Miracle-dz/UniFAR-FTUs huggingface dataset:
Epidemiology of Dandy-Walker Malformation in Europe: A EUROCAT Population-Based Registry Study

Background: Dandy-Walker (DW) malformation is a rare and severe congenital anomaly of the posterior fossa affecting the development of the cerebellum and the fourth ventricle. Objective: The aim of this study was to investigate the epidemiology of DW malformation, using data from the European population-based registries of congenital anomalies in the European Surveillance of Congenital Anomalies network. Methods: Anonymous individual data on cases of DW malformation diagnosed in 2002–2015 from 28 registries in 17 countries were included. Prevalence, prenatal detection rate, proportions and types of associated anomalies were estimated. Cases of DW variant were considered and analysed separately. Results: Out of 8,028,454 surveyed births we identified a total of 734 cases, including 562 DW malformation cases and 172 DW variant cases. The overall prevalence of DW malformation was 6.79 per 100,000 births (95% CI 5.79–7.96) with 39.2% livebirths, 4.3% foetal deaths from 20 weeks gestational age, and 56.5% terminations of pregnancy after prenatal diagnosis of foetal anomaly at any gestation (TOPFA). The livebirth prevalence was 2.74 per 100,000 births (95% CI 2.08–3.61). The prenatal detection rate was 87.6%. Two-hundred and seventy-three cases (48.6%) had an isolated cerebral anomaly and 24.2, 19.2 and 5.5% cases were associated with other structural non-cerebral anomalies, chromosomal anomalies and genetic syndromes respectively. The prevalence of DW variant was 2.08 per 100,000 (95% CI 1.39–3.13). Conclusions: This European population-based study provides the epidemiological profile of DW malformation. All birth outcomes were analysed and TOPFA represented more than half of the cases. About 50% of the cases of DW malformation were associated with other non-cerebral anomalies. Large populations and all birth outcomes are essential in epidemiological studies of rare and severe congenital anomalies.
The effects of radio-frequency radiation (RFR) exposure on the analgesic efficacy of morphine in healthy rats and rats with inflammation.

OBJECTIVES The aim of this study, conducted at the Military Institute of Hygiene and Epidemiology in Warsaw in 2017, was to evaluate the effects of a single (15 min) and repeated (5 times for 15 min) radio-frequency radiation (RFR) exposure of 1800 MHz frequency on the analgesic efficacy of morphine in healthy rats and rats with complete Freund's adjuvant (CFA) induced inflammation. MATERIAL AND METHODS Rats were injected intraperitoneally with morphine (MF) in the dose of 8 mg/kg or drug vehicle 15 min before RFR exposure. The authors used the plantar analgesia meter and the radiant heat paw-withdrawal test to assess the pain threshold. RESULTS A single RFR exposure slightly influenced paw withdrawal latency (PWL) in healthy rats in the single exposure baseline group, and influenced PWL, 30 and 60 min after morphine or vehicle injection, in the repeated exposure group. There were differences between the sham-exposed groups (vehicle), 30, 60 and 90 min after injection, both in the single and repeated RFR-exposure groups. The antinociceptive effect of morphine in healthy rats was slightly decreased by RFR exposure at 60 and 90 min, both in the single and repeated exposure groups. The PWL was slightly decreased, both in the single and repeated exposure groups with inflammation (CFA and CFA/MF), at 30, 60 and 90 min, and PWL was increased in the sham-exposed groups (CFA and CFA/MF), both in the single and repeated exposure groups, at 30, 60 and 90 min. The antinociceptive effect of morphine in healthy rats was significantly increased by RFR exposure at 30 min after drug injection in the single exposure group, and increased at 30 and 60 min in the repeated exposure group. CONCLUSIONS The authors observed a minor influence of RFR exposure on the antinociceptive effects of morphine in healthy rats after repeated exposures and a statistically significant influence of repeated exposure on morphine mediated antinociceptive effects in the inflammation group. Int J Occup Med Environ Health. 2019;32(4):465-74.
A randomized controlled trial of problem-solving training (PST) for hematopoietic stem cell transplant (HSCT) patients: Effects on anxiety, depression, distress, coping and pain

Abstract The effect of problem-solving training (PST) on psychological distress, coping, pain, overall distress, and problem-solving behavior in hematopoietic stem cell transplant (HSCT) patients was investigated in a randomized controlled trial. The intervention was performed during aplasia and included five 1-hour individual sessions; it was started 2 days before HSCT. Forty-five patients were included in the intervention group (IG) and 46 in the control group (CG). The effects were measured at 11 (t2) and 21 days (t3) after HSCT. At t2, 31 patients remained in the IG and 36 patients in the CG. Patients > 18 years, with adequate cognitive performance, and with adequate command of the German language, were included. They were assessed with regard to anxiety and depression (Hospital Anxiety and Depression Scale), psychological distress (Symptom Checklist short version–9), coping (Brief Cope), problem-solving (Social Problem Solving Inventory-Revised), pain (Questions of Pain), and distress (National Comprehensive Cancer Network Distress Thermometer). The data were analyzed using analyses of covariance (general linear model) to examine the differences between the two conditions. Anxiety, psychological distress, pain, and general stress were reduced after PST in the IG compared with those in the CG. Active coping was reinforced in the IG. The IG patients were also better able to reduce negative problem orientation and improve problem implementation. The effect of the PST on these features was between Eta2=. 13 and . 45 and can thus be described as medium to strong. There were no changes in depression and social support. After careful interpretation of the results, it can be said that PST affects patients’ mental health, problem-solving, and coping. Because these psychological changes occur shortly after the transplantation in the phase of aplasia, HSCT patients are likely to be given a more favorable starting position for the course of recovery.
Optimal transport and colossal ionic mechano-conductance in graphene crown ethers

Minute strain flattens the free-energy terrain: Picometer deformations yield a colossal ionic conductance in graphene crown ethers. Biological ion channels balance electrostatic and dehydration effects to yield large ion selectivity alongside high transport rates. These macromolecular systems are often interrogated through point mutations of their pore domain, limiting the scope of mechanistic studies. In contrast, we demonstrate that graphene crown ether pores afford a simple platform to directly investigate optimal ion transport conditions, i.e., maximum current densities and selectivity. Crown ethers are known for selective ion adsorption. When embedded in graphene, however, transport rates lie below the drift-diffusion limit. We show that small pore strains (1%) give rise to a colossal (100%) change in conductance. This process is electromechanically tunable, with optimal transport in a primarily diffusive regime, tending toward barrierless transport, as opposed to a knock-on mechanism. These observations suggest a novel setup for nanofluidic devices while giving insight into the physical foundation of evolutionarily optimized ion transport in biological pores.
Self-microemulsifying drug delivery system (SMEDDS) for improved oral delivery and photostability of methotrexate

Purpose: The objective of this study was to exploit a novel methotrexate (MTX)-loaded solid self-microemulsifying drug delivery system (SMEDDS) with enhanced bioavailability and photostability. Materials and methods: The optimized liquid SMEDDS was composed of castor oil, Tween® 80, and Plurol® diisostearique at a voluminous ratio of 27:63:10. The solid SMEDDS was formulated by spray drying liquid SMEDDS with the solid carrier (calcium silicate). Particle size analyzer, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and Fourier transform infrared (FTIR) spectroscopy experiments characterized the physiochemical properties of the MTX-loaded solid SMEDDS. These properties include a z-average diameter of emulsion around 127 nm and the amorphous form of the solid SMEDDS. Furthermore, their solubility, dissolution, and pharmacokinetics in Sprague-Dawley rats were analyzed in comparison with the MTX powder. Results: The final dissolution rate and required time for complete release of solid SMEDDS were 1.9-fold higher and 10 min shorter, respectively, than those of MTX powder. Pharmacokinetic analysis demonstrated 2.04- and 3.41-fold increments in AUC and Cmax, respectively in comparison to MTX powder. The AUC and Cmax were significantly increased in solid SMEDDS. Finally, the photostability studies revealed the substantially enhanced photostability of the MTX-loaded SMEDDS under the forced degradation and confirmatory conditions. Conclusion: This solid SMEDDS formulation could be an outstanding candidate for improving the oral bioavailability and photostability of MTX.
Healthcare providers’ perspectives of providing primary healthcare services to persons with physical disabilities in rural Ghana

Abstract Background: A growing body of evidence has shown that persons with physical disabilities experience substantial barriers in accessing primary healthcare (PHC) services in rural areas. Negative attitudes from healthcare providers and inaccessible healthcare facilities and equipment are common experiences that negatively affect access to quality healthcare for persons with physical disabilities. However, there is limited research that explores this issue from the perspectives of healthcare providers. This qualitative study explores the perspectives of healthcare providers in delivering PHC services to persons with physical disabilities in rural Ghana. Understanding healthcare providers’ perspectives could help leverage previous findings from clients’ experiences to more fully inform the development of specific and actionable research and interventions to improve healthcare delivery for disabled people. Methods: We conducted in-depth interviews with 15 healthcare providers and used thematic analysis to analyze the data. Results: Participants reported their perspectives in three major themes: challenges in providing healthcare (eg, limited availability of drugs and medical equipment, limited healthcare providers, financial constraints, and inaccessible facilities and equipment); strategies in navigating the challenges (eg, improvising techniques and employing professional values, referring clients, and providing financial assistance to clients); and positive experience in providing healthcare (eg, feeling rewarded and appreciated). Conclusion: The findings reinforce the need to consider the availability of rehabilitation professionals and services to address the specific healthcare needs of disabled people at the PHC level in Ghana. The findings also point to a need for further research on the perspectives of healthcare policymakers about how to navigate the systemic barriers encountered by providers in providing care to persons with physical disabilities in rural Ghana in particular, and other similar rural areas.
Differences in the perception of dental sounds: a preliminary study

Purpose The sound of dental treatments can evoke anxiety in some dental patients. While women have shown greater dental anxiety than men, little is known about the gender differences in the perception of dental sounds. The purpose of this preliminary study was to evaluate differences in the perception of dental sounds according to the level of dental fear and gender. Patients and methods Based on the level of dental fear, 69 adults (39 women, 30 men; average age, 28.1±8.1 years) were categorized into four groups. Three types of sounds were presented to participants: two sounds associated with dental treatment and a neutral sound. All participants rated their emotional reaction to each sound on a visual analog scale. Results Significant differences were observed for ratings of valence and disgust for a dental drilling sound among the four groups (p=0.007 and 0.004, respectively). Female participants in the dental fear group rated the dental drilling sound as more negative and disgusting than did female participants in the control group (p=0.002 for both ratings). However, no significant differences were found in ratings between males in the dental fear and control groups. Conclusion Perception of dental sounds appears to differ by level of dental fear and by gender. Considering these differences may contribute to reducing fear in dental patients.
The Effects of Folic Acid Administration on Cardiac Oxidative Stress and Cardiovascular Biomarkers in Diabetic Rats

The aim of this study was to examine the effects of folic acid administration on the antioxidant enzyme (superoxide dismutase (SOD) and catalase (CAT)) activities, lactate and malate dehydrogenase (LDH and MDH) activities, and certain LDH and MDH isoform distribution in the cardiac tissue of diabetic Wistar male rats. Diabetes mellitus (DM) was induced by streptozotocin (STZ). There were five groups: C1—control (physiological saline 1 ml/kg, i.p. one day), C2—control with daily physiological saline treatment (1 ml/kg, i.p. 28 days), DM—diabetes mellitus (STZ 100 mg/kg in physiological saline, i.p. one day), FA—folic acid (5 mg/kg in physiological saline, i.p. 28 days), and DM+FA—diabetes mellitus and folic acid group (STZ 100 mg/kg in physiological saline, i.p. one day, and folic acid 5 mg/kg in physiological saline, i.p. 28 days). After four weeks, animal hearts were isolated for measurement of enzyme activities, as well as for histomorphometry analyses. An elevated glucose level and a decreased insulin level were obtained in the DM group. SOD, CAT, and MDH activities were elevated in the DM group, while there was no difference in LDH activity among the groups. In all tested groups, four LDH and three MDH isoforms were detected in the heart tissue, but with differences in their relative activities among the groups. Left ventricular cardiomyocyte transversal diameters were significantly smaller in both diabetic groups. Folic acid treatment of diabetic rats induced a reduced glucose level and reduced CAT, SOD, and MDH activities and alleviated the decrease in cardiomyocyte diameters. In conclusion, increased activities of antioxidant enzymes and MDH may be the consequence of oxidative stress caused by DM. Administration of the folic acid has a protective effect since it leads to reduction in glycemia and activities of the certain examined enzymes in the rats with experimentally induced DM.
Pollinators, pests and soil properties interactively shape oilseed rape yield

Pollination, pest control, and soil properties are well known to affect agricultural production. These factors might interactively shape crop yield, but most studies focus on only one of these factors at a time. We used 15 winter oilseed rape (Brassica napus L.) fields in Sweden to study how variation among fields in pollinator visitation rates, pollen beetle pest attack rates and soil properties (soil texture, pH and organic carbon) interactively determined crop yield. The fields were embedded in a landscape gradient with contrasting proportions arable and semi-natural land. Pollinator, pest and soil property variables formed bundles across the sites. In general, pollinator visitation and pest levels were negatively correlated and varied independently of soil properties. Because above- and below-ground processes reacted at contrasting spatial scales, it was difficult to predict bundle composition based on the surrounding landscape structure. The above-ground biotic interactions and below-ground abiotic factors interactively affected crop yield. Pollinator visitation was the strongest predictor positively associated with yield. High soil pH also benefited yield, but only at lower pest loads. Surprisingly, high pest loads increased the pollinator benefits for yield. Synthesis and applications Implementing management plans at different spatial scales can create synergies among bundles of above- and below-ground ecosystem processes, but both scales are needed given that different processes react to different spatial scales.
GP38-targeting monoclonal antibodies protect adult mice against lethal Crimean-Congo hemorrhagic fever virus infection

An antibody targeting the CCHFV GP38 molecule protects adult mice against lethal infection in a severe disease model. Crimean-Congo hemorrhagic fever virus (CCHFV) is an important human pathogen. Limited evidence suggests that antibodies can protect humans against lethal CCHFV disease but the protective efficacy of antibodies has never been evaluated in adult animal models. Here, we used adult mice to investigate the protection provided against CCHFV infection by glycoprotein-targeting neutralizing and non-neutralizing monoclonal antibodies (mAbs). We identified a single non-neutralizing antibody (mAb-13G8) that protected adult type I interferon–deficient mice >90% when treatment was initiated before virus exposure and >60% when administered after virus exposure. Neutralizing antibodies known to protect neonatal mice from lethal CCHFV infection failed to confer protection regardless of immunoglobulin G subclass. The target of mAb-13G8 was identified as GP38, one of multiple proteolytically cleaved glycoproteins derived from the CCHFV glycoprotein precursor polyprotein. This study reveals GP38 as an important antibody target for limiting CCHFV pathogenesis and lays the foundation to develop immunotherapeutics against CCHFV in humans.
Urinary orosomucoid: a new marker of cardiovascular risk in psoriatic patients?

Purpose Psoriasis is one of the most common lifelong lasting dermatologic diseases. According to the latest studies, psoriatic patients have a higher risk of developing cardiovascular diseases. Psoriasis is considered as a systemic inflammatory disease. Several oxidative stress markers have been shown to be elevated in psoriasis. However, a panel of biomarkers has not been used yet. This study was aimed at exploring the connection between a panel of biomarkers (C-reactive protein, asymmetric dimethylarginine, uric acid, total antioxidant capacity, malondialdehyde, and orosomucoid [ORM]) and cardiovascular risk in psoriatic patients. Patients and methods The inclusion criterion was the onset of psoriasis with skin lesions. Exclusion criteria were impaired renal function (eGFR<60 mL/min/1.73 m2), acute inflammations (urinary, respiratory, skin inflammation, etc), autoimmune disorders (rheumatoid arthritis, systemic lupus erythematosus, or inflammatory bowel disease), and any kind of biological antipsoriatic treatment. Patients with a medical history of myocardial infarction, coronary heart disease, stroke, transient ischemic attack, and carotid artery stenosis were also excluded. Biomarkers were measured by routine procedures, ELISA and HPLC. QRISK®2-2017 was used to assess 10-year risk of cardiovascular disease development. Psoriasis severity was measured by the Psoriasis Area and Severity Index. Results One hundred and fourteen psoriatic patients were enrolled. Only urinary orosomucoid and urinary orosomucoid/urinary creatinine (u-ORM/u-CREAT) ratio showed significant correlation with QRISK score (u-ORM, r=0.245; u-ORM/u-CREAT, r=0.309). When comparing mild psoriatic patients to moderate psoriatic patients, significant differences could only be found in u-ORM and u-ORM/u-CREAT ratio. Conclusion There seems to be a connection between urinary ORM and cardiovascular risk. U-ORM and u-ORM/u-CREAT ratio could be used as an indicator of low-grade inflammation in mild and moderate psoriasis. However, it is the 10-year follow-up of cardiovascular events that will determine the usefulness of this biomarker panel.
A quantitative insight of the interactions of prescribers with pharmaceutical organization’s representatives in clinical settings of Karachi

Objectives: The study was conducted with the aim to evaluate the prescribers’ approach of interaction with medical representatives for drug promotion. Methods: An explanatory, cross-sectional design was used to evaluate prescribers’ interactions with the medical sales representatives (MSRs) through an anonymous, self-filled questionnaire from June to December 2017. Data presented as means±SEM or as percentages and statistically analyzed by one way ANOVA, using significance level of 0.05. Results: A response rate of 82.8% was achieved. More than 70% agreed that knowledge obtained from MSRs is reliable and useful. A large proportion of respondents acknowledged that MSRs are a key link between pharmaceutical companies and health care professionals, and their interactions are beneficial as MSRs perform an important teaching function. More than 45% agreed that gifts are influential; however, physicians cannot be compromised with very expensive gifts. The majority of the respondents (76%) considered that promotional items are ethically appropriate; however, 66.21% thought that promotional items influence the practice of prescribing. More than half (52.18%) deemed a promotional material more reliable than a printed advertisement. More than 80% of the respondents opined that medication samples are considered appropriate; however, they should only be given to those patients who cannot financially afford them. Around 69% thought that company-sponsored meetings promote their own drugs under the disguise of CME programs. Conclusion: The present study emphasizes the importance of employing scientifically sound prescribing decision by prescribers in their day to day practice without being influenced by pharmaceutical company’s promotional activities. There is a need for restricting unprincipled practices by the concerned regulatory authorities to evade preventable harm to the patient’s well-being.
The Possible Pathogenesis of Idiopathic Pulmonary Fibrosis considering MUC5B

Background Overexpression of the MUC5B protein is associated with idiopathic pulmonary fibrosis (IPF), but little information is available regarding the pathogenic effects and regulatory mechanisms of overexpressed MUC5B in IPF. Main Body The overexpression of MUC5B in terminal bronchi and honeycomb cysts produces mucosal host defensive dysfunction in the distal airway which may play an important role in the development of IPF. This review addresses the possible association of overexpression of MUC5B, with MUC5B promoter polymorphism, MUC5B gene epigenetic changes, effects of some transcriptional factors, and inflammatory mediators in IPF. In addition, the associated signaling pathways which may influence the expression of MUC5B are also discussed. Conclusion This work has important implications for further exploration of the mechanisms of overexpression of MUC5B in IPF, and future personalized treatment.