Miracle-dz/UniFAR-FTUs huggingface dataset:
Glucose regulation and cognitive function after bariatric surgery

Introduction: Obesity is associated with cognitive impairment, and bariatric surgery has been shown to improve cognitive functioning. Rapid improvements in glycemic control are common after bariatric surgery and likely contribute to these cognitive gains. We examined whether improvements in glucose regulation are associated with better cognitive function following bariatric surgery. Method: A total of 85 adult bariatric surgery patients underwent computerized cognitive testing and fasting blood draw for glucose, insulin, and glycated hemoglobin (HbA1c) at baseline and 12 months postoperatively. Results: Significant improvements in both cognitive function and glycemic control were observed among patients. After controlling for baseline factors, 12-month homeostatic model assessment of insulin resistance HOMA-IR predicted 12-month digits backward (β = –.253, p < .05), switching of attention–A (β = .156, p < .05), and switching of attention–B (β = –.181, p < .05). Specifically, as HOMA-IR decreased over time, working memory, psychomotor speed, and cognitive flexibility improved. Decreases in HbA1c were not associated with postoperative cognitive improvements. After controlling for baseline cognitive test performance, changes in body mass index (BMI) were also not associated with 12-month cognitive function. Conclusions: Small effects of improved glycemic control on improved aspects of attention and executive function were observed following bariatric surgery among severely obese individuals. Future research is needed to identify the underlying mechanisms for the neurocognitive benefits of these procedures.
Causal Hierarchy within the Thalamo-Cortical Network in Spike and Wave Discharges

Background Generalised spike wave (GSW) discharges are the electroencephalographic (EEG) hallmark of absence seizures, clinically characterised by a transitory interruption of ongoing activities and impaired consciousness, occurring during states of reduced awareness. Several theories have been proposed to explain the pathophysiology of GSW discharges and the role of thalamus and cortex as generators. In this work we extend the existing theories by hypothesizing a role for the precuneus, a brain region neglected in previous works on GSW generation but already known to be linked to consciousness and awareness. We analysed fMRI data using dynamic causal modelling (DCM) to investigate the effective connectivity between precuneus, thalamus and prefrontal cortex in patients with GSW discharges. Methodology and Principal Findings We analysed fMRI data from seven patients affected by Idiopathic Generalized Epilepsy (IGE) with frequent GSW discharges and significant GSW-correlated haemodynamic signal changes in the thalamus, the prefrontal cortex and the precuneus. Using DCM we assessed their effective connectivity, i.e. which region drives another region. Three dynamic causal models were constructed: GSW was modelled as autonomous input to the thalamus (model A), ventromedial prefrontal cortex (model B), and precuneus (model C). Bayesian model comparison revealed Model C (GSW as autonomous input to precuneus), to be the best in 5 patients while model A prevailed in two cases. At the group level model C dominated and at the population-level the p value of model C was ∼1. Conclusion Our results provide strong evidence that activity in the precuneus gates GSW discharges in the thalamo-(fronto) cortical network. This study is the first demonstration of a causal link between haemodynamic changes in the precuneus - an index of awareness - and the occurrence of pathological discharges in epilepsy.
In vivo experiments do not support the charge zipper model for Tat translocase assembly

The twin-arginine translocase (Tat) transports folded proteins across the bacterial cytoplasmic membrane and the plant thylakoid membrane. The Tat translocation site is formed by substrate-triggered oligomerization of the protein TatA. Walther and co-workers have proposed a structural model for the TatA oligomer in which TatA monomers self-assemble using electrostatic ‘charge zippers’ (Cell (2013) 132: 15945). This model was supported by in vitro analysis of the oligomeric state of TatA variants containing charge-inverting substitutions. Here we have used live cell assays of TatA assembly and function in Escherichia coli to re-assess the roles of the charged residues of TatA. Our results do not support the charge zipper model. Instead, we observe that substitutions of charged residues located in the TatA amphipathic helix lock TatA in an assembled state, suggesting that these charged residues play a critical role in the protein translocation step that follows TatA assembly.
TNF regulates transcription of NLRP3 inflammasome components and inflammatory molecules in cryopyrinopathies

The NLRP3 inflammasome is a protein complex responsible for caspase-1–dependent maturation of the proinflammatory cytokines IL-1&bgr; and IL-18. Gain-of-function missense mutations in NLRP3 cause the disease spectrum known as the cryopyrin-associated periodic syndromes (CAPS). In this study, we generated Nlrp3-knockin mice on various KO backgrounds including Il1b/Il18-, caspase-1–, caspase-11– (Casp1/11-), and Tnf-deficient strains. The Nlrp3L351P Il1b–/– Il18–/– mutant mice survived and grew normally until adulthood and, at 6 months of age, exhibited marked splenomegaly and leukophilia. Injection of these mice with low-dose LPS resulted in elevated serum TNF levels compared with Nlrp3L351P Casp1/11–/– mice and Il1b–/– Il18–/– littermates. Treatment of Nlrp3A350V mice with the TNF inhibitor etanercept resulted in all pups surviving to adulthood, with normal body and spleen/body weight ratios. Nlrp3A350V Tnf–/– mice showed a similar phenotypic rescue, with marked reductions in serum IL-1&bgr; and IL-18, reduced myeloid inflammatory infiltrate in the skin and spleen, and substantial decreases in splenic mRNA expression of both inflammasome components (Nlrp3, Pycard, pro-Casp1) and pro-cytokines (Il1b, Il18). Likewise, we observed a reduction in the expression of both pro-Casp1 and pro-Il1b in cultured Nlrp3A350V Tnf–/– BM-derived DCs. Our data show that TNF is an important transcriptional regulator of NLRP3 inflammasome components in murine inflammasomopathies. Moreover, these results may have therapeutic implications for CAPS patients with partial responses to IL-1–targeted therapies.
Attractant Binding Induces Distinct Structural Changes to the Polar and Lateral Signaling Clusters in Bacillus subtilis Chemotaxis*

Bacteria employ a modified two-component system for chemotaxis, where the receptors form ternary complexes with CheA histidine kinases and CheW adaptor proteins. These complexes are arranged in semi-ordered arrays clustered predominantly at the cell poles. The prevailing models assume that these arrays are static and reorganize only locally in response to attractant binding. Recent studies have shown, however, that these structures may in fact be much more fluid. We investigated the localization of the chemotaxis signaling arrays in Bacillus subtilis using immunofluorescence and live cell fluorescence microscopy. We found that the receptors were localized in clusters at the poles in most cells. However, when the cells were exposed to attractant, the number exhibiting polar clusters was reduced roughly 2-fold, whereas the number exhibiting lateral clusters distinct from the poles increased significantly. These changes in receptor clustering were reversible as polar localization was reestablished in adapted cells. We also investigated the dynamic localization of CheV, a hybrid protein consisting of an N-terminal CheW-like adaptor domain and a C-terminal response regulator domain that is known to be phosphorylated by CheA, using immunofluorescence. Interestingly, we found that CheV was localized predominantly at lateral clusters in unstimulated cells. However, upon exposure to attractant, CheV was found to be predominantly localized to the cell poles. Moreover, changes in CheV localization are phosphorylation-dependent. Collectively, these results suggest that the chemotaxis signaling arrays in B. subtilis are dynamic structures and that feedback loops involving phosphorylation may regulate the positioning of individual proteins.
Recurrent RET Gene Rearrangements in Intraductal Carcinomas of Salivary Gland

Intraductal carcinoma (IC) is the World Health Organization designation for lesions previously called low-grade cribriform cystadenocarcinoma. The relationship of IC to salivary duct carcinoma (SDC) is controversial, but currently these are considered distinct entities. It is hypothesized that IC and SDC should have different genomic signatures that may be identifiable by next-generation sequencing. A total of 23 ICs were identified: 14 pure IC and 9 invasive carcinomas with an intraductal component. Five invasive carcinomas were subjected to next-generation paired-end RNA sequencing. Data analysis was performed using FusionSeq and Mutation detection algorithms (MuTect and VarScan) for variant callers. Gene fusion candidates were validated by fluorescence in situ hybridization and reverse transcription polymerase chain reaction, and mutations by Sanger sequencing. Among the 9 invasive carcinomas, all except 1 were apocrine SDCs with an intraductal component. The remaining case showed typical intercalated duct type IC with invasive adenocarcinoma. The 14 pure ICs had typical intercalated duct features (2 showed hybrid intercalated/apocrine features). RNA sequencing predicted a NCOA4-RET fusion, confirmed by reverse transcription polymerase chain reaction, in the intercalated duct type IC invasive component. Six additional cases of pure IC showed RET rearrangement by fluorescence in situ hybridization (7/15=47%). No apocrine carcinomas showed RET rearrangement. RNA sequencing and Sanger sequencing identified PIK3CA (p.E545K/p.H1047R) and/or HRAS (p.Q61R) hotspot mutations in 6 of 8 (75%) apocrine carcinomas. In conclusion, 2 distinctive types of intraductal lesions are emerging based on molecular analysis. Classic intercalated type ICs commonly harbor fusions involving RET and rarely show widespread invasion. Apocrine intraductal lesions are typically associated with widespread invasion with no pure examples and show similar PIK3CA and HRAS mutations to SDC.
A Microfluidic Pump/Valve Inspired by Xylem Embolism and Transpiration in Plants

In plants, transpiration draws the water upward from the roots to the leaves. However, this flow can be blocked by air bubbles in the xylem conduits, which is called xylem embolism. In this research, we present the design of a biomimetic microfluidic pump/valve based on water transpiration and xylem embolism. This micropump/valve is mainly composed of three parts: the first is a silicon sheet with an array of slit-like micropores to mimic the stomata in a plant leaf; the second is a piece of agarose gel to mimic the mesophyll cells in the sub-cavities of a stoma; the third is a micro-heater which is used to mimic the xylem embolism and its self-repairing. The solution in the microchannels of a microfluidic chip can be driven by the biomimetic “leaf” composed of the silicon sheet and the agarose gel. The halting and flowing of the solution is controlled by the micro-heater. Results have shown that a steady flow rate of 1.12 µl/min can be obtained by using this micropump/valve. The time interval between the turning on/off of the micro-heater and the halt (or flow) of the fluid is only 2∼3 s. This micropump/valve can be used as a “plug and play” fluid-driven unit. It has the potential to be used in many application fields.
Gambling disorder in adolescents: prevalence, new developments, and treatment challenges

Research on adolescence gambling over the past twenty years has revealed significant incidence and prevalence rates and highlighted the possible negative effects on an adolescent’s well-being. Several risk and protective factors have also been identified. Over the course of the past few years, technological advances have heralded the advent of new avenues for gambling as well as new opportunities to gamble without any direct monetary exchange. This review article examines those established trends as well as the new issues that we are faced with, in order to accurately portray the current challenges in research, prevention, and treatment.
The Variable Metric Forward-Backward Splitting Algorithm Under Mild Differentiability Assumptions

We study the variable metric forward-backward splitting algorithm for convex minimization problems without the standard assumption of the Lipschitz continuity of the gradient. In this setting, we prove that, by requiring only mild assumptions on the smooth part of the objective function and using several types of line search procedures for determining either the gradient descent stepsizes, or the relaxation parameters, one still obtains weak convergence of the iterates and convergence in the objective function values. Moreover, the $o(1/k)$ convergence rate in the function values is obtained if slightly stronger differentiability assumptions are added. We also illustrate several applications including problems that involve Banach spaces and functions of divergence type.
Monogenic Causes of Proteinuria in Children

Glomerular disease is a common cause for proteinuria and chronic kidney disease leading to end-stage renal disease requiring dialysis or kidney transplantation in children. Nephrotic syndrome in children is diagnosed by the presence of a triad of proteinuria, hypoalbuminemia, and edema. Minimal change disease is the most common histopathological finding in children and adolescents with nephrotic syndrome. Focal segmental sclerosis is also found in children and is the most common pathological finding in patients with monogenic causes of nephrotic syndrome. Current classification system for nephrotic syndrome is based on response to steroid therapy as a majority of patients develop steroid sensitive nephrotic syndrome regardless of histopathological diagnosis or the presence of genetic mutations. Recent studies investigating the genetics of nephrotic syndrome have shed light on the pathophysiology and mechanisms of proteinuria in nephrotic syndrome. Gene mutations have been identified in several subcellular compartments of the glomerular podocyte and play a critical role in mitochondrial function, actin cytoskeleton dynamics, cell–matrix interactions, slit diaphragm, and podocyte integrity. A subset of genetic mutations are known to cause nephrotic syndrome that is responsive to immunosuppressive therapy but clinical data are limited with respect to renal prognosis and disease progression in a majority of patients. To date, more than 50 genes have been identified as causative factors in nephrotic syndrome in children and adults. As genetic testing becomes more prevalent and affordable, we expect rapid advances in our understanding of mechanisms of proteinuria and genetic diagnosis will help direct future therapy for individual patients.
Correlation between intake and ingestive behavior of pasture-grazed heifers.

The objective of this study was to evaluate the correlation between intake and ingestive behavior of crossbred heifers in grazing tropical. The experiment was conducted on the Princesa do Mateiro Farm, in the city of Ribeirao do Largo, Bahia. A total of 20 heifers with genetic makeup 5/8 dairy Guzera and 3/8 Holstein, average age of 18 months and body weight of 187 ± 13.1 kg have been used. The experiment lasted 224 days and involved animals raised in a rotational grazing system with Brachiaria brizantha cv. Marandu. Grazing time was not correlated with any of the variables associated with intake. Rumination time showed positive correlations with the intake of forage dry matter (DMIF) and neutral detergent fiber (NDFI). Variables associated with the time spent on feeding at the trough, overall feeding and total chewing were not correlated with intake (P>0.05). There have been positive correlations between the number of grazing periods (NGP) and rumination periods (NRP) and total DM intake (TDMI), organic matter (OMI), forage (DMIF), neutral detergent fiber (NDFI), total carbohydrates (TCHI) and ether extract (EEI). Crude protein intake (CPI) was positively correlated with NGP and NRP. The mouthful rate was positively correlated with TDMI, OMI, DMIF, NDFI, TCHI, EEI and CPI. Average time per swallow was negatively correlated with TDMI, OMI, NDFI, TCHI and EEI. Positive correlations have been observed between the number of mouthfuls per day and TDMI, OMI, DMIF, NDFI, TCHI, EEI. The number of chews per bolus showed negative correlations with DMIS and CPI. The time per cake ruminated has correlated negatively with the intake of crude protein. The number of chews per bolus showed positive correlations with the intakes of dry matter and neutral detergent fiber. The number of boli per day showed positive correlations with DMIF and TCHI. The time spent on chewing showed no significant correlation with intake. In conflict with the national and international literature, the grazing time was not correlated with intake by grass-fed crossbred heifers. The number of activities, the time spent on them and the mouthful rate where shown to be highly associated with the intake variables and can therefore arrange equations to predict intake through the analysis of feeding behavior. The number of mouthfuls performed each day contributes to the intake by pasture-grazed heifers.
Disparities in dental service utilization among Alabama Medicaid children.

OBJECTIVES Access to oral health care and utilization of available services are important factors in minimizing the oral health disparities among underserved minorities. Our objective was to evaluate the racial and other factors related to 'realized access' to oral health care among Alabama Medicaid children. METHODS Data were obtained from 308 538 Alabama Medicaid claims submitted in 1995-96 and analyzed using regression analyses. RESULTS A lower proportion of Blacks (24%) and other racial groups (22%) compared to Whites (31%) and a lower proportion of 15-19-year-olds (15%) compared to younger age groups (30%) obtained dental services (P < 0.05). Odds of males obtaining care were slightly lower compared to females (OR = 0.96; 95% CI = 0.94-0.99). However, there was a significant interaction of race with other factors in determining service utilization. Subjects who were continuously eligible for Medicaid throughout the fiscal year were more likely to obtain care (OR = 2.86; 95% CI = 2.78-2.93). About one-fourth of the visits had an emergency procedure included in the treatment rendered. Availability of a participating dentist within the county of residence and the lower reimbursement-to-charge ratio were among the other related factors for underutilization of services. CONCLUSIONS There is a significant racial disparity in utilization of dental services even among the Medicaid-eligible children. However, this was not a simple function of race, but a complex interaction of race with other factors such as age, gender, and location. ACKNOWLEDGMENT Supported by CDC grant #U48/CCU 409679.
Cost Minimization of Charging Stations With Photovoltaics: An Approach With EV Classification

This paper proposes a novel electric vehicle (EV) classification scheme for a photovoltaic (PV)-powered EV charging station (CS) that reduces the effect of intermittency of electricity supply and the cost of energy trading of the CS. Since not all EV drivers would like to be environmentally friendly, all vehicles in the CS are divided into three categories: 1) premium; 2) conservative; and 3) green, according to their charging behavior. Premium and conservative EVs are considered interested only in charging their batteries, with noticeably higher rates of charging for premium EVs. Green vehicles are more environmentally friendly and thus assist the CS to reduce its cost of energy trading by allowing the CS to use their batteries as distributed storage. A different charging scheme is proposed for each type of EV, which is adopted by the CS to encourage more EVs to be green. A basic mixed-integer programming (MIP) technique is used to facilitate the proposed classification scheme. It is shown that the uncertainty in PV generation can be effectively compensated, along with minimization of total cost of energy trading to the CS, by consolidating more green EVs. Real solar and pricing data are used for performance analysis of the system. It is demonstrated that the total cost to the CS reduces considerably as the percentage of green vehicles increases and that the contributions of green EVs in winter are greater than those in summer.
‘More than a feeling’: An empirical investigation of hedonistic accounts of animal welfare

Many scientists studying animal welfare appear to hold a hedonistic concept of welfare -whereby welfare is ultimately reducible to an animal’s subjective experience. The substantial advances in assessing animal’s subjective experience have enabled us to take a step back to consider whether such indicators are all one needs to know if one is interested in the welfare of an individual. To investigate this claim, we randomly assigned participants (n = 502) to read one of four vignettes describing a hypothetical chimpanzee and asked them to make judgments about the animal’s welfare. Vignettes were designed to systematically manipulate the descriptive mental states the chimpanzee was described as experiencing: feels good (FG) vs. feels bad (FB); as well as non-subjective features of the animal’s life: natural living and physical healthy (NH) vs. unnatural life and physically unhealthy (UU); creating a fully-crossed 2 (subjective experience) X 2 (objective life value) experimental design. Multiple regression analysis showed welfare judgments depended on the objective features of the animal’s life more than they did on how the animal was feeling: a chimpanzee living a natural life with negative emotions was rated as having better welfare than a chimpanzee living an unnatural life with positive emotions. We also found that the supposedly more purely psychological concept of happiness was also influenced by normative judgments about the animal’s life. For chimpanzees with positive emotions, those living a more natural life were rated as happier than those living an unnatural life. Insofar as analyses of animal welfare are assumed to be reflective of folk intuitions, these findings raise questions about a strict hedonistic account of animal welfare. More generally, this research demonstrates the potential utility of using empirical methods to address conceptual problems in animal welfare and ethics.