Oral obeldesivir provides postexposure protection against Marburg virus in nonhuman primates.

The recent outbreak of Marburg virus (MARV) in Rwanda underscores the need for effective countermeasures against this highly fatal pathogen, with case fatality rates reaching 90%. Currently, no vaccines or approved treatments exist for MARV infection, distinguishing it from related viruses like Ebola. Our research demonstrates that the oral drug obeldesivir (ODV), a nucleoside analog prodrug, shows promising antiviral activity against filoviruses in vitro and offers significant protection in animal models.

Expansion and Precise CRISPR-Cas9 Gene Repair of Autologous T-Memory Stem Cells from Patients with T-Cell Immunodeficiencies.

The adoptive transfer of autologous, long-lived, gene-repaired T cells is a promising way to treat inherited T-cell immunodeficiencies. However, adoptive T-cell therapies require a large number of T cells to be manipulated and infused back into the patient. This poses a challenge in primary immunodeficiencies that manifest early in childhood and where only small volumes of blood samples may be available.

Microbial dynamics and pulmonary immune responses in COVID-19 secondary bacterial pneumonia.

Secondary bacterial pneumonia (2°BP) is associated with significant morbidity following respiratory viral infection, yet remains incompletely understood. In a prospective cohort of 112 critically ill adults intubated for COVID-19, we comparatively assess longitudinal airway microbiome dynamics and the pulmonary transcriptome of patients who developed 2°BP versus controls who did not. We find that 2°BP is significantly associated with both mortality and corticosteroid treatment.

Treatment outcomes of mild to moderate Clostridioides difficile infection in inflammatory bowel disease: an Australian experience.

Background: The incidence of Clostridioides difficile infection (CDI) in inflammatory bowel disease (IBD) is rising and associated with adverse outcomes. Optimal treatment for CDI in IBD remains unknown, with various organisations suggesting vancomycin as first-line therapy.

Aim: To compare treatment outcomes for metronidazole versus vancomycin in mild to moderate CDI in IBD.

Out-BREAK!: An IDWeek 2023 Escape Room to Break Out of the Educational Mold.

Background: An escape room is a cooperative game that has been adapted into medical education and major academic conferences.

Methods: We describe the design, development, and implementation of an educational ID-themed escape room activity entitled "Out-BREAK!" at an international conference, IDWeek 2023. An anonymous survey was conducted to collect demographic data, assess participant satisfaction with the escape room puzzles, and gauge participant interest in game-based learning.

Cardiovascular Implantable Electronic Device Infections: A Contemporary Review.

Infections associated with cardiac implantable electronic devices (CIEDs) are increasing and are a cause of significant morbidity and mortality. This article summarizes the latest updates with respect to the epidemiology, microbiology, and risk factors for CIED-related infections. It also covers important considerations regarding the diagnosis, management, and prevention of these infections.

In vivo CRISPR screens identify a dual function of MEN1 in regulating tumor-microenvironment interactions.

Functional genomic screens in two-dimensional cell culture models are limited in identifying therapeutic targets that influence the tumor microenvironment. By comparing targeted CRISPR-Cas9 screens in a two-dimensional culture with xenografts derived from the same cell line, we identified MEN1 as the top hit that confers differential dropout effects in vitro and in vivo. MEN1 knockout in multiple solid cancer types does not impact cell proliferation in vitro but significantly promotes or inhibits tumor growth in immunodeficient or immunocompetent mice, respectively.

Reliability of pre-resection ligament tension assessment in imageless robotic assisted total knee replacement.

Background: Ligament tension balance is a major determinant for the success of total knee replacement (TKR). The present study aimed at determining the inter-rater and intra-rater reliability in performing ligament tension assessment using an imageless robotic-assisted TKR.

Methods: Twenty-four knees in 21 patients who received robotic-assisted TKR for end-stage varus osteoarthritis were examined.

Preexisting Skin-Resident CD8 and γδ T-cell Circuits Mediate Immune Response in Merkel Cell Carcinoma and Predict Immunotherapy Efficacy.

Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer with a ∼50% response rate to immune checkpoint blockade (ICB) therapy. To identify predictive biomarkers, we integrated bulk and single-cell RNA sequencing (RNA-seq) with spatial transcriptomics from a cohort of 186 samples from 116 patients, including bulk RNA-seq from 14 matched pairs pre- and post-ICB. In nonresponders, tumors show evidence of increased tumor proliferation, neuronal stem cell markers, and IL1.

Unearthing new learning opportunities: adapting and innovating through the 'Antibiotics under our feet' citizen science project in Scotland during COVID-19.

'Antibiotics under our feet' is a Scottish citizen science project that aimed to raise science capital in primary school learners and their teachers through measurement of microbial diversity in urban soil samples in the search for novel antimicrobial compounds. Resistance to antibiotics is rising, posing a global threat to human health. Furthermore, science, technology, engineering and mathematics (STEM) skills are in crisis, jeopardising our capacity to mobilise as a society to fight antimicrobial resistance (AMR).

In vivo CRISPR/Cas9-mediated screen reveals a critical function of TFDP1 and E2F4 transcription factors in hematopoiesis.

Hematopoiesis is a continuous process of blood cell production driven by hematopoietic stem and progenitor cells (HSPCs) in the bone marrow. Proliferation and differentiation of HSPCs are regulated by complex transcriptional networks. In order to identify transcription factors with key roles in HSPC-mediated hematopoietic reconstitution, we developed an efficient and robust CRISPR/Cas9-based in vivo genetic screen.

Tummy Time Tracking: Examining Agreement Between Parent Recall and Direct Observation in Infants.

Importance: Parent recall is the primary method for measuring positioning practices such as tummy time in infants. Concerns regarding the accuracy of parent recall have been raised in the literature. To date, no study has examined the agreement of tummy time recall measures with gold-standard methods.

Simultaneous detection of pathogens and antimicrobial resistance genes with the open source, cloud-based, CZ ID pipeline.

Antimicrobial resistant (AMR) pathogens represent urgent threats to human health, and their surveillance is of paramount importance. Metagenomic next generation sequencing (mNGS) has revolutionized such efforts, but remains challenging due to the lack of open-access bioinformatics tools capable of simultaneously analyzing both microbial and AMR gene sequences. To address this need, we developed the CZ ID AMR module, an open-access, cloud-based workflow designed to integrate detection of both microbes and AMR genes in mNGS and whole-genome sequencing (WGS) data.

Doxycycline post-exposure prophylaxis for sexually transmitted infections impacts the gut antimicrobial resistome.

Doxycycline post-exposure prophylaxis (doxy-PEP) reduces bacterial sexually transmitted infections (STIs) among men who have sex with men and transgender women. While poised for widespread clinical implementation, the impact of doxy-PEP on antimicrobial resistance remains a primary concern as its effects on the gut microbiome and resistome, or the antimicrobial resistance genes (ARGs) present in the gut microbiome, are unknown. To investigate these effects, we studied participants from a randomized clinical trial who either received doxy-PEP as a one-time doxycycline 200 mg taken after condomless sex (DP arm, n = 100) or standard of care treatment (SOC arm, n = 50).

Simultaneous detection of pathogens and antimicrobial resistance genes with the open source, cloud-based, CZ ID pipeline.

Antimicrobial resistant (AMR) pathogens represent urgent threats to human health, and their surveillance is of paramount importance. Metagenomic next generation sequencing (mNGS) has revolutionized such efforts, but remains challenging due to the lack of open-access bioinformatics tools capable of simultaneously analyzing both microbial and AMR gene sequences. To address this need, we developed the Chan Zuckerberg ID (CZ ID) AMR module, an open-access, cloud-based workflow designed to integrate detection of both microbes and AMR genes in mNGS and whole-genome sequencing (WGS) data.

Long-term Risk of Serious Infections and Mortality Among Patients Surviving Drug Use-Associated Infective Endocarditis.

Among a statewide cohort of 1874 patients surviving hospitalization for drug use-associated endocarditis during 2017-2020, the 3-year risk of death or future hospitalization was 38% (16% for death before later infection, 14% for recurrent endocarditis, 14% for soft tissue, 9% for bacteremia, 5% for bone/joint, and 4% for spinal infections).

Competitive Immunoassay in a Microfluidic Biochip for In-Field Detection of Abscisic Acid in Grapes.

Viticulture and associated products are an important part of the economy in many countries. However, biotic and abiotic stresses impact negatively the production of grapes and wine. Climate change is in many aspects increasing both these stresses.

Oral administration of obeldesivir protects nonhuman primates against .

Obeldesivir (ODV, GS-5245) is an orally administered prodrug of the parent nucleoside of remdesivir (RDV) and is presently in phase 3 trials for COVID-19 treatment. In this work, we show that ODV and its circulating parent nucleoside metabolite, GS-441524, have similar in vitro antiviral activity against filoviruses, including Marburg virus, Ebola virus, and Sudan virus (SUDV). We also report that once-daily oral ODV treatment of cynomolgus monkeys for 10 days beginning 24 hours after SUDV exposure confers 100% protection against lethal infection.