Miracle-dz/UniFAR-FTUs huggingface dataset:
Weight loss is correlated with disease severity in Spinocerebellar ataxia type 2: a cross-sectional cohort study

ABSTRACT Background Body weight changes occur frequently during advanced stages of Spinocerebellar Ataxia type 2 (SCA2), nevertheless limited information exists on biomarkers of nutritional status of these patients. Objective. To assess changes in surrogate nutritional markers of SCA2 patients; to explore their associations with expanded CAG repeats and disease severity. Methods One-hundred-thirteen SCA2 patients and 50 healthy controls underwent a comprehensive anthropometrical and biochemical assessment protocol of the nutritional status. Neurological and genotype assessments were also performed. Results A decrease in weight, body mass index (BMI), cutaneous skinfold thickness, fat mass, arm muscle circumference, calf circumference and skeletal muscle mass was observed in SCA2 patients compared to the controls. The total/HDL cholesterol ratio was significantly reduced in patients. BMI was correlated with the age at onset. Overall, anthropometric measures were correlated with clinical markers of disease severity and were more evident in severe and moderate cases. Conclusions Using anthropometric measures in the assessment of the nutritional status of SCA2 patients might provide hints about pathophysiological mechanisms that underlie metabolic abnormalities in SCA2. Anthropometric are close related with disease severity and progression, and trigger preventive therapies aimed to ameliorate weight loss and wasting in these patients.
Activation of pregnane X receptor induces atherogenic lipids and PCSK9 by a SREBP2‐mediated mechanism

Many drugs and environmental contaminants induce hypercholesterolemia and promote the risk of atherosclerotic cardiovascular disease. We tested the hypothesis that pregnane X receptor (PXR), a xenobiotic‐sensing nuclear receptor, regulates the level of circulating atherogenic lipids in humans and utilized mouse experiments to identify the mechanisms involved.
Alfacalcidol improves the growth velocity in children with vitamin D deficiency/insufficiency: A single center retrospective cohort study

Objectives To investigate the growth velocity-improving effects of vitamin D replacement therapy in pediatric patients diagnosed with vitamin D deficiency and insufficiency. Study design A retrospective cohort study was conducted in 34 pediatric patients diagnosed with vitamin D deficiency/insufficiency. Based on the clinical findings, the subjects were divided into two groups: a bowed leg (BL) group and a non-bowed leg (non-BL) group. After the initiation of alfacalcidol, the standard deviation score (SDS) of their heights, weights and growth velocities in each group were monitored. Results The median age at the first visit was significantly lesser in the BL group (1.58 years old [interquartile range (IQR): 1.33, 2.17]) than that in the non-BL group (3.00 years old [IQR: 2.33, 3.67]). On the contrary, the SDS for height was significantly lower in the non-BL group (-2.27 [IQR: -2.63, -1.94]) than that in the BL group (-1.37 [IQR: -1.91, -1.07]). One-year treatment with alfacalcidol showed significant improvements in both height SDSs and growth velocity SDSs not only in the BL group but also in the non-BL group. Conclusions The current study revealed that vitamin D replacement therapy improved the growth rate in children with vitamin D deficiency/insufficiency, regardless of the presence of BL. This study emphasizes the importance of assessing the vitamin D status in children with poor growth rates and suggests that alfacalcidol could be a valid option for the treatment of short stature.
Examining the Factor Structure and Incremental Validity of the Barkley Deficits in Executive Functioning Scale – Short Form in a Community Sample

Abstract The Barkley Deficits in Executive Functioning Scale – Short Form (BDEFS-SF; Barkley, 2011) was developed to assess deficits in five facets of executive functioning. Theoretical assumptions surrounding the BDEFS-SF presume that executive dysfunction is an overarching construct that consists of five domain-specific factors (i.e., a hierarchical model; Barkley, 2011). Prior research has supported a correlated five-factor model, but the tenability of hierarchical or bifactor models of the BDEFS-SF have not yet been tested. In the present study (N = 1,120 community adults), confirmatory factor analysis was used to compare four theoretically relevant models of the BDEFS-SF (i.e., one-factor, correlated five-factor, hierarchical, and bifactor models). The bifactor model provided the best fit to the data. However, the general factor accounted for the overwhelming majority of variance in BDEFS-SF scores and none of the domain-specific factors exhibited adequate construct replicability or factor determinancy. Further, the general factor accounted for the overhelming majority of variance in criterion variables (i.e., executive attention and health anxiety); the Organization and Emotion factors accounted for a small amount of unique variance in executive attention and the Emotion factor accounted for a small amount of unique variance in health anxiety. Taken together, study findings suggest that the BDEFS-SF has a strong general factor and independent use of the domain-specific factors is contraindicated.
Association of Accelerometer-Measured Physical Activity and Cardiovascular Health in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)

Introduction: Evidence regarding the associations between accelerometer-measured moderate-vigorous physical activity (MVPA) and cardiovascular health (CVH) indicators among Hispanic/Latino adults are unavailable. Methods: Examined cross-sectional data from 12,008 Hispanic/Latino adults aged 18–74 years participating in the Hispanic Community Health Study/Study of Latinos. Accelerometer-measured MVPA was assessed categorically and dichotomously per 2008 PA guidelines. Adverse and ideal CVH indicators were determined by standard cut-points for blood glucose, total cholesterol, blood pressure, body mass index (BMI), and smoking. A composite of low CV risk, defined as achieving all ideal CVH indicators, was included. Adjusted Poisson regression models and complex survey design methods were used for all analyses. Results: Compared to high MVPA, lower MVPA categories were associated with higher prevalence of all adverse CVH indicators, except hypertension, and with lower prevalence of low CV risk and ideal blood glucose, blood pressure, and BMI. Similarly, non-adherence to PA guidelines was associated with a higher prevalence of diabetes (16%), hypercholesterolemia (9%), obesity (28%), and smoking (9%); and lower prevalence of low CV risk (24%), ideal blood glucose (6%), ideal blood pressure (6%), and ideal BMI (22%). Conclusion: Overall, high accelerometer-measured MVPA and meeting PA guidelines were associated with favorable CVH in Hispanic/Latino adults.
Maternal Vitamin B12 Status and Risk of Cleft Lip and Cleft Palate Birth Defects in Tamil Nadu State, India

Background and Objective: The causal role of maternal nutrition in orofacial clefts is uncertain. We tested hypotheses that low maternal vitamin B12 and low folate status are each associated with an increased risk of isolated cleft lip with or without cleft palate (CL±P) in a case–control study in Tamil Nadu state, India. Methods: Case-mothers of CL±P children (n = 47) and control-mothers of unaffected children (n = 50) were recruited an average of 1.4 years after birth of the index child and plasma vitamin B12, methylmalonic acid (MMA), total homocysteine (tHcy), and folate were measured at that time. Logistic regression analyses estimated associations between nutrient biomarkers and case–control status. Results: Odds ratios (ORs) contrasting biomarker levels showed associations between case-mothers and low versus high plasma vitamin B12 (OR = 2.48, 95% CI, 1.02-6.01) and high versus low plasma MMA, an indicator of poor B12 status (OR = 3.65 95% CI, 1.21-11.05). Case–control status was not consistently associated with folate or tHcy levels. Low vitamin B12 status, when defined by a combination of both plasma vitamin B12 and MMA levels, had an even stronger association with case-mothers (OR = 6.54, 95% CI, 1.33-32.09). Conclusions: Mothers of CL±P children in southern India were 6.5 times more likely to have poor vitamin B12 status, defined by multiple biomarkers, compared to control-mothers. Further studies in populations with diverse nutritional backgrounds are required to determine whether poor maternal vitamin B12 or folate levels or their interactions are causally related to CL±P.
Validation of a scoring system for prediction of obstetric complications in placenta accreta spectrum disorders

Abstract Background Placenta accreta spectrum (PAS) refers to a spectrum of conditions characterized by the abnormal adherence of the placenta to the implantation site and has been a challenge due to the risk of postpartum hemorrhage, peripartum hysterectomy and maternal mortality. Despite of sonographic findings, no consensus on the prenatal evaluation of PAS has been established yet. We are aiming to establish a scoring system to increase the accuracy of prediction of PAS severity, especially to differentiate placenta percreta and placenta increta. Methods We conducted a retrospective study and collected 2,219 cases of placenta increta and placenta percreta obtained from 20 tertiary care centers in China. Demographic information, clinical characteristics, and sonographic findings were collected. Logistic regression analysis was used to determine the risk factors and sonographic features that were significantly associated with a clinical diagnosis of placenta percreta. The formula and subsequent scoring system were generated. This scoring system was then verified in 67 cases of placenta increta or placenta percreta in Peking University First Hospital from 2016 to 2017. Diagnosis of placental invasion was confirmed by surgical findings or histopathologic results. The scoring system was evaluated using a receiver operating characteristic (ROC) curve. Results The scoring system combined maternal risk factors and ultrasound features and was then verified in 67 cases. According to ROC curve, the area under the curve (AUC) of our scoring system for prenatal diagnosis of placenta percreta is 0.96 (95%CI, 0.91–1.00, p < .001), for severe postpartum hemorrhage (≥1500 ml) is 0.76 (95%CI, 0.62–0.91, p = .005), for hysterectomy is 0.98 (95%CI, 0.93–1.000, p = .023). Conclusions Our scoring system combining maternal risk factors and ultrasound features can improve the predictive accuracy of placenta percreta and obstetric outcomes (severe hemorrhage and hysterectomy).
Behind the Shield of Czc: ZntR Controls Expression of the Gene for the Zinc-Exporting P-Type ATPase ZntA in Cupriavidus metallidurans

Zinc is an essential metal for numerous organisms, from humans to bacteria. The transportome of zinc uptake and efflux systems controls the overall cellular composition and zinc content in a double-feedback loop. ABSTRACT In the metallophilic betaproteobacterium Cupriavidus metallidurans, the plasmid-encoded Czc metal homeostasis system adjusts the periplasmic zinc, cobalt, and cadmium concentrations, which influences subsequent uptake of these metals into the cytoplasm. Behind this shield, the PIB2-type ATPase ZntA is responsible for removal of surplus cytoplasmic zinc ions, thereby providing a second level of defense against toxic zinc concentrations. ZntA is the counterpart to the Zur-regulated zinc uptake system ZupT and other import systems; however, the regulator of zntA expression was unknown. The chromid-encoded zntA gene is adjacent to the genes czcI2C2B2′, which are located on the cDNA strand and transcribed from a common promoter region. These genes encode homologs of plasmid pMOL30-encoded Czc components. Candidates for possible regulators of zntA were identified and subsequently tested: CzcI, CzcI2, and the MerR-type gene products of the locus tags Rmet_2302, Rmet_0102, and Rmet_3456. This led to the identification of Rmet_3456 as ZntR, the main regulator of zntA expression. Moreover, both CzcI proteins decreased Czc-mediated metal resistance, possibly to avoid “overexcretion” of periplasmic zinc ions, which could result in zinc starvation due to diminished zinc uptake into the cytoplasm. Rmet_2302 was identified as CadR, the regulator of the cadA gene for an important cadmium-exporting PIB2-type ATPase, which provides another system for removal of cytoplasmic zinc and cadmium. Rmet_0102 was not involved in regulation of the metal resistance systems examined here. Thus, ZntR forms a complex regulatory network with CadR, Zur, and the CzcI proteins. Moreover, these discriminating regulatory proteins assign the efflux systems to their particular function. IMPORTANCE Zinc is an essential metal for numerous organisms, from humans to bacteria. The transportome of zinc uptake and efflux systems controls the overall cellular composition and zinc content in a double-feedback loop. Zinc starvation mediates, via the Zur regulator, upregulation of the zinc import capacity via the ZIP-type zinc importer ZupT and amplification of zinc storage capacity, which together raise the cellular zinc content again. On the other hand, an increasing zinc content leads to ZntR-mediated upregulation of the zinc efflux system ZntA, which decreases the zinc content. Together, the Zur regulon components and ZntR/ZntA balance the cellular zinc content under both high external zinc concentrations and zinc starvation conditions.
Chemical Characterization of Water from Saraj Spring in Kosova

Saraj spring is located in south part of Kosova. In this research work we have analyzed 12 metals in the water of Sarai spring. We used ICP-OES for the analysis. Also some physico-chemical parameters are determined: water temperature, pH, conductivity (EC), turbidity, total hardness, consumption of KMnO4, chlorides, sulphates, phosphate, ammonia, nitrates and nitrites. From our results we have seen that this water is acidic and has low hardness. From the results, we found that all metals are under maximum level of WHO standards for drinking water, except chromium (0.06 mg dm -3 ) and nickel (0.022 mg dm -3 ). Also we have classified this water according to the level of metals. In Kosova we don't have standards yet, so we decided to use the Croatian Standards. The Saraj Water based on concentration of Cu, Pb and Cd is classified in first class, but based on the concentration of Zn it can classify in fifth class. From these results we can conclude that this water can be used for drinking but first it should treat to remove Cr and Ni.
The representation of mental state information in schizophrenia and first-degree relatives: a multivariate pattern analysis of fMRI data

Abstract Individuals with a schizophrenia-spectrum disorder (SSD) and those at familial high risk (FHR) for SSDs experience social difficulties that are related to neural abnormalities in the network of brain regions recruited during theory of mind (ToM). Prior work with these groups has focused almost exclusively on characterizing the involvement of these regions in ToM. Here, we examine the representational content of these regions using multivariate pattern analysis. We analyzed two previously collected datasets of SSD, FHR and control participants who, while undergoing functional magnetic resonance imaging, completed the false-belief task in which they read stories describing beliefs or physical representations (e.g. photographs). Univariate and multivariate analyses were performed in regions of interest to evaluate group differences in task-based activation and representational content, respectively. Compared to non-SSDs, SSDs showed reduced decoding accuracy for the category of mental states in the right temporo-parietal junction—which was related to false-belief accuracy—and the dorsal medial prefrontal cortex (DMPFC) and reduced involvement of DMPFC for mental state understanding. FHR showed no differences in decoding accuracy or involvement compared to non-FHR. Given prior studies of disrupted neural involvement in FHR and the lack of decoding differences observed here, the onset of illness may involve processes that corrupt how mental state information is represented.
c-CSN: Single-cell RNA Sequencing Data Analysis by Conditional Cell-specific Network

The rapid advancement of single cell technologies has shed new light on the complex mechanisms of cellular heterogeneity. However, compared with bulk RNA sequencing (RNA-seq), single-cell RNA-seq (scRNA-seq) suffers from higher noise and lower coverage, which brings new computational difficulties. Based on statistical independence, cell-specific network (CSN) is able to quantify the overall associations between genes for each cell, yet suffering from a problem of overestimation related to indirect effects. To overcome this problem, we propose the “conditional cell-specific network” (CCSN) method, which can measure the direct associations between genes by eliminating the indirect associations. CCSN can be used for cell clustering and dimension reduction on a network basis of single cells. Intuitively, each CCSN can be viewed as the transformation from less “reliable” gene expression to more “reliable” gene-gene associations in a cell. Based on CCSN, we further design network flow entropy (NFE) to estimate the differentiation potency of a single cell. A number of scRNA-seq datasets were used to demonstrate the advantages of our approach: (1) one direct association network for one cell; (2) most existing scRNA-seq methods designed for gene expression matrices are also applicable to CCSN-transformed degree matrices; (3) CCSN-based NFE helps resolving the direction of differentiation trajectories by quantifying the potency of each cell. CCSN is publicly available at http://sysbio.sibcb. ac.cn/cb/chenlab/soft/CCSN.zip.
Patterns and Processes of Diploidization in Land Plants.

Most land plants are now known to be ancient polyploids that have rediploidized. Diploidization involves many changes in genome organization that ultimately restore bivalent chromosome pairing, disomic inheritance, and resolve dosage and other issues caused by genome duplication. In this review, we discuss the nature of polyploidy and its impact on chromosome pairing behavior. We also provide an overview of two major and largely independent processes of diploidization: cytological diploidization and genic diploidization/fractionation. Finally, we compare variation in gene fractionation across land plants and highlight the differences in diploidization between plants and animals. Altogether, we demonstrate recent advancements in our understanding of variation in the patterns and processes of diploidization in land plants and provide a road map for future research to unlock the mysteries of diploidization and eukaryotic genome evolution. Expected final online publication date for the Annual Review of Plant Biology, Volume 72 is May 2021. Please see http://www.annualreviews. org/page/journal/pubdates for revised estimates.
Increased Ipsilateral Posterior Cerebral Artery P2-Segment Flow Velocity Predicts Hemodynamic Impairment

Supplemental Digital Content is available in the text. Background and Purpose: Increased Transcranial Doppler flow velocity in the ipsilateral P2-segment of the posterior cerebral artery (PCA-P2: cm/second) is associated with recurrent cerebrovascular events in patients with unilateral internal carotid artery occlusion. However, its predictive value and correlation with hemodynamic impairment in an overall stroke patient cohort remains to be determined. Methods: Transcranial doppler PCA-P2 flow velocity was measured in 88 patients with symptomatic unilateral steno-occlusive disease who also underwent blood oxygenation-level dependent cerebrovascular reactivity imaging (blood oxygenation-level dependent [BOLD]-cerebrovascular reactivity [CVR]). A multivariate linear regression was used to evaluate the independent correlation between the ipsilateral PCA-P2 flow velocity measurements and hemispheric BOLD-CVR. Follow-up BOLD-CVR imaging data, available in 25 patients, were used to evaluate the temporal evolution of the BOLD-CVR and PCA-P2 flow velocity association using a mixed-effect model. Furthermore, a transcranial doppler cutoff for hemodynamic failure stage 2 was determined. Results: The ipsilateral systolic PCA-P2 flow velocity strongly correlated with hemispheric BOLD-CVR (R=0.79; R2=0.61), which remained unchanged when evaluating the follow-up data. Using a PCA-P2 systolic flow velocity cutoff value of 85 cm/second, patients with BOLD-CVR based hemodynamic failure stage 2 were diagnosed with an area under the curve of 95. Conclusions: In patients with symptomatic unilateral steno-occlusive disease, increased ipsilateral transcranial doppler PCA-P2 systolic flow velocity independently correlates with BOLD-CVR based hemodynamic failure. A cutoff value of 85 cm/second appears to indicate hemodynamic failure stage 2, but this finding needs to be validated in an independent patient cohort.
Variety-seeking, learning and performance

According to the variance hypothesis, variety-seeking or exploration is a critical condition for improving learning and performance over time. Extant computational learning models support this hypothesis by showing how individuals who are exposed to diverse knowledge sources are more likely to find superior solutions to a particular problem. Yet this research provides no precise guidelines about how broadly individuals should search. Our goal in this paper is to elucidate the conditions under which variety-seeking in organizations is beneficial. To this end, we developed a computational model in which individuals learn as they interact with other individuals, and update their knowledge as a result of this interaction. The model reveals how the type of learning environment (performance landscape) in which the learning dynamic unfolds determines when the benefits of variety-seeking outweigh the costs. Variety-seeking is performance-enhancing only when the knowledge of the chosen learning targets (i.e., individuals to learn from) provide useful information about the features of the performance landscape. The results further suggest that superior knowledge might be available locally, i.e., in the proximity of an individual’s current location. We also identify the point beyond which variety-seeking causes a sharp performance decline and show how this point depends on the type of landscape in which the learning dynamic unfolds and the degree of specialization of individual knowledge. The presence of this critical point explains why exploration becomes very costly. The implications of our findings for establishing the boundaries of exploration are discussed.