies have suggested an increasing CV risk associated with SBP >110 mmHg, the guidelines for the treatment of HTN provided in The Seventh Report of the Joint National Committee in 2008 and The Eighth Report of the Joint National Committee in 2014 were based on randomized trials in which specific drug regimens (thiazide-based diuretics, calcium channel blockers, and β-receptor blockers) and not specific BP-treatment targets were evaluated. The guidelines were formulated on the basis of strong clinical trial evidence to support the treatment of HTN in patients older than 60 years to a BP goal <150/90 mmHg; and in those of age 30 to 59 years, to a diastolic goal of <90 mmHg. Evidence was insufficient to make stricter or broader treatment recommendations.