Miracle-dz/UniFAR-FTUs huggingface dataset:
Novel and Modified Neutrophil Elastase Inhibitor Loaded in Topical Formulations for Psoriasis Management

Human neutrophil elastase (HNE) is a serine protease that degrades matrix proteins. An excess of HNE may trigger several pathological conditions, such as psoriasis. In this work, we aimed to synthesize, characterize and formulate new HNE inhibitors with a 4-oxo-β-lactam scaffold with less toxicity, as well as therapeutic index in a psoriasis context. HNE inhibitors with 4-oxo-β-lactam scaffolds were synthesized and characterized by NMR, FTIR, melting point, mass spectrometry and elemental analysis. In vitro cytotoxicity and serine protease assays were performed. The compound with the highest cell viability (AAN-16) was selected to be incorporated in an emulsion (AAN-16 E) and in a microemulsion (AAN-16 ME). Formulations were characterized in terms of organoleptic properties, pH, rheology, droplet size distribution, in vitro drug release and in vivo psoriatic activity. All compounds were successfully synthesized according to analytical methodology, with good yields. Both formulations presented suitable physicochemical properties. AAN-16 E presented the most promising therapeutic effects in a murine model of psoriasis. Overall, new HNE inhibitors were synthesized with high and selective activity and incorporated into topical emulsions with potential to treat psoriasis.
Spermatozoa lacking Fertilization Influencing Membrane Protein (FIMP) fail to fuse with oocytes in mice

Significance As the human body is composed of 60 trillion cells that originate from a fertilized egg, sperm–oocyte fusion is the initial event of our life. Few sperm–oocyte fusion factors have been unveiled to date, and only IZUMO1 has been identified as a sperm-specific fusion-mediating protein. Here, we identified the testis-specific 4930451I11Rik gene important for male fertility, playing a role in sperm–oocyte fusion during fertilization. Based on its functional role, we renamed this gene fertilization influencing membrane protein (Fimp). We discovered a factor responsible for sperm–oocyte fusion in mammals, and this knowledge could be used to develop in vitro and in vivo infertility treatments as well as male contraceptives. Sperm–oocyte fusion is a critical event in mammalian fertilization, categorized by three indispensable proteins. Sperm membrane protein IZUMO1 and its counterpart oocyte membrane protein JUNO make a protein complex allowing sperm to interact with the oocyte, and subsequent sperm–oocyte fusion. Oocyte tetraspanin protein CD9 also contributes to sperm–oocyte fusion. However, the fusion process cannot be explained solely by these three essential factors. In this study, we focused on analyzing a testis-specific gene 4930451I11Rik and generated mutant mice using the CRISPR/Cas9 system. Although IZUMO1 remained in 4930451I11Rik knockout (KO) spermatozoa, the KO spermatozoa were unable to fuse with oocytes and the KO males were severely subfertile. 4930451I11Rik encodes two isoforms: a transmembrane (TM) form and a secreted form. Both CRISPR/Cas9-mediated TM deletion and transgenic (Tg) rescue with the TM form revealed that only the TM form plays a critical role in sperm–oocyte fusion. Thus, we renamed this TM form Fertilization Influencing Membrane Protein (FIMP). The mCherry-tagged FIMP TM form was localized to the sperm equatorial segment where the sperm–oocyte fusion event occurs. Thus, FIMP is a sperm-specific transmembrane protein that is necessary for the sperm–oocyte fusion process.
Patient Questions and Physician Responses in a Chinese Health Q&A Website: Content Analysis

Background Since the turn of this century, the internet has become an invaluable resource for people seeking health information and answers to health-related queries. Health question and answer websites have grown in popularity in recent years as a means for patients to obtain health information from medical professionals. For patients suffering from chronic illnesses, it is vital that health care providers become better acquainted with patients’ information needs and learn how they express them in text format. Objective The aims of this study were to: (1) explore whether patients can accurately and adequately express their information needs on health question and answer websites, (2) identify what types of problems are of most concern to those suffering from chronic illnesses, and (3) determine the relationship between question characteristics and the number of answers received. Methods Questions were collected from a leading Chinese health question and answer website called “All questions will be answered” in January 2018. We focused on questions relating to diabetes and hepatitis, including those that were free and those that were financially rewarded. Content analysis was completed on a total of 7068 (diabetes) and 6685 (hepatitis) textual questions. Correlations between the characteristics of questions (number of words per question, value of reward) and the number of answers received were evaluated using linear regression analysis. Results The majority of patients are able to accurately express their problem in text format, while some patients may require minor social support. The questions posted were related to three main topics: (1) prevention and examination, (2) diagnosis, and (3) treatment. Patients with diabetes were most concerned with the treatment received, whereas patients with hepatitis focused on the diagnosis results. The number of words per question and the value of the reward were negatively correlated with the number of answers. The number of words per question and the value of the reward were negatively correlated with the number of answers. Conclusions This study provides valuable insights into the ability of patients suffering from chronic illnesses to make an understandable request on health question and answer websites. Health topics relating to diabetes and hepatitis were classified to address the health information needs of chronically ill patients. Furthermore, identification of the factors affecting the number of answers received per question can help users of these websites to better frame their questions to obtain more valuable answers.
Impact of Bean Consumption on Nutritional Outcomes amongst Adolescents

Brazilian adolescents have undergone a noteworthy nutritional epidemiological transition. There is an increase in the prevalence of overweight and high consumption of ultra-processed foods in parallel with patterns of traditional meals that include beans. This study analyzed associations between bean consumption in the diet of adolescents and nutrition outcomes. Multiple regression analysis showed a significant reduction in body mass index (BMI), body fat percentage (%BF) and LDL-cholesterol (LDL-c) values among those with bean consumption equal to or greater than five times a week. Adolescents who had lunch outside the home and those who did not have the habit of having lunch showed a significantly higher BMI. There was an increase in the %BF among married adolescents and those who did not have lunch. There was a reduction of LDL-c among those with intermediate per capita income and those who consumed processed juice less than 5 times a week, and an increase among those who did not have breakfast. There were significant interactions between sexual maturation, energy consumption, physical activity and energy consumption. Thus, in the context of this study, the presence of beans in the diet, at frequencies equal to or greater than five times a week, can be considered a proxy for healthy eating.
Development and Psychometric Evaluation of the Attitudes and Beliefs Scale about Sexuality during Pregnancy

Abstract This study aims to develop the Attitudes and Beliefs Scale about Sexuality during Pregnancy (ABSSP) and to test its validity and reliability. The study utilized a methodological approach and was conducted at a university hospital. The ABSSP developed in this study consisted of 25 items and 4 sub-scales. As a result, the ABSSP was found to be a valid and reliable measurement tool in Turkish pregnant women. The scale developed is believed to contribute to the literature as a measurement tool to identify attitudes, myths, beliefs, and knowledge of pregnant women and their partners about sexuality in pregnancy.
Quantitative brain histogram of canine epilepsy using magnetic resonance imaging

Background Quantitative magnetic resonance imaging (MRI) is used to study the anatomy of the brain in dogs with idiopathic epilepsy. Purpose To quantitate MRI images in terms of volumetric ratios and histogram analyses of the following regions of interest (ROI) in dogs with idiopathic epilepsy: frontal; parietal; temporal; piriform; thalamic; and hippocampal regions. Material and Methods Nine dogs with epilepsy and four healthy controls were evaluated. We examined the volumetric ratios and histogram analyses of six ROIs in all dogs. Results MR images, in T1-weighted, T2-weighted, FLAIR, diffusion-weighted imaging, and apparent diffusion coefficient sequences detected changes in 4/9 (44%) epileptic dogs found in 5/6 regions: frontal; parietal; temporal; piriform; and hippocampal regions. However, no such changes were observed in the thalamic region. Interestingly, the frontal and piriform volumetric ratios of epileptic dogs were significantly lower than those of control dogs. The histogram analyses in 4/6 regions were significantly increased in epileptic dogs. Conclusion Our results demonstrated MRI finding abnormalities in several regions of the brain in several sequences including T1-weighted, T2-weighted, FLAIR, diffusion-weighted imaging, and apparent diffusion coefficient in epileptic dogs. In several regions of the brain, atrophy may exist, and hyperintensity may be present on MR images in epileptic dogs. These findings suggest that the diagnostic yield of MRI, which is an advanced neuroimaging technique, is high in epileptic dogs and has good reliability and sensitivity in detecting abnormal areas in patients.
Characterization of Mesorhizobium sp. isolated from root nodules of Cicer arietinum.

This study was carried out to be investigate the effect o f salt, pH, antibiotics, carbohydrate and fungicides on growth of Mesorhizobium isolates obtained from root nodules of chick pea plants from different sites of Dehradun. After morphological and bioch emical test, 40 isolates were selected. Isolates were subjected to different (2%, 3%.up to 8%) NaCl concentrations and found that all isolates grew up to 4% NaCl concentration, variation starts from 5% NaCl a nd salt tolerance ability was reduced with increasing salt concentration. All isolates grew at pH 4 . 0 to pH 8.5 and none of the isolates at pH 9.0. Ten carbohydrates were used for describing carbohydrate utilization pattern. Most of the isolates catabolize nine carbohydrates while only 47.5% showed res istance to dextrose. All of the isolates were showed sensitivity to Meropenem, Netillin, Ceftriaxone and Amikacin antibiotics. All isolates were tested for their tolerance to four fungicides. The effect of he fungicides on the isolates was variable, depending on the fungicide and isolate. Further studies are needed to study the genes involved in salt, pH, carbohydrates, fungicides, antibiotic resistance an d the relationship between these genes and the symbiotic genes.
Can non-small cell lung cancer histologic subtypes predict survival? A single institution experience

Introduction. The latest histological classification of lung adenocarcinoma includes lepidic, acinar, papillary, micropapillary, and solid as subtypes. Testing these subtypes for their prognostic and predictive value is an ongoing scientific challenge. The present research article aims to describe the influence this classification has on patient survival. Materials and Methods. Thirty-three patients were included in the trial. The most important enrollment criterion was the clear specification of the adenocarcinoma subtype in the pathology report. Patients were stratified into three groups which included the adenocarcinoma pathological subtypes as follows: lepidic (LEP), acinar and papillary (ACN/PAP), and micropapillary/solid (MIP/SOL). The primary endpoint was progression-free survival. Other endpoints included
Effect of Natesto on Reproductive Hormones, Semen Parameters and Hypogonadal Symptoms: A Single-Center, Open-Label, Single-Arm Trial.

PURPOSE To evaluate the effect of short-acting 4.5% nasal testosterone gel (Natesto) on serum testosterone, gonadotropins, total motile sperm count (TMSC), health-related quality of life, and sexual function. MATERIALS AND METHODS Single-institution, open-label, single-arm trial, conducted between November 2017 and September 2019 at the University of Miami. Men aged 18-55 diagnosed with symptomatic hypogonadism (total testosterone < 300ng/dL on 2 occasions) were included. Men with azoospermia, vasectomy or a TMSC < 5 million were excluded. Enrolled patients were treated with Natesto, a short-acting nasal testosterone (125 uL/nostril, 11.0 mg T/dose, TID) for 6 months. RESULTS In total, 60 men were enrolled in the study. Of these, 44 and 33 patients were evaluated for Testosterone (T) at 3 and 6 months, respectively. A total of 31 patients (93.9%) reached a normal T level (>300ng/dL) at 6 months. Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH) levels were maintained within the normal range in 81.8% and 72.7% of patients at 6 months, respectively. Total motile sperm count was maintained with TMSC >5 million over the treatment period in 88.4% of men at 3 months and 93.9% at 6 months. There were statistically significant improvements on International Index of Erectile Function (IIEF) sexual desire and overall satisfaction domains at 6 months. CONCLUSIONS Natesto appears to increase testosterone while maintaining semen parameters in a majority of men. Natesto has the potential to be a safe and effective treatment for men with functional hypogonadism who wish to preserve semen parameters. Long-term studies beyond 6 months are needed before we can safely prescribe nasal testosterone gel for men interested in fertility.
A study on the outcome of various methods of administration of intratympanic dexamethasone in tinnitus of cochlear pathology

Background: The aim of the study was to compare the outcome of various methods of injecting intra tympanic steroids in patients with tinnitus of cochlear pathology.Methods: A prospective study was conducted on 56 patients with subjective tinnitus of cochlear pathology who were then divided into three groups. After thorough otological and audiological evaluation using standard questionnaire, ENT examination, pure tone audiometry, tone decay test, tinnitogram, CT scans of temporal bone and brain. Each patient underwent one of the three chosen methods of intra tympanic steroids administration randomly. The methods are 1-Tympanomeatal flap elevationand application of steroid soaked gelfoam sponge; 2-Transtympanic steroid injection; 3-Grommet insertion followed by steroid administration. These methods were performed for subjects with tinnitus of cochlear pathology from 2009 to 2011 at a neurotological clinic at Chennai. After following up on 1st, 3rd and 6 months the observations were statistically analysed. Results: Success rate for techniques viz tympanomeatal flap was 70%, transtympanic - 63%, grommet - 50%. But when comparing statistically all the three methods were equally successful.Conclusions: Intratympanic steroids for tinnitus (cochlear pathology) are a safe, simple and promising treatment option. Though all the methods of intra tympanic steroids injection had similar success rate, the tympanomeatal flap elevation method may be preferred since it can be done in a single sitting. However transtympanic injection remains the easiest and cost effective compared to the other two methods.
Plasma iron concentrations and systemic inflammatory response syndrome in neonatal foals

Abstract Background Sparse information regarding plasma iron concentration in neonatal foals and its utility as an inflammatory marker in this population has been published. Objectives To determine the physiologic plasma iron concentration in neonatal foals. To assess its utility as an inflammatory marker to predict systemic inflammatory response syndrome (SIRS) and as a prognostic marker. Animals Forty‐seven ill neonatal foals admitted to a referral equine hospital were divided in 2 groups based on the SIRS criteria (24 SIRS and 23 non‐SIRS). Two control groups of 43 hospital and 135 stud farm healthy neonatal foals were also included. Methods Observational prospective study. Data were summarized by mean and its 95% confidence interval and absolute frequency and percentage for quantitative andqualitative variables. One‐way ANOVA, ANCOVA (group and age effects) and Dunnett as posthoc analysis were used to compare plasma iron concentration among groups. Results Neonatal foals with SIRS did not have had any statistically significant different plasma iron concentrations compared to non‐SIRS (P = .56) and stud farm control group (P = .99), 172.8 μg/dL (95% CI; 126.0‐219.6), 193.1 μg/dL (139.1‐247.2), and 181.8 μg/dL (171.3‐192.4), respectively. Plasma iron concentration had a large variability in healthy neonatal foals, and was negatively correlated with age in hospital controls (rho = −0.387) and sick neonatal foals (rho = −0.598) (P < .001). Conclusions and Clinical Importance Plasma iron was not a useful marker of SIRS in neonatal foals and was not associated with outcome.
Effects of Aerobic and Resistance Exercise on Myokines in High Fat Diet-Induced Middle-Aged Obese Rats

The objective of this study was to analyze the effects of aerobic and resistance exercise on myokines expression in the skeletal muscle of middle-aged rats with high fat diet-induced obesity, to investigate the feasibility of using exercise training to reduce inflammation. Male 50-week-old Sprague Dawley rats were divided into normal diet, normal diet + exercise, high fat diet, and high fat diet + exercise groups. After six weeks on a high fat diet to induce obesity, a 12-week exercise program was implemented, which combined aerobic exercise (treadmill running) and resistance exercise (ladder climbing) three times a week for 75 min per session. We analyzed the protein levels of interleukins (IL) 6, 7, and 8, C-X-C motif chemokine receptor 2, and vascular endothelial growth factor in skeletal muscles by western blotting. Body weight decreased significantly during the 12-week exercise program in the exercise groups compared to the non-exercise groups (p < 0.05). The levels of all myokines analyzed were significantly lower in the skeletal muscle of the high fat diet group compared to the normal diet group (p < 0.05). After completing the 12-week exercise program, IL-7, IL-8, C-X-C motif chemokine receptor 2, and vascular endothelial growth factor expressions were significantly higher in the high fat diet + exercise group compared to the high fat diet group (p < 0.05). However, while IL-6 expression was significantly lower in the high fat diet and high fat diet + exercise groups compared to the normal diet group (p < 0.05), it was not significantly affected by exercise. In conclusion, high fat diet-induced obesity resulted in decreased myokines in the skeletal muscles, but combined exercise training of aerobic and resistance exercise increased myokines secretion in the skeletal muscle of obese rats, and is thought to help reduce inflammation.
Case fatality rate analysis of Italian COVID‐19 outbreak

The Italian outbreak of COVID‐19 cases is a public health emergency and there is a worldwide tremendous interest in the evaluation of the Italian epidemic evolution. Indeed, from February 2020, Italy is facing an explosion of COVID‐19 cases. In particular, the Italian observed case fatality rate (CFR) is much higher than the other countries. Recently, it has been hypothesized that the extensive number of intergenerational contacts—typical of Italian culture—could contribute to explain the high number of deaths observed in Italy. However, through an analysis performed for all the Italian regions, here it is shown that the deaths are localized in specific regions and that the CFRs of different Italian regions are overlapping with the rates of European countries. Moreover, through correlation analyses between CFRs and different social habits, it is shown that no positive correlation is observed between social behaviors and CFRs. In conclusion, this analysis clearly rejects the possibility that social habits and intergenerational contacts can contribute to explaining such a profound effect on the number of deaths observed in Italy during the COVID‐19 outbreak and more effort should be addressed to evaluate the real amount of positive cases.
Cofactor and glycosylation preferences for in vitro prion conversion are predominantly determined by strain conformation

Prion diseases are caused by the misfolding of a host-encoded glycoprotein, PrPC, into a pathogenic conformer, PrPSc. Infectious prions can exist as different strains, composed of unique conformations of PrPSc that generate strain-specific biological traits, including distinctive patterns of PrPSc accumulation throughout the brain. Prion strains from different animal species display different cofactor and PrPC glycoform preferences to propagate efficiently in vitro, but it is unknown whether these molecular preferences are specified by the amino acid sequence of PrPC substrate or by the conformation of PrPSc seed. To distinguish between these two possibilities, we used bank vole PrPC to propagate both hamster or mouse prions (which have distinct cofactor and glycosylation preferences) with a single, common substrate. We performed reconstituted sPMCA reactions using either (1) phospholipid or RNA cofactor molecules, or (2) di- or un-glycosylated bank vole PrPC substrate. We found that prion strains from either species are capable of propagating efficiently using bank vole PrPC substrates when reactions contained the same PrPC glycoform or cofactor molecule preferred by the PrPSc seed in its host species. Thus, we conclude that it is the conformation of the input PrPSc seed, not the amino acid sequence of the PrPC substrate, that primarily determines species-specific cofactor and glycosylation preferences. These results support the hypothesis that strain-specific patterns of prion neurotropism are generated by selection of differentially distributed cofactors molecules and/or PrPC glycoforms during prion replication.
Investigating sex differences in structural and functional neuroimaging correlates of empathy in conduct disorder

Conduct Disorder (CD) is a childhood psychiatric disorder characterised by antisocial and aggressive behaviours. The overarching aim of this thesis was to investigate potential sex differences in the structural and functional neuroimaging correlates of empathy in CD. Studies in chapters 5 and 6 showed that youths with CD had decreased structural covariance between the anterior insula (AI) and thalamus compared to TD (typically developing) youths, but the groups did not differ in grey matter volume and no interactions with sex were observed. Studies in chapters 7 and 8 revealed that youths with CD exhibited reduced brain response in the AI and cerebellum when viewing others in pain. A sex-by-group interaction was also observed in the amygdala whereby females with CD had reduced brain response compared to TD females, with no differences between males with CD and TD males. Youths with CD exhibited decreased functional connectivity between the AI and the occipital lobe, but increased connectivity between the cerebellum and amygdala compared to TD youths. These findings suggest that structural and functional abnormalities in the AI are key features of both males and females with CD, while only females exhibit functional abnormalities in the amygdala when processing pain in others.