Repurposing Licensed Drugs with Activity Against Epstein-Barr Virus for Treatment of Multiple Sclerosis: A Systematic Approach.

Background: Epstein-Barr virus (EBV) is implicated as a necessary factor in the development of multiple sclerosis (MS) and may also be a driver of disease activity. Although it is not clear whether ongoing viral replication is the driver for MS pathology, MS researchers have considered the prospect of using drugs with potential efficacy against EBV in the treatment of MS. We have undertaken scientific and lived experience expert panel reviews to shortlist existing licensed therapies that could be used in later-stage clinical trials in MS.

Cardiovascular-Liver-Metabolic Health: Recommendations in Screening, Diagnosis, and Management of Metabolic Dysfunction-Associated Steatotic Liver Disease in Cardiovascular Disease via Modified Delphi Approach.

There is a new awareness of the widespread nature of metabolic dysfunction-associated steatotic liver disease (MASLD) and its connection to cardiovascular disease (CVD). This has catalyzed collaboration between cardiologists, hepatologists, endocrinologists, and the wider multidisciplinary team to address the need for earlier identification of those with MASLD who are at increased risk for CVD. The overlap in the pathophysiologic processes and parallel prevalence of CVD, metabolic syndrome, and MASLD highlight the multisystem consequences of poor cardiovascular-liver-metabolic health.

Structural and antigenic characterization of novel and diverse glycoproteins.

(HNVs), a genus within the family, includes the highly virulent Nipah and Hendra viruses that cause yearly reoccurring outbreaks of deadly disease. Recent discoveries of several new species, including the zoonotic Langya virus, have revealed much higher antigenic diversity than currently characterized. Here, to explore the limits of structural and antigenic variation in HNVs, we construct an expanded, antigenically diverse panel of HNV fusion (F) and attachment (G) glycoproteins from 56 unique HNV strains that better reflects global HNV diversity.

Levofloxacin for the Prevention of Multidrug-Resistant Tuberculosis in Vietnam.

Background: Prevention of drug-resistant tuberculosis is a global health priority. However, trials evaluating the effectiveness of treating infection among contacts of persons with drug-resistant tuberculosis are lacking.

Methods: We conducted a double-blind, randomized, controlled trial comparing 6 months of daily levofloxacin (weight-based doses) with placebo to treat infection.

The QIBA Profile for Dynamic Susceptibility Contrast MRI Quantitative Imaging Biomarkers for Assessing Gliomas.

The dynamic susceptibility contrast (DSC) MRI measures of relative cerebral blood volume (rCBV) play a central role in monitoring therapeutic response and disease progression in patients with gliomas. Previous investigations have demonstrated promise of using rCBV in classifying tumor grade, elucidating tumor viability after therapy, and differentiating pseudoprogression and pseudoresponse. However, the quantification and reproducibility of rCBV measurements across patients, devices, and software remain a critical barrier to routine or clinical trial use of longitudinal DSC MRI in patients with gliomas.

Spatial omics-based machine learning algorithms for the early detection of hepatocellular carcinoma.

Background: Worldwide, hepatocellular carcinoma (HCC) is the second most lethal cancer, although early-stage HCC is amenable to curative treatment and can facilitate long-term survival. Early detection has proved difficult, as proteomics, transcriptomics, and genomics have been unable to discover suitable biomarkers.

Methods: To find new biomarkers of HCC, we utilized a spatial omics N-glycan imaging method to identify altered glycosylation in cancer tissue (n = 53) and in paired serum of individuals with HCC (n = 23).

Blood-based tumor mutational burden impacts clinical outcomes of immune checkpoint inhibitor treated breast and prostate cancers.

Background: Breast and prostate tumors are known to be less responsive to immune checkpoint inhibitors (ICIs). Tissue-based tumor mutation burden (tTMB) has emerged as a predictive biomarker of response to ICIs, including in these "cold tumors". In clinical practice, when tTMB is not available, blood-based TMB score (bTMB) can be used to consider treatment with ICIs.

Different abnormalities of mismatch negativity in schizophrenia and depression as assessed with magnetoencephalography.

Mismatch negativity (MMN) is widely considered a candidate diagnostic biomarker for schizophrenia (SCZ). Although blunted MMN responses have been reliably observed in psychosis, the evidence for MMN deficits in other disorders, such as major depressive disorder (MDD), is mixed. This study explores whether MMN alterations in amplitude or latency are unique to SCZ or extend to non-psychotic MDD patients.

Public Health Impact of Introducing a Pentavalent Vaccine Against Invasive Meningococcal Disease in the United States.

Background: Invasive meningococcal disease (IMD) is primarily associated with five Neisseria meningitidis serogroups: A, B, C, W, or Y. In the United States (US), available vaccines protect against serogroups B (MenB), A, C, W, and Y (MenACWY), and A, B, C, W, and Y (MenABCWY). The Advisory Committee on Immunization Practices is re-evaluating the adolescent meningococcal vaccination schedule with varying recommendation formats.

Critical Data for Critical Care: A Primer on Leveraging Electronic Health Record Data for Research From Society of Critical Care Medicine's Panel on Data Sharing and Harmonization.

A growing body of critical care research draws on real-world data from electronic health records (EHRs). The bedside clinician has myriad data sources to aid in clinical decision-making, but the lack of data sharing and harmonization standards leaves much of this data out of reach for multi-institution critical care research. The Society of Critical Care Medicine (SCCM) Discovery Data Science Campaign convened a panel of critical care and data science experts to explore and document unique advantages and opportunities for leveraging EHR data in critical care research.

Survey for spp. in wildlife in the eastern United States.

is a diverse genus of piroplasms that parasitize the red blood cells of a wide variety of mammals and avian species, including humans. There is a lack of knowledge on the species of carnivores and mesomammals in the eastern United States and the potential impacts of these species on the health of humans and domestic animals. We surveyed 786 wild mammals in the eastern United States by testing blood, spleen, and heart samples with PCR targeting the 18S rRNA region of apicomplexan parasites.

In-depth genomic characterisation of SARS-CoV-2 variants from Egypt exhibited heterogeneous lineages.

Background: Genetic variation of SARS-CoV-2 remains a public health challenge worldwide because of it influences the pathogenicity and transmissibility of the virus.

Aims: To determine the genomic mutations of SARS-CoV-2 isolated in Egypt.

Methods: This was an in silico cross-sectional study of 200 SARS-CoV-2 variants of concern, which were retrieved from the National Centre for Biotechnology Information on 11 January 2021 and aligned with the original Wuhan strain (NC_045512).

Genotype-Phenotype Correlation and Feminizing Surgery in Danish Children with Congenital Adrenal Hyperplasia.

Introduction: Congenital adrenal hyperplasia (CAH) is characterized by a broad spectrum of symptoms. This study aimed to describe genotype-phenotype correlations, clinical manifestations at diagnosis, and the frequency of feminizing surgery in childhood.

Methods: A nationwide retrospective cohort study of patients diagnosed with CAH, at the age of ≤18 years, between 1943 and 2018.

Proteomics Reveals Age as Major Modifier of Inflammatory CSF Signatures in Multiple Sclerosis.

Background And Objectives: Multiple sclerosis (MS) can start as relapsing or progressive. While their clinical features and treatment responses are distinct, it has remained uncertain whether their pathomechanisms differ. A notable age-related effect on MS phenotype and response to immunotherapies is well acknowledged, but the underlying pathophysiologic reasons are yet to be fully elucidated.

Mechanistic Insights Into Redox Damage of the Podocyte in Hypertension.

Podocytes are specialized cells within the glomerular filtration barrier, which are crucial for maintaining glomerular structural integrity and convective ultrafiltration. Podocytes exhibit a unique arborized morphology with foot processes interfacing by slit diaphragms, ladder-like, multimolecular sieves, which provide size and charge selectivity for ultrafiltration and transmembrane signaling. Podocyte dysfunction, resulting from oxidative stress, dysregulated prosurvival signaling, or structural damage, can drive the development of proteinuria and glomerulosclerosis in hypertensive nephropathy.

Outcomes of Community-Acquired Acute Kidney Injury: A Cohort Study of US Veterans.

Background: Community-acquired acute kidney injury (CA-AKI) occurs outside of the hospital and is the most common form of AKI. CA-AKI is not well understood, which hinders efforts to prevent, identify, and manage CA-AKI.

Objective: Examine 30-day outcomes following CA-AKI using national administrative and lab data from the Veterans Health Administration (VA).

Remembering change: Interdependence between change awareness and meaningful connection in achieving proactive facilitation.

Two experiments investigated proactive facilitation (PF) or proactive interference (PI) in the recall of recently learned targets, under conditions of assessing the detection and recollection of target changes across two learning phases (with A-B/A-D word pairs). Some changes established meaningful connections across the phases; others did not. Task instructions on the subsequent cued-recall test (Experiment 1) or during Phase 2 study (Experiment 2) guided participants (university students) to monitor and report the changes.

Managing Select Immune-Related Adverse Events in Patients Treated with Immune Checkpoint Inhibitors.

The increased use of immune checkpoint inhibitors (ICIs) across cancer programs has created the need for standardized monitoring and management of immune-related adverse events (irAEs). Delayed recognition without appropriate treatment can have serious and life-threatening consequences. The management of irAEs presents a unique set of challenges that must be addressed at a multidisciplinary level.