Miracle-dz/UniFAR-FTUs huggingface dataset:
Increased amygdala-visual cortex connectivity in youth with persecutory ideation

Abstract Background Subclinical delusional ideas, including persecutory beliefs, in otherwise healthy individuals are heritable symptoms associated with increased risk for psychotic illness, possibly representing an expression of one end of a continuum of psychosis severity. The identification of variation in brain function associated with these symptoms may provide insights about the neurobiology of delusions in clinical psychosis. Methods A resting-state functional magnetic resonance imaging scan was collected from 131 young adults with a wide range of severity of subclinical delusional beliefs, including persecutory ideas. Because of evidence for a key role of the amygdala in fear and paranoia, resting-state functional connectivity of the amygdala was measured. Results Connectivity between the amygdala and early visual cortical areas, including striate cortex (V1), was found to be significantly greater in participants with high (n = 43) v. low (n = 44) numbers of delusional beliefs, particularly in those who showed persistence of those beliefs. Similarly, across the full sample, the number of and distress associated with delusional beliefs were positively correlated with the strength of amygdala-visual cortex connectivity. Moreover, further analyses revealed that these effects were driven by those who endorsed persecutory beliefs. Conclusions These findings are consistent with the hypothesis that aberrant assignments of threat to sensory stimuli may lead to the downstream development of delusional ideas. Taken together with prior findings of disrupted sensory-limbic coupling in psychosis, these results suggest that altered amygdala-visual cortex connectivity could represent a marker of psychosis-related pathophysiology across a continuum of symptom severity.
Post-Stress Fructose and Glucose Ingestion Exhibit Dissociable Behavioral and Physiological Effects

An acute traumatic event can lead to lifelong changes in stress susceptibility and result in psychiatric disease such as Post-Traumatic Stress Disorder (PTSD). We have previously shown that access to a concentrated glucose solution for 24 h beginning immediately after trauma decreased stress-related pathology in the learned helplessness model of PTSD and comorbid major depression. The current study sought to investigate the peripheral physiological effects of post-stress glucose consumption. We exposed 128 male Sprague-Dawley rats to inescapable and unpredictable 1-milliamp electric tail shocks or simple restraint in the learned helplessness procedure. Rats in each stress condition had access to a 40% glucose solution, 40% fructose solution, or water. Blood and liver tissue were extracted and processed for assay. We assessed corticosterone, corticosteroid-binding globulin (CBG), glucose, and liver glycogen concentrations at various time points following stress. We found that rats given access to glucose following exposure to traumatic shock showed a transient rise in blood glucose and an increase in liver glycogen repletion compared to those that received water or fructose following exposure to electric shock. We also found that animals given glucose following shock exhibited reduced free corticosterone and increased CBG compared to their water-drinking counterparts. However, this difference was not apparent when glucose was compared to fructose. These data suggest that post-stress glucose prophylaxis is likely not working via modulation of the HPA axis, but rather may provide its benefit by mitigating the metabolic challenges of trauma exposure.
Circulating follicular helper T cells are increased in systemic sclerosis and promote plasmablast differentiation through the IL-21 pathway which can be inhibited by ruxolitinib

Objectives Systemic sclerosis (SSc) is an autoimmune disease characterised by widespread fibrosis, microangiopathy and autoantibodies. Follicular helper T (Tfh) cells CD4+CXCR5+PD-1+ cooperate with B lymphocytes to induce the differentiation of plasmocytes secreting immunoglobulins (Ig). Circulating Tfh (cTfh) cells are increased in several autoimmune diseases. However, there are no data about cTfh cells and their interaction with B cells in SSc. The aim of this study was to perform a quantitative and functional analysis of cTfh cells in SSc. Methods Using flow cytometry, we analysed cTfh cells from 50 patients with SSc and 32 healthy controls (HC). In vitro coculture experiments of sorted cTfh and B cells were performed for functional analysis. IgG and IgM production were measured by ELISA. Results We observed that cTfh cell numbers are increased in patients with SSc compared with HC. Furthermore, the increase in cTfh cells was more potent in patients with severe forms of SSc such as diffuse SSc and in the presence of arterial pulmonary hypertension. cTfh cells from patients with SSc present an activated Tfh phenotype, with high expression of BCL-6, increased capacity to produce IL-21 in comparison with healthy controls. In vitro, cTfh cells from patients with SSc had higher capacity to stimulate the differentiation of CD19+CD27+CD38hi B cells and their secretion of IgG and IgM through the IL-21 pathway than Tfh cells from healthy controls. Blocking IL-21R or using the JAK1/2 inhibitor ruxolitinib reduced the Tfh cells’ capacity to stimulate the plasmablasts and decreased the Ig production. Conclusions Circulating Tfh cells are increased in SSc and correlate with SSc severity. The IL-21 pathway or JAK1/2 blockade by ruxolitinib could be a promising strategy in the treatment of SSc.
Individualising difference, negotiating culture: Intersections of culture and care

In this article, we focus on developing a critical sociology of ‘cultural and linguistic diversity’ as evident in cancer care praxis, drawing on the perspectives of cancer care health professionals. Set within the context of increasing efforts on the part of healthcare providers to ‘accommodate difference’ and ‘incorporate diversity’, we aimed to utilise participants’ accounts of practice to ask: how do we and how should we think about and operationalise ‘culture’ (if at all) in cancer care settings. Drawing on eight focus groups with doctors, nurses, allied health staff and multicultural community workers, here we explore their accounts of: othering and over-simplification; the role of absences in biographical reciprocity; intimacy, care and carelessness; and entanglements of culture with other aspects of the person. Based on their accounts, we argue for a broadening of the examination of the nexus of culture and care, to focus on the problematics of othering, intimacy, reciprocity and complexity.
Current Knowledge, Barriers to Implementation, and Future Directions in Palliative Care for End‐Stage Liver Disease

End‐stage liver disease (ESLD) is associated with a high degree of morbidity and mortality as well as symptom burden. Despite this, the rate of consultation with palliative care (PC) providers remains low, and invasive procedures near the end of life are commonplace. Studies show that involvement of PC providers improves patient satisfaction, and evidence from other chronic diseases demonstrates reduced costs of care and potentially increased survival. Better integration of PC is imperative but hindered by patient and provider misconceptions about its role in the care of patients with ESLD, specifically among candidates for liver transplantation. Additionally, reimbursement barriers and lack of provider knowledge may contribute to PC underutilization. In this review, we discuss the benefits of PC in ESLD, the variability of its delivery, and key stakeholders’ perceptions about its use. Additionally, we identify barriers to more widespread PC adoption and highlight areas for future research.
The Experimental Infections of the Human Isolate of Strongyloides Stercoralis in a Rodent Model (The Mongolian Gerbil, Meriones Unguiculatus)

Strongyloidiasis is life-threatening disease which is mainly caused by Strongyloides stercoralis infection. Autoinfection of the parasite results in long-lasting infection and fatal conditions, hyperinfection and dissemination (primarily in immunosuppressed hosts). However, mechanisms of autoinfection and biology remain largely unknown. Rodent models including mice and rats are not susceptible to the human isolate of S. stercoralis. Variations in susceptibility of the human isolate of S. stercoralis are found in dogs. S. ratti and S. venezuelensis infections in rats are an alternative model without the ability to cause autoinfection. The absence of appropriate model for the human isolate of strongyloidiasis hampers a better understanding of human strongyloidiasis. We demonstrated the maintenance of the human isolate of the S. stercoralis life cycle in the Mongolian gerbil (Meriones unguiculatus). The human isolate of S. stercoralis caused a patent infection in immunosuppressed gerbils, more than 18 months. The mean number of recovery adult parasitic worms were 120 ± 23 (1.2% of the initial dose) and L1s were 12,500 ± 7500 after day 28 post-inoculation (p.i.). The prepatent period was 9–14 days. Mild diarrhoea was found in gerbils carrying a high number of adult parasitic worms. Our findings provided a promising model for studying biology and searching new alternative drugs against the parasites. Further studies about the hyperinfection and dissemination would be performed.
Reliability and validity of body weight and body image perception in children and adolescents from the South American Youth/Child Cardiovascular and Environmental (SAYCARE) Study

Abstract Objective To assess the reliability and validity of body weight (BW) and body image (BI) perception reported by parents (in children) and by adolescents in a South American population. Design Cross-sectional study. BW perception was evaluated by the question, ‘Do you think you/your child are/is: severely wasted, wasted, normal weight, overweight, obese? ’ BI perception was evaluated using the Gardner scale. To evaluate reliability, BW and BI perceptions were reported twice, two weeks apart. To evaluate validity, the BW and BI perceptions were compared with WHO BMI Z-scores. Kappa and Kendall’s tau-c coefficients were obtained. Setting Public and private schools and high schools from six countries of South America (Argentina, Peru, Colombia, Uruguay, Chile, Brazil). Participants Children aged 3–10 years (n 635) and adolescents aged 11–17 years (n 400). Results Reliability of BW perception was fair in children’s parents (κ=0·337) and substantial in adolescents (κ=0·709). Validity of BW perception was slight in children’s parents (κ=0·176) and fair in adolescents (κ=0·268). When evaluating BI, most children were perceived by parents as having lower weight. Reliability of BI perception was slight in children’s parents (κ=0·124) and moderate in adolescents (κ=0·599). Validity of BI perception was poor in children’s parents (κ=−0·018) and slight in adolescents (κ=0·023). Conclusions Reliability of BW and BI perceptions was higher in adolescents than in children’s parents. Validity of BW perception was good among the parents of the children and adolescents with underweight and normal weight.
Analgesic strategies for day‐case knee surgery

1 Specialty Trainee, 2 Anaesthetic Consultant, Guy’s and St Thomas’NHS Foundation Trust, 3 Honorary Senior Lecturer, King’s College London, UK . Correspondence to:K. El-Boghdadly Email: elboghdadly@gmail.com Accepted: 20December 2018
Molecular basis for pore blockade of human Na+ channel Nav1.2 by the μ-conotoxin KIIIA

Targeting sodium channels Voltage-gated sodium (Nav) channels have been implicated in cardiac and neurological disorders. There are many subtypes of these channels, making it challenging to develop specific therapeutics. A core α subunit is sufficient for voltage sensing and ion conductance, but function is modulated by β subunits and by natural toxins that can either act as pore blockers or gating modifiers (see the Perspective by Chowdhury and Chanda). Shen et al. present the structures of Nav1.7 in complex with both β1 and β2 subunits and with animal toxins. Pan et al. present the structure of Nav1.2 bound to β2 and a toxic peptide, the µ-conotoxin KIIIA. The structure shows why KIIIA is specific for Nav1.2. These and other recently determined Nav structures provide a framework for targeted drug development. Science, this issue p. 1303, p. 1309; see also p. 1278 Structural insight into subtype-specific modulation of voltage-gated sodium channels provides a framework for drug discovery. The voltage-gated sodium channel Nav1.2 is responsible for the initiation and propagation of action potentials in the central nervous system. We report the cryo–electron microscopy structure of human Nav1.2 bound to a peptidic pore blocker, the μ-conotoxin KIIIA, in the presence of an auxiliary subunit, β2, to an overall resolution of 3.0 angstroms. The immunoglobulin domain of β2 interacts with the shoulder of the pore domain through a disulfide bond. The 16-residue KIIIA interacts with the extracellular segments in repeats I to III, placing Lys7 at the entrance to the selectivity filter. Many interacting residues are specific to Nav1.2, revealing a molecular basis for KIIIA specificity. The structure establishes a framework for the rational design of subtype-specific blockers for Nav channels.
Pulmonary , gastrointestinal and urogenital pharmacology Glucose-independent renoprotective mechanisms of the tissue dipeptidyl peptidase-4 inhibitor , saxagliptin , in Dahl salt-sensitive hypertensive rats

Although previous studies have shown an important role of renal dipeptidyl peptidase-4 (DPP-4) inhibition in ameliorating kidney injury in hypertensive rats, the renal distribution of DPP-4 and mechanisms of renoprotective action of DPP-4 inhibition remain unclear. In this study, we examined the effects of the DPP-4 inhibitor saxagliptin on DPP-4 activity in renal cells (using in situ DPP-4 staining) and on renal gene expression related to inflammation and fibrosis in the renal injury in hypertensive Dahl salt-sensitive (Dahl-S) rats. Male rats fed a high-salt (8% NaCl) diet received vehicle (water) or saxagliptin (12.7 mg/kg/day) for 4 weeks. Blood pressure (BP), serum glucose and 24-h urinary albumin and sodium excretions were measured, and renal histopathology was performed. High salt-diet increased BP and urinary albumin excretion, consequently resulting in glomerular sclerosis and tubulointerstitial fibrosis. Although saxagliptin did not affect BP and blood glucose levels, it significantly ameliorated urinary albumin excretion. In situ staining showed DPP-4 activity in glomerular and tubular cells. Saxagliptin significantly suppressed DPP-4 activity in renal tissue extracts and in glomerular and tubular cells. Saxagliptin also significantly attenuated the increase in inflammation and fibrosis-related gene expressions in the kidney. Our results demonstrate that saxagliptin inhibited the development of renal injury independent of its glucose-lowering effect. Glomerular and tubular DPP-4 inhibition by saxagliptin was associated with improvements in albuminuria and the suppression of inflammation and fibrosis-related genes. Thus, local glomerular and tubular DPP-4 inhibition by saxagliptin may play an important role in its renoprotective effects in Dahl-S rats. & 2016 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Novel specific human and mouse stromelysin‐1 (MMP‐3) and stromelysin‐2 (MMP‐10) antibodies for biochemical and immunohistochemical analyses

Matrix metalloproteinases (MMP) are a family of more than 25 zinc‐dependent enzymes that are centrally involved in cellular migration, tissue remodeling, cancer invasion and metastasis. Besides degrading extracellular matrix proteins, MMPs are crucial for growth factor and cytokine release and activation. At the same time, they can inactivate inflammatory mediators and enzymes themselves through protein degradation. Subclasses of MMPs include collagenases, gelatinases, stromelysins, membrane‐bound MMPs, and others. With regard to the stromelysin subfamily, three members exist, e.g., stromelysin‐1 (MMP‐3), stromelysin‐2 (MMP‐10), and stromelysin‐3 (MMP‐11). MMP‐3, and MMP‐10 share extensive similarities at the amino acid level that made it difficult to develop specific antibodies distinguishing between MMP‐3 and MMP‐10. Scrutinizing published data on and performing different analyses with detection of both stromelysins with commercially available or lab‐made antibodies showed ambiguous results with regard to specificity of antibodies used to date. We developed new specific antibodies against the most divergent parts of the active forms of both proteins. We assessed the specificity of our novel specific anti‐human and anti‐mouse MMP‐3 and MMP‐10 antibodies in cell lysates and different human and murine skin tissues. Tests analyzing specificity of the novel antibodies included Western immunoblotting, immunofluorescence, and immunohistochemistry on paraffin sections. Analyses demonstrated specific detection of respective protein for human or mouse samples except for the anti‐human MMP‐3 antibody. The aim of this summary was to call attention the MMP research community to distinguish clearly between both enzymes. Our new specific anti‐mouse MMP‐3 and both MMP‐10 antibodies allow us to address this detection problem and to enable comparative studies between both stromelysins with regard to their respective location and function in the tissue.
Symptom Subtypes of Obstructive Sleep Apnea Predict Incidence of Cardiovascular Outcomes.

RATIONALE Symptom subtypes have been described in clinical and population samples of obstructive sleep apnea (OSA) patients. It is unclear whether these subtypes have different cardiovascular consequences. OBJECTIVES This study aimed to characterize OSA symptom subtypes and assess their association with prevalent and incident cardiovascular disease in the Sleep Heart Health Study. METHODS Data from 1,207 OSA patients (apnea-hypopnea index [AHI]≥15 events/hour) were used to evaluate the existence of symptom subtypes using latent class analysis. Associations between subtypes and prevalence of overall cardiovascular disease (CVD), as well as its components (coronary heart disease [CHD]), heart failure [HF] and stroke) were assessed using logistic regression. Kaplan-Meier survival analysis and Cox proportional hazards models were used to evaluate whether subtypes were associated with incident events, including cardiovascular mortality. MEASUREMENTS AND MAIN RESULTS Four symptom subtypes were identified (Disturbed Sleep [12.2%], Minimally Symptomatic [32.6%], Excessively Sleepy [16.7%], and Moderately Sleepy [38.5%]), similar to prior studies. In adjusted models, while no significant associations with prevalent CVD were found, the Excessively Sleepy subtype was associated with over 3-fold increased risk of prevalent HF compared to each of the other subtypes. Symptom subtype was also associated with incident CVD (p<0.001), CHD (p=0.015) and HF (p=0.018), with the Excessively Sleepy again demonstrating increased risk (hazard ratios of 1.7-2.4) compared to other subtypes. When compared to individuals without OSA (AHI<5), significantly increased risk for prevalent and incident cardiovascular events were observed mostly for patients in the Excessively Sleepy subtype. CONCLUSIONS OSA symptom subtypes are reproducible and associated with cardiovascular risk, providing important evidence of their clinical relevance.
Burkholderia and Paraburkholderia are Predominant Soybean Rhizobial Genera in Venezuelan Soils in Different Climatic and Topographical Regions

The climate, topography, fauna, and flora of Venezuela are highly diverse. However, limited information is currently available on the characterization of soybean rhizobia in Venezuela. To clarify the physiological and genetic diversities of soybean rhizobia in Venezuela, soybean root nodules were collected from 11 soil types located in different topographical regions. A total of 395 root nodules were collected and 120 isolates were obtained. All isolates were classified in terms of stress tolerance under different concentrations of NaCl and Al3+. The tolerance levels of isolates to NaCl and Al3+ varied. Based on sampling origins and stress tolerance levels, 44 isolates were selected for further characterization. An inoculation test indicated that all isolates showed the capacity for root nodulation on soybean. Based on multilocus sequence typing (MLST), 20 isolates were classified into the genera Rhizobium and Bradyrhizobium. The remaining 24 isolates were classified into the genus Burkholderia or Paraburkholderia. There is currently no evidence to demonstrate that the genera Burkholderia and Paraburkholderia are the predominant soybean rhizobia in agricultural fields. Of the 24 isolates classified in (Para) Burkholderia, the nodD–nodB intergenic spacer regions of 10 isolates and the nifH gene sequences of 17 isolates were closely related to the genera Rhizobium and Bradyrhizobium, respectively. The root nodulation numbers of five (Para) Burkholderia isolates were higher than those of the 20 α-rhizobia. Furthermore, among the 44 isolates tested, one Paraburkholderia isolate exhibited the highest nitrogen-fixation activity in root nodules.
Mechano-microbial systems: An ecofriendly approach for copper bioleaching from waste printed circuit board

Waste printed circuit board (PCB) is attracting serious concerns because the recycling of its valuable metallic portion is made difficult by the existence of hazardous substances. The objective of the present study was to develop a simplified approach for copper bioleaching from waste PCB. In this context, we intended mechano-microbial systems symbolized as SET-I (spore suspension + potato dextrose broth medium + waste PCB powder), SET-II (pre-cultured until the logarithmic phase, without waste PCB powder), and SET-III (fungal metabolites produced at stationary phase). The results of bioleaching studies showed that the developed method achieved the highest copper leaching of 85% by the SET-III approach. This study provides an insight for bioleaching copper from waste PCB. Furthermore, this approach can be established as an ecofriendly method for copper bioleaching by using an integrated system.
RingText: Dwell-free and hands-free Text Entry for Mobile Head-Mounted Displays using Head Motions

In this paper, we present a case for text entry using a circular keyboard layout for mobile head-mounted displays (HMDs) that is dwell-free and does not require users to hold a dedicated input device for letter selection. To support the case, we have implemented RingText whose design is based on a circular layout with two concentric circles. The outer circle is subdivided into regions containing letters. Selection is made by using a virtual cursor controlled by the user's head movements—entering a letter region triggers a selection and moving back into the inner circle resets the selection. The design of RingText follows an iterative process, where we initially conduct one first study to investigate the optimal number of letters per region, inner circle size, and alphabet starting location. We then optimize its design by selecting the most suitable features from the first study: one letter per region, narrowing the trigger area to lower error rates, and creating candidate regions that incorporate two suggested words to appear next to the current letter region (close to the cursor) using a dynamic (rather than fixed) approach. Our second study compares text entry performance of RingText with four other hands-free techniques and the results show that RingText outperforms them. Finally, we run a third study lasting four consecutive days with 10 participants (5 novice users and 5 expert users) doing two daily sessions and the results show that RingText is quite efficient and yields a low error rate. At the end of the eighth session, the novice users can achieve a text entry speed of 11.30 WPM after 60 minutes of training while the expert (more experienced) users can reach an average text entry speed of 13.24 WPM after 90 minutes of training.