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In the past, several scaling tests have been performed on the HTCondor batch system regarding its job scheduling capabilities. In this talk we report on a first set of scalability measurements of the file transfer capabilities of the HTCondor batch system. Motivated by the GlueX experiment needs we evaluate the limits and possible use of HTCondor as a solution to transport the output of jobs back to a submitter as a function of the number of concurrent jobs, the size of the output and the distance between a submitting node and computing node. We conclude that HTCondor transfer system satisfies the current GlueX computing demands.

With the increase of power and reduction of cost of GPU accelerated processors a corresponding interest in their uses in the scientific domain has spurred. OSG users are no different and they have shown an interest in accessing GPU resourcesvia their usual workload infrastructures. Grid sites that have these kinds of resources also want to make them grid available. In this talk, we discuss the software and infrastructure challenges and limitations of the OSG implementations to make GPU’s widely accessible over the grid. Two use cases are considered for this. First: IceCube, a big VO with a well-curated software stack taking advantage of GPUs with OpenCL. Second, a more general approach to supporting the grid use of industry and academia maintained machine learning libraries like Tensorflow, and Keras on the grid using Singularity.

A key aspect of pilot-based grid operations are the GlideinWMS pilot factories. A proper and efficient use of any central block in the grid infrastructure for operations is inevitable, and GlideinWMS factories are no exception. The monitoring package for the GlideinWMS factory was originally developed when the factories were serving a couple of VOs and tens of sites. Today with the factories serving tens of VOs and hundreds of sites around the globe an update of the monitoring is due. Moreover with the new availability of industry open source storage and graphing packages an opportunity remains open.This work presents the changes made to the factory monitoring to leverage different technologies: Elasticsearch, RabbitMQ, Grafana, and InfluxDB to provide a centralized view of the status and work of several GlideinWMS factories located in different continents around the globe.

Purpose: Thoracic endovascular aortic repair (TEVAR) has been described to be superior to an open surgical approach, and previous studies have found superiority in TEVAR by reducing overall morbidity and mortality rates. This study aimed to describe the outcomes of TEVAR for patients with thoracic aortic disease at a high complexity., Materials and Methods: Descriptive study, developed by a retrospective review of a prospectively collected database. Patients aged above 18 years who underwent TEVAR between 2012 and 2022 were included. Patient demographics, perioperative data, surgical outcomes, morbidity, and mortality were described. Statistical and multivariate analyses were made. Statistical significance was reached when p values were <0.05., Results: A total of 66 patients were included. Male patients were 60.61% and the mean age was 69.24 years. Associated aortic diseases were aneurysms (68.18%), ulcer-related (4.55%), intramural-related hematoma (7.58%), trauma-related pathology (1.52%), and aortic dissection (30.30%). The mean hospital stay was 18.10 days, and intensive care unit was required for 98.48%. At 30 days, the mortality rate was 10.61% and the reintervention rate was 21.21%. Increased intraoperative blood loss (p=0.001) and male sex (p=0.04) showed statistical relationship with mortality. Underweight patients have 6.7 and 11.4 times more risk of complications and endoleak compared with higher body mass index values (p=0.04, 95% confidence interval [CI]=0.82-7.21) and (p=0.02, 95% CI=1.31-12.57), respectively., Conclusion: Thoracic endovascular aortic repair seems to be a feasible option for patients with thoracic aortic pathologies, with adequate rates of mortality and morbidity. Underweight patients seem to have an increased risk of overall morbidity and increased risk for endoleak. Further prospective studies are needed to prove our results., Clinical Impact: Obesity and BMI are widely studied in the surgical literature. According to our study, there is a paradox regarding the outcomes of patients treated with TEVAR in terms of postoperative complications and mortality related to the body mass index. And shouldn't be considered as a high-risk feature in terms of postoperative morbidity and mortality in this procedure., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background/aim: Recently developed vaccines for the SARS-CoV-2 virus utilize endogenous production of the virus' spike protein (SP), allowing the host to develop an immune response. As a result of the novelty of this virus and its vaccines, little is known overall about the potential effects of the SP on the pathogenesis of neoplasia, either from vaccination or from infection. This study was designed to investigate whether SARS-CoV-2 SP has any direct effect on SiHa cervical cancer cells., Materials and Methods: The effects of SARS-CoV-2 SP on cervical cancer cell proliferation and apoptosis were investigated by using clonogenic cell survival assay, quick cell proliferation assay, and caspase-3 activity kits in a widely-used cervical cancer cell line, SiHa. RT-PCR and immunohistochemistry were also performed to determine the potential molecular mechanisms., Results: The growth and proliferation of SiHa cancer cells were inhibited by SARS-CoV-2 SP. SARS-CoV-2 SP also induced apoptosis in SiHa cancer cells. The anti-proliferative effect of SARS-CoV-2 SP on SiHa cancer cells was associated with the up-regulation of the anti-proliferative molecule p53. The pro-apoptotic effect of SARS-CoV-2 SP on SiHa cells was associated with the up-regulation of the pro-apoptotic molecule TRAIL., Conclusion: SARS-CoV-2 SP inhibits the growth of cervical cancer via up-regulation of p53 and TRAIL. Further studies are needed to elaborate on the potential effects of the SARS-CoV-2 SP on other cancer cell lines and normal physiological cell lines for comparison., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Transcriptome analysis through next-generation sequencing (NGS) is an invaluable tool for investigating changes in gene expression across diverse organisms. The nematode Caenorhabditis elegans ( C. elegans ) serves as an excellent model organism for dissecting host responses to bacterial infections. Here, our dataset obtained from bulk RNA-sequencing (RNA-seq) can be used to provide in-depth characterization of the mRNA transcriptome profiles of wild-type N2 animals and null mutants of the cytoskeletal regulatory gene unc-53 /Nav2 following exposure to distinct bacterial environments: their natural laboratory food source, Escherichia coli OP50, the human and nematode pathogen Pseudomonas aeruginosa PA14, and the emerging pathogen Elizabethkingia anophelis Ag1. As proof of the dataset quality, downstream differential gene expression analysis reveals significant shifts in gene expression patterns within N2 and unc-53 mutants under varying bacterial conditions that will be useful for our companion studies investigating these pathways. These data provide an effective methodological framework for future investigators to investigate the interplay between cytoskeletal proteins and the innate immune response. The raw FASTQ files generated from our transcriptome experiment is deposited in the publicly available NCBI Sequence Read Archive (SRA) under the BioProject accession number PRJNA1010192, for further exploration and validation by the C. elegans research community., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Hepatitis C self-testing (HCVST) is emerging as an additional strategy that could help to expand access to HCV testing. We conducted a study to assess the usability and acceptability of two types of HCVST, oral fluid- and blood-based, among the general population and men who have sex with men (MSM) in Malaysia. An observational study was conducted in three primary care centres in Malaysia. Participants who were layman users performed the oral fluid- and blood-based HCVST sequentially. Usability was assessed by calculating the rate of errors observed, the rate of difficulties faced by participants as well as inter-reader (self-test interpreted by self-tester vs interpreted by trained user) and inter-operator concordances (self-test vs test performed by trained user). The acceptability of HCV self-testing was assessed using an interviewer-administered semi-structured questionnaire. Participants were also required to read contrived test results which included "positive", "negative", and "invalid". There was a total of 200 participants (100 general population, 100 MSM; mean age 33.6 ± 14.0 years). We found a high acceptability of oral fluid- and blood-based HCVST across both general population and MSM. User errors, related to timekeeping and reading within stipulated time, were common. However, the majority of the participants were still able to obtain and interpret results correctly, including that of contrived results, although there was substantial difficulty interpreting weak positive results. The high acceptability of HCVST among the participants did not appreciably change after they had experienced both tests, with 97.0% of all participants indicating they would be willing to use HCVST again and 98.5% of them indicating they would recommend it to people they knew. There was no significant difference between the general population and MSM in these aspects. Our study demonstrates that both oral fluid- and blood-based HCVST are highly acceptable among both the general population and MSM. Both populations also showed comparable ability to conduct the tests and interpret the results. Overall, this study suggests that HCVST could be introduced as an addition to existing HCV testing services in Malaysia. Further studies are needed to establish the optimal positioning of self-testing alongside facility-based testing to expand access to HCV diagnosis in the country., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Chan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: In 2019, the WHO released guidelines on HIV testing service (HTS). We aim to assess the adoption of six of these recommendations on HIV testing strategies among African countries., Design: Policy review., Setting: 47 countries within the WHO African region., Participants: National HTS policies from the WHO African region as of December 2021., Primary and Secondary Outcome Measures: Uptake of WHO recommendations across national HTS policies including the standard three-test strategy; discontinuation of a tiebreaker test to rule in HIV infection; discontinuation of western blotting (WB) for HIV diagnosis; retesting prior to antiretroviral treatment (ART) initiation and the use of dual HIV/syphilis rapid diagnostic tests (RDTs) in antenatal care. Country policy adoption was assessed on a continuum, based on varying levels of complete adoption., Results: National policies were reviewed for 96% (n=45/47) of countries in the WHO African region, 38% (n=18) were published before 2019 and 60% (n=28) adopted WHO guidance. Among countries that had not fully adopted WHO guidance, not yet adopting a three-test strategy was the most common reason for misalignment (45%, 21/47); of which 31% and 22% were in low-prevalence (<5%) and high-prevalence (≥5%) countries, respectively. Ten policies (21%) recommended the use of WB and 49% (n=23) recommended retesting before ART initiation. Dual HIV/syphilis RDTs were recommended in 45% (n=21/47) of policies., Conclusions: Many countries in the African region have adopted WHO-recommended HIV testing strategies; however, efforts are still needed to fully adopt WHO guidance. Countries should accelerate their efforts to adopt and implement a three-test strategy, retesting prior to ART initiation and the use of dual HIV/syphilis RDTs., Competing Interests: Competing interests: None declared., (© World Health Organization 2023. Licensee BMJ.)

Introduction: Arterial injuries following central venous catheterization (CVC) range between 0.1%-2.7%. The open surgical approach could be related to increased rates of morbidity and mortality. Vascular closure devices (VCD) are often used for the management of these patients with a success rate of up to 80%., Objectives: Describe our experience in managing arterial vascular injuries following central venous catheterization with Perclose ProGlide (Abbott Vascular IncSanta Clara, CA, USA)., Methods: A retrospective review of all patients over 18 years old who underwent percutaneous closure of arterial injuries following central venous catheterization in our center between January 2018 and May 2023 was included and reported with a 90-day follow-up., Results: 3 Patients were included, in all cases, access to the CVC were right with a subclavian artery injury. Ultrasound and fluoroscopy guide was used in all cases. For the 3 cases, a percutaneous technique using Perclose ProGlide (Abbott Vascular IncSanta Clara, CA, USA) was performed. With a 100% success rate, and no complications evidenced after 90 days of follow-up., Conclusion: Inadvertent arterial catheterization it's a non-negligible complication after CVC placement. VCD could be considered a safe and feasible approach for the management of these traumatic injuries., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Rey Chaves, Orozco, Posada, Gómez Zuleta, Fajardo, Barón and Hernández Rodríguez.)

MXenes are a rapidly growing family of 2D transition metal carbides and nitrides that are promising for various applications, including energy storage and conversion, electronics, and healthcare. Hydrofluoric-acid-based etchants are typically used for large-scale and high-throughput synthesis of MXenes, which also leads to a mixture of surface terminations that impede MXene properties. Herein, a computational thermodynamic model with experimental validation is presented to explore the feasibility of fluorine-free synthesis of MXenes with uniform surface terminations by dry selective extraction (DSE) from precursor MAX phases using iodine vapors. A range of MXenes and respective precursor compositions are systematically screened using first-principles calculations to find candidates with high phase stability and low etching energy. A thermodynamic model based on the "CALculation of PHAse Diagrams" (CALPHAD) approach is further demonstrated, using Ti 3 C 2 I 2 as an example, to assess the Gibbs free energy of the DSE reaction and the state of the byproducts as a function of temperature and pressure. Based on the assessment, the optimal synthesis temperature and vapor pressure are predicted and further verified by experiments. This work opens an avenue for scalable, fluorine-free dry synthesis of MXenes with compositions and surface chemistries that are not accessible using wet chemical etching., (© 2023 Wiley-VCH GmbH.)

Background: Preservation solutions may be used intraoperatively during coronary artery bypass grafting (CABG) to flush and preserve vein grafts. The aim of this study is to evaluate the effect of DuraGraft, an endothelial damage inhibitor (EDI) preservation solution on major adverse cardiac events (MACEs) after CABG., Methods: We conducted an observational, prospective, longitudinal, single-center study that included patients who underwent isolated CABG. The cohort treated with an EDI was matched 1:1 with a control group treated with conventional vein preservation, and matching was adjusted for possible confounding factors through propensity score (PS) matching. Three years follow-up was conducted, and the occurrence of MACE [defined as all cause-death, acute coronary syndrome (ACS), and new unplanned revascularization] was analyzed using Kaplan-Meier method., Results: The study included 180 patients, 90 in each group. There were no significant differences in baseline characteristics across study groups. The EDI group had a significantly better event-free survival at 3 years (89% vs . 78%, log-rank test P=0.035), with an incidence rate ratio of 0.41 [95% confidence interval (CI): 0.16-0.96]. In the pre-specified subgroups analysis, the use of an EDI was associated with a significantly better event-free survival in diabetic patients (log-rank test P=0.041) and those with two or more saphenous vein grafts (log-rank test P=0.015)., Conclusions: The utilization of an EDI for vein flushing and storage after vein harvest in CABG procedures has been shown to significantly decrease the incidence of MACE at 3 years post-surgery. This protective effect is particularly notable in diabetic patients and in individuals who have multiple vein grafts., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-636/coif). The authors have no conflicts of interest to declare., (2023 Journal of Thoracic Disease. All rights reserved.)

Background: Many people who have a positive hepatitis C virus (HCV) antibody (Ab) test never receive a confirmatory HCV RNA viral load (VL) test. Reflex VL testing may help address this problem. We undertook a systematic review to evaluate the effectiveness of reflex VL testing compared with standard nonreflex approaches on outcomes across the HCV care cascade., Methods: We searched 4 databases for studies that examined laboratory-based reflex or clinic-based reflex VL testing approaches, with or without a nonreflex comparator, and had data on the uptake of HCV RNA VL test and treatment initiation and turnaround time between Ab and VL testing. Both laboratory- and clinic-based reflex VL testing involve only a single clinic visit. Summary estimates were calculated using random-effects meta-analyses., Results: Fifty-one studies were included (32 laboratory-based and 19 clinic-based reflex VL testing). Laboratory-based reflex VL testing increased HCV VL test uptake versus nonreflex testing (RR: 1.35; 95% CI: 1.16-1.58) and may improve linkage to care among people with a positive HCV RNA test (RR: 1.47; 95% CI: .81-2.67) and HCV treatment initiation (RR: 1.03; 95% CI: .46-2.32). The median time between Ab and VL test was <1 day for all laboratory-based reflex studies and 0-5 days for 13 clinic-based reflex testing., Conclusions: Laboratory-based and clinic-based HCV reflex VL testing increased uptake and reduced time to HCV VL testing and may increase HCV linkage to care. The World Health Organization now recommends reflex VL testing as an additional strategy to promote access to HCV VL testing and treatment., Clinical Trials Registration: PROSPERO CRD42021283822., Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Melanoma is the most lethal malignancy in skin cancers. About 97,610 new cases of melanoma are projected to occur in the United States (US) in 2023. Artichoke is a very popular plant widely consumed in the US due to its nutrition. In recent years, it has been shown that artichoke shows powerful anti-cancer effects on cancers such as breast cancer, colon cancer, liver cancer, and leukemia. However, there is little known about its effect on melanoma. This study was designed to investigate if artichoke extract (AE) has any direct effect on the growth of melanoma. Clonogenic survival assay, cell proliferation, and caspase-3 activity kits were used to evaluate the effects AE has on cell survival, proliferation, and apoptosis of the widely studied melanoma cell line HTB-72. We further investigated the possible molecular mechanisms using RT-PCR and immunohistochemical staining. The percentage of colonies of HTB-72 melanoma cells decreased significantly after treated with AE. This was paralleled with the decrease in the optic density (OD) value of cancer cells after treatment with AE. This was further supported by the decreased expression of PCNA mRNA after treated with AE. Furthermore, the cellular caspase-3 activity increased after treated with AE. The anti-proliferative effect of AE on melanoma cells correlated with increased p21, p27, and decreased CDK4. The pro-apoptotic effect of AE on melanoma cells correlated with decreased survivin. Artichoke inhibits growth of melanoma by inhibition of proliferation and promotion of apoptosis. Such a study might be helpful to develop a new promising treatment for melanoma., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Globally, there are approximately 58 million people with chronic hepatitis C virus infection (HCV) but only 20% have been diagnosed. HCV self-testing (HCVST) could reach those who have never been tested and increase uptake of HCV testing services. We compared cost per HCV viraemic diagnosis or cure for HCVST versus facility-based HCV testing services. We used a decision analysis model with a one-year time horizon to examine the key drivers of economic cost per diagnosis or cure following the introduction of HCVST in China (men who have sex with men), Georgia (men 40-49 years), Viet Nam (people who inject drugs, PWID), and Kenya (PWID). HCV antibody (HCVAb) prevalence ranged from 1%-60% across settings. Model parameters in each setting were informed by HCV testing and treatment programmes, HIV self-testing programmes, and expert opinion. In the base case, we assume a reactive HCVST is followed by a facility-based rapid diagnostic test (RDT) and then nucleic acid testing (NAT). We assumed oral-fluid HCVST costs of $5.63/unit ($0.87-$21.43 for facility-based RDT), 62% increase in testing following HCVST introduction, 65% linkage following HCVST, and 10% replacement of facility-based testing with HCVST based on HIV studies. Parameters were varied in sensitivity analysis. Cost per HCV viraemic diagnosis without HCVST ranged from $35 2019 US dollars (Viet Nam) to $361 (Kenya). With HCVST, diagnosis increased resulting in incremental cost per diagnosis of $104 in Viet Nam, $163 in Georgia, $587 in Kenya, and $2,647 in China. Differences were driven by HCVAb prevalence. Switching to blood-based HCVST ($2.25/test), increasing uptake of HCVST and linkage to facility-based care and NAT testing, or proceeding directly to NAT testing following HCVST, reduced the cost per diagnosis. The baseline incremental cost per cure was lowest in Georgia ($1,418), similar in Viet Nam ($2,033), and Kenya ($2,566), and highest in China ($4,956). HCVST increased the number of people tested, diagnosed, and cured, but at higher cost. Introducing HCVST is more cost-effective in populations with high prevalence., Competing Interests: EI and SS are current employees of FIND, EF is a former employee of FIND. JGW and PV have received unrestricted research funding from Gilead Sciences unrelated to this research. All authors declare no other conflicts of interest. The views expressed in this manuscript are those of the authors and do not necessarily represent the official position, decisions, policy or views of the WHO or UNAIDS. There are no patents, products in development or marketed products associated with this research to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Walker et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Point-of-care (POC) hepatitis C virus (HCV) RNA nucleic acid test viral load assays are being used increasingly as an alternative to centralised, laboratory-based standard-of-care (SOC) viral load assays to reduce loss to follow-up. We aimed to evaluate the impact of using POC compared with SOC approaches on uptake of HCV RNA viral load testing and treatment, and turnaround times from testing to treatment along the HCV care cascade., Methods: We searched PubMed, Embase, and Web of Science for studies published in English between Jan 1, 2016, and April 13, 2022. We additionally searched for accepted conference abstracts (2016-20) not identified in the main search. The contacts directory of the WHO Global Hepatitis Programme was also used to solicit additional studies on use of POC RNA assays. We included studies if they evaluated use of POC HCV RNA viral load with or without a comparator laboratory-based SOC assay, and had data on uptake of viral load testing and treatment, and turnaround times between these steps in cascade. We excluded studies with a sample size of ten or fewer participants. The POC studies were categorised according to whether the POC assay was based onsite at the clinic, in a mobile unit, or in a laboratory. Studies using the POC assay or comparator SOC assays were further stratified according to four models of care: whether HCV testing and treatment initiation were performed in the same or different site, and on the same or a different visit. The comparator was centralised, laboratory-based HCV RNA SOC assays. For turnaround times, we calculated the weighted median of medians with 95% CIs. We analysed viral load testing and treatment uptake using random-effects meta-analysis. The quality of evidence was rated using the GRADE framework. This study is registered with PROSPERO, CRD42020218239., Findings: We included 45 studies with 64 within-study arms: 28 studies were in people who inject drugs, were homeless, or both; four were in people incarcerated in prison; nine were in the general or mixed (ie, includes high-risk groups) populations; and four were in people living with HIV. All were observational studies. The pooled median turnaround times between HCV antibody test and treatment initiation was shorter with onsite POC assays (19 days [95% CI 14-53], ten arms) than with either laboratory-based POC assays (64 days [64-64], one arm) or laboratory-based SOC assays (67 days [50-67], two arms). Treatment uptake was higher with onsite POC assays (77% [95% CI 72-83], 34 arms) or mobile POC assays (81% [60-97], five arms) than with SOC assays (53% [31-75], 12 arms); onsite and mobile POC assay vs SOC assay p=0·029). For POC and SOC arms, higher RNA viral load testing uptake was seen with the same-site models for testing and treatment than with different-site models (all within-category p≤0·0001). For onsite and mobile POC arms, there was higher treatment uptake for same-site than different-site models (within-category p<0·0001). Four studies had direct within-study POC versus SOC comparisons for RNA viral load testing uptake (pooled relative risk 1·11 [95% CI 0·89-1·38]), and there were ten studies on treatment uptake (1·32 [1·06-1·64]). Overall, the quality of evidence was rated as low., Interpretation: Compared with use of laboratory-based SOC HCV viral load testing, the use of POC assays was associated with reduced time from antibody test to treatment initiation and increased treatment uptake. The effect of POC viral load testing is greatest when positioned within a simplified care model in which testing and treatment are provided at the same site, and, where possible, on the same day. POC HCV RNA viral load testing is now recommended in WHO guidelines as an alternative strategy to laboratory-based viral load testing., Funding: Unitaid., Competing Interests: Declaration of interests We declare no competing interests., (© 2023 World Health Organization; licensee Elsevier. This is an Open Access article published under the CC BY 3.0 IGO license which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. In any use of this article, there should be no suggestion that WHO endorses any specific organisation, products or services. The use of the WHO logo is not permitted. This notice should be preserved along with the article's original URL.)

The prevalence of respiratory failure is increasing in the contemporary cardiac intensive care unit (CICU) and is associated with a significant increase in morbidity and mortality. For patients that survive their initial respiratory decompensation, liberation from invasive mechanical ventilation (IMV) and the decision to extubate requires careful clinical assessment and planning. Therefore, it is essential for the CICU clinician to know how to assess and manage the various stages of IMV liberation, including ventilator weaning, evaluation of extubation readiness, and provide post-extubation care. In this review, we provide a comprehensive approach to liberation from IMV in the CICU, including cardiopulmonary interactions relative to withdrawal from positive pressure ventilation, evaluation of readiness for and assessment of spontaneous breathing trials, sedation management to optimize extubation, strategies for patients at a high risk for extubation failure, and tracheostomy in the cardiovascular patient., Competing Interests: Dr Miller has received research funding from Fisher & Paykel. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2023 The Authors.)

Background and Aims: The benefits of Mediterranean Diet (MeDiet) in prevention of cardiovascular diseases (CVD) in general and ischemic stroke (IS) have been extensively studied and reported. We hypothesize that the consumption of nutrients typical of MeDiet would also reduce the rate of silent brain infarcts (SBI) among AF patients., Methods and Results: Patients with a history of AF who scored 0 to 1 in the CHADS2 score, ⩾50 years and with absence of neurological symptoms were selected from Seville urban area using the Andalusian electronic healthcare database. A 3T brain MRI was performed to all participants. Demographic and clinical data and food-frequency questionnaire (FFQ) were collected. Of the 443 scanned patients, 66 presented SBI. Of them 52 accepted to be scheduled for a clinical visit and were included in the diet sub study and 41 controls were matched per age and sex. There were no statistically significant differences in baseline characteristics. After logistic regression analysis, we found that a higher consumption of fiber from fruit was independently associated with a lower risk of SBI, while a higher consumption of high glycemic load (GL) foods was associated with a higher risk of SBI in a population with AF., Conclusion: Our findings support that MeDiet could be suggested as a prevention strategy for SBI in patients with AF., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Background: Both pulmonary and mental health are affected following hospitalization for COVID-19 pneumonia. Pulmonary rehabilitation therapy has demonstrated benefits in improving mental health, but no validated combined programs that include mental health have been proposed., Objective: This article presents the design of a trial that aimed to assess whether the participation in a combined rehabilitation program that includes home-based respiratory physiotherapy and telephone-based psychological support is associated with a greater improvement of pulmonary and mental health outcomes 7-12 weeks after COVID-19 hospitalization discharge compared with posthospital usual care provided by a public Peruvian hospital., Methods: WAYRA (the word for air in the Quechua language) was an open-label, unblinded, two-arm randomized controlled trial. We recruited 108 participants aged 18-75 years who were discharged from the hospital after COVID-19 pneumonia that required >6 liters/minute of supplemental oxygen during treatment. Participants were randomly assigned at a 1:1 ratio to receive the combined rehabilitation program or usual posthospital care provided by a public Peruvian hospital. The intervention consisted of 12 at-home respiratory rehabilitation sessions and 6 telephone-based psychological sessions. The primary outcome was the 6-minute walk distance. Secondary outcomes included lung function, mental health status (depression, anxiety, and trauma), and quality of life. Outcomes were assessed at baseline (before randomization) and at 7 and 12 weeks after hospital discharge to assess the difference between arms., Results: This study was funded by the Peruvian National Council of Science Technology and Technology Innovation in July 2020. Ethics approval was obtained on September 2, 2020. Recruitment and data collection occurred between October 2020 and June 2021. Results are expected to be published by the end of 2022., Conclusions: WAYRA was the first randomized controlled trial evaluating combined pulmonary-mental health rehabilitation for hospitalized COVID-19 survivors in resource-limited settings, potentially providing a foundation for the cost-effective scale-up of similar multidisciplinary rehabilitation programs., Trial Registration: ClinicalTrials.gov NCT04649736; https://clinicaltrials.gov/ct2/show/NCT04649736., International Registered Report Identifier (irrid): RR1-10.2196/36001., (©Anderson N Soriano-Moreno, Elaine C Flores, Stella M Hartinger, Claudia Y Mallma, Arnold A Diaz, Gonzalo E Gianella, Juan A Galvez-Buccollini, Abdiel H Coico-Lama, German Malaga, Eufemia Fajardo, Rubí Paredes-Angeles, Sharlyn Otazú-Alfaro, Andres G Lescano, William Checkley, WAYRA Trial Investigators. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 24.10.2022.)

Background: People who inject drugs (PWID) are disproportionally affected by hepatitis C virus (HCV) infection and many remain undiagnosed. HCV self-testing (HCVST) may be an effective approach to increase testing uptake, but has rarely been used among PWID. We assessed the usability and acceptability of HCVST among PWID in Kenya., Methods: We conducted a cross-sectional study nested within a cohort study between August and December 2020 on Kenya's North Coast region. Participants were handed a prototype oral fluid HCVST kit and asked to conduct the test relying on the instructions for use. Usability was assessed by documenting errors made and difficulties faced by participants. Acceptability was assessed using an interviewer-administered semi-structured questionnaire., Results: Among 150 participants, 19% were female and 65.3% had primary level education or lower. 71.3% made at least one error, 56.7% experienced some difficulty during at least one step, and the majority of participants (78%) required assistance during at least one step of the procedure. Most common errors occurred when placing the tube into the stand (18%), collecting the oral fluid sample (24%) and timing of reading results (53%). There was a strong association between presence of symptoms of opiate withdrawals and observed errors (94% vs 62%; p = 0.016) in a sub-group of 74 participants assessed. Inter-reader and inter-operator concordance were 97.7% (kappa: 0.92) and 99.2% (kappa: 0.95), respectively. Acceptability assessed by asking whether participants would choose to use HCVST prior to and after conducting HCVST was 98% and 95%, respectively., Conclusions: We found a high acceptability of oral fluid HCVST among PWID. User errors were common and were associated with the presence of withdrawal symptoms among users. Despite errors, most participants were able to obtain and interpret results correctly. These findings suggest that this group of users may benefit from greater messaging and education including options to receive direct assistance when self-testing for HCV., (© 2022. The Author(s).)

The insulin receptor (INSR) is an evolutionarily conserved signaling protein that regulates development and cellular metabolism. INSR signaling promotes neurogenesis in Drosophila; however, a specific role for the INSR in maintaining adult neural stem cells (NSCs) in mammals has not been investigated. We show that conditionally deleting the Insr gene in adult mouse NSCs reduces subventricular zone NSCs by ∼70% accompanied by a corresponding increase in progenitors. Insr deletion also produced hyposmia caused by aberrant olfactory bulb neurogenesis. Interestingly, hippocampal neurogenesis and hippocampal-dependent behaviors were unperturbed. Highly aggressive proneural and mesenchymal glioblastomas had high INSR/insulin-like growth factor (IGF) pathway gene expression, and isolated glioma stem cells had an aberrantly high ratio of INSR:IGF type 1 receptor. Moreover, INSR knockdown inhibited GBM tumorsphere growth. Altogether, these data demonstrate that the INSR is essential for a subset of normal NSCs, as well as for brain tumor stem cell self-renewal., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Hepatitis C virus self-testing (HCVST) is an additional approach that may expand access to HCV testing. We conducted a mixed-methods cross-sectional observational study to assess the usability and acceptability of HCVST among people who inject drugs (PWID), men who have sex with men (MSM) and transgender (TG) people in Tbilisi, Georgia., Methods: The study was conducted from December 2019 to June 2020 among PWID at one harm reduction site and among MSM/TG at one community-based organization. We used a convergent parallel mixed-methods design. Usability was assessed by observing errors made and difficulties faced by participants. Acceptability was assessed using an interviewer-administered semi-structured questionnaire. A subset of participants participated in cognitive and in-depth interviews., Results: A total of 90 PWID, 84 MSM and 6 TG were observed performing HCVST. PWID were older (median age 35 vs 24) and had a lower level of education compared to MSM/TG (27% vs 59%). The proportion of participants who completed all steps successfully without assistance was 60% among PWID and 80% among MSM/TG. The most common error was in sample collection and this was observed more often among PWID than MSM/TG (21% vs 6%; p = 0.002). More PWID requested assistance during HCVST compared to MSM/TG (22% vs 8%; p = 0.011). Acceptability was high in both groups (98% vs 96%; p = 0.407). Inter-reader agreement was 97% among PWID and 99% among MSM/TG. Qualitative data from cognitive (n = 20) and in-depth interviews (n = 20) was consistent with the quantitative data confirming a high usability and acceptability., Conclusions: HCVST was highly acceptable among key populations in Georgia of relatively high educational level, and most participants performed HCVST correctly. A significant difference in usability was observed among PWID compared to MSM/TG, indicating that PWID may benefit from improved messaging and education as well as options to receive direct assistance when self-testing for HCV., (© 2022. The Author(s).)

Despite the widespread availability of curative treatment with direct-acting antivirals, a significant proportion of people with HCV remain undiagnosed and untreated. New point-of-care (PoC) HCV RNA assays that can be used in clinical settings may help expand access to testing and treatment. This study aimed to evaluate the diagnostic performance of PoC HCV viral load assays compared to laboratory-based testing. Methods: We searched three databases for studies published before May 2021 that evaluated PoC HCV RNA assays against a laboratory NAT reference standard (Prospero CRD42021269022). Random effects bivariate models were used to summarize the estimates. Stratified analyses were performed based on geographic region, population (PWID, etc.), and specimen type (serum/plasma or fingerstick; fresh or frozen). We used the GRADE approach to assess the certainty of the evidence. Results: A total of 25 studies were eligible. We evaluated five different commercially available viral load assays. The pooled sensitivity and specificity were 99% (95% CI: 98−99%) and 99% (95% CI: 99−100%), respectively. High sensitivity and specificity were observed across different assays, study settings (including LMICs and HICs), and populations. There was a small but statistically significant reduction in sensitivity for fingersticks compared to serum or plasma samples (98% vs. 100%, p < 0.05), but the specificity was similar between frozen and fresh samples. The evidence was rated as moderate-high certainty. Conclusions: PoC HCV viral load assays demonstrate excellent diagnostic performance in various settings and populations. The WHO now recommends using PoC HCV viral load assays as an additional strategy to promote access to confirmatory viral load testing and treatment.

The coronavirus disease 2019 (COVID-19) pandemic has revealed that even the best-resourced hospitals may lack sufficient ventilators to support patients under surge conditions. During a pandemic or mass trauma, an affordable, low-maintenance, off-the-shelf device that would allow health care teams to rapidly expand their ventilator capacity could prove lifesaving, but only if it can be safely integrated into a complex and rapidly changing clinical environment. Here, we define an approach to safe ventilator sharing that prioritizes predictable and independent care of patients sharing a ventilator. Subsequently, we detail the design and testing of a ventilator-splitting circuit that follows this approach and describe our clinical experience with this circuit during the COVID-19 pandemic. This circuit was able to provide individualized and titratable ventilatory support with individualized positive end-expiratory pressure (PEEP) to 2 critically ill patients at the same time, while insulating each patient from changes in the other's condition. We share insights from our experience using this technology in the intensive care unit and outline recommendations for future clinical applications., Competing Interests: Conflicts of Interest: See Disclosures at the end of the article., (Copyright © 2021 International Anesthesia Research Society.)

To investigate the effects of isolated SARS-CoV-2 spike protein on prostate cancer cell survival. The effects of SARS-CoV-2 spike protein on LNCaP prostate cancer cell survival were assessed using clonogenic cell survival assay, quick cell proliferation assay, and caspase-3 activity kits. RT-PCR and immunohistochemistry were performed to investigate underlying molecular mechanisms. SARS-CoV-2 spike protein was found to inhibit prostate cancer cell proliferation as well as promote apoptosis. Further investigation revealed that anti-proliferative effects were associated with downregulation of the pro-proliferative molecule cyclin-dependent kinase 4 (CDK4). The increased rate of apoptosis was associated with the upregulation of pro-apoptotic molecule Fas ligand (FasL). SARS-CoV-2 spike protein inhibits the growth of LNCaP prostate cancer cells in vitro by a two-pronged approach of downregulating the expression of CDK4 and upregulating FasL. The introduction of SARS-CoV-2 spike protein into the body via COVID-19 vaccination may have the potential to inhibit prostate cancer in patients. This potential beneficial association between COVID-19 vaccines and prostate cancer inhibition will require more extensive studies before any conclusions can be drawn about any in vivo effects in a human model., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Craniopharyngiomas (CPs) are rare tumors of the sellar and suprasellar regions of embryonic origin. The primary treatment for CPs is surgery but it is often unsuccessful. Although CPs are considered benign tumors, they display a relatively high recurrence rate that might compromise quality of life. Previous studies have reported that CPs express sex hormone receptors, including estrogen and progesterone receptors. Here, we systematically analyzed estrogen receptor α (ERα) and progesterone receptor (PR) expression by immunohistochemistry in a well-characterized series of patients with CP ( n = 41) and analyzed their potential association with tumor aggressiveness features. A substantial proportion of CPs displayed a marked expression of PR. However, most CPs expressed low levels of ERα. No major association between PR and ERα expression and clinical aggressiveness features was observed in CPs. Additionally, in our series, β-catenin accumulation was not related to tumor recurrence.

Background: Melanoma is the deadliest variant of skin cancer and its incidence continues to increase. There are limited treatment options for advanced and metastatic cases of melanoma, despite advances in immunotherapy and chemotherapy. Melanoma is notorious as a radioresistant tumor. Previous studies found that phytochemicals, such as resveratrol and those found in green tea and blueberry, can sensitize various cancer cells, including melanoma, to radiotherapy. Our previous study also revealed that kiwifruit extract (KE) has antitumor activity to melanoma cells. This study was designed to expand upon our previous investigation and determine KE's potential as a radiosensitizer on CRL-11147 melanoma cancer cells and elucidate the possible mechanisms behind its potential., Materials and Methods: Proliferation and apoptosis of CRL-11147 melanoma cells under radiation therapy (RT) plus KE versus RT alone were investigated using Proliferative cell nuclear antigen (PCNA) staining, quick cell proliferation assay, clonogenic assay, and caspase-3 activity assay. Reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC) were then used to investigate the mechanisms behind the observed results., Results: The percentage of CRL-11147 colonies, PCNA staining intensity, and the optic density value of CRL-11147 cells decreased with RT/KE vs. RT alone. Relative caspase-3 activity was increased with RT/KE vs. RT alone. Increased expression of the anti-proliferative molecule p27 and pro-apoptotic molecule TRAILR1 correlated with the anti-tumor effect seen in the RT/KE group versus the RT alone group., Conclusion: KE augments radiosensitivity of CRL-11147 by up-regulating both p27 and TRAILR1 to inhibit proliferation and increase apoptosis, respectively., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: In 2018, Rwanda launched a 5-year hepatitis C virus (HCV) elimination plan as per the World Health Organization global targets to eliminate HCV by 2030. To improve awareness of HCV status, strategies are needed to ensure easy access to HCV testing by as-yet unreached populations. HCV-self-testing, an innovative strategy, could further increase HCV testing uptake. This assessment explores perceptions around HCV self-testing among members of the public and healthcare workers in Rwanda., Methods: A qualitative study was undertaken in Masaka District Hospital, comprising individual interviews, group interviews and participatory action research (PAR) activities. Purposive and snowball sampling methods guided the selection of informants. Informed consent was obtained from all participants. A thematic analysis approach was used to analyse the findings., Results: The participants comprised 36 members of the public and 36 healthcare workers. Informants appreciated HCV self-testing as an innovative means of increasing access to HCV testing, as well as an opportunity to test privately and subsequently autonomously decide whether to seek further HCV care. Informants further highlighted the need to make HCV self-testing services free of charge at the nearest health facility. Disadvantages identified included the lack of pre/post-test counselling, as well as the potential psychosocial harm which may result from the use of HCV self-testing., Conclusion: HCV self-testing is perceived to be an acceptable method to increase HCV testing in Rwanda. Further research is needed to assess the impact of HCV self-testing on HCV cascade of care outcomes., (© 2021. The Author(s).)

Background: The prevalence of hepatitis C virus (HCV) among people who inject drugs (PWID) continues to be a major public-health burden in this highly stigmatised population. To halt transmission of HCV, rapid HCV self-testing kits represent an innovative approach that could enable PWID to know their HCV status and seek treatment. As no HCV test has yet been licenced for self-administration, it is crucial to obtain knowledge around the factors that may deter or foster delivery of HCV self-testing among PWID in resource-constrained countries., Methods: A qualitative study to assess values and preferences relating to HCV self-testing was conducted in mid-2020 among PWID in the Bishkek and Chui regions of Kyrgyzstan. Forty-seven PWID participated in 15 individual interviews, two group interviews (n = 12) and one participatory action-research session (n = 20). Responses were analysed using a thematic analysis approach with 4 predefined themes: awareness of HCV and current HCV testing experiences, and acceptability and service delivery preferences for HCV self-testing. Informants' insights were analysed using a thematic analysis approach. This research received local ethics approval., Results: Awareness of HCV is low and currently PWID prefer community-based HCV testing due to stigma encountered in other healthcare settings. HCV self-testing would be accepted and appreciated by PWID. Acceptability may increase if HCV self-testing: was delivered in pharmacies or by harm reduction associations; was free of charge; was oral rather than blood-based; included instructions with images and clear information on the test's accuracy; and was distributed alongside pre- and post-testing counselling with linkage to confirmatory testing support., Conclusions: HCV self-testing could increase awareness of and more frequent testing for HCV infection among PWID in Kyrgyzstan. It is recommended that peer-driven associations are involved in the delivery of any HCV self-testing. Furthermore, efforts should be maximised to end discrimination against PWID at the healthcare institutions responsible for confirmatory HCV testing and treatment provision.