Miracle-dz/UniFAR-FTUs huggingface dataset:
672. Activity of Ibrexafungerp (Formerly SCY-078) Against Candida auris: In vitro, In Vivo, and Clinical Case Studies of Candidemia

Abstract Background Candida auris is a growing global threat; a pathogen associated with high mortality (up to 60%), multidrug resistance, the ability to spread from person-to-person and surface-to-person, presenting high risk for outbreaks in healthcare facilities. Ibrexafungerp is a novel IV/oral glucan synthase inhibitor (triterpenoid) antifungal with activity against Candida, Aspergillus, and Pneumocystis spp. , in Phase 3 development. Methods In vitro studies tested ibrexafungerp against >100 clinical isolates of C. auris. Other in vitro studies evaluated the effects of ibrexafungerp against C. auris biofilms. In vivo activity against C. auris was evaluated using a disseminated murine model and a cutaneous infection guinea pig model. In humans, an ongoing open-label trial of ibrexafungerp for treatment of patients with infections caused by C. auris (the CARES study) has been initiated in the United States and India. Results In vitro and in vivo studies demonstrated that ibrexafungerp is active against C. auris, including MDR strains. The MIC mode for ibrexafungerp was 1 μg/mL and the MIC50 and MIC90 were 0.5 and 1 μg/mL, respectively. Many echinocandin-resistant C. auris isolates have shown susceptibility to ibrexafungerp. Furthermore, ibrexafungerp has been shown to reduce biofilm thickness. In animal models of C. auris infection, treatment with ibrexafungerp resulted in improved survival and reduced fungal burden in both the murine model of disseminated infection and the guinea pig model of cutaneous infection as compared with untreated controls. In humans, two patients with difficult to treat C. auris candidemias were enrolled in the CARES study and responded positively to oral ibrexafungerp with eradication of the infection. Conclusion These data demonstrate that ibrexafungerp possess potent in vitro and in vivo activity as well as promising clinical activity. Therefore, continued clinical evaluation of ibrexafungerp as an option to treat C. auris infections is warranted. Disclosures All authors: No reported disclosures.
Evaluating the Delivery of a Teen Pregnancy and Parenting Program Across Two Settings

This article describes the challenges of evaluating an ongoing social work intervention after a change in delivery setting and offers several approaches to acquiring a fuller understanding of the program differences. The Teenage Pregnancy and Parenting (TAPP) program is a case management intervention operated by Families First in DeKalb County, Georgia, that is designed to help teen mothers (a) complete a high school diploma, (b) have a healthy pregnancy and develop parenting skills, and (c) avoid additional pregnancies. This article presents intake, service, and outcome data on program participants across two delivery settings—from the program's initial public health clinic-based setting to its current public school-based setting. Overall, the work demonstrates the strengths of the school-based version of TAPP and the difficulties of assessing the true effects of an ongoing program in the agency context.
An eight-mRNA signature predicts the prognosis of patients with bladder urothelial carcinoma

Background Bladder cancer is one of the most common cancers, and its histopathological type is mainly bladder urothelial carcinoma, accounting for about 90%. The prognostic biomarkers of bladder cancer are classified into clinical features biomarkers and molecular biomarkers. Nevertheless, due to the existence of individual specificity, patients with similar pathological characteristics still have great differences in the risk of disease recurrence. Therefore, it is often inaccurate to predict the survival status of patients based on clinical characteristic biomarkers, and a prognostic molecular biomarker that can grade the risk of bladder cancer patients is needed. Methods A total of three bladder urothelial carcinoma datasets were used in this study from the Cancer Genome Atlas database and Gene Expression Omnibus database. In order to avoid overfitting, all samples were randomly divided into one training set and three validation sets, which were used to construct and test the prognostic biomarker model of bladder urothelial carcinoma. Univariate and multivariate Cox regression were used to screen candidate mRNAs and construct prognostic biomarkers model. Kaplan–Meier survival analysis and the receiver operating characteristic (ROC) curve were used to evaluate the predictive performance of the model. Results A prognostic biomarker model of bladder urothelial carcinoma combining with eight mRNA was constructed. Kaplan–Meier analyses indicated that a significant difference in the survival time of patients between the high-risk and the low-risk group. The area under the ROC curve were 0.632 (95% confidence interval (CI) [0.541–0.723]), 0.693 (95% CI [0.601–0.784]) and 0.686 (95% CI [0.540–0.831]) when the model was used to predict the patient’s survival time in three validation datasets. The model showed high accuracy and applicability.
Impact of Air Pollution on Public Health

The air we breathe contains emissions from many different sources: industry, motor vehicles, heating and commercial sources, household fuels as well as tobacco smoke. The effects of air pollution on health have been intensively studied in recent years. The results of these studies showed that air pollution harms human health and particularly is harmful for those who are already vulnerable because of their age as children and older people or existing health problems. The epidemiological evidence suggests that adverse health effects are dependent on both exposure concentrations and length of exposure, and that long-term exposures have larger, more persistent cumulative effects than short-term exposures [1]. Ambient air pollution has been associated with a multitude of health effects, including mortality, respiratory and cardiovascular hospitalizations, changes in lung function and asthma attacks. Current scientific evidence indicates that air pollution from the combustion of fossil fuels causes a spectrum of health effects from allergy to death. Recent assessments suggest that the public health impacts may be considerable. Air pollution is associated with a broad spectrum of acute and chronic health effects, the nature of which may vary depending on constituent of the pollutants as well as the group of the population. Current exposure to PM from anthropogenic sources leads to the loss of 8.6 months of life expectancy in Europe – from around 3 months in Finland to more than 13 months in Belgium. The most recent estimates of impacts of PM on mortality, based on PM10 and PM2.5 monitoring data in 40 European countries, indicate that close to 500 000 deaths per year are accelerated due to exposure to ambient PM in those countries. According to the WHO Health Reports, air pollution at current levels in European cities is responsible for a significant burden of deaths, hospital admissions and exacerbation of symptoms, especially for cardiovascular disease. Because of the tremendous number of people affected, the impact of air pollution on cardiovascular disease represents a serious public health problem. Results from research studies have demonstrated a strong relationship between levels of airborne particles, sulfur dioxide and other fossil fuel emissions and risk of early death from heart disease. People with pre-existing conditions such as high blood pressure, previous heart disease, diabetes, respiratory disease and high cholesterol have been shown to be especially vulnerable. The results of a long-term study on influence of common air pollutants on health of US residents showed that individuals living in the more polluted cities had a higher risk of hospitalization and early death from pulmonary and heart
EL EMBARAZO EN ADOLESCENTES COMO FACTOR DE RIESGO ASOCIADO AL INCREMENTO DE LA MORBILIDAD NEONATAL EN PACIENTES QUE ACUDIERON AL SERVICIO DE OBSTETRICIA DE LA CLINICA SAN SEBASTIÁN DE AMBATO DE ENERO A DICIEMBRE / 2013

This current research work goes through the universe of pregnancy among teenage mothers attended in San Sebastian de Ambato Clinic during the year 2013, looking forward to determining the possible risk factors that affect teenage mothers and to the new being due to anatomical and physiological conditions of its parent, who presents high probability of immaturity complications, low weight when born, among others, that reach 40% in developing countries such as Ecuador. Very few of these pregnancies have been planned or desired by the teenagers, in some other cases they are forced because of the social pressure to get married early and therefore premature pregnancies, or they are also result of teenagers who do not have opportune and clear information on sexuality. Pregnancy among teenagers could have unfavorable consequences for health in a short or long term, for both teenage mothers and specially the newborn babies. This has been proven by several studies, identifying very specific morbidity such as low weight and immaturity with all the consequences this involves, increasing the congenital malformation risk, infectious pathologies, among others. This current research, determines the existent correlation between teenage pregnancy and the newborn baby morbidity increase in relation to general newborn baby morbidity, considering as study population to the pregnant teenagers who attended the pre-birth, birth and post-birth in the period between January to December 2013 in the obstetrics service of San Sebastian de Ambato Clinic.
Cabozantinib in advanced non-clear-cell renal cell carcinoma: is it the way clearer now?

Martinez Chanza et al. (1) investigated the activity of cabozantinib (an inhibitor of multiple tyrosine kinase receptors) in a multicentre, retrospective, cohort study carried out by 22 centres that involved 122 patients with metastatic renal cell carcinoma (RCC) with confirmed non clear cell histology treated in any line of therapy between 2015 and 2018.
Neuropsychiatric symptoms and activities of daily living in Alzheimer’s disease: ALSOVA 5-year follow-up study

ABSTRACT Background: Neuropsychiatric symptoms (NPSs) in Alzheimer’s disease (AD) are related to activities of daily living (ADLs), but longitudinal studies are sparse. Objectives: We investigated which NPSs were related to decline in instrumental ADLs (IADLs) and basic ADLs (BADLs) in a 5-year follow-up of individuals with AD. Methods: ALSOVA 5-year follow-up study data of 236 individuals with very mild or mild AD at baseline and their caregiver were analyzed. IADLs and BADLs were assessed with Alzheimer’s Disease Cooperative Study ADL inventory, and NPSs with Neuropsychiatric Inventory at annual follow-up visits. Generalized estimating equations (GEEs) were used for longitudinal data analysis, and NPS–ADL networks were estimated to demonstrate symptom interactions. Results: Apathy [rate ratio (RR) 1.23, 95% CI 1.06–1.44, p = 0.007], aberrant motor behavior (RR 1.24, 95% CI 1.07–1.44, p = 0.005), and appetite disturbances (RR 1.22, 95% CI 1.06–1.41, p = 0.005) were related to impairment in BADLs, and the same symptoms (RR 1.13, 95% CI 1.07–1.21, p < 0.001; RR 1.13, 95% CI 1.07–1.20, p < 0.001; RR 1.14; 95% CI 1.08–1.21, p < 0.001, for apathy, aberrant motor behavior, and appetite disturbances, respectively), in addition to delusions (RR 1.09, 95% CI 1.03–1.15, p = 0.004), were related to IADL impairment. Symptom networks varied at different time points. Conclusion: As AD progresses, common (apathy) and uncommon NPSs (aberrant motor behavior, appetite disturbances, delusions) seem to be related to ADLs through various symptom interactions. Previous literature suggests that frontal pathology could underlie these relationships.
DNA Methylation and its Association with Prenatal Exposures and Pregnancy Outcomes

Objective: We assessed the impact of prenatal smoking on DNA methylation and the association between methylation and risk of small for gestational age (SGA). Methods: Medical record data and biological samples from 90 singleton births were obtained from an ongoing, cross-sectional study. Cigarette smoke exposure was determined by measuring cotinine in plasma and CpG site-specific methylation in DNA extracted from umbilical cord blood was measured with the Illumina Infinium Methylation27 assay. Gene-level methylation was calculated by averaging the methylation levels over the CpG sites interrogated in that gene. Maternal and infant characteristics were compared by SGA status as well as by hypermethylation status using fisher’s exact test and t-tests as appropriate. Logistic regression was used to generate adjusted odds ratios (OR) and 95% confidence intervals (CI) for the association between SGA and methylation of CYP1A1, HIF1A, GSTT1, and GSTM1 and the association between cotinine level and hypermethylation of the aforementioned genes. Results: SGA infants were less likely to have adequate prenatal care and were more likely to be black and female. Infants with hypermethylation of GSTT1 were more likely to be black. A 0.10 unit increase in methylation of GSTT1 increased the risk of SGA
The role of online support groups in empowering individuals affected by prostate cancer

The psychosocial challenges of living with prostate cancer have been well documented. Whilst information and support can help ameliorate these challenges, research points towards several barriers to obtaining support face-to-face. Recent research suggests that online support groups can help empower members to become active healthcare participants. Few studies, however, have examined the role of these groups in the context of prostate cancer. This research programme seeks to examine how, if at all, participation within prostate cancer online support groups empowers members. In Study 1, an analysis of 631 messages posted to prostate cancer online support groups was undertaken to explore the beneficial processes observed in members’ communication. In Study 2, open-ended surveys were employed to collect qualitative data from 147 members to explore their perception of empowering processes and outcomes within the groups. In Study 3, quantitative surveys (n=195) were employed to examine the extent to which members experience these processes and outcomes and the relationship between the two. The findings point towards the existence of several empowering processes, such as informational and emotional support exchange, encountering similar others and the ability to discuss sensitive issues. Empowering outcomes commonly experienced by the members included increased knowledge, the ability to participate in treatment-related decisions, an increased sense of community and enhanced communication with their medical practitioner. The processes significantly predicted the outcomes, with ‘information exchange’ consistently being the most significant predictor. This indicates that the processes, and particularly informational support in these groups, play an important role in empowering members. Although some negative processes have been identified, the positive aspects outweigh the negatives. These findings suggests that prostate cancer online support groups can be an effective and cost-efficient source of support and information for prostate cancer patients and their caregivers, and have a significant impact on their sense of empowerment.
THE ROLE OF THE GUT MICROBIOTA IN LIVER DISEASE.

The gut microbiome is the natural intestinal inhabitant that has been recognized recently as a major player in the maintenance of human health and the pathophysiology of many diseases. Those commensals produce metabolites that have various effects on host biologic functions. Therefore, alterations in the normal composition or diversity of microbiome have been implicated in various diseases, including liver cirrhosis and nonalcoholic fatty liver disease. Moreover, accumulating evidence suggests that progression of dysbiosis can be associated with worsening of liver disease. Here, we review the possible roles for gut microbiota in the development, progression and complication of liver disease.
The Allocation of Publicly-Funded Biomedical Research

We develop a simple theoretical model of the allocation of public biomedical research expenditure, and present some empirical evidence about the determinants of this allocation. The structure of expenditure should depend on the relative costs as well as the relative benefits of different kinds of research. Analysts of technical change typically have data on neither of these, but the measures of disease burden we use are indicative of the benefit of achieving advances against different diseases. We calculate distributions of government-funded biomedical research expenditure, by disease, from records of all research projects supported by the US Public Health Service: to obtain a reasonably complete accounting of disease burden, we utilize data on both the dying (from the Vital Statistics-Mortality Detail file) and the living (from the National Health Interview Survey). We find a very strong positive relationship across diseases between total life-years lost before age 65 and public R&D expenditure. But the amount of publicly-funded research on a disease decreases with the share of life-years before age 65 lost to the deases by non-whites, perhaps because lack of scientific knowledge is a less important cause of premature mortality among non-whites than it is among whites. The number of research grants mentioning a chronic condition is completely uncorrelated with the number of people with the condition but very strongly positively related to the number of people whose activities are limited by that condition. There tends to be more research about chronic conditions that are prevalent among people living in low-income households, and that are prevalent among the young (under age 18) and the old (above age 75).
Allylic hydroxylation of triterpenoids by a plant cytochrome P450 triggers key chemical transformations that produce a variety of bitter compounds

Cucurbitacins are highly oxygenated triterpenoids characteristic of plants in the family Cucurbitaceae and responsible for the bitter taste of these plants. Fruits of bitter melon (Momordica charantia) contain various cucurbitacins possessing an unusual ether bridge between C5 and C19, not observed in other Cucurbitaceae members. Using a combination of next-generation sequencing and RNA-Seq analysis and gene-to-gene co-expression analysis with the ConfeitoGUIplus software, we identified three P450 genes, CYP81AQ19, CYP88L7, and CYP88L8, expected to be involved in cucurbitacin biosynthesis. CYP81AQ19 co-expression with cucurbitadienol synthase in yeast resulted in the production of cucurbita-5,24-diene-3β,23α-diol. A mild acid treatment of this compound resulted in an isomerization of the C23-OH group to C25-OH with the concomitant migration of a double bond, suggesting that a nonenzymatic transformation may account for the observed C25-OH in the majority of cucurbitacins found in plants. The functional expression of CYP88L7 resulted in the production of hydroxylated C19 as well as C5-C19 ether-bridged products. A plausible mechanism for the formation of the C5-C19 ether bridge involves C7 and C19 hydroxylations, indicating a multifunctional nature of this P450. On the other hand, functional CYP88L8 expression gave a single product, a triterpene diol, indicating a monofunctional P450 catalyzing the C7 hydroxylation. Our findings of the roles of several plant P450s in cucurbitacin biosynthesis reveal that an allylic hydroxylation is a key enzymatic transformation that triggers subsequent processes to produce structurally diverse products.
Resistencia a insecticidas en larvas y adultos de Aedes aegypti: prevalencia de la esterasa A4 asociada con la resistencia a temefos

: 2 strains of Aedes aegypti from 2 people's councils with high indexes of infestation of this vector were studied due to the need of carrying out an effective control of larvae and adults in the municipality of Guanabacoa. The levels of susceptibility and/or resistance to organophosphate insecticides, pyrethroids and a carbamate were determined. The results of the bioassays in larvae showed a complete susceptibility to organophosphate insecticides, malathion, clorpirifos, methyl-pyrimifos and propoxur carbamate in both people's councils. However, it was observed a high resistance to temephos and fenthion. No resistance to fenitrothion was found in one of the people's councils. At the adult stage and at the dose recommended by the World Health Organizaton or by the product manufacturers, it was observed resistance to malathion, fenitrothion and propoxur; nevertheless, better results were obtained with the pyrethroids, with mortality percentages over 90%. According to the results obtained, by using the SSS tributyl phosphotritiade sinergist (DEF) and piperonyl butoxide, it was demonstrated that the multiple function esterases and oxidases played an important role in the resistance to temephos and fenthion. It was proved that he amplified activity of these enzymes was at an elevated frequency in both people's councils, the same as the glutathione transferase (GST) in one of the 2 people's councils. It was observed that in both people's councils prevailed the amplified activity of A4 esterases by polyacrylamide gel electrophoresis.
Clinical predictors of asthmatics in identifying subgroup requiring long-term tiotropium add-on therapy: a real-world study.

Background According to several phase III studies, tiotropium [a long-acting muscarinic antagonist (LAMA)] is a well-tolerated add-on therapy to inhaled corticosteroids (ICS) for asthmatics with or without the addition of long-acting beta2-agonists (LABAs). However, real-world studies based on clinical phenotypes to predict the long-term need of tiotropium as an add-on therapy for asthmatics are limited. Methods This is a retrospective study conducted at a single medical center in Taiwan from July 2016 to July 2018. An asthma control test (ACT) is applied to uncontrolled asthmatics to evaluate the effectiveness of tiotropium as an add-on therapy. Asthmatic subgroups with different clinical phenotypes and needing long-term tiotropium as a maintenance treatment are identified. The effectiveness of tiotropium add-on therapy is defined as an improvement of ACT score ≥3 points 3 months after the treatment (vs. baseline), while the long-term requirement of tiotropium is defined as tiotropium dependency >1 year. Results The study analyzed a total of 160 uncontrolled asthmatics regardless of low- or medium-to-high-dose ICS plus LABA. One hundred and twelve patients responded well (ACT score increased ≥3 points) to tiotropium. These patients were further divided into two subgroups: one with tiotropium add-on therapy for ≥1 year due to patients' difficulties in stepping down from tiotropium; the other with tiotropium add-on therapy for <1 year due to successful step-down treatment according to Global Initiative for Asthma (GINA) score. All clinical characteristics of these two groups were collected and analyzed. Univariate and multivariate analyses showed that asthma-and-chronic obstructive pulmonary disease (COPD)-overlap (ACO), initial forced expiratory volume-one second (FEV1) % predicted <80%, or body mass index (BMI) >30 kg/m2 were predictors for asthmatics requiring long-term tiotropium add-on therapy. Conclusions Tiotropium add-on therapy is effective for uncontrolled asthmatics. Moreover, patients with ACO, initial FEV1% predicted <80%, or BMI >30 kg/m2 require long-term tiotropium add-on therapy for asthma control.