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Introduction: Fibrolamellar carcinoma (FLC) displays upregulation of several oncogenes, including HER2, and multiple immune-suppressive mechanisms. We investigated the efficacy and safety of the pan-HER tyrosine kinase inhibitor neratinib as monotherapy (SUMMIT phase 2 basket study) or with immune checkpoint and/or mammalian target of rapamycin (mTOR) inhibitors (compassionate-use program) in patients with FLC. Methods: Patients received neratinib 240 mg/day orally in SUMMIT, or as doublet or triplet combinations with pembrolizumab 2 mg/kg intravenously every 3 weeks, nivolumab 240 mg intravenously every 2 weeks, everolimus 7.5 mg/day orally, or sunitinib 37.5 mg/day orally under compassionate use. The primary endpoint in SUMMIT was objective response rate; safety was a secondary endpoint. Results: Fifteen patients with FLC received neratinib monotherapy in SUMMIT. The objective response rate was 5% (95% confidence interval [CI]: 0–21.8) and the disease control rate was 13.3% (95% CI: 1.7–40.5). Upon progression, five had added immune checkpoint inhibitors with or without everolimus or sunitinib. Two additional patients received neratinib-based combinations outside of SUMMIT, for a total of 17 neratinib-treated patients. One patient who received neratinib plus pembrolizumab had a confirmed partial response, one treated with neratinib plus everolimus had stable disease lasting 6 months, and one who received neratinib plus pembrolizumab plus sunitinib had stable disease lasting 16 months. Grade 3/4 adverse events with neratinib monotherapy occurred in 10 (66.7%)/2 (13.3%) patients, respectively. Grade 3 adverse events with neratinib-based combinations were hyperglycemia (n = 1; neratinib plus pembrolizumab), hepatic failure, and anaphylaxis (n = 1 each, neratinib plus pembrolizumab plus everolimus). There were no grade 4 adverse events with combination therapy. Conclusion: In patients with FLC, single-agent neratinib had limited efficacy, but clinical benefit was observed with neratinib in combination with immunotherapy and/or mTOR-targeted agents.

Estimating mortality of sea turtles incidentally captured in fishing gear is essential to understanding fishery impacts on sea turtle populations. Loggerhead turtles (Caretta caretta) are a component of bycatch in pelagic longline fisheries, including those operating in Atlantic Canada. In this study, we used pop-up satellite archival tags (PSATs) attached to 62 loggerhead turtles incidentally hooked in Atlantic Canadian shallow-set pelagic longline gear (2012–2018) to estimate associated post-release survival. Consistent with conventional fishing practices, hooks were not removed from turtles prior to release. Analysis of diving behaviour, ocean temperature, and ambient light level was used to assign fates to turtles. Post-release survival was calculated using the Kaplan-Meier estimator with right censoring. Based on this method, the annual survival probability of an individual loggerhead post-release is 0.877 ± SE 0.052. While it is commonly assumed that hook location is an important variable in predicting fates of turtles after release, there was no difference in survival of deep-hooked (swallowed hook) versus shallow-hooked turtles. These results indicate higher survivorship among hooked loggerheads captured in shallow-set pelagic longline gear than prevailing wisdom and suggest that at least some of the population impacts on loggerhead turtles conventionally attributed to pelagic longline interactions may be linked to other threats.

Communities across the United States and particularly in the Midwest continue to grapple with the complications associated with aging infrastructure. This includes the presence of lead (Pb)-bearing plumbing components such as lead service lines, downstream galvanized iron pipes, and Pb/tin solder. The community of Benton Harbor, MI, experienced six Pb action level exceedances between 2018 and 2021, leading to increasing community concern and a request from the state of Michigan for the US Environmental Protection Agency involvement. Between 9 November and 17 December 2021, US EPA Region 5 and Office of Research and Development, along with the state of Michigan, conducted a water filter efficacy and Pb-nanoparticulate (

Background: Myocardial injury has been described in coronavirus-2019 (COVID-19). Few studies have reported cardiovascular imaging data with transthoracic echocardiography (TTE) and electrocardiography (ECG) findings in COVID-19 patients, and their correlation with mortality. Methods: We conducted a retrospective cohort study that included COVID-19 patients from March 2020 through February 2021 who had TTE and ECG during hospital admission. Myocardial injury was defined by an elevated high-sensitivity troponin T level > 20 ng/L. Bivariate analysis was used to compare patients with myocardial injury and those without. Multivariate logistic regression analysis was performed to identify the variables associated with mortality. Results: A total of 438 patients were included. The mean age was 62.1 ± 14.9 years, and 58.9% were male. A total of 149 patients died, with a mortality rate of 34%. A total of 260 patients (59.4%) had myocardial injury. The average left ventricular ejection fraction was 59.8% ± 11.2%, with 30 patients (6.8%) having an ejection fraction of < 40%. Patients with myocardial injury had higher mortality than those without (P < 0.05, χ2 test). A multiple regression analysis model indicated that age, race and/or ethnicity, the development of acute respiratory distress syndrome, shock, the need for vasopressors, mechanical ventilation, and hemodialysis were the variables significantly associated with mortality. Conclusion: COVID-19 patients with myocardial injury had higher mortality than those without. Age, race and/or ethnicity, acute respiratory distress syndrome, shock, the need for vasopressors, mechanical ventilation, and hemodialysis were the clinical variables associated with mortality. The TEE and ECG variables studied were not significantly associated with mortality. Résumé: Contexte: Des atteintes myocardiques ont été décrites en présence d’une infection par le coronavirus 2019 (COVID-19). Quelques études ont rapporté des données d’imagerie cardiovasculaire obtenues par échocardiographie transthoracique (ETT) et électrocardiographie (ECG) chez des patients atteints de la COVID-19, et leur corrélation avec la mortalité. Méthodologie: Nous avons mené une étude de cohorte rétrospective comprenant des patients atteints de la COVID-19 entre mars 2020 et février 2021 qui ont été soumis à une ETT ou à une ECG pendant leur hospitalisation. L’atteinte myocardique était définie comme un taux élevé de troponine T de haute sensibilité > 20 ng/L. Une analyse à deux variables a été utilisée pour comparer les patients présentant une atteinte myocardique et ceux qui n’en présentaient pas. Une analyse de régression logistique à multiples variables a été menée pour définir les variables qui étaient associées à la mortalité. Résultats: L’étude comptait un total de 438 patients. L’âge moyen était de 62,1 ± 14,9 ans; 58,9 % étaient des hommes. Un total de 149 patients sont décédés, soit un taux de mortalité de 34 %. Un total de 260 patients (59,4 %) présentaient une atteinte myocardique. La fraction d’éjection ventriculaire gauche moyenne était de 59,8 % ± 11,2 %, alors que 30 patients (6,8 %) affichaient une fraction d’éjection inférieure à 40 %. Le taux de mortalité était plus élevé chez les patients qui présentaient une atteinte myocardique que chez ceux qui n’en présentaient pas (p < 0,05, test χ2). Selon un modèle d’analyse de régression multiple, l’âge, la race et/ou l’ethnicité, l’apparition du syndrome de détresse respiratoire aiguë, l’état de choc, le besoin de vasopresseurs, la ventilation artificielle et l’hémodialyse étaient les variables fortement liées à la mortalité. Conclusion: Parmi les patients atteints de la COVID-19, la mortalité était plus élevée chez ceux qui présentaient une atteinte myocardique que chez ceux qui n’en présentaient pas. L’âge, la race et/ou l’ethnicité, le syndrome de détresse respiratoire aiguë, l’état de choc, le besoin de vasopresseurs, la ventilation artificielle et l’hémodialyse étaient les variables cliniques liées à la mortalité. Les variables d’ETT et d’ECG étudiées n’avaient pas de lien important avec la mortalité.

Abstract. Over the past few years, the human virome and its complex interactions with microbial communities and the immune system have gained recognition as a crucial factor in human health. Individuals with compromised immune function encounter distinctive challenges due to their heightened vulnerability to a diverse range of infectious diseases. This review aims to comprehensively explore and analyze the growing evidence regarding the role of the virome in immunocompromised disease status. By surveying the latest literature, we present a detailed overview of virome alterations observed in various immunodeficiency conditions. We then delve into the influence and mechanisms of these virome changes on the pathogenesis of specific diseases in immunocompromised individuals. Furthermore, this review explores the clinical relevance of virome studies in the context of immunodeficiency, highlighting the potential diagnostic and therapeutic gains from a better understanding of virome contributions to disease manifestations.

ABSTRACTThe SARS-CoV-2 pandemic was marked with emerging viral variants, some of which were designated as variants of concern (VOCs) due to selection and rapid circulation in the human population. Here, we elucidate functional features of each VOC linked to variations in replication rate. Patient-derived primary nasal cultures grown at air-liquid interface were used to model upper respiratory infection and compared to cell lines derived from human lung epithelia. All VOCs replicated to higher titers than the ancestral virus, suggesting a selection for replication efficiency. In primary nasal cultures, Omicron replicated to the highest titers at early time points, followed by Delta, paralleling comparative studies of population sampling. All SARS-CoV-2 viruses entered the cell primarily via a transmembrane serine protease 2 (TMPRSS2)-dependent pathway, and Omicron was more likely to use an endosomal route of entry. All VOCs activated and overcame dsRNA-induced cellular responses, including interferon (IFN) signaling, oligoadenylate ribonuclease L degradation, and protein kinase R activation. Among the VOCs, Omicron infection induced expression of the most IFN and IFN-stimulated genes. Infections in nasal cultures resulted in cellular damage, including a compromise of cell barrier integrity and loss of nasal cilia and ciliary beating function, especially during Delta infection. Overall, Omicron was optimized for replication in the upper respiratory tract and least favorable in the lower respiratory cell line, and Delta was the most cytopathic for both upper and lower respiratory cells. Our findings highlight the functional differences among VOCs at the cellular level and imply distinct mechanisms of pathogenesis in infected individuals.IMPORTANCEComparative analysis of infections by SARS-CoV-2 ancestral virus and variants of concern, including Alpha, Beta, Delta, and Omicron, indicated that variants were selected for efficiency in replication. In infections of patient-derived primary nasal cultures grown at air-liquid interface to model upper respiratory infection, Omicron reached the highest titers at early time points, a finding that was confirmed by parallel population sampling studies. While all infections overcame dsRNA-mediated host responses, infections with Omicron induced the strongest interferon and interferon-stimulated gene response. In both primary nasal cultures and lower respiratory cell line, infections by Delta were most damaging to the cells as indicated by syncytia formation, loss of cell barrier integrity, and nasal ciliary function.

Preview: /Scott Shapiro interviewed by Eli Kramer / EK: Thanks for talking with me today. Your book, The Internationalists: How a Radical Plan to Outlaw War Remade the World is not only kind of groundbreaking in the way it changes how we think about the role of international law in the history and philosophy of culture, and some of our progressive success of not having disastrous violence shape us each generation, but it has only become more relevant since the war in Ukraine was launched. As a starting point for our conversation, can you summarize the main premise of the work? SS: It’s a story about the modern international order. Despite its imperfections, it needs to be defended now more than ever. The central argument of the book is that the origins of the modern international order can be traced to a specific date in history. Namely August 27th, 1928, when the great leaders of the world gathered in Paris to outlaw war. The treaty that was signed on that day is sometimes called the Kellogg-Briand Pact, the Peace Pact, or the Paris Peace Pact. Its actual formal designation was “The General Treaty for the Renunciation of War,” basically saying it all was an attempt to outlaw war. Now, of course most people have never heard of it. It’s amazing that basically all the countries in the world decide to outlaw war, which in itself is initially a strange thing to do, but then nobody knows about it.

Introduction: Rectal duplication is a rare condition with less than 100 cases documented in the literature. There are eleven reported cases of rectal duplication and anorectal malformation occurring concurrently. We present one such case with intraoperative discovery of the duplication and discuss intraoperative techniques and postoperative management. Case Presentation: A term male was transferred to our institution with an anorectal malformation noted on exam. Routine prenatal imaging had revealed an absent right kidney without any other anatomic abnormalities noted. Physical exam revealed a perineal fistula anterior to the sphincter complex. The patient was initially managed with twice daily dilations of the fistula until 2 months of life. He was then taken to the operating room for planned posterior sagittal anorectoplasty (PSARP). Intraoperatively, a blind ending tubular duplication was discovered anterior to the true rectum. This was managed with creation of a common channel and tapering rectoplasty followed by completion of the anoplasty. A diverting loop ileostomy was performed. Prior to ileostomy closure at 6 months of life, a contrast enema was performed and demonstrated that the duplication extended to the level of the splenic flexure. A Tc99 scan was obtained to rule out ectopic gastric mucosa. Conclusion: This case illustrates a rare presentation and operative management of a colon and rectal duplication associated with an anorectal malformation and emphasizes the importance of adequate mobilization of the rectal fistula when performing a PSARP. Level Of Evidence: Level V

Abstract Background Cardiovascular disease (CVD) is the leading cause of death in the world. In the United Arab Emirates (UAE), it accounts for 40% of mortality. CVD is caused by multiple cardiometabolic risk factors (CRFs) including obesity, dysglycemia, dyslipidemia, hypertension and central obesity. However, there are limited studies focusing on the CVD risk burden among young Emirati adults. This study investigates the burden of CRFs in a sample of young Emiratis, and estimates the distribution in relation to sociodemographic and behavioral determinants. Methods Data was used from the baseline data of the UAE Healthy Future Study volunteers. The study participants were aged 18 to 40 years. The study analysis was based on self-reported questionnaires, anthropometric and blood pressure measurements, as well as blood analysis. Results A total of 5167 participants were included in the analysis; 62% were males and the mean age of the sample was 25.7 years. The age-adjusted prevalence was 26.5% for obesity, 11.7% for dysglycemia, 62.7% for dyslipidemia, 22.4% for hypertension and 22.5% for central obesity. The CRFs were distributed differently when compared within social and behavioral groups. For example, obesity, dyslipidemia and central obesity in men were found higher among smokers than non-smokers (p

The Framingham Heart Study (FHS) began in 1949 with the goal of defining the epidemiology of hypertensive or arteriosclerotic heart disease in the population of Framingham, Massachusetts, a primarily Caucasian suburb west of Boston with a population of approximately 28,000. The participants were without previous symptoms of heart disease and were followed for the occurrence of Cardiovascular Disease (CVD). The study documented a comprehensive medical history that included current symptoms, family history, past cardiac history, social history, and medications. The medical exam included diagnostic studies of chest X-ray, electrocardiogram (EKG), complete blood count (CBC), uric acid level, blood glucose, urinalysis, and venereal disease research laboratory test; Syphilis (VDRL). Serum lipids, recognized at the time to be associated with cardiovascular disease, were also measured. These included cholesterol, total phospholipids, and the Gofman’s Sf 10–20 fraction. Study participants underwent four examinations at 6-month intervals to document any clinical manifestation of CVD. The present understanding of the epidemiologic factors that influence cardiovascular disease risk (CVD-R) is based on the first report of study results at a 6-year median follow-up and numerous subsequent analyses of long-term follow-up data from the original Framingham cohort as well as their offspring. In this paper, we review the Framingham cohort study with regards to the risk factors of peripheral vascular disease.

Introduction Smoking remains the leading preventable cause of death in the USA. Low utilisation of treatments for smoking cessation remains a major barrier for reducing smoking rates. Financial incentives represent an innovative approach to increasing use of therapies for smoking cessation. This paper will describe the rationale and design of the Financial Incentives for Smoking Treatment II (FIESTA II) study, a randomised controlled trial to evaluate the effectiveness and feasibility of goal-directed and outcome-based financial incentives to promote smoking cessation among hospitalised smokers.Methods and analysis We are recruiting adult participants who smoked tobacco in the 30 days prior to initial interview and are contemplating quitting smoking. These participants will come from two hospitals in underserved communities in New York City and Los Angeles. They will be randomised into one of three arms. The first arm consists of goal-directed financial incentives plus enhanced usual care, which includes hospital-directed information about quitting smoking, nicotine replacement therapy and referral to a Quitline. The second arm involves outcome-based financial incentives plus enhanced usual care. The third arm consists of enhanced usual care alone. Multiple phone interviews with the participants will be completed after randomisation to assess smoking cessation. Participants will earn $20 for each follow-up interview completed and $30 for each smoking cessation test completed. Those who are randomised to the financial incentive groups can earn an additional $700. The participants in the outcome-based group will receive payments solely for exhibiting cessation, whereas the participants in the goal-based group are also eligible for receiving payments after meeting milestones such as speaking with a helpline coach.Ethics Human research protection committees at New York University School of Medicine and the University of California Los Angeles (UCLA) David Geffen School of Medicine granted ethics approval.Protocol number: IRB#19-000 084.Trial registration number NCT03979885.

Abstract Objective The Department of Veterans Affairs’ (VA) electronic health records (EHR) offer a rich source of big data to study medical and health care questions, but patient eligibility and preferences may limit generalizability of findings. We therefore examined the representativeness of VA veterans by comparing veterans using VA healthcare services to those who do not. Methods We analyzed data on 3051 veteran participants age ≥ 18 years in the 2019 National Health Interview Survey. Weighted logistic regression was used to model participant characteristics, health conditions, pain, and self-reported health by past year VA healthcare use and generate predicted marginal prevalences, which were used to calculate Cohen’s d of group differences in absolute risk by past-year VA healthcare use. Results Among veterans, 30.4% had past-year VA healthcare use. Veterans with lower income and members of racial/ethnic minority groups were more likely to report past-year VA healthcare use. Health conditions overrepresented in past-year VA healthcare users included chronic medical conditions (80.6% vs. 69.4%, d = 0.36), pain (78.9% vs. 65.9%; d = 0.35), mental distress (11.6% vs. 5.9%; d = 0.47), anxiety (10.8% vs. 4.1%; d = 0.67), and fair/poor self-reported health (27.9% vs. 18.0%; d = 0.40). Conclusions Heterogeneity in veteran sociodemographic and health characteristics was observed by past-year VA healthcare use. Researchers working with VA EHR data should consider how the patient selection process may relate to the exposures and outcomes under study. Statistical reweighting may be needed to generalize risk estimates from the VA EHR data to the overall veteran population.

Abstract Background The United Arab Emirates Healthy Future Study (UAEHFS) is one of the first large prospective cohort studies and one of the few studies in the region which examines causes and risk factors for chronic diseases among the nationals of the United Arab Emirates (UAE). The aim of this study is to investigate the eight-item Patient Health Questionnaire (PHQ-8) as a screening instrument for depression among the UAEHFS pilot participants. Methods The UAEHFS pilot data were analyzed to examine the relationship between the PHQ-8 and possible confounding factors, such as self-reported happiness, and self-reported sleep duration (hours) after adjusting for age, body mass index (BMI), and gender. Results Out of 517 participants who met the inclusion criteria, 487 (94.2%) participants filled out the questionnaire and were included in the statistical analysis using 100 multiple imputations. 231 (44.7%) were included in the primary statistical analysis after omitting the missing values. Participants’ median age was 32.0 years (Interquartile Range: 24.0, 39.0). In total, 22 (9.5%) of the participant reported depression. Females have shown significantly higher odds of reporting depression than males with an odds ratio = 3.2 (95% CI:1.17, 8.88), and there were approximately 5-fold higher odds of reporting depression for unhappy than for happy individuals. For one interquartile-range increase in age and BMI, the odds ratio of reporting depression was 0.34 (95% CI: 0.1, 1.0) and 1.8 (95% CI: 0.97, 3.32) respectively. Conclusion Females are more likely to report depression compared to males. Increasing age may decrease the risk of reporting depression. Unhappy individuals have approximately 5-fold higher odds of reporting depression compared to happy individuals. A higher BMI was associated with a higher risk of reporting depression. In a sensitivity analysis, individuals who reported less than 6 h of sleep per 24 h were more likely to report depression than those who reported 7 h of sleep.

BackgroundPatients with chronic lymphocytic leukemia (CLL) have reduced seroconversion rates and lower binding antibody (Ab) and neutralizing antibody (NAb) titers than healthy individuals following Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) mRNA vaccination. Here, we dissected vaccine-mediated humoral and cellular responses to understand the mechanisms underlying CLL-induced immune dysfunction.Methods and findingsWe performed a prospective observational study in SARS-CoV-2 infection-naïve CLL patients (n = 95) and healthy controls (n = 30) who were vaccinated between December 2020 and June 2021. Sixty-one CLL patients and 27 healthy controls received 2 doses of the Pfizer-BioNTech BNT162b2 vaccine, while 34 CLL patients and 3 healthy controls received 2 doses of the Moderna mRNA-1273 vaccine. The median time to analysis was 38 days (IQR, 27 to 83) for CLL patients and 36 days (IQR, 28 to 57) for healthy controls. Testing plasma samples for SARS-CoV-2 anti-spike and receptor-binding domain Abs by enzyme-linked immunosorbent assay (ELISA), we found that all healthy controls seroconverted to both antigens, while CLL patients had lower response rates (68% and 54%) as well as lower median titers (23-fold and 30-fold; both p < 0.001). Similarly, NAb responses against the then prevalent D614G and Delta SARS-CoV-2 variants were detected in 97% and 93% of controls, respectively, but in only 42% and 38% of CLL patients, who also exhibited >23-fold and >17-fold lower median NAb titers (both p < 0.001). Interestingly, 26% of CLL patients failed to develop NAbs but had high-titer binding Abs that preferentially reacted with the S2 subunit of the SARS-CoV-2 spike. Since these patients were also seropositive for endemic human coronaviruses (HCoVs), these responses likely reflect cross-reactive HCoV Abs rather than vaccine-induced de novo responses. CLL disease status, advanced Rai stage (III-IV), elevated serum beta-2 microglobulin levels (β2m >2.4 mg/L), prior therapy, anti-CD20 immunotherapy (ConclusionsCLL pathogenesis is characterized by a progressive loss of adaptive immune functions, including in most treatment-naïve patients, with preexisting memory being preserved longer than the capacity to mount responses to new antigens. In addition, higher NAb titers and response rates identify mRNA-1273 as a superior vaccine for CLL patients.

IntroductionAsthma and polycystic ovarian syndrome (PCOS) are linked in several possible ways. To date, there has been no study evaluating whether pediatric asthma is an independent risk factor for adult PCOS. Our study aimed to examine the association between pediatric asthma (diagnosed at 0-19 years) and adult PCOS (diagnosed at ≥20 years). We further assessed whether the aforementioned association differed in two phenotypes of adult PCOS which were diagnosed at 20-25 years (young adult PCOS), and at >25 years (older adult PCOS). We also evaluated whether the age of asthma diagnosis (0-10 vs 11-19 years) modified the association between pediatric asthma and adult PCOS.Material and methodsThis is a retrospective cross-sectional analysis using the United Arab Emirates Healthy Future Study (UAEHFS) collected from February 2016 to April 2022 involving 1334 Emirati females aged 18-49 years. We fitted a Poisson regression model to estimate the risk ratio (RR) and its 95% confidence interval (95% CI) to assess the association between pediatric asthma and adult PCOS adjusting for age, urbanicity at birth, and parental smoking at birth.ResultsAfter adjusting for confounding factors and comparing to non-asthmatic counterparts, we found that females with pediatric asthma had a statistically significant association with adult PCOS diagnosed at ≥20 years (RR=1.56, 95% CI: 1.02-2.41), with a stronger magnitude of the association found in the older adult PCOS phenotype diagnosed at >25 years (RR=2.06, 95% CI: 1.16-3.65). Further, we also found females reported thinner childhood body size had a two-fold to three-fold increased risk of adult PCOS diagnosed at ≥20 years in main analysis and stratified analyses by age of asthma and PCOS diagnoses (RR=2.06, 95% CI: 1.08-3.93 in main analysis; RR=2.74, 95% CI: 1.22-6.15 among those diagnosed with PCOS > 25 years; and RR=3.50, 95% CI: 1.38-8.43 among those diagnosed with asthma at 11-19 years).ConclusionsPediatric asthma was found to be an independent risk factor for adult PCOS. More targeted surveillance for those at risk of adult PCOS among pediatric asthmatics may prevent or delay PCOS in this at-risk group. Future studies with robust longitudinal designs aimed to elucidate the exact mechanism between pediatric asthma and PCOS are warranted.

Characterization of intertextual references among authors is fundamental for the study of Latin literature. In this paper, we describe a large-scale intertextuality dataset compiled from three modern commentaries on Valerius Flaccus’ epic poem Argonautica. The dataset includes 945 references to earlier and contemporary Roman authors, as well as associated metadata required for use of multiple intertext search tools. To illustrate the dataset’s reuse potential, we perform a new benchmark analysis of Fīlum, a sequence alignment tool for intertextuality detection.

Abstract Background The need to engage adults, age 65 and older, in clinical trials of conditions typical in older populations, (e.g. hypertension, diabetes mellitus, Alzheimer’s disease and related dementia) is exponentially increasing. Older adults have been markedly underrepresented in clinical trials, often exacerbated by exclusionary study criteria as well as functional dependencies that preclude participation. Such dependencies may further exacerbate communication challenges. Consequently, the evidence of what works in subject recruitment is less generalizable to older populations, even more so for those from racial and ethnic minority and low-income communities. Methods To support capacity of research staff, we developed a virtual, three station simulation (Group Objective Structured Clinical Experience—GOSCE) to teach research staff communication skills. This 2-h course included a discussion of challenges in recruiting older adults; skills practice with Standardized Participants (SPs) and faculty observer who provided immediate feedback; and debrief to highlight best practices. Each learner had opportunities for active learning and observational learning. Learners completed a retrospective pre-post survey about the experience. SP completed an 11-item communication checklist evaluating the learner on a series of established behaviorally anchored communication skills (29). Results In the research staff survey, 92% reported the overall activity taught them something new; 98% reported it provided valuable feedback; 100% said they would like to participate again. In the SP evaluation there was significant variation: the percent well-done of items by case ranged from 25–85%. Conclusions Results from this pilot suggest that GOSCEs are a (1) acceptable; (2) low cost; and (3) differentiating mechanism for training and assessing research staff in communication skills and structural competency necessary for participant research recruitment.

Abstract Evidence has suggested that built environments are significantly associated with residents’ health and the conditions of built environments vary between neighborhoods. Recently, there have been remarkable technological advancements in using deep learning to detect built environments on fine spatial scale remotely sensed images. However, integrating the extracted built environment information by deep learning with geographic information systems (GIS) is still rare in existing literature. This method paper presents how we harnessed deep leaning techniques to extract built environments and then further utilized the extracted information as input data for analysis and visualization in a GIS environment. Informative guidelines on data collection with an unmanned aerial vehicle (UAV), greenspace extraction using a deep learning model (specifically U-Net for image segmentation), and mapping spatial distributions of greenspace and sidewalks in a GIS environment are offered. The novelty of this paper lies in the integration of deep learning into the GIS decision-making system to identify the spatial distribution of built environments at the neighborhood scale.

ABSTRACT HIV-1 and its SIV precursors share a broadly neutralizing antibody (bNAb) epitope in variable loop 2 (V2) at the envelope glycoprotein (Env) trimer apex. Here, we tested the immunogenicity of germ line-targeting versions of a chimpanzee SIV (SIVcpz) Env in human V2-apex bNAb heavy-chain precursor-expressing knock-in mice and as chimeric simian-chimpanzee immunodeficiency viruses (SCIVs) in rhesus macaques (RMs). Trimer immunization of knock-in mice induced V2-directed NAbs, indicating activation of V2-apex bNAb precursor-expressing mouse B cells. SCIV infection of RMs elicited high-titer viremia, potent autologous tier 2 neutralizing antibodies, and rapid sequence escape in the canonical V2-apex epitope. Six of seven animals also developed low-titer heterologous plasma breadth that mapped to the V2-apex. Antibody cloning from two of these animals identified multiple expanded lineages with long heavy chain third complementarity determining regions that cross-neutralized as many as 7 of 19 primary HIV-1 strains, but with low potency. Negative stain electron microscopy (NSEM) of members of the two most cross-reactive lineages confirmed V2 targeting but identified an angle of approach distinct from prototypical V2-apex bNAbs, with antibody binding either requiring or inducing an occluded-open trimer. Probing with conformation-sensitive, nonneutralizing antibodies revealed that SCIV-expressed, but not wild-type SIVcpz Envs, as well as a subset of primary HIV-1 Envs, preferentially adopted a more open trimeric state. These results reveal the existence of a cryptic V2 epitope that is exposed in occluded-open SIVcpz and HIV-1 Env trimers and elicits cross-neutralizing responses of limited breadth and potency. IMPORTANCE An effective HIV-1 vaccination strategy will need to stimulate rare precursor B cells of multiple bNAb lineages and affinity mature them along desired pathways. Here, we searched for V2-apex germ line-targeting Envs among a large set of diverse primate lentiviruses and identified minimally modified versions of one chimpanzee SIV Env that bound several human V2-apex bNAb precursors and stimulated one of these in a V2-apex bNAb precursor-expressing knock-in mouse. We also generated chimeric simian-chimpanzee immunodeficiency viruses and showed that they elicit low-titer V2-directed heterologous plasma breadth in six of seven infected rhesus macaques. Characterization of this antibody response identified a new class of weakly cross-reactive neutralizing antibodies that target the V2-apex, but only in occluded-open Env trimers. The existence of this cryptic epitope, which in some Env backgrounds is immunodominant, needs to be considered in immunogen design.

Football exposes its players to traumatic brain, neck, and spinal injury. It is unknown whether the adolescent football player develops imaging abnormalities of the brain and spine that are detectable on magnetic resonance imaging (MRI). The objective of this observational study was to identify potential MRI signatures of early brain and cervical spine (c-spine) injury in high school football players. Eighteen football players (mean age, 17.0???1.5 years; mean career length, 6.3???4.0 years) had a baseline brain MRI, and 7 had a follow-up scan 9?42 months later. C-spine MRIs were performed on 11 of the 18 subjects, and 5 had a follow-up scan. C-spine MRIs from 12 age-matched hospital controls were also retrospectively retrieved. Brain MRIs were reviewed by a neuroradiologist, and no cerebral microbleeds were detected. Three readers (a neuroradiologist, a neurosurgeon, and an orthopedic spine surgeon) studied the cervical intervertebral discs at six different cervical levels and graded degeneration using an established five-grade scoring system. We observed no statistically significant difference in disc degeneration or any trend toward increased disc degeneration in the c-spine of football players as compared with age-matched controls. Further research is needed to validate our findings and better understand the true impact of contact sports on young athletes.

Lipid peroxidation-derived aldehydes, such as acrolein, the most reactive aldehyde, have emerged as key culprits in sustaining post-spinal cord injury (SCI) secondary pathologies leading to functional loss. Strong evidence suggests that mitochondrial aldehyde dehydrogenase-2 (ALDH2), a key oxidoreductase and powerful endogenous anti-aldehyde machinery, is likely important for protecting neurons from aldehydes-mediated degeneration. Using a rat model of spinal cord contusion injury and recently discovered ALDH2 activator (Alda-1), we planned to validate the aldehyde-clearing and neuroprotective role of ALDH2. Over an acute 2 day period post injury, we found that ALDH2 expression was significantly lowered post-SCI, but not so in rats given Alda-1. This lower enzymatic expression may be linked to heightened acrolein-ALDH2 adduction, which was revealed in co-immunoprecipitation experiments. We have also found that administration of Alda-1 to SCI rats significantly lowered acrolein in the spinal cord, and reduced cyst pathology. In addition, Alda-1 treatment also resulted in significant improvement of motor function and attenuated post-SCI mechanical hypersensitivity up to 28 days post-SCI. Finally, ALDH2 was found to play a critical role in in vitro protection of PC12 cells from acrolein exposure. It is expected that the outcome of this study will broaden and enhance anti-aldehyde strategies in combating post-SCI neurodegeneration and potentially bring treatment to millions of SCI victims. All animal work was approved by Purdue Animal Care and Use Committee (approval No. 1111000095) on January 1, 2021.

BackgroundThe gut microbiome is believed to contribute to bloodstream infection (BSI) via translocation of dominant gut bacteria in vulnerable patient populations. However, conclusively linking gut and blood organisms requires stringent approaches to establish strain-level identity.MethodsWe enrolled a convenience cohort of critically ill patients and investigated 86 bloodstream infection episodes that occurred in 57 patients. Shotgun metagenomic sequencing was used to define constituents of their gut microbiomes, and whole genome sequencing and assembly was done on 23 unique bloodstream isolates that were available from 21 patients. Whole genome sequences were downloaded from public databases and used to establish sequence-identity distribution and define thresholds for unrelated genomes of BSI species. Gut microbiome reads were then aligned to whole genome sequences of the cognate bloodstream isolate and unrelated database isolates to assess identity.ResultsGut microbiome constituents matching the bloodstream infection species were present in half of BSI episodes, and represented >30% relative abundance of gut sequences in 10% of episodes. Among the 23 unique bloodstream organisms that were available for whole genome sequencing, 14 were present in gut at the species level. Sequence alignment applying defined thresholds for identity revealed that 6 met criteria for identical strains in blood and gut, but 8 did not. Sequence identity between BSI isolates and gut microbiome reads was more likely when the species was present at higher relative abundance in gut.ConclusionIn assessing potential gut source for BSI, stringent sequence-based approaches are essential to determine if organisms responsible for BSI are identical to those in gut: of 14 evaluable patients in which the same species was present in both sites, they were identical in 6/14, but were non-identical in 8/14 and thus inconsistent with gut source. This report demonstrates application of sequencing as a key tool to investigate infection tracking within patients.

For a bus transit system with peak and normal periods, we derived an approximated formulated solution, to provide a patchwork for a published paper. Based on the same numerical example of the original model, our approximated solution attains the minimum cost within 0.3% to indicate that our approximated formulated solution is a good supplementary tool to estimate the optimal solution.

Background and objectives: Diabetes is an increasing public health concern worldwide. The impact of extreme heat exposure on diabetes healthcare utilization such as diabetes-related hospital admissions and emergency department (ED) visits was understudied although extreme temperature exposure was linked with diabetes mortality. In addition, very few systematic reviews have been conducted in this field. This review aims to systematically evaluate the currently available evidence on the association between extreme ambient heat exposure and hospital admissions/ED visits for diabetes and the vulnerable population to heat extremes. Methods: A systematic literature review was conducted by using the keywords/terms “ambient temperature or heatwave or heat wave or extreme temperature or high temperature effect” and “diabetes morbidity or diabetes hospital admissions or diabetes emergency room visits” for available publications until August 2022. The heat exposure was categorized into four groups using difference definitions. The outcomes were diabetes-related hospital admissions/ED visits. A meta-analysis was performed to estimate the pooled effects of relative risk (RR)/odds ratio (OR) and 95% confidence intervals (CI) for each of the associations of interest. Results: Eighteen articles were selected from forty full-text, English written papers based on the inclusion and exclusion criteria. The overall pooled effect of excessive heat on diabetes, across all groups, was 1.045 (95% CI: 1.024-1.066). The pooled effects for each exposure group were significant/borderline significant. Additionally, the pooled effect of the RR/OR was 1.100 (95% CI: 1.067-1.135) among adults aged 65 years or older. The most controlled confounders were air pollutants. The commonly listed limitation in those studies was misclassification of exposure. Conclusions: The body of evidence supports that ambient extreme heat exposure is associated with diabetes-related hospital admissions/ED visits. Additionally, adults 65 years of age or older with diabetes are vulnerable to heat extremes. Future studies should consider controlling for various biases and confounders.

Not all persons recovering from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection develop SARS-CoV-2–specific antibodies. We show that nonseroconversion is associated with younger age and higher reverse transcription PCR cycle threshold values and identify SARS-CoV-2 viral loads in the nasopharynx as a major correlate of the systemic antibody response.

ABSTRACT The SARS-CoV-2 pandemic began by viral spillover from animals to humans; today multiple animal species are known to be susceptible to infection. White-tailed deer, Odocoileus virginianus, are infected in North America at substantial levels, and genomic data suggests that a variant in deer may have spilled back to humans. Here, we characterize SARS-CoV-2 in deer from Pennsylvania (PA) sampled during fall and winter 2021. Of 123 nasal swab samples analyzed by RT-qPCR, 20 (16.3%) were positive for SARS-CoV-2. Seven whole genome sequences were obtained, together with six more partial spike gene sequences. These annotated as alpha and delta variants, the first reported observations of these lineages in deer, documenting multiple new jumps from humans to deer. The alpha lineage persisted in deer after its displacement by delta in humans, and deer-derived alpha variants diverged significantly from those in humans, consistent with a distinctive evolutionary trajectory in deer. IMPORTANCE Coronaviruses have been documented to replicate in numerous species of vertebrates, and multiple spillovers of coronaviruses from animals into humans have founded human epidemics. The COVID-19 epidemic likely derived from a spillover of SARS-CoV-2 from bats into humans, possibly via an intermediate host. There are now several examples of SARS-CoV-2 jumping from humans into other mammals, including mink and deer, creating the potential for new animal reservoirs from which spillback into humans could occur. For this reason, data on formation of new animal reservoirs is of great importance for understanding possible sources of future infection. Here, we identify extensive infection in white-tailed deer in Pennsylvania, including what appear to be multiple independent transmissions. Data further suggests possible transmission among deer. These data thus help identify a potential new animal reservoir and provide background information relevant to its management.

IntroductionVitamin D deficiency and insufficiency are highly prevalent among several populations across the globe. Numerous studies have shown a significant correlation between body-mass-index (BMI) and Vitamin D status, however, some results differed according to ethnicity. Despite the abundance of sunshine throughout the year, vitamin D deficiency is prominent in the United Arab Emirates (UAE). In this study, we analyzed the UAE Healthy Future Study (UAEHFS) pilot data to investigate the association between serum 25-hydroxyvitamin D (25(OH)D) and % body fat (BF) composition as well as BMI.Material and methodsData from a total of 399 Emirati men and women aged ≥ 18 years were analyzed. Serum 25(OH)D and standard measures of weight and height were included in the analyses. Vitamin D deficiency was defined as serum 25(OH)D concentration

Abstract Background Rapid spread of SARS-CoV-2 has led to a global pandemic, resulting in the need for rapid assays to allow diagnosis and prevention of transmission. Reverse transcription-polymerase chain reaction (RT-PCR) provides a gold standard assay for SARS-CoV-2 RNA, but instrument costs are high and supply chains are potentially fragile, motivating interest in additional assay methods. Reverse transcription and loop-mediated isothermal amplification (RT-LAMP) provides an alternative that uses orthogonal and often less expensive reagents without the need for thermocyclers. The presence of SARS-CoV-2 RNA is typically detected using dyes to report bulk amplification of DNA; however, a common artifact is nonspecific DNA amplification, which complicates detection. Results Here we describe the design and testing of molecular beacons, which allow sequence-specific detection of SARS-CoV-2 genomes with improved discrimination in simple reaction mixtures. To optimize beacons for RT-LAMP, multiple locked nucleic acid monomers were incorporated to elevate melting temperatures. We also show how beacons with different fluorescent labels can allow convenient multiplex detection of several amplicons in “single pot” reactions, including incorporation of a human RNA LAMP-BEAC assay to confirm sample integrity. Comparison of LAMP-BEAC and RT-qPCR on clinical saliva samples showed good concordance between assays. To facilitate implementation, we developed custom polymerases for LAMP-BEAC and inexpensive purification procedures, which also facilitates increasing sensitivity by increasing reaction volumes. Conclusions LAMP-BEAC thus provides an affordable and simple SARS-CoV-2 RNA assay suitable for population screening; implementation of the assay has allowed robust screening of thousands of saliva samples per week.

Spontaneous coronary artery dissection (SCAD) is an infrequent cause of acute coronary syndrome (ACS) caused by a nontraumatic tear in the coronary artery wall. The true incidence is thought to be underestimated owing to its diagnostic difficulty as coronary angiography is insensitive in assessing the arterial wall structure, thereby warranting additional diagnostic modalities such as intravascular ultrasound. We report a case of a young woman who had been taking oral contraceptives, and presented with acute non-ST segment elevation myocardial infarction due to SCAD with superimposed thrombosis.

Studies to identify maternal variants associated with preeclampsia have been limited by sample size. Here, the authors meta-analyze eight GWAS of 9,515 preeclamptic women, identifying five variants associated with preeclampsia and showing that genetic predisposition to hypertension is a major risk factor for preeclampsia.

ABSTRACT The severe acute respiratory coronavirus-2 (SARS-CoV-2) is the cause of the global outbreak of COVID-19. Evidence suggests that the virus is evolving to allow efficient spread through the human population, including vaccinated individuals. Here, we report a study of viral variants from surveillance of the Delaware Valley, including the city of Philadelphia, and variants infecting vaccinated subjects. We sequenced and analyzed complete viral genomes from 2621 surveillance samples from March 2020 to September 2021 and compared them to genome sequences from 159 vaccine breakthroughs. In the early spring of 2020, all detected variants were of the B.1 and closely related lineages. A mixture of lineages followed, notably including B.1.243 followed by B.1.1.7 (alpha), with other lineages present at lower levels. Later isolations were dominated by B.1.617.2 (delta) and other delta lineages; delta was the exclusive variant present by the last time sampled. To investigate whether any variants appeared preferentially in vaccine breakthroughs, we devised a model based on Bayesian autoregressive moving average logistic multinomial regression to allow rigorous comparison. This revealed that B.1.617.2 (delta) showed 3-fold enrichment in vaccine breakthrough cases (odds ratio of 3; 95% credible interval 0.89-11). Viral point substitutions could also be associated with vaccine breakthroughs, notably the N501Y substitution found in the alpha, beta and gamma variants (odds ratio 2.04; 95% credible interval of1.25–3.18). This study thus overviews viral evolution and vaccine breakthroughs in the Delaware Valley and introduces a rigorous statistical approach to interrogating enrichment of breakthrough variants against a changing background. IMPORTANCE SARS-CoV-2 vaccination is highly effective at reducing viral infection, hospitalization and death. However, vaccine breakthrough infections have been widely observed, raising the question of whether particular viral variants or viral mutations are associated with breakthrough. Here, we report analysis of 2621 surveillance isolates from people diagnosed with COVID-19 in the Delaware Valley in southeastern Pennsylvania, allowing rigorous comparison to 159 vaccine breakthrough case specimens. Our best estimate is a 3-fold enrichment for some lineages of delta among breakthroughs, and enrichment of a notable spike substitution, N501Y. We introduce statistical methods that should be widely useful for evaluating vaccine breakthroughs and other viral phenotypes.

In 2017, the NYU Clinical and Translational Science Institute’s Recruitment and Retention Unit created a Patient Advisory Council for Research (PACR) to provide feedback on clinical trials and health research studies. We collaborated with our clinical research informatics team to generate a random sample of patients, based on the International Classification of Diseases, Tenth Revision codes and demographic factors, for invitation via the patient portal. This approach yielded in a group that was diverse with regard to age, race/ethnicity, sex, and health conditions. This report highlights the benefits and limitations of using an electronic health record-based strategy to identify and recruit members for a PACR.

BackgroundSignificant concerns about mental health were raised during the COVID-19 pandemic. We investigated the prevalence of depression and anxiety symptoms among the participants of the United Arab Emirates Healthy Future Study (UAEHFS); a national cohort study. We further explored the change in the prevalence of depression symptoms among those with comparable pre-pandemic data.MethodsA sample of UAEHFS participants were invited to complete a COVID-19 online questionnaire during the first wave of the pandemic. Depression and anxiety symptoms were assessed using the Patient Health Questionnaire Depression Scale (PHQ-8) and the Generalized Anxiety Disorder-7 Scale (GAD-7) respectively. Unpaired analyses were done to examine the effect of COVID-19 on depression and anxiety symptoms during the pandemic. Paired analysis was conducted to examine the change in depression symptoms.ResultsDuring the pandemic, we reported a prevalence of 32.8% (95% CI: 27.0, 39.1) for depression and 26.4% (95% CI: 21.0, 32.6) for anxiety symptoms. Younger people reported higher levels of depression (40.4%) and anxiety (34.5%) symptoms. Females reported higher levels of depression (36.5%) and anxiety (32.7%) symptoms. In paired analysis, the prevalence of depression symptoms during the pandemic was 34% (95% CI: 26.5, 42.4) compared to 29.9% (95% CI: 22.7, 38.1) before the pandemic. No statistically significant difference was observed, p-value = 0.440. Adjusted multivariate logistic regression models for PHQ-8 and GAD-7 during the pandemic showed that participants, who were experiencing flu-like symptoms, had higher odds of reporting depression symptoms compared to those without symptoms. Additionally, age was significantly negatively associated with anxiety symptoms.ConclusionsOverall, we found that depression and anxiety symptoms were more prevalent among young people and females. However, we did not find a significant change in the prevalence of depression symptoms among those with comparable pre-pandemic data. Identifying vulnerable groups and understanding trajectories through longitudinal studies would help with planning for effective mental health interventions for the current and future pandemics.

Background: Transthyretin amyloid cardiomyopathy (ATTR-CM) is one of the most common types of cardiac amyloidosis. Amyloid cardiomyopathy more commonly affects men, elderly, and 3% to 4% of the African-American population. ATTR-CM suspicion and diagnosis is challenging; however, awareness of the disease is increasing, and best practices to identify it are being proposed. The approach to suspected cases of ATTR-CM relies on the presence of heart failure, red flag signs and symptoms, and age >65 or >70 for men and women respectively. Little is known about cases when it presents in early ages. Case: We report a 62-year-old African American male with past medical history of hyperlipidemia, prostate cancer, hypertension, bilateral carpal tunnel surgery that had debuted with a cardiac arrhythmia at age 55 and was diagnosed with heart failure several years later. Restrictive cardiomyopathy was suspected, and genetic screening was sent for ATTRm which confirmed a pathogenic trasnthyretin gene mutation. Endomyocardial biopsy was performed which confirmed cardiac amyloid deposition. Discussion: ATTR-CM is a rare disease with an increasing prevalence. Cases with out of proportion signs and symptoms of heart failure with preserved ejection fractions should raise the suspicion of ATTR-CM despite age.

In the United States, CRC is the third most common type of cancer and the second leading cause of cancer-related death. Although the incidence of CRC among the Hispanic population has been declining, recently, a dramatic increase in CRC incidents among HL younger than 50 years of age has been reported. The incidence of early-onset CRC is more significant in HL population (45%) than in non-Hispanic Whites (27%) and African-Americans (15%). The reason for these racial disparities and the biology of CRC in the HL are not well understood. We performed this study to understand the biology of the disease in HL patients. We analyzed formalin-fixed paraffin-embedded tumor tissue samples from 52 HL patients with mCRC. We compared the results with individual patient clinical histories and outcomes. We identified commonly altered genes in HL patients (APC, TP53, KRAS, GNAS, and NOTCH). Importantly, mutation frequencies in the APC gene were significantly higher among HL patients. The combination of mutations in the APC, NOTCH, and KRAS genes in the same tumors was associated with a higher risk of progression after first-line of chemotherapy and overall survival. Our data support the notion that the molecular drivers of CRC might be different in HL patients.

Background Contemporary real‐world data on stroke in patients presenting with ST‐segment–elevation myocardial infarction (STEMI) are scarce. Methods and Results We evaluated the incidence, trends, cause, and predictors of stroke from 2003 to 2019 in 4 large regional STEMI programs in the upper Midwest that use similar transfer and treatment protocols. We also evaluated the long‐term impact of stroke on 5‐year mortality. Multivariate logistic and Cox regression analysis was used to identify variables independently associated with stroke in patients presenting with STEMI and identify variables associated with 5‐year mortality. A total of 12 868 patients presented with STEMI during the study period. Stroke occurred in 98 patients (0.76%). The incidence of stroke remained stable over time (0.5% in 2003, 1.2% in 2019; P‐trend=0.22). Most (75%) of strokes were ischemic, with a median time to stroke symptoms of 14 hours after primary percutaneous coronary intervention (interquartile range, 4–72 hours), which led to a small minority (3%) receiving endovascular treatment and high in‐hospital mortality (18%). On multivariate regression analysis, age (increment of 10 years) (odds ratio [OR], 1.32; 95% CI, 1.10–1.58; P‐value=0.003) and preintervention cardiogenic shock (OR, 2.03; (95% CI, 1.03–3.78; P=0.032)) were associated with a higher risk of in‐hospital stroke. In‐hospital stroke was independently associated with increased risk of 5‐year mortality (hazard ratio, 2.01; 95% CI, 1.13–3.57; P=0.02). Conclusions In patients presenting with STEMI, the risk of stroke is low (0.76%). A stroke in patients presenting with STEMI is associated with significantly higher in‐hospital (18%) and long‐term mortality (35% at 5 years). Stroke was associated with double the risk of 5‐year death.

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Background: Ebola virus emerged in West Africa in December 2013. The ease of mobility, porous borders, and lack of public health infrastructure led to the largest Ebola virus disease (EVD) outbreak to date. Intervention: The 2013 EVD outbreak signalled the need for laboratory diagnostic capabilities in areas without strong public health systems. As part of the United States’ Department of Defense response, MRIGlobal was contracted to design, fabricate, equip, deploy, and operate two mobile diagnostic laboratories (MDLs). The first laboratory analysed blood samples from patients in an adjacent Ebola Treatment Centre (ETC) and buccal swabs from the deceased in the community in Moyamba, Sierra Leone. The second laboratory was deployed to support an ETC in Conakry, Guinea. The Department of Defense provided real-time quantitative reverse transcription polymerase chain reaction assays that were deployed and validated on-site. Lessons Learnt: Prompt and accurate molecular diagnostics reduced sample turn-around times from over 24 h to under 4 h. Experienced laboratory staff tested up to 110 samples per day and on-site engineering proved necessary for MDL setup and operation. As the Ebola response slowed, the sustainment of the MDLs’ operations was prioritised, including staff training and the transition of the MDLs to local governments. Training programmes for local staff were prepared in Sierra Leone and Guinea. Recommendations: The MRIGlobal MDL team significantly contributed to establishing increased laboratory capacity during the EVD outbreak in West Africa. Using the MDLs for molecular diagnosis is highly recommended until more sustainable solutions can be provided.

Transmission of dengue virus is a complex process with interactions between virus, mosquitoes and humans, influenced by multiple factors simultaneously. Studies have examined the impact of climate or socio-ecological factors on dengue, or only analyzed the individual effects of each single factor on dengue transmission. However, little research has addressed the interactive effects by multiple factors on dengue incidence. This study uses the geographical detector method to investigate the interactive effect of climate and socio-ecological factors on dengue incidence from two perspectives: over a long-time series and during outbreak periods; and surmised on the possibility of dengue outbreaks in the future. Results suggest that the temperature plays a dominant role in the long-time series of dengue transmission, while socio-ecological factors have great explanatory power for dengue outbreaks. The interactive effect of any two factors is greater than the impact of single factor on dengue transmission, and the interactions of pairs of climate and socio-ecological factors have more significant impact on dengue. Increasing temperature and surge in travel could cause dengue outbreaks in the future. Based on these results, three recommendations are offered regarding the prevention of dengue outbreaks: mitigating the urban heat island effect, adjusting the time and frequency of vector control intervention, and providing targeted health education to travelers at the border points. This study hopes to provide meaningful clues and a scientific basis for policymakers regarding effective interventions against dengue transmission, even during outbreaks.

BackgroundCOVID-19 pathology is associated with exuberant inflammation, vascular damage, and activation of coagulation. In addition, complement activation has been described and is linked to disease pathology. However, few studies have been conducted in cancer patients.ObjectiveThis study examined complement activation in response to COVID-19 in the setting of cancer associated thromboinflammation.MethodsMarkers of complement activation (C3a, C5a, sC5b-9) and complement inhibitors (Factor H, C1-Inhibitor) were evaluated in plasma of cancer patients with (n=43) and without (n=43) COVID-19 and stratified based on elevated plasma D-dimer levels (>1.0 μg/ml FEU). Markers of vascular endothelial cell dysfunction and platelet activation (ICAM-1, thrombomodulin, P-selectin) as well as systemic inflammation (pentraxin-3, serum amyloid A, soluble urokinase plasminogen activator receptor) were analyzed to further evaluate the inflammatory response.ResultsIncreases in circulating markers of endothelial cell dysfunction, platelet activation, and systemic inflammation were noted in cancer patients with COVID-19. In contrast, complement activation increased in cancer patients with COVID-19 and elevated D-dimers. This was accompanied by decreased C1-Inhibitor levels in patients with D-dimers > 5 ug/ml FEU.ConclusionComplement activation in cancer patients with COVID-19 is significantly increased in the setting of thromboinflammation. These findings support a link between coagulation and complement cascades in the setting of inflammation.

The nature of gold (Au) ore deposits plays an essential role in determining the best gold recovery method as an alternative to cyanidation, considering environmental concerns. Thiourea (Tu) leaching of gold is an alternative lixiviant for treating sulfide gold ores and concentrates. The present study investigated the leaching behavior of Au from sulfide gold ore concentrates obtained from the Cripple Creek site (Newmont operated mine) using acidified thiourea solution. The concentrates containing pyrite, K-feldspar, quartz, and gypsum as major minerals were roasted before leaching to break down complex sulfides and improve the gold’s leachability. Parameters investigated include the leaching time (1–7 h), temperature (20–60 °C), pulp density (20–60 g/L), and thiourea concentration (20–60 g/L) to determine optimum conditions for Au dissolution. Hydrogen peroxide (H2O2) was used as an oxidizing agent and sulfuric acid (H2SO4) to maintain an acidic environment during the leaching process. The highest Au dissolution percentage of 96.2 was obtained after 6 h of leaching with 40 g/L thiourea at 60 °C, pH 1, and pulp density of 20 g/L. Based on the results presented in this work, the dissolution of gold with thiourea in an acidic solution would be a potential alternative to the traditional cyanide process, with the increase in understanding of the green leaching of Au from sulfide gold ores.

We report a patient who has cognitive sequalae including verbal retrieval deficits after severe traumatic brain injury (TBI). The cortico-caudate-thalamic circuit involving the pre-Supplementary Motor Area (pre-SMA) has been proposed to underlie verbal retrieval functions. We hypothesized that High Definition-transcranial Direct Current Stimulation (HD-tDCS) targeting the pre-SMA would selectively modulate this circuit to remediate verbal retrieval deficits. After the patient underwent 10 sessions of 20 min of 1 mA HD-tDCS targeting the pre-SMA, we documented significant improvements for verbal fluency and naming, and for working memory and executive function tasks that involve the frontal lobes. The effects persisted for up to 14 weeks after completion of HD-tDCS treatment. We also demonstrated normalization of the event-related potentials suggesting modulation of the underlying neural circuit. Our study implicates that region-specific non-invasive brain stimulation, such as HD-tDCS, serves as a potential individualized therapeutic tool to treat cognitive deficits by inducing longer-lasting neuroplasticity even in the chronic phase of TBI.

Background: We explored characteristics and beliefs associated with e-cigarette use patterns among cigarette smokers requiring inpatient detoxification for opioid and/or alcohol use disorder(s). Methods: Adult cigarette smokers (≥18 years), admitted to inpatient detoxification for alcohol and/or opioid use disorder(s) in a safety-net tertiary referral center in New York City were surveyed in 2015 (n = 158). Descriptive statistics (proportions) were used to assess for demographic, clinical diagnosis, cigarette smoking patterns (exclusive and dual use of e-cigarettes). Chi-square, t-test statistics, and logistic regression models were used. Results: Among our sample of combustible cigarette users, 13.9% (n = 22) reported dual use with electronic cigarettes. Dual use did not differ by demographic or clinical variables. Compared to exclusive smokers, dual users were more likely to have tried to quit in the past year (Adjusted Odds ratio = 8.59; CI: 2.58, 28.35; p

Background: The 2014–2016 West Africa Ebola virus disease outbreak heavily impacted the Republics of Guinea, Sierra Leone, and Liberia. The outbreak uncovered the weaknesses of the public health systems, including inadequately trained and insufficient health personnel as well as limited and poorly equipped health infrastructures. These weaknesses represent significant threats to global health security. In the wake of the outbreak, affected countries made urgent requests for international engagement to help strengthening the public health systems.Methods: This work describes the successful multi-year implementation of a laboratory capacity building program in the Republic of Guinea. The program integrated biorisk and quality management systems training, infectious diseases diagnostic training, facility engineering and maintenance training, and mentorship to strengthen Guinea's bio-surveillance capacity.Results: The major outcome of these efforts was an established and local staff-operated public health laboratory that performs disease surveillance and reporting and diagnostic of priority diseases and pathogens of security concerns.Conclusions: This work has improved the Guinea country's capabilities to address country public health issues and preparedness to respond to future infectious disease threats.

Abstract Background Fel d1 is the most important allergen from cats. Fel d1 is produced primarily in saliva and spread to the haircoat during grooming and then transferred to the environment via hair and dander. Objectives A novel approach to reducing allergenic Fel d1 exposure was evaluated, involving binding the Fel d1 with an anti‐Fel d1 polyclonal egg IgY antibody. The hypothesis was that hair from cats who had been fed foods containing anti‐Fel d1 IgY would show a significant reduction in active Fel d1 (aFel d1). Methods Hair collected from 105 cats completing a 12‐week study was evaluated for aFel d1 via ELISA. Hair was collected four times over a 2‐week baseline period, then weekly during the 10 week treatment period during which cats consumed a food containing the anti‐Fel d1 IgY. Results Baseline aFel d1 (μg/g hair) varied greatly among the cats in this study. From week 3, there was a significant reduction in mean aFel d1 with an overall average decrease of 47% by week 10, ranging from a 33–71% decrease vs baseline. Cats with the highest baseline aFel d1 showed the greatest decrease in aFel d1. Conclusions & Clinical Implications Feeding anti‐Fel d1 IgY to cats successfully reduced aFel d1 on their haircoat with the greatest decreases observed in cats with initially high levels. Feeding a diet with anti Fel d1 IgY significantly reduced the active Fel d1 on the hair of cats.