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Research investigating substance use among Arab Americans is very limited. The purpose of this study is to determine rates of substance use among Arab American young adults. A cross-sectional online survey was distributed in Dearborn, MI, and surrounding cities. The survey measured substance use among Arab Americans aged 18–30 within a community in Michigan. The analytic sample included 423 respondents. The rate of hookah “ever users” was highest followed by alcohol, cigarettes, and marijuana at 55%, 33%, 29%, and 28%, respectively. Rates of “current use” for these four substances also followed an identical order. Of note, rates of “ever use” for prescription stimulants, E-cigarettes, and opioid use were 19%, 12%, and 11.2%, respectively. The use of tobacco products, alcohol, and marijuana use among males was significantly higher when compared to females. Near or above national average rates of substance use lends credence to the importance of this issue within Arab American communities. Tobacco, alcohol, and illicit drug use are multifactorial issues requiring increased attention and further exploration into factors associated with substance use, including potential stigma and the challenges of cultural acceptability.

A percentage of the population suffers prolonged and persistent post-concussion symptoms (PCS) following average head injuries or develops severe neurological dysfunction following minor head trauma. Genetic variants that may contribute to individual response to head trauma have been investigated in some studies, but to date none have explored the use of machine learning (ML) methods with genomic data to specifically explore outcomes of head trauma. Whole exome sequencing (WES) was completed for three groups of individuals (N = 60): (a) 16 individuals with severe neurological responses to minor head trauma, (b) 26 individuals with persistent PCS and (c) 18 individuals with normal recovery from concussion or mTBI. Gradient boosted tree algorithms were applied to the data using XGBoost. By using variants with CADD scores above 15 in the training set (randomly sampled 70%), we identified signatures that accurately distinguish to accurately distinguish the test groups with an average area under the curve (AUC) of 0.8 (SE = 0.019). Metrics including positive and negative prediction values, as well as kappa were all within acceptable range to support the prediction accuracy. This study illustrates how ML methods in combination with WES data have the potential to predict severe or prolonged responses to head trauma from healthy recovery. KEY MESSAGES: Linear association analysis has been inconclusive in concussion genetics. Non-linear methods as boosted trees can offer better insights in small samples. Strong discrimination trends can be achieved from exome data of cases and controls.

Introduction: The study aimed to construct and validate a risk prediction model for incidence of postoperative renal failure (PORF) following radical nephrectomy and nephroureterectomy. Methods: The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database years 2005–2014 were used for the derivation cohort. A stepwise multivariate logistic regression analysis was conducted, and the final model was validated with an independent cohort from the ACS-NSQIP database years 2015–2017. Results: In cohort of 14,519 patients, 296 (2.0%) developed PORF. The final 9-factor model included age, gender, diabetes, hypertension, BMI, preoperative creatinine, hematocrit, platelet count, and surgical approach. Model receiver-operator curve analysis provided a C-statistic of 0.79 (0.77, 0.82; p < 0.001), and overall calibration testing R2 was 0.99. Model performance in the validation cohort provided a C-statistic of 0.79 (0.76, 0.81; p < 0.001). Conclusion: PORF is a known risk factor for chronic kidney disease and cardiovascular morbidity, and is a common occurrence after unilateral kidney removal. The authors propose a robust and validated risk prediction model to aid in identification of high-risk patients and optimization of perioperative care.

INTRODUCTION Lowering blood pressure (BP) reduces the risk for cognitive impairment and the progression of cerebral white matter lesions. It is unclear whether hypertension control also influences plasma biomarkers related to Alzheimer's disease and non-disease-specific neurodegeneration. METHODS We examined the effect of intensive (

Introduction Longitudinal positron emission tomography (PET) studies of tau accumulation in Alzheimer's disease (AD) have noted reduced increases or frank decreases in tau signal. We investigated how such reductions related to analytical confounds and disease progression markers in atypical AD. Methods We assessed regional and interindividual variation in longitudinal change on 18 F-flortaucipir PET imaging in 24 amyloid beta (Aβ)+ patients with atypical, early-onset amnestic or non-amnestic AD plus 62 Aβ- and 132 Aβ+ Alzheimer's Disease Neuroimaging Initiative (ADNI) participants. Results In atypical AD, 18 F-flortaucipir uptake slowed or declined over time in areas with high baseline signal and older, more impaired individuals. ADNI participants had reduced longitudinal change in early Braak stage regions relative to late-stage areas. Discussion Results suggested radioligand uptake plateaus or declines in advanced neurodegeneration. Further research should investigate whether results generalize to other radioligands and whether they relate to changes of the radioligand binding site structure or accessibility.

BackgroundRefugees are prone to injury due to often austere living conditions, social and economic disadvantages, and limited access to health care services in host countries. This study systematically quantified the prevalence of physical injuries and burns among the refugee community in Western Lebanon and examined injury characteristics, risk factors and outcomes.MethodWe conducted a cluster-based population survey across 21 camps in the Bekaa region of Lebanon from February to April 2019. A modified version of the ‘Surgeons Overseas Assessment of Surgical Need (SOSAS)’ tool v 3.0 was administered to the head of the refugee household and documented all injuries sustained by family members over the last 12 months. Descriptive and univariate regression analyses were performed to understand the association between variables.Results750 heads of household were surveyed. 112 (14.9%) household sustained injuries in the past 12 months, 39 of which (34.9%) reported disabling injuries that affected their work and daily living. Most injuries occurred inside the tent (29.9%). A burn was sustained by at least one household member in 136 (18.1%) households. The majority (63.7%) of burns affected children under 5 years and were mainly due to boiling liquid (50%). Significantly more burns were reported in households where caregivers have the inability to lockout children while cooking (25.6% vs 14.9%, p-value=0.001). Similarly, households with unemployed head significantly had more reported burns (19.7% vs 13.3%, p-value=0.05). Nearly 16.1% of injured refugees were unable to seek health care due to lack of health insurance coverage and financial liability.ConclusionRefugees suffer injuries and burns with substantial human and economic repercussions on individuals, their families and the host healthcare system. Resources should be allocated to designing safe camps and implementing educational and awareness programs with special focus on heating and cooking methods.

Background/Objectives. The prevalence of vitamin D deficiency in the Middle Eastern population remains among the highest in the world, despite the region enjoying sunlight most days of the year. This study aimed at assessing the status of serum vitamin D and determining factors associated with vitamin D deficiency among community-dwelling adults residing in Greater Beirut, Lebanon. Methods. A random sample of Lebanese adults residing in the Greater Beirut area was selected based on area probability and multistage cluster sampling. Data from 446 participants (68% females) with mean age 45.3 ± 15 years were used for the analyses. Participants were recruited between March and May. Serum 25-hydroxyvitamin D levels were measured using electrochemiluminescent immunoassay. Results. Vitamin D deficiency was highly prevalent whether using the cutoff of 50 nmol/L or using the more conservative cutoff of 30 nmol/L; more specifically, 71.9% and 39.1% of the study population were deficient using the above cutoffs, respectively In the bivariate analyses, gender, BMI and body fat mass, socioeconomic factors (income and education level), alcohol consumption, dietary intake of fat and of vitamin D, serum LDL-cholesterol, and serum creatinine were all associated with vitamin D status. After adjustment for multiple covariates, age, income, alcohol consumption, and serum creatinine were independent predictors of vitamin D deficiency. Conclusion. Vitamin D deficiency is highly prevalent in Lebanon. Preventive measures should target the modifiable risk factors.

Extraneural metastases of glioblastoma (GBM), although rare, are becoming an increasingly recognized occurrence. Currently, the biological mechanism underlying this rare occurrence is not understood. To explore the potential genomic drivers of extraneural metastasis in GBM, we present the molecular features of 4 extraneural metastatic GBMs, along with a comprehensive review and analysis of previously reported cases that had available molecular characterization. In addition to our 4 cases, 42 patients from 35 publications are reviewed. To compare the molecular profiles between GBM cases with extraneural metastasis and the general GBM population, genomic data from GBM samples in The Cancer Genome Atlas (TCGA) database were also analyzed. We found that 64.5% (20/31) of the cases with extraneural metastasis that were tested for TP53 changes had at least 1 TP53 pathogenic variant detected in either 1 or both primary and metastatic tumors. In contrast, TP53 mutation was significantly less frequent in the unselected GBM from TCGA (22.6%, 56/248) (P=0.000). In addition, O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation was more common in unselected TCGA GBM cases (48.6%, 170/350) than in cases with extraneural metastasis (31.8%, 7/22), although not statistically significant. Although isocitrate dehydrogenase (IDH) mutation is a rare occurrence in high-grade astrocytomas, IDH-mutant grade 4 astrocytomas are at least as likely to metastasize as IDH wild-type GBMs; 3 metastatic cases definitively harbored an IDH1 (p.R132H) mutation in our analysis. Our findings not only provide potential biomarkers for earlier screening of extraneural metastasis, but could also suggest clues to understanding biological mechanisms underlying GBM metastasis, and for the development of therapeutic modalities.

Background: Respiratory syncytial virus (RSV) is a major cause of lower respiratory infection among children and no vaccine is available. The stabilized form of the fusion (F) protein – pre-F – is a leading vaccine candidate to target different populations, including pregnant women. This study aimed to determine the magnitude and nature of RSV-directed maternal antibodies (matAbs) in hospitalized children with RSV infection. Methods: Sixty-five paired blood samples were collected from RSV-infected children aged

BACKGROUND. Neuroinflammation is a well-known feature of early Alzheimer disease (AD) yet astrocyte activation has not been extensively evaluated with in vivo imaging in Mild Cognitive Impairment (MCI) due to amyloid plaque pathology. Unlike neurons, astrocytes metabolize acetate, which has potential as a glial biomarker in neurodegeneration in response to AD pathologic features. Since the medial temporal lobe (MTL) is a hotspot for AD neurodegeneration and inflammation, we assessed astrocyte activity in the MTL and compared to amyloid and cognition. METHODS. We evaluate spatial patterns of in vivo astrocyte activation and their relationships to amyloid deposition and cognition in a cross-sectional pilot study of 6 participants with MCI and 5 cognitively normal (CN) participants. We measure (11)C-acetate and (18)F-florbetaben amyloid standardized uptake values ratios (SUVRs) and kinetic flux compared to cerebellum on positron emission tomography (PET), with magnetic resonance imaging and neurocognitive testing. RESULTS. Medial temporal lobe (MTL) (11)C-acetate SUVR was significantly elevated in MCI compared to CN participants (P = 0.03; Cohen d = 1.76). Moreover, MTL (11)C-acetate SUVR displayed significant associations with global and regional amyloid burden in MCI. Greater MTL (11)C-acetate retention was significantly related with worse neurocognitive measures including the Montreal Cognitive Assessment (P = 0.001), Word List Recall memory (P = 0.03), Boston Naming Test (P = 0.04) and Trails B test (P = 0.04). CONCLUSIONS. While further validation is required, this exploratory pilot study suggests a potential role for (11)C-acetate PET as a neuroinflammatory biomarker in MCI and early AD to provide clinical and translational insights into astrocyte activation as a pathological response to amyloid.

Traumatic brain injury (TBI) has been proposed as a risk factor for Alzheimer’s disease (AD), although the mechanisms underlying the putative association are poorly understood. We investigated elderly individuals with a remote history of TBI, aiming to understand how this may have influenced amyloidosis, neurodegeneration, and clinical expression along the AD continuum. Total of 241 individual datasets including amyloid beta (Aβ) positron emission tomography ([18F]-AV45), structural MRI, and neuropsychological measures, were obtained from the Alzheimer’s Disease Neuroimaging Initiative. The data were stratified into groups with (TBI +) or without (TBI −) history of head injury, and by clinical dementia rating (CDR) scores, into subgroups with normal cognition (CDR = 0) and those with symptomatic cognitive decline (CDR ≥ 0.5). We contrasted the TBI + and TBI − subgroups with respect to the onset age and extent of cognitive decline, cortical thickness changes, and Aβ standard uptake value (SUVr). Compared to the TBI −/CDR ≥ 0.5 subgroup, the TBI + /CDR ≥ 0.5 subgroup showed a 3–4 year earlier age of cognitive impairment onset (ACIO, p = 0.005). Among those participants on the AD continuum (Aβ + , as defined by a cortical SUVr ≥ 1.23), irrespective of current CDR, a TBI + history was associated with greater Aβ deposition and more pronounced cortical thinning. When matched for severity of cognitive status, the TBI + /CDR ≥ 0.5 group showed greater Aβ burden, but earlier ACIO as compared to the TBI −/CDR ≥ 0.5, suggesting a more indolent clinical AD progression in those with TBI history. Remote TBI history may alter the AD onset trajectory, with approximately 4 years earlier ACIO, greater amyloid deposition, and cortical thinning.

This study is done to estimаte in‐hоsрitаl mоrtаlity in раtients with severe асute resрirаtоry syndrоme соrоnаvirus 2 (SАRS‐СоV‐2) strаtified by Vitamin‐D (Vit‐D) levels. Раtients were strаtified ассоrding tо by serum 25‐hydroxy‐vitamin D (25(OH)Vit‐D) levels intо twо grоuрs, that is, 25(OH)Vit‐D less thаn 40 nmol/L аnd 25(OH)Vit‐D greаter thаn 40 nmol/L. А tоtаl оf 231 раtients were inсluded. Оf these, 120 (50.2%) оf the раtients hаd 25(OH)Vit‐D levels greаter thаn 40 nmol/L. The meаn аge wаs 49 ± 17 yeаrs, аnd 67% оf the раtients were mаles. The mediаn length оf оverаll hоsрitаl stаy wаs 18 [6; 53] dаys. The remаining 119 (49.8%) раtients hаd а 25(OH)Vit‐D less thаn 40 nmol/L. Vitamin D levels were seen as deficient in 63% of patients, insufficient in 25% and normal in 12%. Оverаll mоrtаlity wаs 17 раtients (7.1%) but statistically not signifiсаnt among the grоuрs (p = 0.986). The Kарlаn–Meier survivаl аnаlysis shоwed no significance based on an alpha of 0.05, LL = 0.36, df = 1, p = 0.548, indicating Vitamin_D_Levels was not able to adequately predict the hazard of Mortality. In this study, serum 25(OH)Vit‐D levels were found have no significance in terms of predicting the in‐hоsрitаl mortality in раtients with SАRS‐СоV‐2., Highlights This is one among a very few studies which show serum Vitamin‐D levels have no role in predicting the in‐hospital mortality in раtients with SARS‐CoV‐2.

Over the months of April and May 2021, South Africa has witnessed several outbreaks of highly infective avian influenza (H5N1) in different poultry farms. This came as a shock to a country that was already battling with the deadly COVID‐19 pandemic. The emergence of the virus has spurred import bans and massive culls in the poultry business. Local experts have also called for a restriction on the movement of people and cars in and out of their chicken farms. Employees have also been encouraged to shower in the mornings when they arrive at the farms and wear fresh clothes, as the flu spreads very quickly. In a country that is already facing the economic implications of the COVID‐19, this has the potential to cause a significant dent in the economy, as well as severely impact people's day‐to‐day life. Bird flu—also called avian influenza—is a viral infection that can infect not only birds but also humans and other animals. The threat of a new influenza pandemic has prompted countries to draft national strategic preparedness plans to prevent, contain and mitigate the next human influenza pandemic. This paper describes the South African burden, current efforts, and preparedness against the avian influenza virus.

McArdle disease, also known as glycogen storage disease type V, is an autosomal recessive disease due to the absence of myophosphorylase activity, leading to the complete disruption of glycogen breakdown in muscles. We present a rare case of a Caucasian male, aged 26 years, who developed rhabdomyolysis-induced acute renal failure and uremic encephalopathy. Neurological examination and histopathological studies supported the diagnosis of McArdle disease. The severity of his symptoms necessitated urgent hemodialysis, upon which the patient reported improvement in status. Acute renal failure in McArdle disease usually resolves with supportive treatment and maintenance of regular physical activity. Nevertheless, in more severe cases, intensive care with urgent hemodialysis may be needed. A multidisciplinary approach is necessary for the adequate management of similar cases.

While the dire cardiometabolic consequences of the hypercaloric modern ‘Western’ diet are well known, there is not much information on the health impact of a high sucrose diet not inducing weight gain. Here, we tested the hypothesis that rats reared with intermittent binge access to sucrose in addition to normal chow would develop an inflammatory response in brain. To test this hypothesis, we undertook serial PET/MRI scans with the TSPO ligand [18F]DPA714 in a group of (n=9) rats at baseline and again after voluntarily consuming 5% sucrose solution three days a week for three months. Compared to a control group fed with normal chow (n=9), the sucrose rats indeed showed widespread increases in the availability of cerebral binding sites for the microglial marker, despite normal weight gain compared to the control diet group. Subsequent immunofluorescence staining of the brains confirmed the PET findings, showing a widespread 20% increase in the abundance of IBA-1-positive microglia with characteristic ‘semi-activated’ morphology in the binge sucrose rats, which had 23% lower density of microglial endpoints and 25% lower mean process length compared to microglia in the control rats with ordinary feeding. GFAP immunofluorescence showed no difference in astroglial coverage in the sucrose rats, except for a slight reduction in hypothalamus. The binge sucrose diet-induced neuroinflammation was associated with a significant elevation of white blood cell counts. Taking these results together, we find that long-term intake of sucrose in a binge paradigm, similar in sucrose content to the contemporary Western diet, triggered a low-grade systemic and central inflammation in non-obese rats. The molecular mechanism of this phenomenon remains to be established.

Introduction: Sodium-glucose cotransporter 2 inhibitors such as empagliflozin (EMPA) protect against diabetic kidney disease. Prostaglandin E2 (PGE2) the main renal product of cyclooxygenase-2, inhibits vasopressin (AVP)-water reabsorption in the collecting duct (CD). The novelty of this study is that for the first time, we examined if EMPA affects the renal PGE2/EP receptor system and determined if CD responses to EMPA prevent water loss. Methods: Four groups of adult male mice were studied after 6 weeks of treatment: control (db/m), db/m+EMPA (10 mg/kg/day in chow), type 2 diabetic diabetic/dyslipidemia (db/db), and db/db+EMPA. Tubules were microdissected for quantitative polymerase chain reaction (qPCR) and CD water transport was measured in response to AVP, with or without PGE2. Results: Hyperglycemia and albuminuria were attenuated by EMPA. Renal mRNA expression for COX, PGE synthase, PGE2 (EP) receptor subtypes, CD AVP V2 receptors and aquaporin-2 was elevated in db/db mice, but unchanged by EMPA. Urine PGE2 levels increased in db/db but were unchanged by EMPA. AVP-water reabsorption was comparable in db/m and db/m+EMPA, and equally attenuated to 50% by PGE2. In db/db mice, AVP-water reabsorption was reduced by 50% compared to non-diabetic mice, and this reduction was unaffected by EMPA. In db/db mice, AVP-stimulated water transport was more significantly attenuated with PGE2 (62%), compared to non-diabetic mice, but this attenuation was reduced in response to EMPA, to 28%. Conclusion: In summary, expression of renal PGE2/EP receptors is increased in db/db mice, and this expression is unaffected by EMPA. However, in diabetic CD, PGE2 caused a greater attenuation in AVP-stimulated water reabsorption, and this attenuation is reduced by EMPA. This suggests that EMPA attenuates diabetes-induced excess CD water loss.

Background The aim of this study was to characterize severe immune-related adverse events (irAEs) seen among hospitalized patients and to examine risk factors for irAE admissions and clinically relevant outcomes, including length of stay, immune checkpoint inhibitor (ICI) discontinuation, readmission, and death. Methods Patients who received ICI therapy (ipilimumab, pembrolizumab, nivolumab, atezolizumab, durvalumab, avelumab, or any ICI combination) at Massachusetts General Hospital (MGH) and were hospitalized at MGH following ICI initiation between January 1, 2011, and October 24, 2018, were identified using pharmacy and hospital admission databases. Medical records of all irAE admissions were reviewed, and specialist review with defined criteria was performed. Demographic data, relevant clinical history (malignancy type and most recent ICI regimen), and key admission characteristics, including dates of admission and discharge, immunosuppressive management, ICI discontinuation, readmission, and death, were collected. Results In total, 450 admissions were classified as irAE admissions and represent the study's cohort. Alongside the increasing use of ICIs at our institution, the number of patients admitted to MGH for irAEs has gradually increased every year from 9 in 2011 to 92 in 2018. The hospitalization rate per ICI recipient has declined over that same time period (25.0% in 2011 to 8.5% in 2018). The most common toxicities leading to hospitalization in our cohort were gastrointestinal (30.7%; n = 138), pulmonary (15.8%; n = 71), hepatic (14.2%; n = 64), endocrine (12.2%; n = 55), neurologic (8.4%; n = 38), cardiac (6.7%; n = 30), and dermatologic (4.4%; n = 20). Multivariable logistic regression revealed statistically significant increases in irAE admission risk for CTLA-4 monotherapy recipients (odds ratio [OR], 2.02; p < .001) and CTLA-4 plus PD-1 combination therapy recipients (OR, 1.88; p < .001), relative to PD-1/PD-L1 monotherapy recipients, and patients with multiple toxicity had a 5-fold increase in inpatient mortality. Conclusion This study illustrates that cancer centers must be prepared to manage a wide variety of irAE types and that CTLA-4 and combination ICI regimens are more likely to cause irAE admissions, and earlier. In addition, admissions for patients with multi-organ involvement is common and those patients are at highest risk of inpatient mortality. Implications for Practice The number of patients admitted to Massachusetts General Hospital for immune-related adverse events (irAEs) has gradually increased every year and the most common admissions are for gastrointestinal (30.7%), pulmonary (15/8%), and hepatic (14.2%) events. Readmission rates are high (29% at 30 days, 49% at 180 days) and 64.2% have to permanently discontinue immune checkpoint inhibitor therapy. Importantly, multiple concurrent toxicities were seen in 21.6% (97/450) of irAE admissions and these patients have a fivefold increased risk of inpatient death.

Pregnant women with moderate symptoms of COVID-19 are at risk for progressing to severe or critical illness. While there are limited data on the management of severe COVID-19 during pregnancy, information on pharmacological treatments of moderate COVID-19 is lacking. We report clinical outcomes of pregnant women hospitalized due to moderate COVID-19 illness treated with a 5-day course of remdesivir, antibiotics, and/or glucocorticoids.Case series of pregnant women hospitalized with moderate symptoms of COVID -19 pneumonia at two INOVA Health System hospitals from April 1 to December 31, 2020. Primary outcome was clinical recovery (breathing on ambient air and/or hospital discharge) on hospital day 7 (HD7). Cox regression analysis was performed to evaluate which variables were associated with the primary outcome.Out of 748 pregnant women with confirmed infection by reverse transcriptase polymerase chain reaction, 35 were hospitalized due to moderate symptoms of COVID-19 pneumonia (median gestational age 29 weeks). There was no maternal death. Seventeen patients received remdesivir within 48 hours of hospitalization: 15 remained with moderate symptoms and 2 (who also received glucocorticoids) had progressed to critical COVID-19 at remdesivir initiation; all 17 women in this group achieved clinical recovery on HD7. Seven women received remdesivir48 hours following admission after they began treatment with glucocorticoids ± antibiotics and worsened to severe or critical disease; they all required supplemental oxygen on HD7. Eleven women were treated with antibiotics ± glucocorticoids but no remdesivir; on HD7, 3/11 achieved clinical recovery. Clinical recovery was significantly different among treatment groups;In our cohort, prompt initiation of remdesivir in pregnant women hospitalized with moderate symptoms of COVID-19 pneumonia within 48 hours of admission prevented worsening and allowed a fast clinical recovery by HD7. Deferring remdesivir for48 hours after hospitalization and duration of symptoms4 days before admission were independently associated with delayed clinical recovery and longer hospital admission. Ultrasound evaluation of the amniotic fluid in patients recovering from COVID-19 hospitalization should be considered.

As new networking paradigms emerge for different networking applications, e.g., cyber-physical systems, and different services are handled under a converged data link technology, e.g., Ethernet, certain applications with mission critical traffic cannot coexist on the same physical networking infrastructure using traditional Ethernet packet-switched networking protocols. The IEEE 802.1Q Time Sensitive Networking (TSN) Task Group is developing protocol standards to provide deterministic properties, i.e., eliminates non-deterministic delays, on Ethernet based packet-switched networks. In particular, the IEEE 802.1Qcc, centralized management and control, and the IEEE 802.1Qbv, Time-Aware Shaper (TAS), can be used to manage and control Scheduled Traffic (ST) streams with periodic properties along with Best-Effort (BE) traffic on the same network infrastructure. We investigate the effects of using the IEEE 802.1Qcc management protocol to accurately and precisely configure TAS enabled switches (with transmission windows governed by Gate Control Lists (GCLs) with Gate Control Entries (GCEs)) ensuring ultra-low bounded latency, zero packet loss, and minimal jitter for ST TSN traffic. We examine both a centralized network/distributed user model (hybrid model) and a fully-distributed (decentralized) 802.1Qcc model on a typical industrial control network with the goal of maximizing the number of ST streams.

INTRODUCTION AND OBJECTIVE:Partial Nephrectomy (PN) is a procedure which aims to preserve renal functionality and minimize morbidity in patients with localized kidney tumors. However, it is associa...

Background Alopecia areata (AA) is a common cause of hair loss. It is mediated by T lymphocytes. Scalp biopsy findings in AA differ according to the disease phase and activity. Objectives To study the cellular infiltrate in the transverse section of scalp biopsy of AA at different disease stages and in relation to disease activity. Methods The study was performed on 40 subjects with AA. A 4-mm punch biopsy was obtained from an AA scalp lesion. Biopsies were sectioned horizontally; 2 anatomical levels were studied (mid dermal and deep dermal levels). Results Ninety-five percent of AA showed noncicatrical alopecia. A significant relation was found between the course of AA and the terminal:vellus ratio. Peribulbar lymphocytic infiltration was seen in 70% of cases. Mast cells were observed in 87.5% of cases, including fibrous tract and around the arrector pili muscles. Eosinophils were detected in the scalp biopsy of 22.5% of cases. Course and activity of AA were significantly related to the peribulbar lymphocytic cell infiltration but not to mast cells and eosinophils. Conclusion Although a peribulbar lymphocytic infiltrate is the classical finding of AA, it is absent in the chronic phase. Mast cells are commonly found in the scalp biopsy of AA and could explain the potential therapeutic effect of antihistamines.

ObjectiveTo estimate the age- and nationality-specific West Nile virus (WNV) seroprevalence in select Middle East and North Africa (MENA) populations residing in Qatar. MethodsSera were collected from male blood donors attending Hamad Medical Corporation. A total of 1,948 sera were tested for anti-WNV antibodies using Serion ELISA classic IgG and IgM kits. ResultsOverall, seroprevalence estimates of WNV-specific IgG and IgM antibodies were 10.4% and 3.3%, respectively. Country-specific WNV-specific IgG seroprevalence was estimated to be 37.0% (34/92) in Sudanese, 33.0% in Egyptians (66/200), 13.0% (26/200) in Indians, 10.6% (11/104) in Iranians, 10.2% (14/137) in Yemenis, 9.2% (18/195) in Pakistanis, 7.0% ( 14/199) in Jordanians, 5.4% (6/111) in Filipinos, 2.5% (5/200) in Palestinians, 2.5% (5/200) in Syrians, 1.5% (3/200) in Qataris, and 0.9% (1/110) in Lebanese. Seroprevalence of WNV-specific IgM was lowest in Iranians (0/77), Lebanese (0/108), and Filipinos (0/107) at 0.0%, and was highest in Sudanese at 10.0% (8/80). While there seemed to be apparent trends in the prevalence of WNV-IgM and WNV-IgG antibodies, none of these trends were found statistically significant. ConclusionThe findings support the circulation of WNV in human populations in the different countries of the MENA region. Seroprevalence was highest in Sudanese and Egyptians and lowest in Qataris and nationals of the Levant. The findings call for further animal, vector, and human studies, such as studying the actual prevalence of the viral RNA in blood donors to assess risk of viral transmission through blood donation and for a better characterization of the epidemiology of this infection in this part of the world. Qatar University internal grant (QUCG-CHS-19/20-1), Qatar National Research Fund (UREP20-020-3-003 and NPRP 9-040-3-008), and the Biomedical Research Program at Weill Cornell Medicine-Qatar.

This work aimed to develop an assessment tool that can help local officials and the public understanding the main effects surrounding location of quarrying activities and improper disposal of CDW. The specific objectives were to (1) assess the visual impact of quarries and CDW dumpsites at the landscape level and (2) investigate the effect of land conversion to quarries and CDW dumpsites on water runoff volume. The methodology of work involved digitization of individual quarries and CDW dumpsites using very high-resolution satellite imagery. The volume of exploited material was estimated with the use of a Digital Elevation Model. Geographic Object-Based Image Analysis was employed to assess the state of soil cover on identified sites. Visual impact maps were developed using Geographic Information System analysis. The Natural Resource Conservation Service-Curve Number model was adopted to estimate changes in volume of annual surface water runoff. The assessment resulted in mapping individual quarries (i.e., 1,425 quarries over an area of 61,723,800 m2) and CDW dumpsites (i.e., 219 dumpsites over an area of 5,012,100 m2) showing (1) low to complete absence of vegetation recovery on identified sites, (2) improper location of quarries and large extent of visually polluted landscape and (3) increase in surface water runoff. This work demonstrated the ability of using an operational tool to spatially characterize quarries and CDW dumpsites and their impacts on the landscape in the absence of extensive site-specific datasets. The transferability and replicability of this tool count on systematic use of the investigated geospatial techniques.

Highlights • Performances of five commercial ELISA (EDI, AnshLabs, Dia.Pro, NovaTec, and Lionex) for detecting anti-SARS-CoV-2 IgG was evaluated. • Samples used in this study are from diverse national background and the negative group contains samples that are seropositive for all other HCoV. • All assays showed low sensitivity during the early stages (≤7 from symptom onset); however, it was greatly improved overtime. • Lionex showed the highest specificity (98.6%), followed by EDI and Dia.Pro (97.1%,), NovaTec (85.7%), and AnshLabs (75.7%). • Lionex, which measures antibodies to the S1 protein, demonstrated the best performance and doesn’t cross-react with any other HCoV., Objectives To evaluate and compare the performances of five commercial ELISA assays (EDI, AnshLabs, Dia.Pro, NovaTec, and Lionex) for detecting anti-SARS-CoV-2 IgG. Methods 70 negative control samples (collected before the COVID-19 pandemic) and samples from 101 RT-PCR-confirmed SARS-CoV-2 patients (collected at different time points from symptoms onset: ≤7, 8-14, and >14 days) were used to compare the sensitivity, specificity, agreement, positive and negative predictive values of each assay with RT-PCR. A concordance assessment between the five assays was also conducted. Cross-reactivity with other HCoV, non-HCoV respiratory viruses, non-respiratory viruses, and nuclear antigens was investigated. Results Lionex showed the highest specificity (98.6%, 95%CI: 92.3-99.8), followed by EDI and Dia.Pro (97.1%, 95%CI: 90.2-99.2), NovaTec (85.7%, 95%CI: 75.7-92.1), then AnshLabs (75.7%, 95%CI: 64.5-84.2). All ELISA kits cross-reacted with one anti-MERS IgG positive sample except Lionex. The sensitivity was low during the early stages of the disease but improved over time. After 14 days from symptoms onset, Lionex and NovaTec showed the highest sensitivity at 87.9% (95%CI: 72.7-95.2) and 86.4% (95%CI: 78.5-91.7), respectively. The agreement with RT-PCR results based on Cohen’s kappa was as follows: Lionex (0.89)> NovaTec (0.70)> Dia.Pro (0.69)> AnshLabs (0.63)> EDI (0.55). Conclusion The Lionex ELISA, which measures antibodies solely to the S1 protein, demonstrated the best performance.

Background and Purpose: Triage of patients with emergent large vessel occlusion stroke to primary stroke centers followed by transfer to comprehensive stroke centers leads to increased time to endovascular therapy. A Mobile Interventional Stroke Team (MIST) provides an alternative model by transferring a MIST to a Thrombectomy Capable Stroke Center (TSC) to perform endovascular therapy. Our aim is to determine whether the MIST model is more time-efficient and leads to improved clinical outcomes compared with standard drip-and-ship (DS) and mothership models. Methods: This is a prospective observational cohort study with 3-month follow-up between June 2016 and December 2018 at a multicenter health system, consisting of one comprehensive stroke center, 4 TSCs, and several primary stroke centers. A total of 228 of 373 patients received endovascular therapy via 1 of 4 models: mothership with patient presentation to a comprehensive stroke center, DS with patient transfer from primary stroke center or TSC to comprehensive stroke center, MIST with patient presentation to TSC and MIST transfer, or a combination of DS with patient transfer from primary stroke center to TSC and MIST. The prespecified primary end point was initial door-to-recanalization time and secondary end points measured additional time intervals and clinical outcomes at discharge and 3 months. Results: MIST had a faster mean initial door-to-recanalization time than DS by 83 minutes ( P P =0.83). A greater proportion had a complete recovery (National Institutes of Health Stroke Scale of 0 or 1) at discharge in MIST compared with DS (37.9% versus 16.7%; P P =0.10). Conclusions: MIST led to significantly faster initial door-to-recanalization times compared with DS, which was comparable to mothership. This decrease in time has translated into improved short-term outcomes and a trend towards improved long-term outcomes. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT03048292.

Frequent emergency department (ED) utilization is an indicator of unmet health and social needs, especially among patients with mental and physical health problems. The authors aimed to characterize frequent ED utilizers and drivers of multiple ED use, including presence of serious mental illness (SMI), across 2 large health care systems in Northern California. Using electronic health records and a data-sharing platform, a cross-sectional analysis was conducted of patients aged 18+ years with ≥10 ED visits in 2016. Logistic regression was used to determine factors associated with multiple ED use versus single ED use. Among the 8036 patients who met inclusion criteria, the mean age was 55.9 years (95% CI = 55.5-56.4), 53% were female, 54% were non-Hispanic white, and 38% had any SMI. Overall, 51% of patients were single ED utilizers. Patients ages ≥65 years were less likely to use multiple EDs compared to younger patients (ages 18-23) (OR = 0.3, 95% CI = 0.2-0.4). African Americans exhibited more than 3 times the likelihood of multi-ED use compared to non-Hispanic whites (OR = 3.8, 95% CI = 3.3-4.3). A diagnosis of any SMI (OR = 2.3 [95% CI: 2.1-2.6]), major depressive disorder (OR = 1.3, 95% CI = 1.1-1.4), schizophrenia (OR = 2.1, 95% CI = 1.6-2.6), or suicidal attempts/ideation (OR = 2.7, 95% CI = 2.1-3.6) was significantly associated with increased likelihood of multi-ED use. Findings indicate heterogeneity in regional utilization patterns among frequent ED utilizers, with mental illness increasing the likelihood of multi-ED use.

Objective To determine the incidence of pituitary incidentalomas in the paediatric population and among its different age subgroups as well as to identify the characteristics of these lesions. Additionally, we aim to give a perspective on the management and follow-up of these patients. Design and patients We retrospectively studied MRI of children aged 18 years or below who underwent MRI with sellar region within their field of view between January 2010 and December 2018. Measurements Pituitary lesions were considered incidental according to the definition by the Endocrine Society. We reported the size, location and signal characteristics of each lesion. Medical charts of the subjects were reviewed for age, sex, the MRI indication and the hormonal assays levels. Results We identified 40 pituitary lesions of which 31 were incidental lesions. The incidence of pituitary incidentaloma in our cohort was 22 per 1000 patients with female predisposition ( 64.5%) and a mean age of 11 ± 6 years. Rathke's cleft cyst was the most prevalent lesion, accounting for 67.7% followed by cystic pituitary lesions and microadenomas. The most common indications for imaging were growth disturbance (12.9%) followed by headache (9.7%). Abnormal laboratory workup was present in 13% of the subjects. Incidental lesions were more common in the older age groups compared to young children. Conclusion Incidental pituitary lesions in the paediatric population are relatively infrequent and increases with age. Rathke's cleft cyst is the most common incidentally encountered pituitary lesion followed by cystic pituitary lesions and microadenomas.

The group of CNS mesenchymal (non‐meningothelial) and primary glial/neuronal tumors in association with EWSR1‐non‐ETS rearrangements comprises a growing spectrum of entities, mostly reported in isolation with incomplete molecular profiling. Archival files from three pediatric institutions were queried for unusual cases of pediatric (≤21 years) CNS EWSR1‐rearranged tumors confirmed by at least one molecular technique. Extra‐axial tumors and cases with a diagnosis of Ewing sarcoma (EWSR1‐ETS family fusions) were excluded. Additional studies, including anchored multiplex‐PCR with next‐generation sequencing and DNA methylation profiling, were performed as needed to determine fusion partner status and brain tumor methylation class, respectively. Five cases (median 17 years) were identified (M:F of 3:2). Location was parenchymal (n = 3) and undetermined (n = 2) with topographic distributions including posterior fossa (n = 1), frontal (n = 1), temporal (n = 1), parietal (n = 1) and occipital (n = 1) lobes. Final designation with fusion findings included desmoplastic small round cell tumor (EWSR1‐WT1; n = 1) and tumors of uncertain histogenesis (EWSR1‐CREM, n = 1; EWSR1‐CREB1, n = 1; EWSR1‐PLAGL1, n = 1; and EWSR1‐PATZ1, n = 1). Tumors showed a wide spectrum of morphology and biologic behavior. For EWSR1‐CREM, EWSR1‐PLAGL1 and EWSR1‐PATZ1 tumors, no significant methylation scores were reached in the known brain tumor classes. Available outcome (4/5) was reported as favorable (n = 2) and unfavorable (n = 2) with a median follow‐up of 30 months. In conclusion, we describe five primary EWSR1‐non‐ETS fused CNS tumors exhibiting morphologic and biologic heterogeneity and we highlight the clinical importance of determining specific fusion partners to improve diagnostic accuracy, treatment and monitoring. Larger prospective clinicopathological and molecular studies are needed to determine the prognostic implications of histotypes, anatomical location, fusion partners, breakpoints and methylation profiles in patients with these rare tumors., Pediatric EWSR1‐non‐ETS tumors of the CNS are rare and have not been addressed comprehensively, apart from conventional Ewing sarcoma. Here, we characterize the pathological and molecular features of five such tumors.

PURPOSE To construct a multi-institutional radiomic model that supports upfront prediction of progression-free survival (PFS) and recurrence pattern (RP) in patients diagnosed with glioblastoma multiforme (GBM) at the time of initial diagnosis. PATIENTS AND METHODS We retrospectively identified data for patients with newly diagnosed GBM from two institutions (institution 1, n = 65; institution 2, n = 15) who underwent gross total resection followed by standard adjuvant chemoradiation therapy, with pathologically confirmed recurrence, sufficient follow-up magnetic resonance imaging (MRI) scans to reliably determine PFS, and available presurgical multiparametric MRI (MP-MRI). The advanced software suite Cancer Imaging Phenomics Toolkit (CaPTk) was leveraged to analyze standard clinical brain MP-MRI scans. A rich set of imaging features was extracted from the MP-MRI scans acquired before the initial resection and was integrated into two distinct imaging signatures for predicting mean shorter or longer PFS and near or distant RP. The predictive signatures for PFS and RP were evaluated on the basis of different classification schemes: single-institutional analysis, multi-institutional analysis with random partitioning of the data into discovery and replication cohorts, and multi-institutional assessment with data from institution 1 as the discovery cohort and data from institution 2 as the replication cohort. RESULTS These predictors achieved cross-validated classification performance (ie, area under the receiver operating characteristic curve) of 0.88 (single-institution analysis) and 0.82 to 0.83 (multi-institution analysis) for prediction of PFS and 0.88 (single-institution analysis) and 0.56 to 0.71 (multi-institution analysis) for prediction of RP. CONCLUSION Imaging signatures of presurgical MP-MRI scans reveal relatively high predictability of time and location of GBM recurrence, subject to the patients receiving standard first-line chemoradiation therapy. Through its graphical user interface, CaPTk offers easy accessibility to advanced computational algorithms for deriving imaging signatures predictive of clinical outcome and could similarly be used for a variety of radiomic and radiogenomic analyses.

Idiopathic pulmonary fibrosis (IPF), the most common form of idiopathic interstitial pneumonia, is a progressive, irreversible, and typically lethal disease characterized by an abnormal fibrotic response involving vast areas of the lungs. Given the poor knowledge of the mechanisms underpinning IPF onset and progression, a better understanding of the cellular processes and molecular pathways involved is essential for the development of effective therapies, currently lacking. Besides a number of established IPF-associated risk factors, such as cigarette smoking, environmental factors, comorbidities, and viral infections, several other processes have been linked with this devastating disease. Apoptosis, senescence, epithelial-mesenchymal transition, endothelial-mesenchymal transition, and epithelial cell migration have been shown to play a key role in IPF-associated tissue remodeling. Moreover, molecules, such as chemokines, cytokines, growth factors, adenosine, glycosaminoglycans, non-coding RNAs, and cellular processes including oxidative stress, mitochondrial dysfunction, endoplasmic reticulum stress, hypoxia, and alternative polyadenylation have been linked with IPF development. Importantly, strategies targeting these processes have been investigated to modulate abnormal cellular phenotypes and maintain tissue homeostasis in the lung. This review provides an update regarding the emerging cellular and molecular mechanisms involved in the onset and progression of IPF.

Summary Background Results from the Systolic Blood Pressure Intervention Trial (SPRINT) showed that intensive control of systolic blood pressure significantly reduced the occurrence of mild cognitive impairment, but not probable dementia. We investigated the effects of intensive lowering of systolic blood pressure on specific cognitive functions in a preplanned substudy of participants from SPRINT. Methods SPRINT was an open-label, multicentre, randomised controlled trial undertaken at 102 sites, including academic medical centres, Veterans Affairs medical centres, hospitals, and independent clinics, in the USA and Puerto Rico. Participants were adults aged 50 years or older with systolic blood pressure higher than 130 mm Hg, but without diabetes, history of stroke, or dementia. Participants were randomly assigned (1:1) to a systolic blood pressure goal of less than 120 mm Hg (intensive treatment) versus less than 140 mm Hg (standard treatment). All major classes of antihypertensive agents were included. A subgroup of randomly assigned participants including, but not limited to, participants enrolled in an MRI substudy was then selected for a concurrent substudy of cognitive function (target 2800 participants). Each individual was assessed with a screening cognitive test battery and an extended cognitive test battery at baseline and biennially during the planned 4-year follow-up. The primary outcomes for this substudy were standardised composite scores for memory (Logical Memory I and II, Modified Rey-Osterrieth Complex Figure [immediate recall], and Hopkins Verbal Learning Test-Revised [delayed recall]) and processing speed (Trail Making Test and Digit Symbol Coding). SPRINT was registered with ClinicalTrials.gov , NCT01206062 . Findings From Nov 23, 2010, to Dec 28, 2012, 2921 participants (mean age 68·4 years [SD 8·6], 1080 [37%] women) who had been randomly assigned in SPRINT were enrolled in the substudy (1448 received intensive treatment and 1473 received standard treatment). SPRINT was terminated early due to benefit observed in the primary outcome (composite of cardiovascular events). After a median follow-up of 4·1 years (IQR 3·7–5·8), there was no between-group difference in memory, with an annual decline in mean standardised domain score of −0·005 (95% CI −0·010 to 0·001) in the intensive treatment group and −0·001 (–0·006 to 0·005) in the standard treatment group (between-group difference −0·004, 95% CI −0·012 to 0·004; p=0·33). Mean standardised processing speed domain scores declined more in the intensive treatment group (between-group difference −0·010, 95% CI −0·017 to −0·002; p=0·02), with an annual decline of −0·025 (–0·030 to −0·019) for the intensive treatment group and −0·015 (–0·021 to 0·009) for the standard treatment group. Interpretation Intensive treatment to lower systolic blood pressure did not result in a clinically relevant difference compared with standard treatment in memory or processing speed in a subgroup of participants from SPRINT. The effect of blood pressure lowering might not be evident in specific domains of cognitive function, but instead distributed across multiple domains. Funding National Heart, Lung, and Blood Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute on Aging, National Institute of Neurological Disorders and Stroke, and the Alzheimer's Association.

Background: Individuals with advanced cancer and their families have negative end-of-life experiences when the care they receive is not aligned with their values and preferences. Objective: To obtain in-depth information on how patients with advanced cancer and the oncology and palliative care (PC) clinicians who care for them discuss goals of care (GoC). Design: The research team conducted in-depth interviews and qualitative data analysis using open coding to identify how perspectives on GoC discussions vary by stage of illness, and experience with PC teams. Setting/Subjects: Twenty-five patients and 25 oncology and PC team members in a large multi-specialty group in Northern California. Results: At the time of diagnosis participants described having establishing GoC conversations about understanding the goal of treatment (e.g. to extend life), and prognosis (“How much time do I have?”). Patients whose disease progressed or pain/symptoms increased reported changing GoC conversations about stopping treatment, introducing hospice care, prognostic awareness, quality of life, advance care planning, and end-of-life planning. Participants believed in the fluidity of prognosis and preferences for prognostic communication varied. Patients appreciated how PC teams facilitated changing GoC conversations. Timing was challenging; some patients desired earlier conversations and PC involvement, others wanted to wait until things were “going downhill.” Conclusion: Patients and clinical teams acknowledged the complexity and importance of GoC conversations, and that PC teams enhanced conversations. The frequency, quality, and content of GoC conversations were shaped by patient receptivity, stage of illness, clinician attitudes and predispositions toward PC, and early integration of PC.

Highlights • The true incidence of SARS-COV-2 is much higher than the reported number of cases. • Large sample size studies showed 1.2-12.9% incidence of SARS-COV-2 among asymptomatics. • Studies with a small sample size showed up to 87.9% incidence among asymptomatics. • Asymptomatic individuals could be a potential source of infection to the community., Background the recent outbreak of the coronavirus disease 2019 (COVID‐19) has quickly spread globally since its discovery in Wuhan, China, in December 2019. A comprehensive strategy, including surveillance, diagnostics, research, and clinical treatment is urgently needed to win the battle against COVID-19. Recently, numerous studies reported the incidence of SARS-CoV-2 in asymptomatic patients. Yet, the incidence and viral transmission from the asymptomatic cases are not apparent yet. Aim this study aims to systematically review the published literature on SARS-CoV-2 in the asymptomatic patients to estimate the incidence of COVID-19 among asymptomatic cases, as well as describe its epidemiological and clinical significance. Method the literature was searched through four scientific databases: PubMed, Web of Science, Scopus, and Science Direct. Results a total of 63 studies satisfied the inclusion criteria where the majority of the reported studies were from China. However, there was a lack of SARS-CoV-2 epidemiological studies from several countries worldwide, tracing the actual incidence of COVID-19, especially in asymptomatic patients. Studies with a large sample size (n>1000) estimated that percentage of people contracting SARS-CoV-2 and are likely to be asymptomatic ranges from 1.2-12.9%. However, the other studies with a smaller sample size reported a much higher incidence and indicated that up to 87.9% of COVID-19 infected individuals could be asymptomatic. Most of these studies indicated that asymptopatics are a potential source of infection to the community. Conclusion this review highlighted the need for more robust and well-designed studies to better estimate COVID-19 incidence among asymptomatic patients worldwide. The early identification of the asymptomatic cases, as well as monitoring and tracing close contact, could help in mitigating the spread of COVID-19.

Objectives: Cloud computing technology is in continuous development, and with numerous challenges regarding security. In this context, one of the main concerns for cloud computing is represented by the trustworthiness of cloud services in the Pakistan Information Technology (IT) industry. This problem requires prompt resolution because IT organizations in Pakistan adopting cloud services would be exposed to increased expenditures while at a higher risk. A survey conducted by International Data Corporation (IDC) in August 2008 confirms that security is the major barrier for cloud users in Pakistan.Material/methods: We have proposed the mathematical-based model for an estimate of our user’s requirements regarding our resource investment based on queuing theory to overcome these security issues in cloud technology. We are adopting a system and real-world analysis using data set experiments.Result: In this article, we proposed a solution to overcome the Distributed Denial of Service (DDoS) attacks in a cloud computing environment in the Pakistan IT services; because along with discussed above phenomena, we also used DST and FTA (Fault Tree Analysis) for mentioned attacks. Conclusion:Our proposed solution based on Dempsters combination rule is to analyzed mixture proof of different types of cloud attacks in IT industries in Pakistan. Keywords: DDoS attacks; IT Services; attack detection; cryptography; cloud computing

Objective Controversy exists regarding an association between Helicobacter pylori infection and asthma in children. We examined the hypotheses of inverse associations of H. pylori seroprevalence and pepsinogen (PG) levels, as markers of gastric inflammation, with asthma in children. Methods A hospital-based case-control study was conducted among children aged 4.8 to 17.3 years in Israel. Confirmed asthma cases (n = 75) were recruited through a pulmonary clinic, and controls (n = 160) without asthma were enrolled. Using enzyme-linked immunosorbent assays we measured the presence of H. pylori immunoglobulin G (IgG) antibodies, IgG antibodies to cytotoxin-associated gene A antigen (CagA) (virulent factor), serum PG levels and exposure to other enteric pathogens (Shigella flexneri). Multivariable logistic regression models were applied. Results H. pylori IgG seropositivity was 25% and 40% among cases and controls, respectively (P = .03). H. pylori CagA IgG seropositivity was associated with reduced risk of asthma (adjusted odds ratio [OR], 0.33 [95% CI, 0.11-0.95] but not for the CagA negative serology (adjusted OR, 0.70 [95% CI, 0.32-1.54]). Children who were H. pylori seropositive with a PGI:PGII of ≤6.78 (severe gastric inflammation) had a lower likelihood of asthma (adjusted OR, 0.31 [95% CI, 0.10-0.89]) than did seronegative children. Exposure to Shigella flexneri did not differ between cases and controls, nor according to H. pylori seropositivity. Among the asthmatic children, pulmonary function did not differ according to H. pylori seropositivity. Conclusions H. pylori infection and its related gastric inflammation may have a protective role in the risk of pediatric asthma and further research into a potential causal pathway is required.

Background Trauma systems are designed to provide specialized treatment for the most severely injured. As populations change, it is imperative for trauma centers to remain dynamic to provide the best care to all members of the community. Methods A retrospective review of all trauma patients treated at one Level II trauma center in Southern CA over 5 years. Three cohorts of patients were studied: geriatric (> 65 years), the homeless, and all other trauma patients. Triage, hospitalization, and outcomes were collected and analyzed. Results Of 8431 patients treated, 30% were geriatric, 3% homeless and 67% comprised all other patients. Trauma activation criteria was met for 84% of all other trauma patients, yet only 61% of homeless and geriatric patients combined. Injury mechanism for homeless included falls (38%), pedestrian/bicycle related (27%) and assaults (24%), often while under the influence of alcohol and drugs. Average length of hospital stay (LOS) was greater for homeless and geriatric patients and frequently attributed to discharge planning challenges. Both the homeless and geriatric groups demonstrated increased complications, comorbidities, and death rates. Conclusions Homeless trauma patients reflect similar challenges in care as with the elderly, requiring additional resources and more complex case management. It is prudent to identify and understand the issues surrounding patients transported to our trauma center requiring a higher level of care yet are under-triaged upon arrival to the Emergency Department. Although a monthly review is done for all under-triaged patients, and geriatric patients are acknowledged to be a cohort continually having delays, the homeless cohort continues to be under-triaged. The admitted homeless trauma patient has similar complex case management issues as the elderly related to pre-existing health issues and challenges with discharge planning, both which can add to longer lengths of hospital stay as compared to other trauma patients. Given the lack of social support that is endemic to both populations, these cohorts represent a unique challenge to trauma centers. Further research into specialized care is required to determine best practices to address disparities evident in the homeless and elderly, and to promote health equity in marginalized populations.

Fusions involving neurotrophic tyrosine receptor kinase (NTRK) genes are detected in ≤2% of gliomas and can promote gliomagenesis. The remarkable therapeutic efficacy of TRK inhibitors, which are among the first Food and Drug Administration-approved targeted therapies for NTRK-fused gliomas, has generated significant clinical interest in characterizing these tumors. In this multi-institutional retrospective study of 42 gliomas with NTRK fusions, next generation DNA sequencing (n = 41), next generation RNA sequencing (n = 1), RNA-sequencing fusion panel (n = 16), methylation profile analysis (n = 18), and histologic evaluation (n = 42) were performed. All infantile NTRK-fused gliomas (n = 7) had high-grade histology and, with one exception, no other significant genetic alterations. Pediatric NTRK-fused gliomas (n = 13) typically involved NTRK2, ranged from low- to high-histologic grade, and demonstrated histologic overlap with desmoplastic infantile ganglioglioma, pilocytic astrocytoma, ganglioglioma, and glioblastoma, among other entities, but they rarely matched with high confidence to known methylation class families or with each other; alterations involving ATRX, PTEN, and CDKN2A/2B were present in a subset of cases. Adult NTRK-fused gliomas (n = 22) typically involved NTRK1 and had predominantly high-grade histology; genetic alterations involving IDH1, ATRX, TP53, PTEN, TERT promoter, RB1, CDKN2A/2B, NF1, and polysomy 7 were common. Unsupervised principal component analysis of methylation profiles demonstrated no obvious grouping by histologic grade, NTRK gene involved, or age group. KEGG pathway analysis detected methylation differences in genes involved in PI3K/AKT, MAPK, and other pathways. In summary, the study highlights the clinical, histologic, and molecular heterogeneity of NTRK-fused gliomas, particularly when stratified by age group.

Gallbladder cancer (GBC) is the most common malignancy of the biliary tract. The median survival of the disease is around 6 months. In this study, we explore clinical trials related to non-resectable GBC, determine the shortcomings leading to the lack of development of new treatment, and shed light on possible areas of improvement. On April 20, 2019 the authors completed a search on ClinicalTrials.gov for all therapeutic and interventional clinical trials involving non-resectable GBC, without any limits on date or location. Trial characteristics such as duration, phase, sample size, and whether a publication was produced were collected and analyzed. Sixty-two trials met our selection criteria. The average duration of trials was 5 years. Trials were conducted in 8 different countries: most of them in North America (USA and Canada). About 88% of trials were in early phases (I, I/II, and II) and 85% of trials were completed. Only 4 relevant publications were produced from all the trials in our study. Gemcitabine was the most common drug used. Use of gemcitabine alone or in combination with either capecitabine or cisplatin showed significant increase mean progression-free survival. This study revealed a low number of trials, lack of geographic diversity, and scarcity of publications concerning non-resectable GBC. Adequate management of is of great importance to reach effective therapies for this disease.

Background: Chronic obstructive pulmonary disease [COPD] is a chronic lung disease affecting other body systems, like musculoskeletal system causing weakness. Muscle weakness is a major problem, causing poor functional lung capacity; and a negative impact on daily life activity. Muscle weakness in COPD may be a form of disuse and/or a form of myopathy is a question need answer. Exercise is a basic unit of pulmonary rehabilitation causing increased quality of life. So, PR regarded as effective non-pharmacological treatments in COPD. Aim of the work: Whole-body vibration [WBV] is a type of exercise that improve muscle function specially in debilitated patients like COPD,WBV not yet studied in Egyptian patients with COPD. Patients and Methods:Fifty patients with COPD were assessed for an 18-weeks in outpatient rehabilitation center, the patients were randomly assigned into: Group 1, using dynamic exercise on a side alternating vibration platform at 25–30 Hz three times per week [WBV], and group 2 as a control group [CON] with the same amount of exercise without WBV. Results: Pulmonary function tests results: showing FEV1 pred. 39.8 ± 12.2 and 41.3±4.6 before and after intervention respectively. PaO2: 49.60 ± 80and 82±90 before and after intervention respectively; PaCO2: 65 ± 70and 33±50before and after intervention respectively the difference was significant in intervention group than in control. The distance walked [DW] increased after the WBV period [397±133m] compared with the control period [359±111m]. Conclusion: WBV was good complementary training exercise which could be an effective new modality for COPD patients.

Prostaglandin E2 receptor EP1 (PGE2/EP1) promotes diabetic renal injury, and EP1 receptor deletion improves hyperfiltration, albuminuria, and fibrosis. The role of EP1 receptors in hypertensive kidney disease (HKD) remains controversial. We examined the contribution of EP1 receptors to HKD. EP1 null (EP1-/-) mice were bred with hypertensive TTRhRen mice (Htn) to evaluate kidney function and injury at 24 weeks. EP1 deletion had no effect on elevation of systolic blood pressure in Htn mice (HtnEP1-/-) but resulted in pronounced albuminuria and reduced FITC-inulin clearance, compared with Htn or wild-type (WT) mice. Ultrastructural injury to podocytes and glomerular endothelium was prominent in HtnEP1-/- mice; including widened subendothelial space, subendothelial lucent zones and focal lifting of endothelium from basement membrane, with focal subendothelial cell debris. Cortex COX2 mRNA was increased by EP1 deletion. Glomerular EP3 mRNA was reduced by EP1 deletion, and EP4 by Htn and EP1 deletion. In WT mice, PGE2 increased chloride reabsorption via EP1 in isolated perfused thick ascending limb (TAL), but PGE2 or EP1 deletion did not affect vasopressin-mediated chloride reabsorption. In WT and Htn mouse inner medullary collecting duct (IMCD), PGE2 inhibited vasopressin-water transport, but not in EP1-/- or HtnEP1-/- mice. Overall, EP1 mediated TAL and IMCD transport in response to PGE2 is unaltered in Htn, and EP1 is protective in HKD.

Background Ureteral stones pose a high economic and medical burden among Emergency Department (ED) admissions. Management strategies vary from expectant therapy to surgical interventions. Since predictors of ureteral spontaneous stone passage (SSP) are still not well understood, we sought to create a novel nomogram to guide management decisions. Methods Charts were retrospectively reviewed for patients who presented to our institution's ED with non-febrile renal colic and received a radiological diagnosis of ureteral stone ≤10 mm. Demographic, clinical, laboratory, and non-contrast CT data were collected. This novel nomogram incorporates the serum neutrophil-to-lymphocyte ratio (NLR) as a potential predictor of SSP. The model was derived from a multivariate logistic regression and was validated on a different cohort. A receiver operator characteristic (ROC) curve was constructed and the area under the curve (AUC) was computed. Results A total of 1186 patients presented to our ED between January 2010 and October 2018. We randomly divided our population into a derivation and validation cohort in one to five ratio. A stone size ≥ 7 mm was the strongest predictor of SSP failure; OR=9.47; 95%CI (6.03-14.88). Similarly, a NLR ≥ 3.14 had 2.17; (1.58-2.98) the odds of retained stone. SSP failure was also correlated with proximal position, severe hydronephrosis, and leukocyte esterase ≥ 75, p=0.02, p=0.05, and p=0.006, respectively. The model had an AUC of 0.804 (0.776-0.832). The nomogram was also used to compute the risk of SSP failure (AUC 0.769 (0.709 - 0.829). Conclusions Our novel nomogram can be used as a predictor for SSP and can be used clinically in decision making.

International audience; The hazards of dyes on the water have driven researchers to develop strategies to remove them. Our choice for this study was photocatalysis. In view of this, semiconductor CoCr2O4 (CCO) by the co-precipitation method was synthesized and explored for its photo-catalytic efficiency by the possible elimination of basic blue 41 (BB41) by degradation in the visible light irradiation. The phase of synthesized CCO was refined and characterized structurally using X-ray diffraction (XRD) associated with the Rietveld method to illustrate the structural form of this spinel. The characteristic bands of CCO were identified for the vibrational groups using the FT-IR spectrum. Using the diffused reflectance data, an optical gap band of 1.65 eV was determined. The energy diagram resulting after the electrochemical study confirmed that the catalyst adopts the nature of n-type semiconductors. The photocatalytic degradation of BB41 by CCO as a function of time of irradiation, pH of BB41 solution, CCO dose and initial BB41 concentration was determined. The degradation percentage of 99% was studied for. 300 min but the efficiency decreased as the initial dye concentration was decreased. The photo-degradation mechanism and the compliance of pseudo-first-order models are discussed in this contribution. © 2021 Elsevier B.V.

Background In the medical imaging domain, deep learning-based methods have yet to see widespread clinical adoption, in part due to limited generalization performance across different imaging devices and acquisition protocols. The deviation between estimated brain age and biological age is an established biomarker of brain health and such models may benefit from increased cross-site generalizability. Purpose To develop and evaluate a deep learning-based image harmonization method to improve cross-site generalizability of deep learning age prediction. Study type Retrospective. Population Eight thousand eight hundred and seventy-six subjects from six sites. Harmonization models were trained using all subjects. Age prediction models were trained using 2739 subjects from a single site and tested using the remaining 6137 subjects from various other sites. Field strength/sequence Brain imaging with magnetization prepared rapid acquisition with gradient echo or spoiled gradient echo sequences at 1.5 T and 3 T. Assessment StarGAN v2, was used to perform a canonical mapping from diverse datasets to a reference domain to reduce site-based variation while preserving semantic information. Generalization performance of deep learning age prediction was evaluated using harmonized, histogram matched, and unharmonized data. Statistical tests Mean absolute error (MAE) and Pearson correlation between estimated age and biological age quantified the performance of the age prediction model. Results Our results indicated a substantial improvement in age prediction in out-of-sample data, with the overall MAE improving from 15.81 (±0.21) years to 11.86 (±0.11) with histogram matching to 7.21 (±0.22) years with generative adversarial network (GAN)-based harmonization. In the multisite case, across the 5 out-of-sample sites, MAE improved from 9.78 (±6.69) years to 7.74 (±3.03) years with histogram normalization to 5.32 (±4.07) years with GAN-based harmonization. Data conclusion While further research is needed, GAN-based medical image harmonization appears to be a promising tool for improving cross-site deep learning generalization. Level of evidence 4 TECHNICAL EFFICACY: Stage 1.

Heterogeneity of brain diseases is a challenge for precision diagnosis/prognosis. We describe and validate Smile-GAN (SeMI-supervised cLustEring-Generative Adversarial Network), a semi-supervised deep-clustering method, which examines neuroanatomical heterogeneity contrasted against normal brain structure, to identify disease subtypes through neuroimaging signatures. When applied to regional volumes derived from T1-weighted MRI (two studies; 2,832 participants; 8,146 scans) including cognitively normal individuals and those with cognitive impairment and dementia, Smile-GAN identified four patterns or axes of neurodegeneration. Applying this framework to longitudinal data revealed two distinct progression pathways. Measures of expression of these patterns predicted the pathway and rate of future neurodegeneration. Pattern expression offered complementary performance to amyloid/tau in predicting clinical progression. These deep-learning derived biomarkers offer potential for precision diagnostics and targeted clinical trial recruitment., Alzheimer’s disease is heterogeneous in its neuroimaging and clinical phenotypes. Here the authors present a semi-supervised deep learning method, Smile-GAN, to show four neurodegenerative patterns and two progression pathways providing prognostic and clinical information.

Summary We have shown that the improvement in hippocampal-based learning in aged mice following physical exercise observed is dependent on neurogenesis in the dentate gyrus (DG) and is regulated by changes in growth hormone levels. The changes in neurocircuitry, however, which may underlie this improvement, remain unclear. Using in vivo multimodal magnetic resonance imaging to track changes in aged mice exposed to exercise, we show the improved spatial learning is due to enhanced DG connectivity, particularly the strengthening of the DG-Cornu Ammonis 3 and the DG-medial entorhinal cortex connections in the dorsal hippocampus. Moreover, we provide evidence that these changes in circuitry are dependent on neurogenesis since they were abrogated by ablation of newborn neurons following exercise. These findings identify the specific changes in hippocampal circuitry that underlie the cognitive improvements resulting from physical activity and show that they are dependent on the activation of neurogenesis in aged animals., Graphical abstract, Highlights • Exercise can enhance connectivity in the dorsal hippocampus to improve spatial learning • Circuitry changes depend on increased neurogenesis in the hippocampus of aged animals • Identification of the specific changes in circuitry underlying cognitive improvements • Enhanced connectivity occurs only after exercise of a specific duration: the sweet spot, Cognitive neuroscience, Behavioral neuroscience, Biological sciences

Major affective disorder are common and disabling conditions linked to significant psychosocial impairment as well as negative outcome (e.g., suicidal behaviors) . According to a molecular perspective, major depressive disorder and suicidal behavior have been associated with structural and synaptic plasticity disturbances. Small non-coding RNAs, such as microRNAs (miRNAs), may play a significant role in the translational regulation of the synapse. This comprehensive overview is aimed to carefully review the preclinical and clinical literature results regarding the involvement of miRNAs in the pathophysiology and pharmacotherapy of major psychiatric conditions . MiRNAs may act as gene expression regulators critically affecting brain development. The alteration of some intracellular mechanisms together with impaired assembly, localization, and translational regulation of specific RNA binding proteins may affect important functions such as learning and memory contributing to the pathophysiology of major depressive disorder and suicidal behavior. Based on the main findings, most of the miRNAs which have been identified to date are expressed in human brain, where they regulate prominent neurobiological processes, such as neurogenesis and neuroplasticity. The main implications of the present findings are critically discussed.

This article is protected by copyright. All rights reserved. With the accelerating pace of global change, it is imperative that we obtain rapid inventories of the status and distribution of wildlife for ecological inferences and conservation planning. To address this challenge, we launched the SNAPSHOT USA project, a collaborative survey of terrestrial wildlife populations using camera traps across the United States. For our first annual survey, we compiled data across all 50 states during a 14-week period (17 August - 24 November of 2019). We sampled wildlife at 1509 camera trap sites from 110 camera trap arrays covering 12 different ecoregions across four development zones. This effort resulted in 166,036 unique detections of 83 species of mammals and 17 species of birds. All images were processed through the Smithsonian's eMammal camera trap data repository and included an expert review phase to ensure taxonomic accuracy of data, resulting in each picture being reviewed at least twice. The results represent a timely and standardized camera trap survey of the USA. All of the 2019 survey data are made available herein. We are currently repeating surveys in fall 2020, opening up the opportunity to other institutions and cooperators to expand coverage of all the urban-wild gradients and ecophysiographic regions of the country. Future data will be available as the database is updated at eMammal.si.edu/snapshot-usa, as well as future data paper submissions. These data will be useful for local and macroecological research including the examination of community assembly, effects of environmental and anthropogenic landscape variables, effects of fragmentation and extinction debt dynamics, as well as species-specific population dynamics and conservation action plans. There are no copyright restrictions; please cite this paper when using the data for publication. Publisher PDF

Background and Objective There is a pressing need for evidence-based interventions to address the devastating clinical and public health effects of the coronavirus disease 2019 (COVID-19) pandemic. The number of registered trials related to COVID-19 is increasing by the day. The objective of this study was to describe the characteristics of the currently registered interventional clinical trials related to COVID-19. Methods We searched the World Health Organization's International Clinical Trials Registry Platform on May 15th, 2020. We included any entry that is related to COVID-19. We abstracted and then descriptively analyzed the following characteristics of the registered trials: study design, status, phase, primary endpoints, experimental interventions, and geographic location among other qualifiers. Results We identified 1,308 eligible registered trials. Most trials were registered with ClinicalTrials.gov (n = 703; 53.7%) and the Chinese Clinical Trial Registry (n = 291; 22.2%). The number of participants to be enrolled across these trials was 734,657, with a median of 110 participants per trial. The most commonly studied intervention category was pharmacologic (n = 763; 58.3%), with antiparasitic medications being the most common subcategory. Although over half of the trials were already recruiting, we identified published peer-reviewed results for only 8 of those trials. Conclusion There is a relatively large number of registered trials but with very few results published so far. Although our findings suggest an appropriate initial response by the research community, the real challenge will be to get these trials completed, published, and translated into practice and policy.

BACKGROUNDGrowing evidence suggests that COVID-19 vaccines differ in effectiveness against breakthrough infection or severe COVID-19, but vaccines have yet to be investigated in controlled studies that head-to-head compare immunity of one to another. This study compared protection offered by the mRNA-1273 (Moderna) vaccine with that of the BNT162b2 (Pfizer-BioNTech) vaccine in Qatar.METHODSIn a population of 1,531,736 vaccinated persons, two matched retrospective cohort studies were designed and used to investigate differences in mRNA-1273 and BNT162b2 vaccine protection, after the first and second doses, from December 21, 2020 to October 20, 2021.RESULTSAfter dose 1, cumulative incidence of breakthrough infection was 0.79% (95% CI: 0.75-0.83%) for mRNA-1273-vaccinated individuals and 0.86% (95% CI: 0.82-0.90%) for BNT162b2-vaccinated individuals, 21 days post-injection. Adjusted hazard ratio (AHR) for breakthrough infection was 0.89 (95% CI: 0.83-0.95; p=0.001). AHR was constant in the first two weeks at 1, but it declined to 0.67 (95% CI: 0.57-0.77; pCONCLUSIONSmRNA-1273 vaccination is associated with lower SARS-CoV-2 breakthrough infection and COVID-19 hospitalization and death than BNT162b2 vaccination, but the number of hospitalizations and deaths was exceedingly small for both vaccines. Both vaccines demonstrated strikingly similar patterns of build-up of protection after the first dose and waning of protection after the second dose.

Differentiation of true tumor progression (TP) from pseudoprogression (PsP) is a major unmet need in patients with glioblastoma. [18F]Fluciclovine is a synthetic amino acid PET radiotracer that is FDA-approved in biochemical recurrence in prostate cancer. The study aim was to assess the value of [18F]Fluciclovine PET in differentiation of histologically confirmed (“true”) TP and PsP in post-treatment of glioblastoma. METHODS: 23 patients with glioblastoma with new contrast-enhancing lesions or lesions showing increased enhancement ( > 25% increase) on standard MRI after completion of radiation underwent 60-minutes dynamic [18F]Fluciclovine PET imaging. Patients subsequently underwent resection of enhancing lesion and tumor percentage vs. treatment-related changes were quantified on histopathology. Patients were considered "true” TP if tumor represented ≥ 50% of the resected specimen, mixed TP-PsP if < 50% and > 10%, and PsP if tumor represented ≤ 10%. Summed 30- to 40-minute post-injection PET images were used to measure SUVpeak and SUVmax (g/mL units). RESULTS: 15 patients with “true” TP, 3 with mixed TP-PsP, and 5 with PsP were included. There was a positive correlation between SUVpeak by PET and tumor percentage by histology (Rho= 0.56, p= 0.006). Patients who demonstrated “true” TP had significantly higher SUVpeak compared to patients with histological PsP (4.8±1.6 vs 2.9± 1.0, p= 0.02, AUC= 0.91, n=20). SUVpeak cut-off of 3.3 provided 93% sensitivity, 80% specificity, and 90% accuracy for differentiation of “true” TP from PsP. Patients with “true” TP/mixed TP-PsP also had significantly higher SUVpeak than patients with PsP (4.6±1.5 vs 2.9± 1.0, p= 0.03, AUC= 0.88, n=23). SUVmax and partial volume-corrected SUVpeak and SUVmax exhibited similar performance. CONCLUSION: Our results indicated that [18F]Fluciclovine PET imaging can accurately differentiate “true” TP from PsP. Further studies are required to confirm these promising early results and determine optimal criteria for interpreting [18F]Fluciclovine PET to distinguish PsP from TP.