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Abstract Objective To assess asymptomatic rates and severity of SARS‐CoV‐2 infection in people with epilepsy and their healthcare workers in a long‐term care facility which had implemented weekly surveillance testing between April 2020 and June 2022. Methods Questionnaires focused on objective and subjective COVID‐19 symptoms for people with epilepsy residing in and their healthcare workers at the Chalfont Centre for Epilepsy in June 2022. Demographic information, comorbidities, and seizure frequency were gathered from medical records. We also collected responses on objective and subjective COVID‐19 symptoms from healthcare workers who participated in a prospective study assessing the reaction to COVID‐19 vaccinations (SAFER). Results Fifty‐five out of 89 (62%) residents tested positive at least once on weekly PCR testing for SARS‐CoV‐2 during the period of interest; 20 of those (37%) were asymptomatic. In comparison, of those 63 healthcare workers who tested positive at least once on weekly testing during the same period, only four (6%) were asymptomatic. Of the 159 healthcare workers who also participated in the SAFER study, 41 tested positive at least once, and seven (17%) were completely asymptomatic during infection with SARS‐CoV‐2. Significance People with epilepsy living in a long‐term care facility were more likely to present with asymptomatic SARS‐CoV‐2 infections than healthcare workers at the same facility. Despite possible bias in the reporting of subjective symptoms due to management‐by‐proxy, there is no evidence that vulnerable people living in an epilepsy long‐term care facility showed reduced resilience towards infections. Plain Language Summary People with epilepsy living in care home facilities had a surprisingly high degree of asymptomatic infections with SARS‐CoV‐2. Very few residents had severe or fatal outcomes. This is in stark contrast to the widely reported bad outcomes for people without epilepsy in other care homes. People with epilepsy reported significantly less symptoms than their healthcare workers. No changes in seizure frequency during or after infection were observed.

Background Exposure to fine particulate matter (

Abstract Background Pamiparib is a potent, selective, poly (ADP‐ribose) polymerase 1/2 inhibitor that demonstrates synthetic lethality in cells with breast cancer susceptibility gene mutations or other homologous recombination deficiency. This two‐stage phase 1b study (NCT03150810) assessed pamiparib in combination with temozolomide (TMZ) in adult patients with histologically confirmed locally advanced and metastatic solid tumors. Methods Oral pamiparib 60 mg was administered twice daily. During the dose‐escalation stage, increasing doses of TMZ (40–120 mg once daily pulsed or 20–40 mg once daily continuous) were administered to determine the recommended dose to be administered in the dose‐expansion stage. The primary objectives were to determine safety and tolerability, maximum tolerated/administered dose, recommended phase 2 dose and schedule, and antitumor activity of pamiparib in combination with TMZ. Pharmacokinetics of pamiparib and TMZ and biomarkers were also assessed. Results Across stages, 139 patients were treated (dose escalation, n = 66; dose expansion, n = 73). The maximum tolerated dose of TMZ, which was administered during dose expansion, was 7‐day pulsed 60 mg once daily. The most common treatment‐emergent adverse events (TEAEs) were anemia (dose escalation, 56.1%; dose expansion, 63.0%), nausea (dose escalation, 54.5%; dose expansion, 49.3%), and fatigue (dose escalation, 48.5%; dose expansion, 47.9%). In the dose‐escalation stage, four patients experienced dose‐limiting toxicities (three neutropenia and one neutrophil count decreased). No TEAEs considered to be related to study drug treatment resulted in death. Antitumor activity was modest, indicated by confirmed overall response rate (dose escalation, 13.8%; dose expansion, 11.6%), median progression‐free survival (3.7 and 2.8 months), and median overall survival (10.5 and 9.2 months). Administration of combination therapy did not notably impact pamiparib or TMZ pharmacokinetics. Conclusions Pamiparib in combination with TMZ had a manageable safety profile. Further investigation of the efficacy of this combination in tumor types with specific DNA damage repair deficiencies is warranted.

Abstract Primary renal involvement by T lymphoblasts is rare among adults with T acute lymphoblastic leukaemia. We report a 28‐year‐old man presenting with acute renal failure due to infiltration by T lymphoblasts and his response to paediatric‐inspired modified BFM‐90 protocol. The patient achieved an initial complete remission (CR) but developed central nervous system relapse. He achieved CR2 with cranial irradiation and intrathecal chemotherapy. He underwent a haploidentical transplant in CR2 and remains in remission post‐transplant day 330. An early kidney biopsy helped confirm the diagnosis. Such presentations remain responsive to modified BFM‐90. An early allotransplant in CR2 remains the standard of care.

Abstract Background and Objectives Ethanol has been reported to improve tremor severity in approximately two thirds of patients with essential tremor (ET), but the accuracy of that proportion is not certain and the mechanism of action is unknown. The goal of this study was to investigate alcohol response on tremor by applying an a priori objective response definition and subsequently to describe the responder rate to a standardized ethanol dose in a cohort of 85 ET patients. A secondary analysis evaluated other tremor and nontremor features, including demographics, tremor intensity, breath alcohol concentration, nontremor effects of alcohol, self‐reported responder status to ethanol, and prior ethanol exposure. Methods This was a prospective, open‐label, single‐dose challenge of oral ethanol during which motor and nonmotor measurements were obtained starting immediately prior to ethanol administration and subsequently every 20 min for 120 min. We defined tremor reduction as a 35% decline in power in the patient's tremor frequency recorded during spiral drawing 60 min after ethanol administration. Results In total, 80% of patients were considered alcohol responsive using our objective definition. Responder status and change in the objective tremor metrics were significantly correlated with the change in breath alcohol concentration levels after ethanol administration, but no other relationships to nontremor metrics were found. Discussion A high percentage of patients actually respond to acute ethanol. However, their self‐reported response does not correlate well with their objective response. Objective response correlates with breath alcohol level but not with sedation, indicating a specific effect of ethanol on tremor.

Key Clinical Message Heme oxygenase deficiency, a rare condition disrupting heme metabolism, has only nine reported cases. We present a 3‐year‐old boy with dysmorphic facies, asplenia, and normal bilirubin levels despite ongoing hemolysis. Blood transfusions sustained hemoglobin while IV steroids managed inflammation.

Key Clinical Message Advanced MRI techniques, including SWI, MinIP, and QSM, are instrumental in detecting the “motor band sign” in ALS, aiding in the early diagnosis and assessment of upper motor neuron involvement, which is critical for therapeutic interventions.

Background Cytochrome P450 2C19 (CYP2C19) intermediate and poor metabolizer patients exhibit diminished clopidogrel clinical effectiveness after percutaneous coronary intervention (PCI). However, outcome studies to date have lacked racial diversity. Thus, the impact of CYP2C19 genotype on cardiovascular outcomes in patients treated with clopidogrel who identify as Black or African American remains unclear. Methods and Results Adults among 5 institutions who self‐identified as Black or African American, underwent PCI and clinical CYP2C19 genotyping, and were treated with clopidogrel were included. Data were abstracted from health records. Major atherothrombotic (composite of death, myocardial infarction, ischemic stroke, stent thrombosis, or revascularization for unstable angina) and bleeding event rates within 1 year after PCI were compared across CYP2C19 metabolizer groups using multivariable Cox regression adjusted for potential confounders and baseline variables meeting a threshold of P

Background Studies reporting on the incidence of sudden cardiac arrest and/or death (SCA/D) in athletes commonly lack methodological and reporting rigor, which has implications for screening and preventative policy in sport. To date, there are no tools designed for assessing study quality in studies investigating the incidence of SCA/D in athletes. Methods and Results The International Criteria for Reporting Study Quality for Sudden Cardiac Arrest/Death tool (IQ‐SCA/D) was developed following a Delphi process. Sixteen international experts in sports cardiology were identified and invited. Experts voted on each domain with subsequent moderated discussion for successive rounds until consensus was reached for a final tool. Interobserver agreement between a novice, intermediate, and expert observer was then assessed from the scoring of 22 relevant studies using weighted and unweighted κ analyses. The final IQ‐SCA/D tool comprises 8 domains with a summated score of a possible 22. Studies are categorized as low, intermediate, and high quality with summated IQ‐SCA/D scores of ≤11, 12 to 16, and ≥17, respectively. Interrater agreement was “substantial” between all 3 observers for summated IQ‐SCA/D scores and study categorization. Conclusions The IQ‐SCA/D is an expert consensus tool for assessing the study quality of research reporting the incidence of SCA/D in athletes. This tool may be used to assist researchers, reviewers, journal editors, and readers in contextualizing the methodological quality of different studies with varying athlete SCA/D incidence estimates. Importantly, the IQ‐SCA/D also provides an expert‐informed framework to support and guide appropriate design and reporting practices in future SCA/D incidence trials.

Background Lipoprotein (a) [Lp(a)] is a robust predictor of coronary heart disease outcomes, with targeted therapies currently under investigation. We aimed to evaluate the association of high Lp(a) with standard modifiable risk factors (SMuRFs) for incident first acute myocardial infarction (AMI). Methods and Results This retrospective study used the Mass General Brigham Lp(a) Registry, which included patients aged ≥18 years with an Lp(a) measurement between 2000 and 2019. Exclusion criteria were severe kidney dysfunction, malignant neoplasm, and prior known atherosclerotic cardiovascular disease. Diabetes, dyslipidemia, hypertension, and smoking were considered SMuRFs. High Lp(a) was defined as >90th percentile, and low Lp(a) was defined as

Abstract This paper presents the first quantitative relationship between the cold point tropopause (CPT) and tropical easterly jet (TEJ) using radiosonde observations over Gadanki (13.45° N, 79.2° E) during the Indian summer monsoon season 2006–2014. CPT and TEJ peak altitudes (HCPTandHTEJ) show amalgams of two categories of variability on the day‐to‐day scale. In category1 HTEJ occurs close to HCPT and they show in‐phase variation. While in Category2 HTEJ occurs far apart from HCPT and they do not show any relationship. For Category1 HCPT and HTEJ are strongly correlated (0.70), as well as HCPT and TCPT (CPT temperature) are moderately anticorrelated (−0.55) significant at a 95% confidence level, indicating the dominance of adiabatic processes. Whereas in Category2 HCPT and TCPT are not significantly anti‐correlated. Thus, when TEJ and CPT are close to each other, it may serve as an indicator for the prevalence of the synoptic‐scale effect.

Abstract INTRODUCTION A major limitation in Alzheimer's disease (AD) research is the lack of the ability to measure cognitive performance at scale—robustly, remotely, and frequently. Currently, there are no established online digital platforms validated against plasma biomarkers of AD. METHODS We used a novel web‐based platform that assessed different cognitive functions in AD patients (N = 46) and elderly controls (N = 53) who were also evaluated for plasma biomarkers (amyloid beta 42/40 ratio, phosphorylated tau ([p‐tau]181, glial fibrillary acidic protein, neurofilament light chain). Their cognitive performance was compared to a second, larger group of elderly controls (N = 352). RESULTS Patients with AD were significantly impaired across all digital cognitive tests, with performance correlating with plasma biomarker levels, particularly p‐tau181. The combination of p‐tau181 and the single best‐performing digital test achieved high accuracy in group classification. DISCUSSION These findings show how online testing can now be deployed in patients with AD to measure cognitive function effectively and related to blood biomarkers of the disease. Highlights This is the first study comparing online digital testing to plasma biomarkers. Alzheimer's disease patients and two independent cohorts of elderly controls were assessed. Cognitive performance correlated with plasma biomarkers, particularly phosphorylated tau (p‐tau)181. Glial fibrillary acidic protein and neurofilament light chain, and less so the amyloid beta 42/40 ratio, were also associated with performance. The best cognitive metric performed at par to p‐tau181 in group classification.

Abstract Background Although many molecules have been investigated as biomarkers for spinal cord injury (SCI) or ischemic stroke, none of them are specifically induced in central nervous system (CNS) neurons following injuries with low baseline expression. However, neuronal injury constitutes a major pathology associated with SCI or stroke and strongly correlates with neurological outcomes. Biomarkers characterized by low baseline expression and specific induction in neurons post‐injury are likely to better correlate with injury severity and recovery, demonstrating higher sensitivity and specificity for CNS injuries compared to non‐neuronal markers or pan‐neuronal markers with constitutive expressions. Methods In animal studies, young adult wildtype and global Atf3 knockout mice underwent unilateral cervical 5 (C5) SCI or permanent distal middle cerebral artery occlusion (pMCAO). Gene expression was assessed using RNA‐sequencing and qRT‐PCR, while protein expression was detected through immunostaining. Serum ATF3 levels in animal models and clinical human samples were measured using commercially available enzyme‐linked immune‐sorbent assay (ELISA) kits. Results Activating transcription factor 3 (ATF3), a molecular marker for injured dorsal root ganglion sensory neurons in the peripheral nervous system, was not expressed in spinal cord or cortex of naïve mice but was induced specifically in neurons of the spinal cord or cortex within 1 day after SCI or ischemic stroke, respectively. Additionally, ATF3 protein levels in mouse blood significantly increased 1 day after SCI or ischemic stroke. Importantly, ATF3 protein levels in human serum were elevated in clinical patients within 24 hours after SCI or ischemic stroke. Moreover, Atf3 knockout mice, compared to the wildtype mice, exhibited worse neurological outcomes and larger damage regions after SCI or ischemic stroke, indicating that ATF3 has a neuroprotective function. Conclusions ATF3 is an easily measurable, neuron‐specific biomarker for clinical SCI and ischemic stroke, with neuroprotective properties. Highlights ATF3 was induced specifically in neurons of the spinal cord or cortex within 1 day after SCI or ischemic stroke, respectively. Serum ATF3 protein levels are elevated in clinical patients within 24 hours after SCI or ischemic stroke. ATF3 exhibits neuroprotective properties, as evidenced by the worse neurological outcomes and larger damage regions observed in Atf3 knockout mice compared to wildtype mice following SCI or ischemic stroke.

Background While the impacts of social and environmental exposure on cardiovascular risks are often reported individually, the combined effect is poorly understood. Methods and Results Using the 2022 Environmental Justice Index, socio‐environmental justice index and environmental burden module ranks of census tracts were divided into quartiles (quartile 1, the least vulnerable census tracts; quartile 4, the most vulnerable census tracts). Age‐adjusted rate ratios (RRs) of coronary artery disease, strokes, and various health measures reported in the Prevention Population‐Level Analysis and Community Estimates data were compared between quartiles using multivariable Poisson regression. The quartile 4 Environmental Justice Index was associated with a higher rate of coronary artery disease (RR, 1.684 [95% CI, 1.660–1.708]) and stroke (RR, 2.112 [95% CI, 2.078–2.147]) compared with the quartile 1 Environmental Justice Index. Similarly, coronary artery disease 1.057 [95% CI,1.043‐1.0716] and stroke (RR, 1.118 [95% CI, 1.102–1.135]) were significantly higher in the quartile 4 than in the quartile 1 environmental burden module. Similar results were observed for chronic kidney disease, hypertension, diabetes, obesity, high cholesterol, lack of health insurance, sleep 14 days. Conclusions The prevalence of CVD and its risk factors is highly associated with increased social and environmental adversities, and environmental exposure plays an important role independent of social factors.

Abstract Objective The aim of this study was to describe the epilepsy phenotype in a large international cohort of patients with KBG syndrome and to study a possible genotype–phenotype correlation. Methods We collected data on patients with ANKRD11 variants by contacting University Medical Centers in the Netherlands, an international network of collaborating clinicians, and study groups who previously published about KBG syndrome. All patients with a likely pathogenic or pathogenic ANKRD11 variant were included in our patient cohort and categorized into an “epilepsy group” or “non‐epilepsy group”. Additionally, we included previously reported patients with (likely) pathogenic ANKRD11 variants and epilepsy from the literature. Results We included 75 patients with KBG syndrome of whom 26 had epilepsy. Those with epilepsy more often had moderate to severe intellectual disability (42.3% vs 9.1%, RR 4.6 [95% CI 1.7–13.1]). Seizure onset in patients with KBG syndrome occurred at a median age of 4 years (range 12 months – 20 years), and the majority had generalized onset seizures (57.7%) with tonic–clonic seizures being most common (23.1%). The epilepsy type was mostly classified as generalized (42.9%) or combined generalized and focal (42.9%), not fulfilling the criteria of an electroclinical syndrome diagnosis. Half of the epilepsy patients (50.0%) were seizure free on anti‐seizure medication (ASM) for at least 1 year at the time of last assessment, but 26.9% of patients had drug‐resistant epilepsy (failure of ≥2 ASM). No genotype–phenotype correlation could be identified for the presence of epilepsy or epilepsy characteristics. Significance Epilepsy in KBG syndrome most often presents as a generalized or combined focal and generalized type. No distinctive epilepsy syndrome could be identified. Patients with KBG syndrome and epilepsy had a significantly poorer neurodevelopmental outcome compared with those without epilepsy. Clinicians should consider KBG syndrome as a causal etiology of epilepsy and be aware of the poorer neurodevelopmental outcome in individuals with epilepsy.

Abstract Molecular mechanisms driving the escalation of pyrethroid resistance in the major malaria mosquitoes of Central Africa remain largely uncharacterized, hindering effective management strategies. Here, resistance intensity and the molecular mechanisms driving it were investigated in a population of Anopheles coluzzii from northern Cameroon. High levels of pyrethroid and organochloride resistance were observed in An. coluzzii population, with no mortality for 1× permethrin; only 11% and 33% mortalities for 5× and 10× permethrin diagnostic concentrations, and

This paper explores the role of environmental consequences, perceived barriers, policy interventions, public opinions, and knowledge and awareness in using electric vehicles (EVs). We collected 506 responses about their intention to use the EVs to develop our hypothesis. This study uses knowledge and awareness of the EVs as mediating variables towards adopting the EVs and consumers’ residences as moderating variables. It also introduces several control variables in this proposed research model to measure the effect on the intention to use the EVs. In this research study, we test the importance-performance map analysis and check Cohen’s f2 to identify a better output. The measurement and structural equation modelling results show that the environmental consequences are a stronger predictor of intention and policy interventions. The findings suggest that government policies can also have an attractive position in the EV segment. In addition, knowledge and awareness mediate the adoption of the EVs. Perceived barriers do not influence consumers to use an EV in India. We test the moderating role of residence with our construct and find a partial moderation role with policy intervention and public opinion. We introduce three self-created constructs, i.e., intention to use, knowledge, and public opinion. Public opinion for the EVs supports consumers’ intention to use, and knowledge also plays a significant role in using EVs. These newly added constructs will be essential to manufacturers and policymakers while promoting EVs. Also, environmental consequences and policy interventions emerge as significant factors of user behaviour. The paper highlights the critical predictors of consumers’ intention to use the EVs. Thus, it helps society, policymakers, and managers formulate and implement schemes to boost EV purchasing.

Objective. This study explores the impact of infographics on the professional dissemination of medical research. Recognising the burgeoning volume of data in the medical domain, this research aims to bridge the gap by investigating the efficacy of infographics in rendering complex medical concepts understandable to diverse audiences, including policymakers, patients, and the public. Design. The study uses a cross-sectional survey to assess medical professionals’ familiarity with infographic design and data visualisation principles. Setting. The research targets medical professionals with published articles across various subfields, including Clinical Medicine, Epidemiology, Pharmacology, Healthcare Management, Medical Imaging, and Public Health. Method. Data collection involves an online survey distributed to potential participants through professional networks and research institutions. The survey encompasses Likert-scale questions and demographic variables. Ethical considerations include obtaining approval from the institutional review board, ensuring participant consent, and maintaining data anonymity and confidentiality. Results. Demographic analysis reveals a diverse participant profile, with 58.7% male and 41.3% female respondents, spanning various age groups, professional experiences, and geographic locations. Assessing familiarity with infographic design and data visualisation principles demonstrates respondents’ proficiency in certain areas while highlighting potential areas for improvement. Conclusion. The study underscores the multifaceted benefits of infographics in research dissemination, as medical professionals perceive. Infographics can effectively convey various kinds of medical research information across diverse platforms and channels.

Abstract Background We examined the awareness, interest, and information sources relating to cannabis use for cancer management (including management of cancer symptoms and treatment‐related side effects) and determined factors associated with cancer survivors' awareness and interest in learning about cannabis use for cancer management. Methods This was a cross‐sectional study of adult cancer survivors (N = 1886) receiving treatment at a comprehensive cancer center. Weighted prevalence and multivariable logistic regression analyses were conducted. Results Among cancer survivors, 88% were aware and 60% were interested in learning about cannabis use for cancer management. Common sources of information to learn about cannabis use for cancer management were cancer doctors/nurses (82%), other patients with cancer (27%), websites/blogs (26%), marijuana stores (20%), and family/friends (18%). The odds of being aware of cannabis use for cancer management was lower among male compared to female survivors (adjusted odds ratio [AOR]: 0.61; 95% confidence interval [CI]: 0.41–0.90), non‐Hispanic Blacks compared to non‐Hispanic Whites (AOR: 0.36; 95% CI: 0.21–0.62), and survivors who do not support the legalization of cannabis for medical use compared to those who do (AOR: 0.10; 95% CI: 0.04–0.23). On the other hand, the odds of being interested in cannabis use for cancer management was higher among non‐Hispanic Blacks compared to non‐Hispanic Whites (AOR: 1.65; 95% CI: 1.04–2.62), and among cancer survivors actively undergoing cancer treatment compared to patients on non‐active treatment (AOR: 2.25; 95% CI: 1.74–2.91). Conclusion Awareness of cannabis use for cancer management is high within the cancer survivor population. Results indicated health care providers are leading information source and should receive continued medical education on cannabis‐specific guidelines. Similarly, tailored educational interventions are needed to guide survivors on the benefits and risks of cannabis use for cancer management.

Abstract This case report discusses the rare coexistence of Systemic Lupus Erythematosus (SLE) and Rheumatic Heart Disease (RHD) in a 46‐year‐old female patient, challenging the conventional understanding of their distinct presentations. The patient exhibited migratory joint pains, palpitations, and shortness of breath. Diagnostic investigations confirmed SLE based on EULAR/ACR criteria, with positive anti‐nuclear and anti‐dsDNA antibodies. Concurrently, transthoracic echocardiography revealed severe mitral stenosis and regurgitation, leading to the diagnosis of RHD. The patient underwent successful open‐heart surgery with mitral valve replacement. The discussion explores the rarity of this coexistence, emphasizing the need for cautious consideration and further research into potential immunological overlaps between SLE and RHD. The report concludes with a call for comprehensive studies to enhance our understanding of the pathophysiology connecting these two conditions.

Abstract Although numerous models of aerial‐robots/drones and planet landers have been demonstrated to fly autonomously in natural and manmade environments for far‐reaching scientific and technological change to help humankind, no drone flowed yet with a push‐pull dual‐head electromagnetic propulsion (EMP) system ensuring unrestricted flight endurance. The precept of EMP is eminent as it hastens an object using a flowing electrical current, either to charge a field or opposing a magnetic field for locomotive use. Here we present a proof of concept to demonstrate the capability of a newly invented variable speed propulsion and energy conversion system for uninterruptedly generating the reciprocating motion of a magnetic piston by a solar battery‐driven polarity changer timing circuit together with a laser‐based timing circuit for redundancy. The reciprocating crusade of the magnetic piston could be successfully converted into rotary motion to generate continuous power for various multidisciplinary applications on Earth and the other planets effectively in lieu of long‐lasting rechargeable batteries. The proposed concept can also be used for devising various systems and subsystems from underwater to outer space by using light weight supermalloy, which ensures high magnetic fluxes with relatively low current. Lucrative applications include nanomaterial‐enabled locomotive applications. Aerial robots regulated with the EMP system could be used for fostering pharmaceutical florae in the international space station for drug design to negate the recently discovered phenomenon of Sanal flow choking in cardiovascular system at gravity and/or microgravity conditions. This concept is originated from mind and aimed for lucrative product developments of yocto to yotta scale energy systems and beyond by discovering new magnetic materials through the fourth industrial revolution. Herein, a proof of the concept of an unrestricted solar‐battery driven push‐pull electromagnetic propulsion and energy conversion device by use of light weight high power magnetic materials is presented.

Abstract Severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) affects millions of people worldwide. The article aims to review the therapeutic perspective on natural antioxidants, their mechanism of action, pharmacokinetics in management and cure of COVID‐19/ SARS‐CoV‐2 infection. We conducted a literature search including World Health Organization and National Institute of Health guidelines and clinical trials registered with ClinicalTrials.gov limited to antioxidants in COVID‐19 management. Elderly, immunocompromised patients, and others with underlying health conditions or multiple comorbidities have a high mortality rate. Disrupted redox homeostasis and oxidative stress seem to be biological pathways that may increase personal vulnerability to infection. Antioxidants like vitamins C, D, E, epigallocatechin‐3 gallate, and morin have been reported to protect against COVID‐19 disease. Reactive oxygen species are immunological regulatory elements of viral replication. Natural antioxidants exhibit potential action in preventing inflammation and organ dysfunction during viral infection. They also increase glutathione level, oxygenation rate, and immunological responses in the treatment of sepsis and acute respiratory distress syndrome. No wonder the selection of prevention, treatment, and cure of COVID‐19 and SARS‐CoV‐2 mainly depends upon the antiviral and immunoregulatory activity which they possess. Yet, their efficacy against COVID‐19 is of great concern and demands extensive study.

Small‐cell lung cancer (SCLC) is an aggressive neuroendocrine subtype of lung cancer with poor patient prognosis. However, the mechanisms that regulate SCLC progression and metastasis remain undefined. Here, we show that the expression of the slit guidance ligand 2 (SLIT2) tumor suppressor gene is reduced in SCLC tumors relative to adjacent normal tissue. In addition, the expression of the SLIT2 receptor, roundabout guidance receptor 1 (ROBO1), is upregulated. We find a positive association between SLIT2 expression and the Yes1 associated transcriptional regulator (YAP1)‐expressing SCLC subtype (SCLC‐Y), which shows a better prognosis. Using genetically engineered SCLC cells, adenovirus gene therapy, and preclinical xenograft models, we show that SLIT2 overexpression or the deletion of ROBO1 restricts tumor growth in vitro and in vivo. Mechanistic studies revealed significant inhibition of myeloid‐derived suppressor cells (MDSCs) and M2‐like tumor‐associated macrophages (TAMs) in the SCLC tumors. In addition, SLIT2 enhances M1‐like and phagocytic macrophages. Molecular analysis showed that ROBO1 knockout or SLIT2 overexpression suppresses the transforming growth factor beta 1 (TGF‐β1)/β‐catenin signaling pathway in both tumor cells and macrophages. Overall, we find that SLIT2 and ROBO1 have contrasting effects on SCLC tumors. SLIT2 suppresses, whereas ROBO1 promotes, SCLC growth by regulating the Tgf‐β1/glycogen synthase kinase‐3 beta (GSK3)/β‐catenin signaling pathway in tumor cells and TAMs. These studies indicate that SLIT2 could be used as a novel therapeutic agent against aggressive SCLC.

Abstract Background This study examines the impact that the COVID‐19 pandemic has had on computed tomography (CT)‐based oncologic imaging utilization. Methods We retrospectively analyzed cancer‐related CT scans during four time periods: pre‐COVID (1/5/20–3/14/20), COVID peak (3/15/20–5/2/20), post‐COVID peak (5/3/20–12/19/20), and vaccination period (12/20/20–10/30/21). We analyzed CTs by imaging indication, setting, and hospital type. Using percentage decrease computation and Student's t‐test, we calculated the change in mean number of weekly cancer‐related CTs for all periods compared to the baseline pre‐COVID period. This study was performed at a single academic medical center and three affiliated hospitals. Results During the COVID peak, mean CTs decreased (−43.0%, p

Abstract Somatic embryogenesis (SE) is a process by which an embryo is derived from somatic tissue. Transcription factors (TFs) have been identified that control this process. One such TF that promotes SE is AGAMOUS‐like 15 (AGL15). Prior work has shown that AGL15 can both induce and repress gene expression. One way this type of dual function TF works is via protein interactions, so a yeast 2‐hybrid (Y2H) screen was undertaken. One intriguing protein with which AGL15 interacted in Y2H was LBD40. LBD40 encodes a LATERAL ORGAN BOUNDARIES (LOB)‐domain TF that is unique to plants and is primarily expressed during seed development. Here, we confirm the AGL15‐LBD40 interaction by quantitative assays and in planta co‐immunoprecipation. We also document a role for LBD40, and the closely related protein LBD41, in supporting SE. To determine downstream genes potentially controlled by LBD40, chromatin immunoprecipitation followed by high throughput sequencing (ChIP‐seq) was used. More than 400 binding regions for LBD40 were consistently found genome‐wide. To determine genes responsive to LBD40/41 accumulation, RNA‐seq analysis of transcriptomes of wild‐type control and loss‐of‐function lbd40/lbd41 was performed. Combining these datasets provides insight into genes directly and indirectly controlled by these LOB domain TFs. The gene ontology (GO) enrichment analysis of these regulated genes showed an overrepresentation of biological processes that are associated with SE, further indicating the importance of LBD40 in SE. This work provides insight into SE, a poorly understood, but essential process to generate transgenic plants to meet agricultural demands or test gene function. This manuscript reports on experiments to understand the role that LDB40, a TF, plays in support of SE by investigating genes directly and indirectly controlled by LBD40 and examining physical and genetic interactions with other TFs active in SE. We uncover targets of LBD40 and an interacting TF of the MADS family and investigate targets involvement in SE.

Abstract Innate immune adaptor proteins are critical components of the innate immune system that propagate pro‐inflammatory responses from their upstream receptors, and lead to pathogen clearance from the host. Bacterial pathogens have developed strategies to survive inside host cells without triggering the innate immune surveillance in ways that are still not fully understood. Here, it is reported that Pseudomonas aeruginosa induces its quorum sensing mechanism after macrophage engulfment. Further investigation of its secretome identified a quorum sensing regulated product, LasB, is responsible for innate immune suppression depending on the MyD88‐mediated signaling. Moreover, it is showed that this specific type of pathogen‐mediated innate immune suppression is due to the enzymatic digestion of the death domains of the innate immune adaptors, mainly MyD88, and attributed to LasB's large substrate binding groove. Lastly, it is demonstrated that the secretion of LasB from P. aeruginosa directly contributed to MyD88 degradation within macrophages. Hence, it is discovered an example of bacterial quorum sensing‐regulated cellular innate immune suppression by direct cleavage of immune adaptors.

Background HIV infection and abacavir‐containing antiretroviral regimens are associated with vascular endothelial dysfunction and increased cardiovascular risk. Positron emission tomography (PET)‐derived myocardial blood flow reserve (MBFR), the ratio of vasodilator stress to rest myocardial blood flow, is a well‐validated measure of coronary microvascular health and marker of cardiovascular risk. Our objective was to compare MBFR among people with HIV (PWH) with matched non‐HIV controls and to assess whether switching from dolutegravir/lamivudine/abacavir to the non‐abacavir regimen bictegravir/emtricitabine/tenofovir alafenamide (TAF) would improve MBFR. Methods and Results Thirty‐seven PWH were 1:2 matched on cardiovascular risk factors to 75 people without HIV, and MBFR corrected for differences in resting hemodynamics was compared in a cross‐sectional design. PWH were majority men (68%) with a mean age of 56 years. Mean stress myocardial blood flow (1.83 mL/min per g [95% CI, 1.68–1.98] versus 2.40 mL/min per g [95% CI, 2.25–2.54]; P

Background Although cardiovascular mortality (CVM) rates in the United States have been declining overall, our study evaluated whether this holds true for areas with increased social deprivation. Methods and Results We used county‐level cross‐sectional age‐adjusted CVM rates (aa‐CVM) (2000–2019) linked to the Centers for Disease Control and Prevention Social Vulnerability Index (SVI–2010). We grouped counties as per SVI (Groups I 0–0.2, II 0.21–0.4, III 0.41–0.6, IV 0.61–0.8, and V 0.81–1) and calculated the relative change in the aa‐CVM between 2000 to 2003 and 2016 to 2019. We used adjusted linear regression analyses to explore the association between a higher SVI and temporal aa‐CVM improvement; we studied this temporal change in aa‐CVM across subgroups of race, sex, and location. The median aa‐CVM rate (per 100 000) was 272.6 (interquartile range [IQR]: 237.5–311.7). The aa‐CVM was higher in men (315.6 [IQR: 273.4–363.9]) than women (221.3 [IQR: 189.6–256.7]), and in Black residents (347.2 [IQR: 301.1–391.1]; P

Abstract Background In 2021, the U.S. Preventive Services Task Force (USPSTF) updated its recommendation to expand lung cancer screening (LCS) eligibility and mitigate disparities. Although this increased the number of non‐White individuals who are eligible for LCS, the update's impact on drivers of disparities is less clear. This analysis focuses on racial disparities among Black individuals because members of this group disproportionately share late‐stage lung cancer diagnoses, despite typically having a lower intensity smoking history compared to non‐Hispanic White individuals. Methods We used data from the National Health Interview Survey to examine the impact of the 2021 eligibility criteria on racial disparities by factors such as education, poverty, employment history, and insurance status. We also examined preventive care use and reasons for delaying medical care. Results When comparing Black individuals and non‐Hispanic White individuals, our analyses show significant differences in who would be eligible for LCS: Those who do not have a high school diploma (28.7% vs. 17.0%, p = 0.002), are in poverty (26.2% vs. 14.9%, p

Abstract Background Clinical interpretation of genetic test results is complicated by variants of uncertain significance (VUS) that have an unknown impact on health but can be clarified through reclassification. There is little empirical evidence regarding VUS reclassification in oncology care settings, including the prevalence and outcomes of reclassification, and racial/ethnic differences. Methods This was a retrospective analysis of persons with and without a personal history of cancer carrying VUS (with or without an accompanying pathogenic or likely pathogenic [P/LP] variant) in breast, ovarian, and colorectal cancer predisposition genes seen at four cancer care settings (in Texas, Florida, Ohio, and New Jersey) between 2013 and 2019. Results In 2715 individuals included in the study, 3261 VUS and 313 P/LP variants were reported; 8.1% of all individuals with VUS experienced reclassifications and rates varied significantly among cancer care settings from 4.81% to 20.19% (overall p

Abstract Background This study investigated the association of hearing loss and tinnitus with overall health‐related quality of life (HRQoL) among long‐term oropharyngeal cancer (OPC) survivors. Methods This study included OPC survivors treated between 2000 and 2013 and surveyed from September 2015 to July 2016. Hearing loss and tinnitus were measured by asking survivors to rate their “difficulty with hearing loss and/or ringing in the ears” from 0 (not present) to 10 (as bad as you can imagine). Hearing loss and tinnitus scores were categorized as follows: 0 for none, 1–4 for mild, and 5–10 for moderate to severe. The primary outcome was the mean score of MD nderson Symptom Inventory Head & Neck module interference component as a HRQoL surrogate dichotomized as follows: 0 to 4 for none to mild and 5 to 10 for moderate to severe interference. Results Among 880 OPC survivors, 35.6% (314), reported none, 39.3% (347) reported mild, and 25.1% (221) reported moderate to severe hearing loss and tinnitus. On multivariable analysis, mild (OR, 5.83; 95% CI; 1.48–22.88; p = 0.012) and moderate (OR, 30.01; 95% CI; 7.96–113.10; p

Abstract Introduction Exploration of sexual and drug use behaviours following treatment for recent hepatitis C virus (HCV) is limited. This analysis modelled behavioural trajectories following treatment for recent HCV and assessed reinfection. Methods Participants treated for recent HCV in an international trial (enrolled 2017–2019) were followed at 3‐monthly intervals for up to 2 years to assess longitudinal behaviours. Population‐averaged changes were assessed using generalized estimating equations. Distinct behavioural trajectories were identified using group‐based trajectory modelling. HCV reinfection incidence was calculated using person‐years (PY) of observation. Results During the follow‐up of 212 participants (84% gay and bisexual men [GBM]; 69% HIV; 26% current injecting drug use [IDU]), behavioural trajectories for IDU and stimulant use (past month) did not change. However, population‐averaged decreases in the likelihood of daily IDU (adjusted odds ratio [AOR] 0.83; 95% CI 0.72, 0.95) and opioid use (AOR 0.84; 95% CI 0.75, 0.93) were observed. Among GBM, behavioural trajectories for chemsex did not change. Population‐averaged decreases in condomless anal intercourse with casual male partners (CAI‐CMP) (AOR 0.95; 95% CI 0.90, 0.99) and group‐sex (AOR 0.86; 95% CI 0.80, 0.93) were observed, but masked distinct trajectories. While a proportion had a decreased probability of CAI‐CMP (23%) and group‐sex (59%) post‐treatment, a substantial proportion retained a high probability of these behaviours. High HCV reinfection incidence was observed for the sustained high probability IDU (33.0/100 PY; 95% CI 17.7, 61.3) and chemsex (23.3/100 PY; 95% CI 14.5, 37.5) trajectories. Conclusions Limited sexual and drug use behavioural change was observed following treatment for recent HCV, supporting access to surveillance and (re)treatment.

Abstract The scientific community has widely recognized thermosensitive hydrogels as highly biocompatible material with immense potential in drug delivery systems. When the temperature of these hydrogels approaches that of human body, a phase change occurs, enhancing their usefulness in a range of medical scenarios. This review article highlighted the background of thermosensitive hydrogels, their properties, and their applications in transdermal, oral, ophthalmic, intravaginal, nasal, rectal, cancer therapy, and cell‐loaded drug delivery systems. The literature suggests numerous advantages of these hydrogels over conventional drug delivery systems and find applications in various fields, such as therapeutic systems, filling processes, and sustained drug delivery systems. One of their key benefits is the ability to eliminate invasive procedures like surgery, providing a noninvasive alternative for drug administration. Moreover, they streamline the formulation process for both hydrophilic and hydrophobic drug delivery systems, simplifying the development of effective treatments. The thermosensitive hydrogels have been found to be green materials with negligible side effects and desirable drug delivery properties. The thermosensitive hydrogel's sustained‐release characteristics, immunogenicity, and biodegradability have also gained increased interest. Some of the disadvantages of thermosensitive hydrogels include delayed temperature response, weak mechanical characteristics, and poor biocompatibility, which limits their potential use in drug delivery applications.

Abstract Introduction LANDMARC (CTRI/2017/05/008452), a prospective, observational real‐world study, evaluated the occurrence of diabetes complications, glycemic control and treatment patterns in people with type 2 diabetes mellitus (T2DM) from pan‐India regions over a period of 3 years. Methods Participants with T2DM (≥25 to ≤60 years old at diagnosis, diabetes duration ≥2 years at the time of enrollment, with/without glycemic control and on ≥2 antidiabetic therapies) were included. The proportion of participants with macrovascular and microvascular complications, glycemic control and time to treatment adaptation over 36 months were assessed. Results Of the 6234 participants enrolled, 5273 completed 3 years follow‐up. At the end of 3‐years, 205 (3.3%) and 1121 (18.0%) participants reported macrovascular and microvascular complications, respectively. Nonfatal myocardial infarction (40.0%) and neuropathy (82.0%) were the most common complications. At baseline and 3‐years, 25.1% (1119/4466) and 36.6% (1356/3700) of participants had HbA1c

Background Recent guidelines have emphasized the use of medical management, early diagnosis, and a multidisciplinary team to effectively treat patients with critical limb ischemia (CLI). Previous literature briefly highlighted the current racial disparities in its intervention. Herein, we analyze the trend over a 14‐year time period to investigate whether the disparities gap in CLI management is closing. Methods and Results The National Inpatient Sample was queried between 2005 and 2018 for hospitalizations involving CLI. Nontraumatic amputations and revascularization were identified. Utilization trends of these procedures were compared between races (White, Black, Hispanic, Asian and Pacific Islander, Native American, and Other). Multivariable regression assessed differences in race regarding procedure usage. There were 6 904 562 admissions involving CLI in the 14‐year study period. The rate of admissions in White patients who received any revascularization decreased by 0.23% (P

Abstract Introduction It is critical to develop more inclusive Alzheimer's disease (AD) research protocols to ensure that historically excluded groups are included in preclinical research and have access to timely diagnosis and treatment. If validated in racialized groups, plasma AD biomarkers and measures of subtle cognitive dysfunction could provide avenues to expand diversity in preclinical AD research. We sought to evaluate the utility of two easily obtained, low‐burden disease markers, plasma amyloid beta (Aβ)42/40, and intra‐individual cognitive variability (IICV), to predict concurrent and longitudinal cognitive performance in a sample of Black adults. Methods Two hundred fifty‐seven Black participants enrolled in the African Americans Fighting Alzheimer's in Midlife (AA‐FAIM) study underwent at least one cognitive assessment visit; a subset of n = 235 had plasma samples. Baseline IICV was calculated as the standard deviation across participants’ z scores on five cognitive measures: Rey Auditory Verbal Learning Test Delayed Recall, Trail Making Test Parts A and B (Trails A and B), and Boston Naming Test. Using mixed effects regression models, we compared concurrent and longitudinal models to baseline plasma Aβ42/40 or IICV by age interactions. PrecivityAD assays quantified baseline plasma Aβ42/40. Results IICV was associated with concurrent/baseline performance on several outcomes but did not modify associations between age and cognitive decline. In contrast, plasma Aβ42/40 was unrelated to baseline cognitive performance, but a pattern emerged in interactions with age in longitudinal models of Trails A and B and Rey Auditory Verbal Learning Test total learning trials. Although not significant after correcting for multiple comparisons, low Aβ42/40 was associated with faster cognitive declines over time. Discussion Our results are promising as they extend existing findings to an Black American sample using low‐cost, low‐burden methods that can be implemented outside of a research center, thus supporting efforts for inclusive AD biomarker research.

Key Clinical Message Primary lung cancer was reported by a bilateral lung transplant patient without any risk factors. Single lung transplantation should be contemplated instead of double lung transplantation as it has been shown to increase the risk of lung cancers. Abstract This is a case report of a 37‐year‐old woman, with no history of smoking, who developed adenocarcinoma in her transplanted lung 17 years post transplantation. The development of lung cancer 17 years after transplantation is considered as a rare finding in this case report. According to the Annual Report on Cardiothoracic Organ Transplantation 2019–2020, the NHS Blood and Transplant Data, approximately 156 lung transplants were performed in the UK during 2019–2020. The third most common primary disease group recipient was cystic fibrosis and bronchiectasis. There are several medical complications described in the recipients' post‐lung transplantation, and the increased risk of lung malignancy due to immunosuppression is well‐established in comparison to the general population. Most cancers, however, develop in the native lung following a single lung transplant. Several cases of lymphoproliferative malignancies in the transplanted lung have been reported following bilateral lung transplantation. This is a case report of a 37‐year‐old woman with no history of smoking who developed adenocarcinoma in her transplanted lung 17 years later. This patient underwent lobectomy via thoracotomy and was discharged home in good condition. Only a few cases of patients developing primary lung cancer in the transplanted lung with no recipient risk factor have been reported in the literature to date. The development of lung cancer 17 years after transplantation was a rare finding in this case report.

Abstract Background To evaluate the degeneration of the corticospinal tract (CST) and corpus callosum (CC) in patients with motor neuron disease and upper motor neuron (UMN) dysfunction using diffusion kurtosis imaging (DKI). Methods Twenty‐seven patients and 33 healthy controls underwent magnetic resonance imaging along with clinical and neuropsychological testing. Tractography of diffusion tensor images was performed to extract tracts of the bilateral CST and CC. Group mean differences both across the entire averaged tract and along each tract were assessed, including correlations between diffusion metrics and clinical measures. Tract‐based spatial statistics (TBSS) was performed to evaluate the spatial distribution of whole‐brain microstructural abnormalities in patients. Results In comparison to controls, patients had significantly higher mean and radial diffusivity and lower fractional anisotropy (FA), kurtosis anisotropy, mean kurtosis (MK), and radial kurtosis (RK) in the CST and CC (p

Abstract Aims Limited data on the uptake of guideline‐directed medical therapies (GDMTs) and the mortality of acute decompensated HF (ADHF) patients are available from India. The National Heart Failure Registry (NHFR) aimed to assess clinical presentation, practice patterns, and the mortality of ADHF patients in India. Methods and results The NHFR is a facility‐based, multi‐centre clinical registry of consecutive ADHF patients with prospective follow‐up. Fifty three tertiary care hospitals in 21 states in India participated in the NHFR. All consecutive ADHF patients who satisfied the European Society of Cardiology criteria were enrolled in the registry. All‐cause mortality at 90 days was the main outcome measure. In total, 10 851 consecutive patients were recruited (mean age: 59.9 years, 31% women). Ischaemic heart disease was the predominant aetiology for HF (72%), followed by dilated cardiomyopathy (18%). Isolated right HF was noted in 62 (0.6%) participants. In eligible HF patients, 47.5% received GDMT. The 90 day mortality was 14.2% (14.9% and 13.9% in women and men, respectively) with a re‐admission rate of 8.4%. An inverse relationship between educational class based on years of education and 90 day mortality (high mortality in the lowest educational class) was observed in the study population. Patients with HF with reduced ejection fraction and HF with mildly reduced ejection fraction who did not receive GDMT experienced higher mortality (log‐rank P 120 ms, atrial fibrillation, mitral regurgitation, haemoglobin levels, serum sodium, and GDMT independently predicted 90 day mortality. Conclusion One of seven ADHF patients in the NHFR died during the first 90 days of follow‐up. One of two patients received GDMT. Adherence to GDMT improved survival in HF patients with reduced and mildly reduced ejection fractions. Our findings call for innovative quality improvement initiatives to improve the uptake of GDMT among HF patients in India.

Abstract Aims Heart failure patients with mid‐range ejection fraction (HFmrEF) have overlapping clinical features, compared with patients with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF). We aim to perform a meta‐analysis of studies reporting long‐term outcomes in HFmrEF compared with HFrEF and HFpEF. Methods and results Data from 18 eligible large‐scale studies including 126 239 patients were pooled. Patients with HFmrEF had a lower risk of all‐cause death than those with HFrEF [risk ratio (RR) = 0.92; 95% CI = 0.85–0.98; P 50% of males had higher risk of deaths with HFrEF (RR = 1.15; 95% CI = 1.04–1.26; P = 0.006). When compared with HFpEF, patients with HFmrEF had comparable risk of all‐cause death (RR = 1.02; 95% CI = 0.96–1.09; P = 0.53). Similarly, there were no differences in the 1, 2, and 3 year deaths; CV and non‐CV deaths were insignificant between HFmrEF and HFpEF. Conclusions The results of the study support that HFmrEF has better prognosis than HFrEF but similar prognosis when compared with HFpEF. Gender disparity between studies seems to influence the results between HFmrEF and HFrEF. Transition in left ventricular ejection fraction (LVEF), which could not be addressed in the study, may play a decisive role in determining outcomes. PROSPERO review registration number CRD42021277107.

Key Clinical Message Ectopic mediastinal parathyroid adenoma causes primary hyperparathyroidism presenting as hypercalcemia. When children with hypercalcemia present with slipped capital femoral epiphysis, a detailed evaluation for hypercalcemia must be done before surgery. Abstract The association between slipped capital femoral epiphysis (SCFE) and hyperparathyroidism has been reported and is rare. Each is known to affect different age groups. We report a case of a 13‐year‐old boy with SCFE and primary HPT leading to hypercalcemia and skeletal deformities.