Miracle-dz/UniFAR-FTUs huggingface dataset:
Rhamnose Is Superior to Mannitol as a Monosaccharide in the Dual Sugar Absorption Test: A Prospective Randomized Study in Children With Treatment-Naïve Celiac Disease

Background and Aim We sought to correlate two different measures of gut permeability [lactulose:mannitol (L:M) and lactulose:rhamnose (L:R)] to the severity of duodenal histopathology in children with and without elevated antibodies to tissue transglutaminase (tTG). A secondary objective was to correlate gut permeability with celiac disease (CD) serology and indices of inflammation and bacterial product translocation. Methods We prospectively randomized children undergoing endoscopy with abnormal (n = 54) and normal (n = 10) concentrations of circulating antibodies to tTG, to either L:M or L:R. Biopsies underwent modified Marsh scoring to measure mucosal injury. Circulating anticore Escherichia coli lipopolysaccharide (LPS) IgG, α-1 acid glycoprotein, LPS-binding protein, and C-reactive protein concentrations were measured by enzyme immunoassays. Results Of the 54 cases with positive celiac serology, 31 and 69% had modified Marsh 0/1 scores or ≥3a, respectively. Circulating tTG IgA correlated with the modified Marsh score (p = 0.03). L:R, but not L:M or percent L excreted, differed according to modified Marsh scores (p = 0.01). There was no significant association between any systemic marker of inflammation or gut injury, and modified Marsh scores. Concerningly, most participants had evidence of urinary M before the challenge sugar was administered. Conclusions L:R, but not L:M, is associated with modified Marsh scores in children undergoing small bowel biopsy for suspected CD. Despite increased intestinal permeability, we see scant evidence of systemic exposure to gut microbes in these children. Gut permeability testing with L:R may predict which patients with abnormal celiac serology will have biopsy evidence for celiac disease and reduce the proportion of such patients undergoing endoscopy whose Marsh scores are ≤1. M should not be used as a monosaccharide for permeability testing in children.
Hand-off analysis for CBWL schemes in cellular communications

Channel borrowing without locking (CBWL) allows real-time borrowing of channels from adjacent cells without channel locking in co-channel cells. The schemes provide enhanced traffic performance in homogeneous environments and also relieve hot-spot traffic. Simple channel management and easy implementation are additional features. Two types of hand-off arise in CBWL, intercell hand-offs and intracell hand-offs. A model based on multidimensional birth-death processes is devised and traffic performance characteristics showing blocking and forced termination probabilities are obtained. The results, which are validated by simulation, indicate that CBWL can provide significantly improved traffic and hand-off-performance in comparison with non-borrowing cellular schemes. <<ETX>>
Screening and Identification of HBV Epitopes Restricted by Multiple Prevalent HLA-A Allotypes

Although host T cell immune responses to hepatitis B virus (HBV) have been demonstrated to have important influences on the outcome of HBV infection, the development of T cell epitope-based vaccine and T cell therapy and the clinical evaluation of specific T cell function are currently hampered markedly by the lack of validated HBV T cell epitopes covering broad patients. This study aimed to screen T cell epitopes spanning overall HBsAg, HBeAg, HBx and HBpol proteins and presenting by thirteen prevalent human leukocyte antigen (HLA)-A allotypes which gather a total gene frequency of around 95% in China and Northeast Asia populations. 187 epitopes were in silico predicted. Of which, 62 epitopes were then functionally validated as real-world HBV T cell epitopes by ex vivo IFN-γ ELISPOT assay and in vitro co-cultures using peripheral blood mononuclear cells (PBMCs) from HBV infected patients. Furthermore, the HLA-A cross-restrictions of each epitope were identified by peptide competitive binding assay using transfected HMy2.CIR cell lines, and by HLA-A/peptide docking as well as molecular dynamic simulation. Finally, a peptide library containing 105 validated epitopes which cross-binding by 13 prevalent HLA-A allotypes were used in ELISPOT assay to enumerate HBV-specific T cells for 116 patients with HBV infection. The spot forming units (SFUs) was significantly correlated with serum HBsAg level as confirmed by multivariate linear regression analysis. This study functionally validated 62 T cell epitopes from HBV main proteins and elucidated their HLA-A restrictions and provided an alternative ELISPOT assay using validated epitope peptides rather than conventional overlapping peptides for the clinical evaluation of HBV-specific T cell responses.
Out-of-Pocket Expenditure on Medical Services Among Older Adults: A Longitudinal Analysis

The upturn in life expectancy and its consequence, population aging, are challenging labor, pension, and social-security systems throughout the developed world. The focal aim of this study is to measure the extent of out-of-pocket funding of healthcare services by the older adult population. The study has three objectives: to profile the healthcare services for which older adults pay out of pocket, profile the older adults who pay out of pocket for medical services and detect changes over the years, and identify predictors of out-of-pocket healthcare services funding by older adults. The study is predicated on the SHARE-Israel database (SHARE—Survey of Health, Ageing and Retirement in Europe). Relating to information yielded by the last two waves of SHARE-Israel (Wave 7 and Wave 8), it sheds light on the characteristics of those who reported having paid out-of-pocket for medical services. A large majority of the older-adult population in Israel that consumes healthcare services is asked to pay for services out of pocket. Having supplemental health insurance, personal state of health and changes in it, and economic resources are found to have the strongest effect on the probability of out-of-pocket funding. The motive of financial and/or social support that older adults receive from and/or give to their immediate surroundings makes it more likely that they will pay out of pocket for healthcare services. The probability of such funding varies between nationalities and immigration statuses. It is found with emphasis that the share of out-of-pocket funding of healthcare in older adult households' total annual income is trending upward. Furthermore, economic motives are central in determining whether such expenditure will stabilize over time. The findings stress the need to enhance the healthcare system's awareness of the profile of older adults who find it necessary to pay out of pocket for healthcare services.
Regulation of Proinflammatory Molecules and Tissue Factor by SARS-CoV-2 Spike Protein in Human Placental Cells: Implications for SARS-CoV-2 Pathogenesis in Pregnant Women

SARS-CoV-2 infects cells via binding to ACE2 and TMPRSS2, which allows the virus to fuse with host cells. The viral RNA is detected in the placenta of SARS-CoV-2-infected pregnant women and infection is associated with adverse pregnancy complications. Therefore, we hypothesize that SARS-CoV-2 infection of placental cells induces pro-inflammatory cytokine release to contribute to placental dysfunction and impaired pregnancy outcomes. First, expression of ACE2 and TMPRSS2 was measured by qPCR in human primary cultured term cytotrophoblasts (CTBs), syncytiotrophoblast (STBs), term and first trimester decidual cells (TDCs and FTDCs, respectively), endometrial stromal cells (HESCs) as well as trophoblast cell lines HTR8, JEG3, placental microvascular endothelial cells (PMVECs) and endometrial endothelial cells (HEECs). Later, cultured HTR8, JEG3, PMVECs and HEECs were treated with 10, 100, 1000 ng/ml of recombinant (rh-) SARS-CoV-2 S-protein ± 10 ng/ml rh-IFNγ. Pro-inflammatory cytokines IL-1β, 6 and 8, chemokines CCL2, CCL5, CXCL9 and CXCL10 as well as tissue factor (F3), the primary initiator of the extrinsic coagulation cascade, were measured by qPCR as well as secreted IL-6 and IL-8 levels were measured by ELISA. Immunohistochemical staining for SARS-CoV-2 spike protein was performed in placental specimens from SARS-CoV-2–positive and normal pregnancies. ACE2 levels were significantly higher in CTBs and STBs vs. TDCs, FTDCs and HESCs, while TMPRSS2 levels were not detected in TDCs, FTDCs and HESCs. HTR8 and JEG3 express ACE2 and TMPRSS2, while PMVECs and HEECs express only ACE2, but not TMPRSS2. rh-S-protein increased proinflammatory cytokines and chemokines levels in both trophoblast and endothelial cells, whereas rh-S-protein only elevated F3 levels in endothelial cells. rh-IFNγ ± rh-S-protein augments expression of cytokines and chemokines in trophoblast and endothelial cells. Elevated F3 expression by rh-IFNγ ± S-protein was observed only in PMVECs. In placental specimens from SARS-CoV-2-infected mothers, endothelial cells displayed higher immunoreactivity against spike protein. These findings indicated that SARS-CoV-2 infection in placental cells: 1) induces pro-inflammatory cytokine and chemokine release, which may contribute to the cytokine storm observed in severely infected pregnant women and related placental dysfunction; and 2) elevates F3 expression that may trigger systemic or placental thrombosis.
Idiopathic Aqueductal Stenosis: Late Neurocognitive Outcome in ETV Operated Adult Patients

Objective The aim of the present study is to evaluate a neurocognitive outcome in patients affected by late-onset idiopathic aqueductal stenosis (LIAS) who underwent endoscopic third ventriculostomy (ETV). Materials and Methods A prospective study was conducted between January 2015 and December 2017 in a series of 10 consecutive adult patients referred to the Neurosurgery Department of IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy. All the adult patients admitted with absence of CSF flow through the aqueduct in phase-contrast (PC)—MRI sequences or a turbulence void signal in T2—weighted images in midsagittal thin-slice MR sequences underwent a specific neuroradiological, neurological, and neurocognitive assessment pre- and postoperatively. Results All patients affected by gait and sphincter disturbances improved after ETV. Attentive and executive functions as well as visuo-spatial memory and verbal executive functions improved in several patients. Similarly, the affective and behavioral scales improved in almost 50% of the patients. No major complications have been recorded, and no patients required a second surgery for shunt placement. Conclusion Endoscopic third ventriculostomy represents a safe and effective surgical procedure for the treatment of LIAS. In addition to neurological improvement, we demonstrated also postoperative neurocognitive improvement mainly in attentive and executive functions, visuo-spatial memory, verbal executive functions, and behavioral and affective domains.
Sex and Size Influence the Spatiotemporal Distribution of White Sharks, With Implications for Interactions With Fisheries and Spatial Management in the Southwest Indian Ocean

Human activities in the oceans increase the extinction risk of marine megafauna. Interventions require an understanding of movement patterns and the spatiotemporal overlap with threats. We analysed the movement patterns of 33 white sharks (Carcharodon carcharias) satellite-tagged in South Africa between 2012 and 2014 to investigate the influence of size, sex and season on movement patterns and the spatial and temporal overlap with longline and gillnet fisheries and marine protected areas (MPAs). We used a hidden Markov model to identify ‘resident’ and ‘transient’ movement states and investigate the effect of covariates on the transition probabilities between states. A model with sex, total length and season had the most support. Tagged sharks were more likely to be in a resident state near the coast and a transient state away from the coast, while the probability of finding a shark in the transient state increased with size. White sharks moved across vast areas of the southwest Indian Ocean, emphasising the need for a regional management plan. White sharks overlapped with longline and gillnet fisheries within 25% of South Africa’s Exclusive Economic Zone and spent 15% of their time exposed to these fisheries during the study period. The demersal shark longline fishery had the highest relative spatial and temporal overlap, followed by the pelagic longline fishery and the KwaZulu-Natal (KZN) shark nets and drumlines. However, the KZN shark nets and drumlines reported the highest white shark catches, emphasising the need to combine shark movement and fishing effort with reliable catch records to assess risks to shark populations accurately. White shark exposure to shark nets and drumlines, by movement state, sex and maturity status, corresponded with the catch composition of the fishery, providing support for a meaningful exposure risk estimate. White sharks spent significantly more time in MPAs than expected by chance, likely due to increased prey abundance or less disturbance, suggesting that MPAs can benefit large, mobile marine megafauna. Conservation of white sharks in Southern Africa can be improved by implementing non-lethal solutions to beach safety, increasing the observer coverage in fisheries, and continued monitoring of movement patterns and existing and emerging threats.
Bioinformatics and System Biology Approach to Identify the Influences of COVID-19 on Rheumatoid Arthritis

Background Severe coronavirus disease 2019 (COVID -19) has led to a rapid increase in mortality worldwide. Rheumatoid arthritis (RA) was a high-risk factor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, whereas the molecular mechanisms underlying RA and CVOID-19 are not well understood. The objectives of this study were to analyze potential molecular mechanisms and identify potential drugs for the treatment of COVID-19 and RA using bioinformatics and a systems biology approach. Methods Two Differentially expressed genes (DEGs) sets extracted from GSE171110 and GSE1775544 datasets were intersected to generate common DEGs, which were used for functional enrichment, pathway analysis, and candidate drugs analysis. Results A total of 103 common DEGs were identified in the two datasets between RA and COVID-19. A protein-protein interaction (PPI) was constructed using various combinatorial statistical methods and bioinformatics tools. Subsequently, hub genes and essential modules were identified from the PPI network. In addition, we performed functional analysis and pathway analysis under ontological conditions and found that there was common association between RA and progression of COVID-19 infection. Finally, transcription factor-gene interactions, protein-drug interactions, and DEGs-miRNAs coregulatory networks with common DEGs were also identified in the datasets. Conclusion We successfully identified the top 10 hub genes that could serve as novel targeted therapy for COVID-19 and screened out some potential drugs useful for COVID-19 patients with RA.
High Neutrophil-to-Albumin Ratio Predicts Postoperative Pneumonia in Aneurysmal Subarachnoid Hemorrhage

Background and Aim There is still an absence of objective and easily accessible biomarkers despite the variety of risk factors associated with postoperative pneumonia (POP) in patients with aneurysmal subarachnoid hemorrhage (aSAH). In the present study, we have thus evaluated the relationship between the neutrophil-to-albumin ratio (NAR) and POP in patients with aSAH. Methods Several consecutive patients (n = 395) who had undergone clipping or coiling of the aneurism were retrospectively assessed, of which we were able to analyze the existing population data and the related baseline variables. The patients were divided into POP and revealed not to occur. To identify independent predictors, we used the recipient operation feature (receiver operating characteristic, ROC) curve and a logic regression analysis. Results This cohort was based on POP that occurred in 78 out of the 395 patients (19.7%), and these revealed a significantly higher NAR than those without (0.31 [0.25–0.39] vs. 0.23 [0.18–0.28]; p < 0.001). On the other hand, a multivariate logistic regression analysis showed that NAR (odds ratio = 1.907; 95% confidence interval, 1.232–2.953; p = 0.004) was independently associated with a POP after due adjustment for confounders. Moreover, the predictive performances of NAR for POP were also significant (area under the ROC curve [95% CI] 0.775 [0.717–0.832]; p < 0.001). Conclusion The elevation of NAR at admission in patients with aSAH might help predict POP.
Sema6D Regulates Zebrafish Vascular Patterning and Motor Neuronal Axon Growth in Spinal Cord

Vessels and nerves are closely associated in anatomy as well as functions. Accumulating evidences have demonstrated that axon-guiding signals may affect endothelial cells migration and path finding, which is crucial for the patterning of both the complex vascular network and neural system. However, studies regarding the functional overlap between vascular and neuronal orchestrating are still incomplete. Semaphorin6D (Sema6D) belongs to the Semaphorin family and has been identified as an important regulating factor in diverse biological processes. Its roles in vascular development are still unclear. Here, we confirmed that sema6D is enriched in neural system and blood vessels of zebrafish embryos by in situ hybridization. Then, the deficiency of sema6D caused by specific antisense morpholino-oligonucleotides (MO) led to dramatic path finding defects in both intersegmental vessels (ISVs) and primary motor neurons (PMNs) of spinal cord in zebrafish embryos. Furthermore, these defective phenotypes were confirmed in F0 generation of sema6D knockouts and rescue experiments by overexpression of sema6D mRNA in sema6D morphants. These data collectively indicate that sema6D regulates zebrafish vascular patterning and motor neuronal axon growth in the spinal cord, which might be of great therapeutical use to regulate vessel and nerve guidance in the relevant diseases that affect both systems.
Detection to Hospital Door: Gender Differences of Patients With Acute Stroke Symptoms

Although prehospital stroke management is challenging, it is a crucial part of the acute stroke chain to enable equal access to highly specialised stroke care. It involves a critical understanding of players usually not specialized in acute stroke treatments. There is contradictory information about gender inequity in prehospital stroke detection, dispatch, and delivery to hospital stroke centers. The aim of this narrative review is to summarize the knowledge of gender differences in the first three stages of acute stroke management. Information on the detection of acute stroke symptoms by patients, their relatives, and bystanders is discussed. Women seem to have a better overall knowledge about stroke, although general understanding needs to be improved. However, older age and different social situations of women could be identified as reasons for reduced and delayed help-seeking. Dispatch and delivery lie within the responsibility of the emergency medical service. Differences in clinical presentation with symptoms mainly affecting general conditions could be identified as a crucial challenge leading to gender inequity in these stages. Improvement of stroke education has to be applied to tackle this inequal management. However, specifically designed projects and analyses are needed to understand more details of sex differences in prehospital stroke management, which is a necessary first step for the potential development of substantially improving strategies.
Therapeutic Garden With Contemplative Features Induces Desirable Changes in Mood and Brain Activity in Depressed Adults

The therapeutic values of contact with nature have been increasingly recognized. A growing body of evidence suggests that a unique subcategory of “contemplative landscapes” is particularly therapeutic. Previous studies predominantly focused on observational designs in non-clinical populations. It is not known if these effects can be extrapolated to populations suffering from depression, and experimental designs need to be utilized to establish causality. We examined the effects of in-situ passive exposure to three urban spaces on brain activity, namely a Therapeutic Garden with high Contemplative Landscape scores (TG), Residential Green (RG) and Busy Downtown (BD), and self-reported momentary mood in adults aged 21–74 (n = 92), including 24 clinically depressed and 68 healthy participants. Portable, multimodal electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS) systems were used to record brain activity, and a Profile of Mood States (POMS) questionnaire was used to record mood before and after exposure. We tested the interactions between the site, time and group for the mood, and between site and group for the neuroelectric oscillations and brain hemodynamics. Self-reported pre- post-mood was significant only at the TG (p = 0.032) in both groups. The lowest Total Mood Disturbance (TMD) was reported at TG and the highest in BD (p = 0.026). Results from fNIRS indicated marginally significant lower oxy-Hb in the frontal region at TG as compared to BD (p = 0.054) across both groups. The marginally significant effect of site and group was also observed (p = 0.062), with the Clinical group showing much lower oxy-Hb at TG than Healthy. The opposite pattern was observed at BD. EEG results showed differences between Healthy and Clinical groups in the Frontal Alpha Asymmetry (FAA) pattern across the sites (p = 0.04), with more frontal alpha right in the Clinical sample and more left lateralization in the Healthy sample at TG. Temporal Beta Asymmetry (TBA) analyses suggested that patients displayed lower bottom-up attention than Healthy participants across all sites (p = 0.039). The results suggest that both healthy and depressed adults benefitted from exposure to TG, with possibly different pathways of mood improvement. Visiting therapeutic nature with contemplative features may provide valuable support for the treatment of depression in clinical populations and a self-care intervention in non-clinical populations.
Concurrent RAS and RAS/BRAF V600E Variants in Colorectal Cancer: More Frequent Than Expected? A Case Report

The assessment of RAS and BRAF mutational status is one of the main steps in the diagnostic and therapeutic algorithm of metastatic colorectal cancer (mCRC). Multiple mutations in the BRAF and RAS pathway are described as a rare event, with concurrent variants in KRAS and BRAF genes observed in approximately 0.05% of mCRC cases. Here, we report data from a case series affected by high-risk stage III and stage IV CRC and tested for RAS and BRAF mutation, treated at our Medical Oncology Unit. The analysis of KRAS, NRAS (codons 12, 13, 59, 61, 117, 146), and BRAF (codon 600) hotspot variants was performed in 161 CRC tumors from August 2018 to September 2021 and revealed three (1.8%) patients showing mutations in both KRAS and BRAF (V600E), including two cases with earlier CRC and one with metastatic disease. We also identified one patient (0.6%) with a mutation in both KRAS and NRAS genes and another one (0.6%) with a double KRAS mutation. Notably, the latter was characterized by aggressive behavior and poor clinical outcome. The mutational status, pathological features, and clinical history of these five CRC cases are described. Overall, this study case series adds evidence to the limited available literature concerning both the epidemiological and clinical aspects of CRC cases characterized by the presence of concurrent RAS/BRAF variants. Future multicentric studies will be required to increase the sample size and provide additional value to results observed so far in order to improve clinical management of this subgroup of CRC patients.