Modeling the health and economic implications of adopting a 1-dose 9-valent human papillomavirus vaccination program in adolescents in low/middle-income countries: An analysis of Indonesia.

Background: Recent evidence suggests that 1 dose of the human papillomavirus (HPV) vaccine may have similar effectiveness in reducing HPV infection risk compared to 2 or 3 doses.

Objective: To evaluate the public health impact and cost-effectiveness of implementing a 1-dose or a 2-dose program of the 9-valent HPV vaccine in a low- and middle-income country (LMIC).

Methods: We adapted a dynamic transmission model to the Indonesia setting, and conducted a probabilistic sensitivity analysis using distributions reflecting the uncertainty in levels and durability of protection of a 1-dose that were estimated under a Bayesian framework incorporating 3-year vaccine efficacy data from the KEN SHE trial (base-case) and 10 year effectiveness data from the India IARC study (alternative analysis).

Remarkable Evolutionary Rate Variations Among Lineages and Among Genome Compartments in Malaria Parasites of Mammals.

Genes encoded within organelle genomes often evolve at rates different from those in the nuclear genome. Here, we analyzed the relative rates of nucleotide substitution in the mitochondrial, apicoplast, and nuclear genomes in four different lineages of Plasmodium species (malaria parasites) infecting mammals. The rates of substitution in the three genomes exhibit substantial variation among lineages, with the relative rates of nuclear and mitochondrial DNA being particularly divergent between the Laverania (including Plasmodium falciparum) and Vivax lineages (including Plasmodium vivax).

5-Year Results From the AMPLATZER Amulet Left Atrial Appendage Occluder Randomized Controlled Trial.

Background: The Amulet IDE trial (AMPLATZER Amulet Left Atrial Appendage Occluder [LAAO] Investigational Device Exemption [IDE] Trial) evaluated the safety and effectiveness of the Amulet occluder (Abbott) in patients with nonvalvular atrial fibrillation. The Amulet IDE trial is the largest randomized LAAO trial, comparing the Amulet occluder with the Watchman 2.5 device (Boston Scientific).

The BNT162b2 mRNA vaccine demonstrates reduced age-associated T1 support and .

mRNA vaccines demonstrate impaired immunogenicity and durability in vulnerable older populations. We hypothesized that human modeling and proteomics could elucidate age-specific mRNA vaccine actions. BNT162b2-stimulation changed the plasma proteome of blood samples from young (18-50Y) and older adult (≥60Y) participants, assessed by mass spectrometry, proximity extension assay, and multiplex.

Incidence of pneumococcal disease in children in Germany, 2014-2019: a retrospective cohort study.

Background: Novel, expanded valency pneumococcal conjugate vaccines (PCVs) are in development to reduce the burden of pneumococcal disease (PD) in children. To understand the potential value of new vaccines in Germany, this study estimated the residual burden of PD in children < 16 years old from 2014 to 2019, using administrative health data from a large German claims database.

Methods: Outpatient and inpatient cases of all-cause pneumonia (ACP), pneumococcal pneumonia (PP) and invasive pneumococcal disease (IPD) were identified in the InGef database.

Cephalopod-inspired jetting devices for gastrointestinal drug delivery.

Needle-based injections currently enable the administration of a wide range of biomacromolecule therapies across the body, including the gastrointestinal tract, through recent developments in ingestible robotic devices. However, needles generally require training, sharps management and disposal, and pose challenges for autonomous ingestible systems. Here, inspired by the jetting systems of cephalopods, we have developed and evaluated microjet delivery systems that can deliver jets in axial and radial directions into tissue, making them suitable for tubular and globular segments of the gastrointestinal tract.

Accelerating Parkinson's Disease drug development with federated learning approaches.

Parkinson's Disease is a progressive neurodegenerative disorder afflicting almost 12 million people. Increased understanding of its complex and heterogenous disease pathology, etiology and symptom manifestations has resulted in the need to design, capture and interrogate substantial clinical datasets. Herein we advocate how advances in the deployment of artificial intelligence models for Federated Data Analysis and Federated Learning can help spearhead coordinated and sustainable approaches to address this grand challenge.

Nemvaleukin alfa, a modified interleukin-2 cytokine, as monotherapy and with pembrolizumab in patients with advanced solid tumors (ARTISTRY-1).

Background: Nemvaleukin alfa (nemvaleukin, ALKS 4230) is a novel, engineered cytokine that selectively binds to the intermediate-affinity interleukin-2 receptor, preferentially activating CD8 T cells and natural killer cells, with minimal expansion of regulatory T cells, thereby mitigating the risk of toxicities associated with high-affinity interleukin-2 receptor activation. Clinical outcomes with nemvaleukin are unknown. ARTISTRY-1 investigated the safety, recommended phase 2 dose (RP2D), and antitumor activity of nemvaleukin in patients with advanced solid tumors.

Phase I dose escalation study of IO-108, an anti-LILRB2 antibody, in patients with advanced solid tumors.

Purpose: In this first-in-human dose escalation study, the safety and efficacy of IO-108, a fully human monoclonal antibody targeting leukocyte immunoglobulin-like receptor B2 (LILRB2), was investigated in patients with advanced solid tumors as monotherapy and in combination with pembrolizumab, an anti-programmed cell death protein 1 (PD-1) antibody.

Methods: The study included patients with histologically or cytologically confirmed advanced and relapsed solid tumors, with measurable disease by Response Evaluation Criteria In Solid Tumors (RECIST) V.1.

Health-related quality of life and symptom concordance between patients and physicians in pulmonary arterial hypertension in the United States, Europe, and Japan.

This study involved analyses of a real world, cross-sectional survey of physicians and their patients with pulmonary arterial hypertension (PAH). Physician and patient symptom concordance was assessed, and patients self-reported Health-Related Quality of Life (HRQoL). Data were drawn from the Adelphi PAH Disease Specific Programme (DSP)™ in the United States, France, Germany, Italy, Spain, United Kingdom, and Japan, between March and August 2022.

Hepatic glucose production rises with the histological severity of metabolic dysfunction-associated steatohepatitis.

Metabolic dysfunction-associated steatotic liver disease (MASLD) and steatohepatitis (MASH) are associated with a high prevalence of type 2 diabetes (T2D). Individuals with MASLD exhibit insulin resistance (IR) and hyperglycemia, but it is unclear whether hepatic glucose production (HGP) is increased with MASLD severity. We evaluated HGP in a cohort of histologically characterized individuals with MASL/MASH using stable isotope infusion (6,6-H-glucose, U-H-glycerol) and liver-specific genome-scale metabolic models (GEMs).

Immunomolecular and reactivity landscapes of gut IgA subclasses in homeostasis and inflammatory bowel disease.

The human gut includes plasma cells (PCs) expressing immunoglobulin A1 (IgA1) or IgA2, two structurally distinct IgA subclasses with elusive regulation, function, and reactivity. We show here that intestinal IgA1+ and IgA2+ PCs co-emerged early in life, comparably accumulated somatic mutations, and were enriched within short-lived CD19+ and long-lived CD19- PC subsets, respectively. IgA2+ PCs were extensively clonally related to IgA1+ PCs and a subset of them presumably emerged from IgA1+ precursors.

Evaluation of waning of IgG antibody responses after rVSVΔG-ZEBOV-GP and Ad26.ZEBOV, MVA-BN-Filo Ebola virus disease vaccines: a modelling study from the PREVAC randomized trial.

rVSVΔG-ZEBOV-GP and Ad26.ZEBOV, MVA-BN-Filo are WHO-prequalified vaccination regimens against Ebola virus disease (EVD). Challenges associated with measuring long-term clinical protection warrant the evaluation of immune response kinetics after vaccination.

Delta-like ligand 3 (DLL3) landscape in pulmonary and extra-pulmonary neuroendocrine neoplasms.

Delta-like Ligand 3 (DLL3) targeting therapies are promising in small cell lung cancer (SCLC) treatment. However, DLL3 expression in SCLC and other neuroendocrine neoplasms (NEN) is heterogeneous and not well characterized. We describe the landscape of DLL3 at the mRNA and protein levels across SCLC, large cell neuroendocrine carcinoma (LCNEC), and non-small cell lung cancer.

Respiratory symptoms among e-cigarette users without an established smoking history in the VERITAS cohort.

Prior research on e-cigarettes' health impacts is inconclusive due to confounding by previous tobacco smoking. Studies of e-cigarette use among people without an established smoking history are informative for this question. A cross-sectional survey was administered across six geopolitical world regions to adults aged 18+ without a history of established cigarette smoking or regular use of other nicotine/tobacco products.

A modular platform for bioluminescent RNA tracking.

A complete understanding of RNA biology requires methods for tracking transcripts in vivo. Common strategies rely on fluorogenic probes that are limited in sensitivity, dynamic range, and depth of interrogation, owing to their need for excitation light and tissue autofluorescence. To overcome these challenges, we report a bioluminescent platform for serial imaging of RNAs.

Local wound care management for pyoderma gangrenosum.

Pyoderma gangrenosum (PG) is a rare, painful neutrophilic dermatosis characterized by rapidly progressing skin ulcers. Despite the importance of local wound care in managing PG, there is no consensus or evidence-based guidelines. This systematic review aimed to investigate local wound care strategies for PG.

Transcriptional profile of infection in people living with HIV.

In people with HIV-1 (PWH), (MTB) infection poses a significant threat. While active tuberculosis (TB) accelerates immunodeficiency, the interaction between MTB and HIV-1 during asymptomatic phases remains unclear. Analysis of peripheral blood mononuclear cells (PBMC) transcriptomic profiles in PWH, with and without controlled viral loads, revealed distinct clustering in MTB-infected individuals.

Travelling Waves in a PDE-ODE Coupled Model of Cellulolytic Biofilms with Nonlinear Diffusion.

We analyze travelling wave (TW) solutions for nonlinear systems consisting of an ODE coupled to a degenerate PDE with a diffusion coefficient that vanishes as the solution tends to zero and blows up as it approaches its maximum value. Stable TW solutions for such systems have previously been observed numerically as well as in biological experiments on the growth of cellulolytic biofilms. In this work, we provide an analytical justification for these observations and prove existence and stability results for TW solutions of such models.