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Abstract Endothelial cells are integral components of all vasculature within complex organisms. As they line the blood vessel wall, endothelial cells are constantly exposed to a variety of molecular factors and shear force that can induce cellular damage and stress. However, how endothelial cells are removed or eliminate unwanted cellular contents, remains unclear. The generation of large extracellular vesicles (EVs) has emerged as a key mechanism for the removal of cellular waste from cells that are dying or stressed. Here, we used intravital microscopy of the bone marrow to directly measure the kinetics of EV formation from endothelial cells in vivo under homoeostatic and malignant conditions. These large EVs are mitochondria-rich, expose the ‘eat me’ signal phosphatidylserine, and can interact with immune cell populations as a potential clearance mechanism. Elevated levels of circulating EVs correlates with degradation of the bone marrow vasculature caused by acute myeloid leukaemia. Together, our study provides in vivo spatio-temporal characterization of EV formation in the murine vasculature and suggests that circulating, large endothelial cell-derived EVs can provide a snapshot of vascular damage at distal sites.

Abstract Background Mortality is high within the first few months of starting chronic dialysis. Pre-ESKD trajectory of kidney function has been shown to be predictive of early death after dialysis initiation. We aim to better understand how two key aspects of pre-dialysis kidney function—an abrupt transition pattern and an episode of dialysis-requiring AKI (AKI-D) leading directly to ESKD—are associated with early mortality after dialysis initiation. Methods We extracted national data from U.S. Veterans Health Administration cross-linked with the United States Renal Data System (USRDS) to identify patients who initiated hemodialysis during 2009–2013. We defined abrupt transition as having a mean outpatient eGFR ≥ 30 ml/min/1.73m2 within 1 year prior to ESKD. AKI-D was identified using inpatient serum creatinine measurements (serum Cr increase by at least 50% from baseline) along with billing codes for inpatient receipt of dialysis for AKI within 30 days prior to the ESKD start date. We used multivariable proportional hazards models to examine the association between patterns of kidney function prior to ESKD and all-cause mortality within 90 days after ESKD. Results Twenty-two thousand eight hundred fifteen patients were identified in the final analytic cohort of Veterans who initiated hemodialysis and entered the USRDS. We defined five patterns of kidney function decline. Most (68%) patients (N = 15,484) did not have abrupt transition and did not suffer an episode of AKI-D prior to ESKD (reference group). The remaining groups had abrupt transition, AKI-D, or both. Patients who had an abrupt transition with (N = 503) or without (N = 3611) AKI-D had the highest risk of early mortality after ESKD onset after adjustment for demographics and comorbidities (adjusted HR 2.10, 95% CI 1.66–2.65 for abrupt transition with AKI-D; adjusted HR 2.10, 95% CI 1.90–2.33 for abrupt transition without AKI-D). In contrast, patients who experienced AKI-D without an abrupt transition pattern (N = 2141 had only a modestly higher risk of early death (adjusted HR 1.19, 95% CI 1.01–1.40). Conclusions An abrupt decline in kidney function within 1 year prior to ESKD occurred in nearly 1 in 5 incident hemodialysis patients (18%) in this national cohort of Veterans and was strongly associated with higher early mortality after ESKD onset.

Abstract Brain exposure of systemically administered biotherapeutics is highly restricted by the blood-brain barrier (BBB). Here, we report the engineering and characterization of a BBB transport vehicle targeting the CD98 heavy chain (CD98hc or SLC3A2) of heterodimeric amino acid transporters (TVCD98hc). The pharmacokinetic and biodistribution properties of a CD98hc antibody transport vehicle (ATVCD98hc) are assessed in humanized CD98hc knock-in mice and cynomolgus monkeys. Compared to most existing BBB platforms targeting the transferrin receptor, peripherally administered ATVCD98hc demonstrates differentiated brain delivery with markedly slower and more prolonged kinetic properties. Specific biodistribution profiles within the brain parenchyma can be modulated by introducing Fc mutations on ATVCD98hc that impact FcγR engagement, changing the valency of CD98hc binding, and by altering the extent of target engagement with Fabs. Our study establishes TVCD98hc as a modular brain delivery platform with favorable kinetic, biodistribution, and safety properties distinct from previously reported BBB platforms.

Background: Inflammatory Bowel Disease (IBD)-associated arthritis is a frequent and potentially debilitating complication of IBD, that can affect those with or without active intestinal disease, and is often difficult to treat. The microbiome is known to play a role in IBD development and has been shown to be associated with inflammatory arthritis without concomitant IBD, but its role in IBD-associated arthritis is still unexplored. Further, disease localization is associated with development of IBD-associated arthritis, and stool compositional profiles are predictive of disease localization, yet mucosal location-specific microbiomes have not been well characterized. To address this gap in understanding, we designed a study (LOCATION-IBD) to characterize the mucosa-associated intestinal microbiome and metabolome in IBD-associated arthritis. Methods: Adults with an established diagnosis of IBD undergoing clinical colonoscopy between May of 2021 and February of 2023 were invited to participate in this study; those interested in participation who met inclusion criteria were enrolled. Prior to enrollment, participants were stratified into those with or without IBD-associated arthritis. All participants were interviewed and had clinical and demographic data collected, and 97.8% completed clinical colonoscopy with biopsy collection. Results and conclusion: A total of 182 participants, 53 with confirmed IBD-associated arthritis, were enrolled in this study, resulting in 1151 biopsies obtained for microbiome and metabolome analysis (median 6, mean 6.3 per participant). Clinical and demographic data obtained from the study population will be analyzed with microbiome and metabolome data obtained from biopsies, with the goal of better understanding the mechanisms underpinning the host-microbiome relationship associated the development of IBD-associated arthritis.

This study examines the potential for institutional quality to address Africa's trilemma of food insecurity, rapid urbanization, and extreme weather events.Using a two-stage least squares regression analysis of 28 African countries between 2012Q1 and 2021Q4, our results suggest that extreme weather events have a significant negative impact on food security, particularly in urban areas.We found that institutional quality can have a significant positive impact on food security and can mitigate the negative effects of extreme weather events on food security. Our study also decomposed the food security index into its four components and found that extreme weather events negatively affect the affordability, availability, quality, and natural resource resilience of food. The findings are robust to the use of the feasible generalized least squares and panel-corrected standard errors estimation techniques.The policy implications of our study are significant, as our findings suggest that central governments can take practical steps to minimize the impact of extreme weather events on food security. Specifically, investing in disaster preparedness, improving infrastructure, and promoting agricultural development can all help improve food security. Additionally, improving institutional quality can be an effective way to mitigate the negative impact of extreme weather events on food security.

Background and Aims: Fecal urgency is a common symptom of Ulcerative Colitis (UC). We explored the association between changes in fecal urgency for patient characteristics and evaluated the association between change in treatment and change in fecal urgency. Methods: The study cohort (n = 400) included UC patients in the CorEvitas Inflammatory Bowel Disease Registry between May 3, 2017 and September 1, 2020. Fecal urgency was defined using the Simple Clinical Colitis Activity Index. Urgency groups were formed by urgency at enrollment and 6-month follow-up visit: no persistent urgency at both visits (NPU); change from urgency to no urgency (UN); change from no urgency to urgency (NU); and persistent urgency at both visits (PU). Descriptive statistics were used to explore between urgency group differences at baseline and Kaplan-Meier curves to compare time to first treatment change. Results: Groups included NPU (n = 175), UN (n = 86), NU (n = 56), and PU (n = 83). At enrollment, we found differences between groups for increased depression, anxiety, prior infections, diabetes; also, greater fatigue, pain, work impairment, work hours affected, and daily activities impacted. Compared to NPU patients, UN, NU, and PU patients were more likely to change treatment between enrollment and 6-month follow-up visit, and a higher proportion of UN, NU, and PU patients on a biologic at enrollment changed treatment vs the NPU group between both visits. Conclusion: Among real-world UC patients, fecal urgency status is associated with increased comorbidities and worse patient-reported outcomes and significant differences in change of treatment and time to treatment change. Urgency at any time point diminishes quality of life and may be a sign of inadequate therapy, which often is an indication to switch therapy.

Background and Aims: This study aimed to evaluate adherence to subcutaneous biologic therapy and impact of nonadherence including risk factors and outcomes in academic centers with integrated specialty pharmacies for patients with inflammatory bowel disease (IBD). Methods: This was a multicenter, retrospective cohort analysis of patients aged ≥18 years receiving care in 3 tertiary care outpatient IBD clinics with integrated specialty pharmacies. Subjects were prescribed injectable anti-TNF therapy (adalimumab, certolizumab, golimumab) or anti-IL 12/23 therapy (ustekinumab) with at least 3 consecutive prescription claims. The primary outcomes were medication possession ratio (MPR), percent achieving optimal adherence (MPR > 0.86); in addition, we sought to verify a prior risk factor model including smoking status, narcotic use, psychiatric history, and prior biologic use. Secondary outcomes included emergency department visits (ED) and IBD-related hospitalizations. Statistical analysis was performed using Wilcox rank sum test, Pearson’s Chi-squared test, and logistic regression model as an unordered, factor variable to flexibly estimate the probabilities of adherence. Results: Six hundred eight subjects were included. Overall median MPR was 0.95 (interquartile range 0.47, 1) and adherence was 68%–70%. When the number of risk factors for nonadherence increased, the likelihood of nonadherence increased (P < .05). In unadjusted and adjusted analysis, nonadherence increased the likelihood of ED visits [rate ratio 1.45 (95% confidence interval 1.05, 1.97)] and hospitalizations [rate ratio 1.60 (95% confidence interval 1.16, 2.10)]. Conclusion: Academic centers with integrated pharmacies had high adherence. Prior risk factors for nonadherence remained significant in this multicenter model. Nonadherence was associated with higher likelihood of hospitalizations and ED visits.

The liver plays a central role in the pharmacokinetics of drugs through drug metabolizing enzymes and transporters. Non-alcoholic steatohepatitis (NASH) causes disease-specific alterations to the absorption, distribution, metabolism, and excretion (ADME) processes, including a decrease in protein expression of basolateral uptake transporters, an increase in efflux transporters, and modifications to enzyme activity. This can result in increased drug exposure and adverse drug reactions (ADRs). Our goal was to predict drugs that pose increased risks for ADRs in NASH patients. Bibliographic research identified 71 drugs with reported ADRs in patients with liver disease, mainly non-alcoholic fatty liver disease (NAFLD), 54 of which are known substrates of transporters and/or metabolizing enzymes. Since NASH is the progressive form of NAFLD but is most frequently undiagnosed, we identified other drugs at risk based on NASH-specific alterations to ADME processes. Here, we present another list of 71 drugs at risk of pharmacokinetic disruption in NASH, based on their transport and/or metabolism processes. It encompasses drugs from various pharmacological classes for which ADRs may occur when used in NASH patients, especially when eliminated through multiple pathways altered by the disease. Therefore, these results may inform clinicians regarding the selection of drugs for use in NASH patients.

Abstract The ongoing pandemic of severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2) and subsequently, coronavirus disease 2019 (COVID‐19), has led to the deaths of over 6.1 million people and sparked a greater interest in virology to expedite the development process for antivirals. The US Food and Drug Administration (FDA) granted emergency use authorization for three antivirals: remdesivir, molnupiravir, and nirmatrelvir. Remdesivir and molnupiravir are nucleoside analogs that undergo biotransformation to form active metabolites that incorporate into new viral RNA to stall replication. Unlike remdesivir or molnupiravir, nirmatrelvir is a protease inhibitor that covalently binds to the SARS‐CoV‐2 3C‐like protease to interrupt the viral replication cycle. A recent study identified that remdesivir and the active metabolite of molnupiravir, EIDD‐1931, are substrates of equilibrative nucleoside transporters 1 and 2 (ENT1 and 2). Despite the ubiquitous expression of the ENTs, the preclinical efficacy of remdesivir and molnupiravir is not reflected in wide‐scale SARS‐CoV‐2 clinical trials. Interestingly, downregulation of ENT1 and ENT2 expression has been shown in lung epithelial and endothelial cells in response to hypoxia and acute lung injury, although it has not been directly studied in patients with COVID‐19. It is possible that the poor efficacy of remdesivir and molnupiravir in these patients may be partially attributed to the repression of ENTs in the lungs, but further studies are warranted. This study investigated the interaction between nirmatrelvir and the ENTs and found that it was a poor inhibitor of ENT‐mediated [3H]uridine uptake at 300 μM. Unlike for remdesivir or EIDD‐1931, ENT activity is unlikely to be a factor for nirmatrelvir disposition in humans; however, whether this contributes to the similar in vitro and clinical efficacy will require further mechanistic studies.

The paper investigates the co-movement of COVID-19 pandemic and performance of stock markets of four emerging economies. The Quantile-on-Quantile regression model was applied to daily share prices of stock markets from March 13, 2020 to November 30, 2021 in these economies. The results indicate varied relationships across various quantiles of COVID-19 cases and share prices. Whilst both positive and negative relationships are established at different quantiles of share prices for Brazil and Kenya, negative co-movements are recorded for India and South Africa for all quantiles of share prices. The varying dependence between COVID-19 and stock markets provide critical insights to policy makers.

Adolescent idiopathic scoliosis is a common condition that affects children between the age of 10 and young adulthood. Rigid brace treatment is an effective treatment to control the progression of spinal deformity. However, it limits mobility and causes discomfort, which leads to low treatment compliance. In this study, we developed and characterized a kirigami-inspired CT/MRI compatible spring that could be employed to modify our previously designed exoskeleton hinge vertebrae to provide immediate in-brace correction, good wear comfort, and one that does not inhibit mobility simultaneously. Additive manufacturing has drawn significant interest in academic and industrial terms due to its ability to produce geometrically complex structures. The structural design and dimension of the proposed 3D printed kirigami-inspired springs were optimized with the finite element method (FEM). The carbon-fiber-reinforced nylon material (PA-CF) was selected as the material of the kirigami-inspired spring with the balance of printing easiness and performance of the material. The stiffness of designed kirigami-inspired springs varied between 1.20 and 42.01 N/mm. A case series study with three scoliosis patients has been conducted to investigate the immediate in-brace effect on reducing the spinal curvature and asymmetry of the body contours using radiographic examination. The experiment results show that there are 4.6%–50.5% improvements in Cobb angle for different sections of spines. The X-ray images proved that our kirigami-inspired springs would not block views for Cobb angle measurements.

Temporal bone fracture is a relatively rare but significant complication of traumatic head injury. We present a rare and unique case of traumatic temporal bone fracture with middle ear effusion, in a 76-year-old woman, following a fall. Physical examination on presentation was remarkable for a superficial scalp hematoma in the occipital region, without any focal neurological deficits. An initial non-contrast head CT revealed a large posterior scalp hematoma and subtle changes suggestive of artifact vs. hemorrhage within the right temporal lobe. Over two days, she developed a worsening headache, with new hearing impairment and reduced right sided bone-conduction on auditory testing. A repeat head CT confirmed a right hemorrhagic temporal lobe contusion as well as a right mastoid and middle ear effusion. A dedicated temporal bone CT scan was performed, which revealed an acute longitudinal fracture through the right mastoid bone without extension into the middle ear cavity. She was evaluated by neurosurgery, managed symptomatically, and observed closely. Her neurological status remained stable, and she was discharged with planned outpatient follow-up with her primary care provider and the consulting neurosurgeon. This case illustrates sequalae of traumatic temporal bone fracture, as well as the value of clinical history and heightened clinical concern for an occult, easily overlooked region during imaging.

Early detection and prompt response are key factors in the eradication of ‘huanglongbing’ (HLB) in California. Currently, qPCR testing of leaf tissue guides the removal of infected trees. However, because of the uneven distribution of ‘Candidatus Liberibacter asiaticus’ (CLas) in an infected tree and asymptomatic infection, selecting the best leaves to sample, from a mature tree with more than 200,000 estimated leaves, is a major hurdle for timely detection. The goal of this study was to address this issue by testing alternative tissues that might improve the CLas detection rate. Using two years of field data, old and young leaves, peduncle bark of fruit, and feeder roots were evaluated for the presence of CLas. Quadrant-peduncle (Q-P) tissue sampling consistently resulted in better CLas detection than any other tissue type. Q-P samples had a 30% higher qPCR positivity rate than quadrant-leaf (Q-L) samples. No significant seasonal patterns were observed. Roots and single peduncles had similar detection rates; both were higher than single leaves or Q-L samples. If symptoms were used to guide sampling, 30% of infected trees would have been missed. Taken together, these results suggest that Q-P tissue sampling is the optimal choice for improved CLas detection under California growing conditions.

Background and Aims: This study aimed to evaluate associations between disease severity, patient-reported outcomes (PROs), and work productivity in patients with inflammatory bowel disease (IBD [Crohn’s disease (CD) and ulcerative colitis (UC)]). Methods: Patients diagnosed with CD or UC enrolled in CorEvitas’ IBD Registry (May 2017 to September 2019) were included (N = 1543; CD, n = 812; UC, n = 731). Disease severity was assessed using the Harvey-Bradshaw Index (CD) and partial Mayo Score (UC); psychosocial PROs (Patient-Reported Outcomes Measurement Information System [PROMIS]) and work productivity (Work Productivity and Activity Impairment [WPAI]) were assessed. Univariable and multivariable regression analyses assessed associations between PROs and disease severity. Results: Among CD patients, 67.4% were in remission, 19.2% had mild disease, and 13.4% had moderate/severe disease; among UC patients, 52.7% were in remission, 35.3% had mild disease, and 12.0% had moderate/severe disease. For CD patients in remission, unadjusted percentages of patients with PROMIS scores outside normal limits ranged from 18.9% (depression) to 34.9% (fatigue). For CD patients in remission, 54.3% reported work productivity loss, and 57.1% reported activity impairment. The unadjusted percentage of UC patients in remission with scores outside normal limits ranged from 15.7% (depression) to 28.7% (fatigue) for PROMIS and 10.5% (absenteeism) to 43.5% (activity impairment) for WPAI. Impairment increased with IBD severity. Congruently, adjusted estimates showed significant impairment in PROMIS and WPAI scores for CD and UC patients in remission. Conclusion: In this real-world analysis, IBD patients across the spectrum of activity, from remission to severe disease, experienced impaired psychosocial function and reduced work productivity. Impairment, even among patients in remission, indicates an unmet need in this patient population.

The local onion market in Ghana is dominated by ‘on the spot’ market relationships with little or no coordination of chains to improve quality and performance. This study examines the market structure, conduct and their influence on the performance of the onion market in the southern part of Ghana, using data from 180 actors, comprising 80 farmers, 40 wholesalers and 60 retailers. Descriptive statistics, Gini coefficient, Lorenz curve, Herfindahl-Hirschman index and Garett ranking were the methods of analysis used. The results showed that traders were operating in an oligopolistic market with Gini coefficients of 0.62 and 0.56 for wholesalers and retailers, respectively. The findings also revealed that farmers (69%) were more open to contracts than wholesalers (20%) and retailers (11%). Moreover, onion production proved to be costly for farmers as they had a negative return of 1.55% on their investment while wholesalers and retailers made positive returns of 29.85% and 31.1%, respectively. Finally, high production cost, high marketing cost and unavailability of storage structures were ranked as the most pressing constraints to farmers, wholesalers and retailers, respectively. It is recommended that the government, donor support agencies for agriculture and local NGOs come to the aid of farmers by providing them with fixed assets at a subsidized price. This will relieve the farmers from heavy losses which threaten the future food security of the country.

Microscopic identification of Plasmodium spp. is the gold standard for malaria diagnosis. However, malaria rapid diagnostic test kits are also available for prompt diagnosis. This study evaluated four routinely used malaria rapid diagnostic test kits at the Enyiresi Government Hospital in the Eastern Region of Ghana. This cross-sectional study was conducted among 238 patients suspected of malaria. Venous blood samples were collected to identify Plasmodium falciparum using microscopic techniques. Further, the performances of four malaria rapid diagnostic test kits, First Response Malaria Ag Pf, Carestart Malaria Pf, SD Bioline Ag Pf, and ABON Malaria Pf, were evaluated using the results from the microscopy as the standard reference. As confirmed by microscopy, 65.5% (156/238) of the patients have falciparum malaria. All malaria rapid diagnostic test kits had sensitivities and specificities over 75% compared to microscopy results as the reference standard. However, the SD Bioline Ag Pf kit recorded the highest agreement with the microscopy (Cohen’s kappa=0.879). All the malaria rapid diagnostic test kits performed quite well and can be used in emergencies. However, results from these kits need to be confirmed by microscopy.

Social capital concept has become popular over the past decades. What is not known in literature and worth investigating is the network designs and nature that enhance the development of new learning ideas and knowledge creation. The aim of the paper is to examine network structure dimensions, namely centrality (bonding) and structural holes (bridging or looser ties) of social capital formed within higher education networks that stimulate the development of new ideas and knowledge creation of the participants in the networks across multiple domains of science. This study employs negative binomial regression on a sample of participants within a higher education network to predict the development of new ideas and knowledge creation. The results show that the different features of social capital dimensions influence the development of new ideas and knowledge creation of the participants in the networks differently. Specifically, the study reveals that the brokerage network appears to be more relevant than cohesion in the Ghanaian higher education institution networks. When knowledge creation is decomposed into different fields of science, Health Science is found to be the most productive. The decomposing of the knowledge creation into different fields of science remains a value of this study.

The visualisation of the bone metastasis process in a spatial temporal manner is lacking. Here, the authors use three-dimensional quantitative imaging and show that mouse mammary tumour cells preferentially home to endothelial subtype type H vessels within the bone marrow and remodel this vasculature by producing granulocyte-colony stimulating factor.

Background Corticosteroids are the mainstay of treatment for immune checkpoint inhibitor-associated acute kidney injury (ICPi-AKI), but the optimal duration of therapy has not been established. Prolonged use of corticosteroids can cause numerous adverse effects and may decrease progression-free survival among patients treated with ICPis. We sought to determine whether a shorter duration of corticosteroids was equally efficacious and safe as compared with a longer duration.Methods We used data from an international multicenter cohort study of patients diagnosed with ICPi-AKI from 29 centers across nine countries. We examined whether a shorter duration of corticosteroids (28 days or less) was associated with a higher rate of recurrent ICPi-AKI or death within 30 days following completion of corticosteroid treatment as compared with a longer duration (29–84 days).Results Of 165 patients treated with corticosteroids, 56 (34%) received a shorter duration of treatment and 109 (66%) received a longer duration. Patients in the shorter versus longer duration groups were similar with respect to baseline and ICPi-AKI characteristics. Five of 56 patients (8.9%) in the shorter duration group and 12 of 109 (11%) in the longer duration group developed recurrent ICPi-AKI or died (p=0.90). Nadir serum creatinine in the first 14, 28, and 90 days following completion of corticosteroid treatment was similar between groups (p=0.40, p=0.56, and p=0.89, respectively).Conclusion A shorter duration of corticosteroids (28 days or less) may be safe for patients with ICPi-AKI. However, the findings may be susceptible to unmeasured confounding and further research from randomized clinical trials is needed.

Abstract Background Over the past few years, there has been growing public and research interest in adolescents’ experiences with various forms of bullying victimisation because of their psychological, emotional, and/ or physical consequences. The present study examined the prevalence of bullying victimisation and its associated factors among in-school adolescents in sub-Saharan Africa. Methods Using data from the Global School-based Health Survey (GSHS) from 2010 to 2017 of eleven sub-Saharan African countries, a sample of 25,454 in-school adolescents was used for analysis. Statistical analyses included frequencies, percentages, Pearson chi-square and multivariable logistic regression. Results were presented as adjusted odds ratios (aOR) at 95% confidence intervals (CIs). Results The overall prevalence of bullying victimisation among the respondents was 38.8%. The prevalence was lowest in Mauritius (22.2%) and highest in Sierra Leone (54.6%). Adolescents who felt lonely [aOR = 1.66, 95% CI = 1.53, 1.80], had history of anxiety [aOR = 1.53, 95% CI = 1.41, 1.66], suicidal ideation [aOR = 1.28, 95% CI = 1.17, 1.39], suicidal attempt [aOR = 1.86, 95% CI = 1.72, 2.02], current users of marijuana [aOR = 1.59, 95% CI = 1.38, 1.84], and truants at [aOR = 1.43, 95% CI = 1.34, 1.52] were more likely to be victims of bullying. Conversely, adolescents who had peer support were less likely to be victims of bullying [aOR = 0.78, 95% CI = 0.73, 0.82]. Adolescents aged 15 years or older had lower odds of experiencing bullying victimization compared to their counterparts aged 14 years or younger [aOR = 0.74, 95% CI = 0.69, 0.78]. Conclusion Our findings suggest that age, loneliness, anxiety, suicidal ideation, suicidal attempt, and current use of marijuana are associated with increased risk of bullying victimisation. School-wide preventative interventions (e.g., positive behavioural strategies- Rational Emotive Behavioral Education, [REBE], peer educator network systems, face-face counseling sessions, substance use cessation therapy) are essential in promoting a positive school climate and reduce students’ bullying victimisation behaviours.

Abstract Background There has recently been considerable interest in better understanding how blood pressure should be managed after an episode of hospitalized AKI, but there are scant data regarding the associations between blood pressure measured after AKI and subsequent adverse outcomes. We hypothesized that among AKI survivors, higher blood pressure measured three months after hospital discharge would be associated with worse outcomes. We also hypothesized these associations between blood pressure and outcomes would be similar among those who survived non-AKI hospitalizations. Methods We quantified how systolic blood pressure (SBP) observed three months after hospital discharge was associated with risks of subsequent hospitalized AKI, loss of kidney function, mortality, and heart failure events among 769 patients in the prospective ASSESS-AKI cohort study who had hospitalized AKI. We repeated this analysis among the 769 matched non-AKI ASSESS-AKI enrollees. We then formally tested for AKI interaction in the full cohort of 1538 patients to determine if these associations differed among those who did and did not experience AKI during the index hospitalization. Results Among 769 patients with AKI, 42 % had subsequent AKI, 13 % had loss of kidney function, 27 % died, and 18 % had heart failure events. SBP 3 months post-hospitalization did not have a stepwise association with the risk of subsequent AKI, loss of kidney function, mortality, or heart failure events. Among the 769 without AKI, there was also no stepwise association with these risks. In formal interaction testing using the full cohort of 1538 patients, hospitalized AKI did not modify the association between post-discharge SBP and subsequent risks of adverse clinical outcomes. Conclusions Contrary to our first hypothesis, we did not observe that higher stepwise blood pressure measured three months after hospital discharge with AKI was associated with worse outcomes. Our data were consistent with our second hypothesis that the association between blood pressure measured three months after hospital discharge and outcomes among AKI survivors is similar to that observed among those who survived non-AKI hospitalizations.

Summary: Autism spectrum disorder (ASD) is diagnosed three to four times more frequently in males than in females. Genetic studies of rare variants support a female protective effect (FPE) against ASD. However, sex differences in common inherited genetic risk for ASD are less studied, particularly within families. Leveraging the Danish iPSYCH resource, we found siblings of female ASD cases (n = 1,707) had higher rates of ASD than siblings of male ASD cases (n = 6,270; p

Abstract Background Previous studies found that exercise interventions have positive effects on executive functions of the general population. However, studies seldom target executive functions of children and adolescents with attention-deficit hyperactivity disorder (ADHD). This study aimed to synthesise empirical studies regarding the effects of exercise interventions on executive functions of children and adolescents with ADHD. Methods A systematic search of the relevant literature was conducted in March 2020 through six electronic databases: CINAHL Complete, Eric, MEDLINE, PsychINFO, SPORTDiscus with Full Text, and Web of Science. Randomised controlled trials/quasi-experimental designs that applied exercise interventions and assessed executive functions through neurocognitive tasks among children and adolescents with ADHD were included. Altogether, 314 studies were identified, from which 31 full texts were independently assessed by two authors for eligibility. Finally, 21 studies underwent systematic reviews and 15 were selected for meta-analysis. Data extraction procedures and risk of bias analysis were conducted by two independent authors using the Physiotherapy Evidence Database (PEDro) scale. Results The findings indicated that exercise interventions improved overall executive functions of children and adolescents with ADHD (SMD = 0.611, 95% CI [0.386 to 0.836], p

While the impact of the COVID-19 pandemic has been felt around the world, Miami, Florida is one example of the specific and unique ways in which this pandemic is experienced. Drawing on the concepts of visual culture analysis and disaster literature, this article analyses how the COVID-19 pandemic transformed the everyday lives of people living in this subtropical American city. Specifically, this study draws on data collected from a digital participatory photography project implemented in July 2020, as the novel coronavirus began to rapidly spread. Through an inductive thematic analysis of participants’ photographs and captions, we discovered that the COVID-19 pandemic transformed not only basic daily needs but also lead to recognition of privilege and an awareness of the needs and vulnerabilities of others. While many of the complexities illustrated in this study are left unresolved, the photos and captions are useful examples of how visual depictions can be used to inform and realign the ways in which people interpret and respond to global public health crises.

Abstract Background Wearable ankle robotics could potentially facilitate intensive repetitive task-specific gait training on stair environment for stroke rehabilitation. A lightweight (0.5 kg) and portable exoskeleton ankle robot was designed to facilitate over-ground and stair training either providing active assistance to move paretic ankle augmenting residual motor function (power-assisted ankle robot, PAAR), or passively support dropped foot by lock/release ankle joint for foot clearance in swing phase (swing-controlled ankle robot, SCAR). In this two-center randomized controlled trial, we hypothesized that conventional training integrated with robot-assisted gait training using either PAAR or SCAR in stair environment are more effective to enhance gait recovery and promote independency in early stroke, than conventional training alone. Methods Sub-acute stroke survivors (within 2 months after stroke onset) received conventional training integrated with 20-session robot-assisted training (at least twice weekly, 30-min per session) on over-ground and stair environments, wearing PAAR (n = 14) or SCAR (n = 16), as compared to control group receiving conventional training only (CT, n = 17). Clinical assessments were performed before and after the 20-session intervention, including functional ambulatory category as primary outcome measure, along with Berg balance scale and timed 10-m walk test. Results After the 20-session interventions, all three groups showed statistically significant and clinically meaningful within-group functional improvement in all outcome measures (p

ADHD is often found to be comorbid with disruptive behavior disorders, but the genetic loci underlying this comorbidity are unknown. Here, the authors have performed a GWAS meta-analysis of ADHD with disruptive behavior disorders, finding three genome-wide significant loci in Europeans, and replicating one in a Chinese cohort.

Tensor regression is an important and useful tool for analyzing multidimensional array data. To deal with high dimensionality, CANDECOMP/PARAFAC (CP) low-rank constraints are often imposed on the coefficient tensor parameter in the (penalized) loss functions. However, besides the well-known non-identifiability issue of the CP parameters, we demonstrate that the corresponding optimization may not have any attainable solutions, and thus the estimation of the coefficient tensor is not well-defined when this happens. This is closely related to a phenomenon, called CP degeneracy, in low-rank tensor approximation problems. In this article, we show some useful results of CP degeneracy in the context of tensor regression problems. To overcome the theoretical and numerical issues associated with the degeneracy, we provide a general penalized strategy as a solution to the degeneracy. The related results also explain why some of the existing methods are more stable than the others. The asymptotic properties of the resulting estimation are also studied. Numerical experiments are conducted to illustrate our findings.

Inflammatory bowel disease, consisting of Crohn’s disease and ulcerative colitis, causes chronic gastrointestinal symptoms and can lead to morbidity and mortality if uncontrolled or untreated. However, for patients with moderate-to-severe disease, currently available therapies do not induce or maintain remission in >50% of patients. This underscores the need for additional therapies. In this review, the authors detail the novel therapies vedolizumab, tofacitinib, and ustekinumab and delve into therapies which may come onto the market within the next 10 years, including JAK-1 inhibitors (filgotinib and upadacitinib), IL-23 inhibitors (guselkumab, mirikizumab, and risankizumab), the anti-β4β7 and anti-βEβ7 integrin monoclonal antibody etrolizumab, the sphingosine-1-phosphate subtypes 1 and 5 modulator ozanimod, and mesenchymal stem cells. Further studies are required before these emerging therapies gain approval.

BackgroundElectrical impedance myography (EIM) has been applied to assess muscle health conditions in neuromuscular disorders. This study aimed to detect immediate muscle electrical impedance property alterations in lower extremity of chronic stroke survivors immediately after functional electrical stimulation (FES)-assisted cycling training.MethodsFourteen chronic stroke survivors were recruited for the current study. EIM measurements were conducted before and immediately after 40-min FES-assisted cycling training for each subject. Four interested muscle groups [rectus femoris (RF), biceps femoris (BF), tibialis anterior (TA), and the medial head of gastrocnemius (MG)] were selected. Correlation analysis was performed to reveal a significant correlation between changes in EIM parameters and clinical scales [Fugl–Meyer Assessment of the lower extremity (FMA-LE); 6-min walking test (6MWT)].ResultsImmediately after training, reactance (X) and phase angle (θ) values significantly increased on the TA and MG muscles. Significant correlation was observed between X value and FMA-LE scores (r = 0.649, p = 0.012) at MG as well as X and FMA scores of the ankle joint (r = 0.612, p = 0.02). Resistance (R) and θ were significantly correlated with 6MWT score (R-6MWT: r = 0.651, p = 0.012; θ-6MWT: r = 0.621, p = 0.018).ConclusionThis brief report demonstrated that EIM can reveal the intrinsic property alteration in the paretic muscle of chronic stroke survivors immediately after FES-assisted cycling training. These alterations might be related to muscle hypertrophy (i.e., increases in muscle fiber size). This brief report might aid the understanding of the mechanism of electrical stimulation-assisted exercise in improving muscle function of stroke survivors.

Abstract In recent years, research using biomaterials in drilling fluid design has thrown light on their biodegradability, availability and low cost. Apart from these, they have in some cases shown properties superior to those of synthetic materials. This research assessed Mucuna solannie as a fluid loss control agent, looking at its fluid loss, filter cake quality, rheology and comparing them with those of Sodium Asphalt Sulfonate, a commonly used drilling mud additive. It assessed the additives at varying concentrations of 2 ppb, 4 ppb, 6 ppb and 8 ppb. The results obtained were filtrate volumes of 5.5 against 4.8 at 2 ppb, 5.0 against 4.5 at 4 ppb, 4.5 against 4.2 at 6 ppb, and 4.1 against 3.8 at 8 ppb, all at 30 min. Field standard value is 5.0 ml fluid loss. Filter cake thickness was1mm for all concentrations of Mucuna solannie. On rheology, plastic viscosity, yield point and yield stress were 27cP against 28cP, 19Ib/100ft2 against 19Ib/100ft2, and 5Ib/100ft2 against 6Ib/100ft2, showing slight difference in their rheological properties.

Abstract Background There is considerable state-level variation in the incidence of dialysis-requiring acute kidney injury (AKI-D). However, little is known about reasons for this geographic variation. Methods National cross-sectional state-level ecological study based on State Inpatient Databases (SID) and the Behavioral Risk Factor Surveillance System (BRFSS) in 2011. We analyzed 18 states and six chronic health conditions (diabetes mellitus [diabetes], hypertension, chronic kidney disease [CKD], arteriosclerotic heart disease [ASHD], cancer (excluding skin cancer), and chronic obstructive pulmonary disease [COPD]). Associations between each of the chronic health conditions and AKI-D incidence was assessed using Pearson correlation and multiple regression adjusting for mean age, the proportion of males, and the proportion of non-Hispanic whites in each state. Results The state-level AKI-D incidence ranged from 190 to 1139 per million population. State-level differences in rates of hospitalization with chronic health conditions (mostly

This study examined the mediating role of sleep in the relationship between physical activity and executive function in children with attention deficit hyperactivity disorder (ADHD). Fifty-six children with ADHD were recruited from Shenzhen Children's Hospital. Participants wore an accelerometer for seven consecutive days to measure physical activity and sleep quality. Activity counts were analyzed to measure moderate-to-vigorous physical activity (MVPA). Four sleep parameters, including sleep latency (SL), sleep efficiency, total sleep time, and wake after sleep onset were recorded from the actigraph. Three core executive functions, inhibitory control; working memory (WM); and cognitive flexibility (CF), were assessed from computer-based tasks: the flanker task, and the Tower of London and Trail Making Tests, respectively. The regression results showed that MVPA was negatively associated with SL (−0.169; 95%CI [−0.244, −0.112]). WM (total scores) was positively related to MVPA (0.028, 95%CI [0.008, 0.048]), but negatively related to SL (−0.105, 95%CI [−0.167, −0.030]). CF (part B errors) was negatively associated with MVPA (−0.031, 95%CI [−0.055, −0.005]) and positively correlated with SL (0.184, 95%CI [0.092, −0.260]). The indirect effect of SL was found for MVPA and WM (0.018, 95%CI [0.015, 0.034]), supporting the indirect partial mediation. Similarly, the indirect effect of SL was found between MVPA and CF (−0.031, 95%CI [−0.060, −0.012]), supporting the indirect partial mediation. The mediating role of SL in children with ADHD suggests that the intensity of physical activity plays a key role in linking sleep quality and executive function in this group.

Background Immune checkpoint inhibitor-associated acute kidney injury (ICPi-AKI) has emerged as an important toxicity among patients with cancer.Methods We collected data on 429 patients with ICPi-AKI and 429 control patients who received ICPis contemporaneously but who did not develop ICPi-AKI from 30 sites in 10 countries. Multivariable logistic regression was used to identify predictors of ICPi-AKI and its recovery. A multivariable Cox model was used to estimate the effect of ICPi rechallenge versus no rechallenge on survival following ICPi-AKI.Results ICPi-AKI occurred at a median of 16 weeks (IQR 8–32) following ICPi initiation. Lower baseline estimated glomerular filtration rate, proton pump inhibitor (PPI) use, and extrarenal immune-related adverse events (irAEs) were each associated with a higher risk of ICPi-AKI. Acute tubulointerstitial nephritis was the most common lesion on kidney biopsy (125/151 biopsied patients [82.7%]). Renal recovery occurred in 276 patients (64.3%) at a median of 7 weeks (IQR 3–10) following ICPi-AKI. Treatment with corticosteroids within 14 days following ICPi-AKI diagnosis was associated with higher odds of renal recovery (adjusted OR 2.64; 95% CI 1.58 to 4.41). Among patients treated with corticosteroids, early initiation of corticosteroids (within 3 days of ICPi-AKI) was associated with a higher odds of renal recovery compared with later initiation (more than 3 days following ICPi-AKI) (adjusted OR 2.09; 95% CI 1.16 to 3.79). Of 121 patients rechallenged, 20 (16.5%) developed recurrent ICPi-AKI. There was no difference in survival among patients rechallenged versus those not rechallenged following ICPi-AKI.Conclusions Patients who developed ICPi-AKI were more likely to have impaired renal function at baseline, use a PPI, and have extrarenal irAEs. Two-thirds of patients had renal recovery following ICPi-AKI. Treatment with corticosteroids was associated with improved renal recovery.

Abstract Acute lymphoblastic leukemia (ALL) is the most common cancer in children and adolescents. Although the 5‐year survival rate is high, some patients respond poorly to chemotherapy or have recurrence in locations such as the testis. The blood–testis barrier (BTB) can prevent complete eradication by limiting chemotherapeutic access and lead to testicular relapse unless a chemotherapeutic is a substrate of drug transporters present at this barrier. Equilibrative nucleoside transporter (ENT) 1 and ENT2 facilitate the movement of substrates across the BTB. Clofarabine is a nucleoside analog used to treat relapsed or refractory ALL. This study investigated the role of ENTs in the testicular disposition of clofarabine. Pharmacological inhibition of the ENTs by 6‐nitrobenzylthioinosine (NBMPR) was used to determine ENT contribution to clofarabine transport in primary rat Sertoli cells, in human Sertoli cells, and across the rat BTB. The presence of NBMPR decreased clofarabine uptake by 40% in primary rat Sertoli cells (p = .0329) and by 53% in a human Sertoli cell line (p = .0899). Rats treated with 10 mg/kg intraperitoneal (IP) injection of the NBMPR prodrug, 6‐nitrobenzylthioinosine 5′‐monophosphate (NBMPR‐P), or vehicle, followed by an intravenous (IV) bolus 10 mg/kg dose of clofarabine, showed a trend toward a lower testis concentration of clofarabine than vehicle (1.81 ± 0.59 vs. 2.65 ± 0.92 ng/mg tissue; p = .1160). This suggests that ENTs could be important for clofarabine disposition. Clofarabine may be capable of crossing the human BTB, and its potential use as a first‐line treatment to avoid testicular relapse should be considered.

Abstract Background Approximately 4–6% of incident end stage renal disease (ESRD) patients in the U.S. recover enough kidney function to discontinue dialysis but there is considerable geographic variation. We undertook this study to investigate whether state-level variations in renal recovery among incident ESRD patients correlated with state-level variations in incidence of acute kidney injury requiring dialysis (AKI-D). Methods We conducted a national cross-sectional ecological study at the state-level using data from State Inpatient Databases and U.S. Renal Data System. All hospital admissions and all ESRD patients in 18 US states (AZ, AR, CA, FL, IA, KY, MA, MD, MI, NJ, NM, NY, NV, OR, RI, SC, VT, and WA) were included. Correlation between AKI-D incidence and rate of renal recovery across states was determined using Pearson’s r (overall and in subgroups). We also calculated partial correlations adjusted for sex and age. Results AKI-D incidence ranged from 99.0 per million population (pmp) in Vermont to 490.4 pmp in Nevada. Rate of renal recovery among incident ESRD patients ranged from 8.8 pmp in Massachusetts to 29.3 pmp in Florida. A positive correlation between AKI-D incidence and rate of renal recovery among incident ESRD patients at state level was found overall (unadjusted r = 0.67; p = 0.002) and in age, sex, and race subgroups. The overall correlation persisted after adjusting for age (adjusted r = 0.62; p

Introduction: After dialysis-requiring acute kidney injury (AKI-D), recovery of sufficient kidney function to discontinue dialysis is an important clinical and patient-oriented outcome. Predicting the probability of recovery in individual patients is a common dilemma. Methods: This cohort study examined all adult members of Kaiser Permanente Northern California who experienced AKI-D between January 2009 and September 2015 and had predicted inpatient mortality of

The creation and application of PET nanofibrils for PP composite reinforcement were studied. PET nanofibrils were fibrillated within a PP matrix using a spunbond process and then injection molded to test for the end-use properties. The nanofibril reinforcement helped to provide higher tensile and flexural performance in solid (unfoamed) injection molded parts. With foam injection molding, the nanofibrils also helped to improve and refine the microcellular morphology, which led to improved performance. Easily and effectively increasing the strength of a polymeric composite is a goal for many research endeavors. By creating nanoscale fibrils within the matrix itself, effective bonding and dispersion have already been achieved, overcoming the common pitfalls of fiber reinforcement. As blends of PP and PET are drawn in a spunbond system, the PET domains are stretched into nanoscale fibrils. By adapting the spunbonded blends for use in injection molding, both solid and foamed nanocomposites are created. The injection molded nanocomposites achieved increased in both tensile and flexural strength. The solid and foamed tensile strength increased by 50 and 100%, respectively. In addition, both the solid and foamed flexural strength increased by 100%. These increases in strength are attributed to effective PET nanofibril reinforcement.

BackgroundLittle is known about factors associated with recovery of kidney function-and return to dialysis independence-or temporal trends in recovery after starting outpatient dialysis in the United States. Understanding the characteristics of individuals who may have the potential to recover kidney function may promote better recognition of such events. The goal of this study was to determine factors associated with recovery of kidney function in children compared with adults starting dialysis in the US.Methods and findingsWe determined factors associated with recovery of kidney function-defined as survival and discontinuation of dialysis for ≥90-day period-in children versus adults who started maintenance dialysis between 1996 and 2015 according to the United States Renal Data System (USRDS) followed through 2016 in a retrospective cohort study. We also examined temporal trends in recovery rates over the last 2 decades in this cohort. Among 1,968,253 individuals included for study, the mean age was 62.6 ± 15.8 years, and 44% were female. Overall, 4% of adults (83,302/1,953,881) and 4% of children (547/14,372) starting dialysis in the outpatient setting recovered kidney function within 1 year. Among those who recovered, the median time to recovery was 73 days (interquartile range [IQR] 43-131) in adults and 100 days (IQR 56-189) in children. Accounting for the competing risk of death, children were less likely to recover kidney function compared with adults (sub-hazard ratio [sub-HR] 0.81; 95% CI 0.74-0.89, p-value ConclusionsIn this study, we observed that discontinuation of outpatient dialysis due to recovery occurred in 4% of patients with end-stage kidney disease (ESKD) and was more common among those with ATN or AIN as the cause of their kidney disease. While recovery rates rose initially, they declined starting in 2010. Additional studies are needed to understand how to best recognize and promote recovery in patients whose potential to discontinue dialysis is high in the outpatient setting.

Hand function improvement in stroke survivors in the chronic stage usually plateaus by 6 months. Brain-computer interface (BCI)-guided robot-assisted training has been shown to be effective for facilitating upper-limb motor function recovery in chronic stroke. However, the underlying neuroplasticity change is not well understood. This study aimed to investigate the whole-brain neuroplasticity changes after 20-session BCI-guided robot hand training, and whether the changes could be maintained at the 6-month follow-up. Therefore, the clinical improvement and the neurological changes before, immediately after, and 6 months after training were explored in 14 chronic stroke subjects. The upper-limb motor function was assessed by Action Research Arm Test (ARAT) and Fugl-Meyer Assessment for Upper-Limb (FMA), and the neurological changes were assessed using resting-state functional magnetic resonance imaging. Repeated-measure ANOVAs indicated that long-term motor improvement was found by both FMA (F[2,26] = 6.367, p = 0.006) and ARAT (F[2,26] = 7.230, p = 0.003). Seed-based functional connectivity analysis exhibited that significantly modulated FC was observed between ipsilesional motor regions (primary motor cortex and supplementary motor area) and contralesional areas (supplementary motor area, premotor cortex, and superior parietal lobule), and the effects were sustained after 6 months. The fALFF analysis showed that local neuronal activities significantly increased in central, frontal and parietal regions, and the effects were also sustained after 6 months. Consistent results in FC and fALFF analyses demonstrated the increase of neural activities in sensorimotor and fronto-parietal regions, which were highly involved in the BCI-guided training.Clinical Trial Registration: This study has been registered at ClinicalTrials.gov with clinical trial registration number NCT02323061.

Purpose: This article takes up the view that the Qurʾān was left incomplete as a book and did not take final shape until well after the Prophet’s death. It considers whether this may be deemed valid upon analysis of a type of structural binding occurring in the text. Methodology: The study takes an analytical and historical approach. It examines center-periphery connection between adjacent sūras in various phases of revelation (structural consistency would suggest a single source for the text, whereas inconsistency would imply multiple hands involved in editing). The study furthermore compares results with those from recent statistical and thematic studies. Findings: The research highlights continuity. This accords with recent stylometric analysis of the text, which shows a coherent stylistic trajectory. It also accords with an examination of the theme of jihād in the Qurʾān, which reveals overall consistency and adherence to core principles. Originality: This is the first study to disclose consistency of center-periphery connection in the Qurʾān, strengthening our appreciation of the text’s composition. Furthermore, insofar as this research helps us to perceive links between adjacent sūras, it could aid in textual interpretation. Finally, since the findings call into question the notion that the Qurʾān was arranged later, an updated hypothesis for the early writing and copying of the Qurʾān is presented, taking into account the existence of minor variations in the old codices, the reports about an ʿUthmānic commission issuing a standard text, and the fact that no prototype manuscript has been discovered.

When evaluating a patient with acute onset unilateral leg pain and concurrent inflammatory bowel disease (IBD), keeping a broad differential diagnosis will allow for prompt diagnosis and management. The patient described in this case report is a 32-year-old male with inflammatory ileocolonic Crohn’s disease (CD) status after ileocecectomy with perianal involvement and known Type 1 arthropathy. He presented with a three-day history of unilateral leg swelling and tenderness. Initial evaluation focused on possible thrombosis given the development of erythema and systemic symptoms. Final diagnosis was ruptured Baker’s (popliteal) cyst. This pathology is not well described in existing literature, but should be considered in IBD patients given their chronic inflammatory state and common associated intra-articular pathology.