Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparison of Serum Vitamin D Levels in Relation to Bowel and Bladder Symptoms in Women with Vulvar Diseases.

OBJECTIVES We sought to investigate associations between vitamin D levels and bowel and bladder disorders in women with vulvar diseases. METHODS This is a planned sub-analysis of a cross-sectional study comparing the prevalence of bowel and bladder symptoms in women with biopsy-proven vulvar lichen sclerosus (LS) to a control group of women with non-lichenoid vulvar diseases. All subjects were recruited from a tertiary referral vulvar care clinic in a university-based practice. Serum vitamin D levels were measured and subjects self-completed questionnaires during study recruitment. Pelvic floor disorders were determined from the following questionnaires: Rome III Functional Bowel Disorders Questionnaire, the Bristol stool scale, the Medical, Social and Epidemiologic Aspects of Aging Questionnaire, and the Overactive Bladder-8 Question Version. RESULTS 181 women with vulvar diseases were included: 88 with LS and 93 with non-LS vulvar diseases. The mean age was 52.5 ± 15.3 years, and 94.5% were Caucasian. Vitamin D levels (26.8 ± 13.1 vs 29.5 ± 19.0 ng/mL), prevalence of low vitamin D levels (51.1% vs 45.2%), and vitamin D supplementation (42.0% vs 47.8%) were similar in women with and without LS ( p ≥ 0.27). These factors did not differ between women with and without overactive bladder (OAB) (vitamin D levels 30.1 ± 17.8 vs 26.3 ± 14.8 ng/mL), urinary incontinence (27.9 ± 15.2 vs 26.4 ± 11.0 ng/mL), constipation (26.7 ± 14.8 vs 28.5 ± 16.8 ng/mL), or irritable bowel syndrome (IBS) (30.8 ± 22.1 vs 27.6 ± 13.4 ng/mL). CONCLUSIONS In this cohort of women with vulvar diseases, vitamin D levels and supplementation were not significantly different amongst women with vulvar lichen sclerosus or other non-lichenoid vulvar diseases. Furthermore, vitamin D levels are not serum biomarkers for OAB, urinary incontinence, constipation, or IBS.
Integrated analysis of competing endogenous RNA networks revealing five prognostic biomarkers associated with colorectal cancer

Colorectal cancer (CRC) is a common malignant tumor with high morbidity and mortality around the world. The aim of this study was to determine the genes significantly associated with the overall survival (OS) of CRC patients and predict their function in the competing endogenous RNA (ceRNA) regulation networks. We constructed the lncRNA‐miRNA‐mRNA networks according to the differentially expressed RNAs from the The Cancer Genome Atlas data sets of 561 CRC patients. Twelve differentially expressed messenger RNAs from the ceRNA networks were selected through a univariate Cox proportional hazards regression. Then, these genes were analyzed by using multivariate Cox proportional hazards stepwise regression to construct a prognostic model in which five genes (tensin 1, clusterin, proteolipid protein 1, epiregulin, and transcription factor Spi‐B) were included. The Kaplan‐Meier risk survival analysis showed that this five‐gene signature independently predicted a 5‐year overall survival in CRC patients (P < 0.001). Furthermore, significance was verified according to two irrelevant Gene Expression Omnibus (GEO) data sets (GSE38832 and GSE39582). The verified five‐gene model of CRC can be used to predict patient prognosis and will inform postoperational evaluation and follow‐up strategies.
Wound healing and fibrosis: current stem cell therapies

Scarring is a result of the wound healing response and causes tissue dysfunction after injury. This process is readily evident in the skin, but also occurs internally across organ systems in the form of fibrosis. Stem cells are crucial to the innate tissue healing response and, as such, present a possible modality to therapeutically promote regenerative healing while minimizing scaring. In this review, the cellular basis of scaring and fibrosis is examined. Current stem cell therapies under exploration for skin wound healing and internal organ fibrosis are discussed. While most therapeutic approaches rely on the direct application of progenitor‐type cells to injured tissue to promote healing, novel strategies to manipulate the scarring response are also presented. As our understanding of developmental and stem cell biology continues to increase, therapies to encourage regeneration of healthy functional tissue after damage secondary to injury or disease will continue to expand.
The Neural Substrate for Concrete, Abstract, and Emotional Word Lexica A Positron Emission Tomography Study

Viewing of single words produces a cognitively complex mental state in which anticipation, emotional responses, visual perceptual analysis, and activation of orthographic representations are all occurring. Previous PET studies have produced conflicting results, perhaps due to the conflation of these separate processes or the presence of subtle differences in stimulus material and methodology. A PET study of 10 normal individuals was carried out using the bolus H215O intravenous injection technique to examine components of processing of passively viewed words. Subjects viewed blocks of random-letter strings or abstract, concrete, or emotional words (words with positive or negative emotional salience). Baseline conditions were either passive viewing of plus signs or an anticipatory state (viewing plus signs after being warned to expect words or random letters to appear imminently). All words (and to a lesser extent the random letters) produced robust activation of cerebral blood flow in the left posterior temporal lobe, in addition to bilateral occipital activation. Furthermore, emotional words produced activation in orbital and midline frontal structures. Further activation in the left orbital frontal gyrus, the left inferior temporal gyrus, the left caudate nucleus, the anterior cingulate, and the cerebellum could be ascribed to the anticipatory state. This pattern of activity suggests that the occipital regions are recruited for visual-perceptual analysis of words, and the left temporal lobe represents the neural substrate for the orthographic lexicon. In addition, emotionally relevant material produces further processing in limbic brain structures of the frontal lobes. Detailed analysis of the task therefore substantially clarifies the neuroanatomic basis of single-word processing.
Role of epidermal growth factor inhibition in experimental pulmonary hypertension.

RATIONALE Epidermal growth factor (EGF) and its receptors play a role in cell proliferation and survival and are implicated in the pathobiology of pulmonary arterial hypertension (PAH). OBJECTIVES To study the role of EGF inhibition on experimental pulmonary hypertension. METHODS We investigated (1) the effects of three clinically approved EGF receptor (EGFR) antagonists in vitro on rat pulmonary arterial smooth muscle cell proliferation and in vivo on experimental pulmonary hypertension (PH) induced by monocrotaline injection in rats and by chronic hypoxia in mice, and (2) the expression of EGFR in the lung tissues from experimental and clinical PH. MEASUREMENTS AND MAIN RESULTS The EGFR inhibitors gefitinib, erlotinib, and lapatinib inhibited the EGF-induced proliferation of pulmonary arterial smooth muscle cells. In rats with established PH, gefitinib and erlotinib significantly reduced right ventricular systolic pressure and right ventricular hypertrophy. In addition, the medial wall thickness and muscularization of pulmonary arteries were improved. In contrast, lapatinib did not provide therapeutic benefit. These EGFR antagonists at their highest tolerable dose did not yield significant improvement in right ventricular systolic pressure, right ventricular hypertrophy, and pulmonary vascular remodeling in mice with chronic hypoxic PH. Moreover, no significant alteration in the EGFR expression was detected in the lung tissues from patients with idiopathic PAH. CONCLUSIONS The partial therapeutic efficacy of the EGFR antagonists in animal models of pulmonary hypertension and the absence of significant alteration in EGFR expression in the lungs from patients with idiopathic PAH suggest that EGFRs do not represent a promising target for the treatment of pulmonary hypertension.
Prospective, longitudinal comparison of neurocognitive change in pediatric brain tumor patients treated with proton radiotherapy versus surgery only.

BACKGROUND Proton radiotherapy (PRT) reduces the volume of normal tissue receiving radiation dose, which may lead to better neurocognitive outcomes. We examined change in neurocognitive scores over time in pediatric brain tumor patients treated with proton craniospinal irradiation (CSI), proton focal RT, or surgery only. METHODS Patients received annual neurocognitive evaluations for up to 6 years. We examined Full Scale IQ (FSIQ), Verbal Comprehension Index (VCI), Perceptual Reasoning Index (PRI), Working Memory Index (WMI), and Processing Speed Index (PSI) scores. General linear mixed models examined change in scores over time by treatment group, adjusting for significant covariates. RESULTS Scores from 93 patients treated between 2012 and 2017 (22 proton CSI, 31 proton focal, and 40 surgery only) were examined. Treatment groups were similar on gender (51.6% male), age at treatment (median = 9.7 y), and length of follow-up (median = 2.9 y). The surgery only group had proportionately more gliomas (P < 0.001), and the proton CSI group had more infratentorial tumors (P = 0.001) and higher total RT dose (P = 0.004). The proton focal and surgery only groups exhibited stable neurocognitive scores over time across all indexes (all P > 0.05). In the proton CSI group, WMI, PSI, and FSIQ scores declined significantly (P = 0.036, 0.004, and 0.017, respectively), while VCI and PRI scores were stable (all P > 0.05). CONCLUSIONS Focal PRT was associated with stable neurocognitive functioning into survivorship. Outcomes were similar whether patients received focal PRT or no radiotherapy, even in neurocognitive domains known to be particularly radiosensitive. Proton CSI emerged as a neurocognitive risk factor, consistent with photon outcomes research.
The complete mitochondrial genome of the American lobster, Homarus americanus (Crustacea, Decapoda)

Although relatively a large number of the complete mitochondrial genome sequences have been determined from various decapod species (29 mtDNA sequences reported so far), the information for the infraorder Astacidea (including lobsters, crayfishes, and their relatives) is very limited and represented by only one complete sequence from the Australian freshwater crayfish species Cherax destructor. In this study, we determined the complete mitochondrial DNA sequence of Homarus americanus, the first representative of the family Nephropidae to be fully characterized. Comparison of the gene arrangement reveals that H. americanus mtDNA is identical to those of other pancrustacean species but differs from the other astacidean species (C. destructor). Based on these data, it can be assumed that an idiosyncratic gene order discovered in C. destructor mtDNA may be secondarily acquired from the ancestral lineage of the Astacidea.
Management strategies for anaerobic digestate of organic fraction of municipal solid waste: Current status and future prospects

Anaerobic digestion has emerged as the preferred treatment for organic fraction of municipal solid waste. Digestate management strategies are devised not only for safe disposal but also to increase the value and marketability. Regulations and standards for digestate management are framed to address the pollution concerns, conserve vulnerable zones, prevent communicable diseases, and to educate on digestate storage and applications. Regulations and the desired end uses are the main drivers for the enhancement of digestate through pretreatment, in vessel cleaning, and post-digestion treatment technologies for solid and liquid fractions of digestate. The current management practice involves utilization of digestate for land application either as fertilizer or soil improver. Prospects are bright for alternative usage such as microalgal cultivation, biofuel and bioethanol production. Presently, the focus of optimization of the anaerobic digestion process is directed only towards enhancing biogas yield, ignoring the quality of digestate produced. A paradigm shift is needed in the approach from ‘biogas optimization’ to ‘integrated biogas–digestate optimization’.
Impact of pneumococcal conjugate vaccines on hospitalizations for pneumonia in the United States

ABSTRACT Introduction: Pneumonia is one of the leading causes of morbidity and mortality among children and older adults. Pneumococcal conjugate vaccines (PCVs) were introduced into the US routine infant vaccination schedule leading to substantial reductions of invasive pneumococcal diseases (IPD). PCV introduction also led to reductions in all-cause pneumonia among US children, though the indirect impact of PCVs on pneumonia in adults is difficult to quantify, especially due to the recent US recommendation for direct PCV use in older adults. Areas covered: We described the existing evidence for both the direct and indirect impact of PCVs on pneumonia among children and adults in the US since PCV introduction. Expert commentary: The introduction of PCVs into the US routine infant vaccination schedule led to important reductions in the burden of IPD and non-invasive pneumonia among vaccinated and unvaccinated populations. The impact of direct vaccination of older adults in the US since 2014, though difficult to quantify, is currently being evaluated. As pneumonia remains one of the leading causes of morbidity and mortality in the US, future evaluations of the direct and indirect effects of current and expanded valency PCVs in the US population are needed.
The protective effect of Zataria multiflora Boiss essential oil on CCl4 induced liver fibrosis in rats

Abstract Activation of hepatic stellate cells by free radicals is an initial step in the development of liver fibrosis. Zataria multiflora Boiss (ZM) essential oil as a natural product has antioxidant activity and maybe a suitable candidate for treatment or prevention of the disease. Thus, this study aims to evaluate the protective effect of ZM oil in CCl4 induced liver fibrosis. Male rats were divided into 5 groups, group C: control rats; CO: vehicle control group; CE: rats that received essential oil (500 µl/kg); F: fibrosis group, rat were intraperitoneally injected with CCl4 (1 mL/kg); FE: fibrosis rats that received both CCl4 and ZM essential oil as mentioned above. At the end of the 11th week, serum samples and liver tissues were collected for the evaluation of fibrosis markers, liver enzymes, oxidative stress parameters and histopathological studies. The results showed a significant increase in the activity of serum AST, ALT, total bilirubin, TGF-β1, hyaluronan, and hydroxyproline levels in serum and liver tissues in F group. Also, an abnormality in lipid profile and the existence of oxidative stress was found in serum and liver tissues in F group compared to the control groups. Our study showed that ZM essential oil could ameliorate mentioned parameters. Histopathological examinations confirmed the results of biochemical evaluations.
Manifold Cities : Social variables of urban areas in the UK

In the 21st century ongoing rapid urbanization highlights the need to gain deeper insights into the social structure of cities. While work on this challenge can profit from abundant data sources, the complexity of this data itself proves to be a challenge. In this paper we use diffusion maps, a manifold learning method, to discover hidden manifolds in the UK 2011 census data set. The census key statistics and quick statistics report 1450 different statistical features for each census output area. Here we focus primarily on the city of Bristol and the surrounding countryside, comprising 3490 of these output areas. Our analysis finds the main variables that span the census responses, highlighting that university student density and poverty are the most important explanatory variables of variation in
Screening of ten cytochrome P450 enzyme activities with 12 probe substrates in human liver microsomes using cocktail incubation and liquid chromatography–tandem mass spectrometry

Testing for potential drug interactions of new chemical entities is essential when developing a novel drug. In this study, an assay was designed to evaluate drug interactions with 10 major human cytochrome P450 (P450) enzymes incubated in liver microsomes, involving 12 probe substrates with two cocktail incubation sets used in a single liquid chromatography–tandem mass spectrometry (LC–MS/MS) run. The P450 substrate composition in each cocktail set was optimized to minimize solvent effects and mutual drug interactions among substrates as follows: cocktail A was composed of phenacetin for CYP1A2, bupropion for CYP2B6, amodiaquine for CYP2C8, diclofenac for CYP2C9, S‐mephenytoin for CYP2C19, and dextromethorphan for CYP2D6; cocktail B was composed of coumarin for CYP2A6, chlorzoxazone for CYP2E1, astemizole for CYP2J2, and midazolam, nifedipine, and testosterone for CYP3A. Multiple probe substrates were used for CYP3A owing to the multiple substrate‐binding sites and substrate‐dependent inhibition. After incubation in human liver microsomes, each incubation mixture was pooled and all probe metabolites were simultaneously analysed in a single LC–MS/MS run. Polarity switching was used to acquire the negative‐ion mode for hydroxychlorzoxazone and positive‐ion mode for the remaining analytes. The method was validated by comparing the inhibition data obtained from incubation of each individual probe substrate alone and with the substrate cocktails. The half‐maximal inhibitory concentration values obtained from the cocktail and individual incubations were well correlated and in agreement with previously reported values. This new method will be useful in assessing the drug interaction potential of new chemical entities during new drug development.
Brain imaging in classic nonketotic hyperglycinemia: Quantitative analysis and relation to phenotype

Patients with severe nonketotic hyperglycinemia (NKH) have absent psychomotor development and intractable epilepsy, whereas attenuated patients have variable psychomotor development and absent or treatable epilepsy; differences in brain magnetic resonance imaging (MRI) between phenotypes have not been reported. In a retrospective cross‐sectional study, we reviewed 38 MRI studies from 24 molecularly proven NKH patients, and 2 transient NKH patients. Quantitative analyses included corpus callosum size, apparent diffusion coefficient, automated brain volumetric analysis, and glycine/creatine ratio by spectroscopy. All patients age <3 months had restricted diffusion in the posterior limb of the internal capsule, anterior brainstem, posterior tegmental tracts, and cerebellum, not present in transient NKH. In older infants, the pattern evolved and included generalized diffusion restriction in the supratentorial white matter, which quantitatively peaked between 3 and 12 months. No patient had absent corpus callosum or gyral malformation. The corpus callosum was relatively short in severe compared to attenuated phenotypes, and thin in severe cases only. The corpus callosum growth rate differed by severity; age‐matched Z‐scores of thickness worsened in severe cases only. Cerebral volume was decreased in the hippocampus, globus pallidus, cerebral cortex, thalamus, and cerebellum. Severe patients had greatest glycine/creatine ratios. In this study, no brain malformations were identified. The growth failure of the corpus callosum is worse in severe NKH, whereas the diffusion restriction pattern, reflecting microspongiosis, does not discriminate by phenotypic severity. NKH is therefore a disorder of brain growth best recognized in the corpus callosum, whereas spongiosis is not prognostic.
Genetically elevated circulating homocysteine concentrations increase the risk of diabetic kidney disease in Chinese diabetic patients

Diabetic kidney disease (DKD) is a devastating and frequent complication of diabetes mellitus. Here, we first adopted methylenetetrahytrofolate reductase (MTHFR) gene C677T polymorphism as an instrument to infer the possible causal relevance between circulating homocysteine and DKD risk in a Chinese population and next attempted to build a risk prediction model for DKD. This is a hospital‐based case‐control association study. Total 1107 study participants were diagnosed with type 2 diabetes mellitus, including 547 patients with newly diagnosed and histologically confirmed DKD. MTHFR gene C677T polymorphism was determined using the TaqMan method. Carriers of 677TT genotype (14.55 μmol/L) had significantly higher homocysteine concentrations than carriers of 677CT genotype (12.88 μmol/L) (P < 0.001). Carriers of 677TT genotype had a 1.57‐fold increased risk of DKD (odds ratio: 1.57, 95% CI: 1.21‐2.05, P = 0.001) relative to carriers of 677CT genotype after adjusting for confounders. Mendelian randomization analysis revealed that the odds ratio for DKD relative to diabetes mellitus per 5 μmol/L increment of circulating homocysteine concentrations was 3.86 (95% confidence interval: 1.21‐2.05, P < 0.001). In the Logistic regression analysis, hypertension, homocysteine and triglyceride were significantly associated with an increased risk of DKD and they constituted a risk prediction model with good test performance and discriminatory capacity. Taken together, our findings provide evidence that elevated circulating homocysteine concentrations were causally associated with an increased risk of DKD in Chinese diabetic patients.
When do we fall in neural synchrony with others?

Abstract This study aimed to investigate the situation in which interpersonal brain synchronization (IBS) occurs during a collaborative task and examined its trajectory over time by developing a novel functional near‐infrared spectroscopy (fNIRS)‐based hyperscanning paradigm. Participants were asked to perform a collaborative task in three‐person groups where two of the members are real participants and one is a confederate. Compared to dyads between real participants and confederates, real‐participant pairings showed greater cooperation behavior and IBS between bilateral dorsolateral prefrontal cortex. And, IBS and cooperation increased over time in real‐participant pairings, whereas they remained low and constant in dyads with the confederate. These findings indicate that IBS occurs between individuals engaging in interpersonal interaction during a collaborative task, during which both IBS and cooperatively interpersonal interaction tend to increase over time.