Breast milk delivery of an engineered dimeric IgA protects neonates against rotavirus.

Dimeric IgA (dIgA) is the dominant antibody in many mucosal tissues. It is actively transported onto mucosal surfaces as secretory IgA (sIgA) which plays an integral role in protection against enteric pathogens, particularly in young children. Therapeutic strategies that deliver engineered, potently neutralizing antibodies directly into the infant intestine through breast milk could provide enhanced antimicrobial protection for neonates.

Developmental synchrony and extraordinary multiplication rates in pathogenic organisms.

The multiplication rates of pathogenic organisms influence disease progression, efficacy of immunity and therapeutics, and potential for within-host evolution. Thus, accurate estimates of multiplication rates are essential for biological understanding. We recently showed that common methods for inferring multiplication rates from malaria infection data substantially overestimate true values (i.

Disparities in Rehabilitation Services for Victims of Violence.

Introduction: Access to rehabilitation services after a traumatic injury improves functional outcomes. No study has examined the association between injury intent, violent versus nonviolent, and receipt of rehabilitation services after injury.

Materials And Methods: We conducted a retrospective cohort study of injured adult patients admitted to our level I trauma center from January 1, 2014 to December 31, 2021.

De novo design of peptide binders to conformationally diverse targets with contrastive language modeling.

Designing binders to target undruggable proteins presents a formidable challenge in drug discovery. In this work, we provide an algorithmic framework to design short, target-binding linear peptides, requiring only the amino acid sequence of the target protein. To do this, we propose a process to generate naturalistic peptide candidates through Gaussian perturbation of the peptidic latent space of the ESM-2 protein language model and subsequently screen these novel sequences for target-selective interaction activity via a contrastive language-image pretraining (CLIP)-based contrastive learning architecture.

Microenvironment actuated CAR T cells improve solid tumor efficacy without toxicity.

A major limiting factor in the success of chimeric antigen receptor (CAR) T cell therapy for the treatment of solid tumors is targeting tumor antigens also found on normal tissues. CAR T cells against GD2 induced rapid, fatal neurotoxicity because of CAR recognition of GD2 normal mouse brain tissue. To improve the selectivity of the CAR T cell, we engineered a synthetic Notch receptor that selectively expresses the CAR upon binding to P-selectin, a cell adhesion protein overexpressed in tumor neovasculature.

Recycled Phosphorus Bioamendments from Wastewater Impact Rhizomicrobiome and Benefit Crop Growth: Sustainability Implications at Water-Food Nexus.

Phosphorus recovery through enhanced biological phosphorus removal (EBPR) processes from agricultural wastes holds promise in mitigating the impending global P shortage. However, the complex nutrient forms and the microbial augments, expected to exert a profound impact on crop rhizomicrobiome and thus crop health, remained unexplored. In this study, we investigated the impacts of EBPR biosolids on crops growth and rhizomicrobiome in comparison to chemical fertilizer and Vermont manure compost.

Dual Biological Role and Clinical Impact of De Novo Chromatin Activation in Chronic Lymphocytic Leukemia.

Previous studies have reported that chronic lymphocytic leukemia (CLL) shows a de novo chromatin activation pattern as compared to normal B cells. Here, we explored whether the level of chromatin activation is related to the clinical behavior of CLL. We identified that in some regulatory regions, increased de novo chromatin activation is linked to clinical progression whereas, in other regions, it is associated with an indolent course.

The effects of ultra-selective beta1-antagonism on the metabolic and cytokine profile in septic shock patients receiving noradrenaline: a sub-investigation from the STRESS-L Randomised Study.

Purpose: The landiolol and organ failure in patients with septic shock (STRESS-L study) included a pre-planned sub-study to assess the effect of landiolol treatment on inflammatory and metabolomic markers.

Methods: Samples collected from 91 patients randomised to STRESS-L were profiled for immune and metabolomic markers. A panel of pro- and anti-inflammatory cytokines were measured through commercially acquired multiplex Luminex assays and statistically analysed by individual and cluster-level analysis (patient).

Illness Intrusiveness, Perceived Control, and Quality of Life in Older Adults with Arthritis and Multimorbidity.

Objectives: Arthritis is associated with poor quality of life (QOL) among older adults; and QOL is even worse among those with arthritis and multimorbidity (MM). Illness intrusiveness and perceived control have been identified in studies of single illnesses as modifiable mechanisms for QOL, but are understudied in older adults with arthritis and MM. We investigated the role of these potential mechanisms with QOL among older adults with arthritis and MM.

Initial clinical experience with [Lu]Lu-PNT2002 radioligand therapy in metastatic castration-resistant prostate cancer: dosimetry, safety, and efficacy from the lead-in cohort of the SPLASH trial.

Introduction: SPLASH (NCT04647526) is a multicenter phase III trial evaluating the efficacy and safety of [Lu]Lu-PNT2002 radioligand therapy in metastatic castration-resistant prostate cancer (mCRPC). This study leveraged a lead-in phase to assess tissue dosimetry and evaluate preliminary safety and efficacy, prior to expansion into a randomized phase. Here we report those results.

Impact of race-based calculations of eGFR on the management of muscle invasive bladder cancer.

Purpose: The estimated glomerular filtration rate (eGFR) has historically been calculated with a race-coefficient multiplier (RCM); however, the RCM has been broadly criticized as inaccurate and a potential contributor to exacerbating disparities. We evaluated the impact of the RCM on eGFR and examined the 30-day post-cystectomy complications in a muscle-invasive bladder cancer cohort.

Materials And Methods: We retrospectively analyzed patients diagnosed with MIBC who underwent cystectomy in the ACS NSQIP database from 2006 to 2020 using CPT and ICD codes.

Biochemical characterization of collagen I in Warmblood Fragile Foal Syndrome horse lysyl hydroxylase 1 mutation.

Mutations in the collagen-modifying enzyme lysyl hydroxylase 1 (LH1) cause Warmblood Fragile Foal Syndrome (WFFS) in horses. We investigated the impact of this mutation on collagen structure and function. Our results show that LH1 deficiency leads to reduced lysine hydroxylation, altered collagen fibril organization, and tissue abnormalities resembling human Ehlers-Danlos syndrome.

Anterior Uveitis and Uveal Depigmentation in a Dog With Vitiligo.

The objective of this study is to describe the clinical and histologic features of a dog that developed anterior uveitis and uveal depigmentation in association with vitiligo. A 3-year-old, female-spayed, Bernese Mountain Dog with a history of bilateral idiopathic anterior uveitis developed iris depigmentation, leukotrichia, and skin depigmentation. The initial diagnostic evaluation for uveitis was unremarkable, including general bloodwork, urinalysis, infectious disease testing, thoracic radiographs, and abdominal ultrasound.

Promoting Evidence-Based Tobacco Cessation Treatment in Community Mental Health Clinics: Results of a Pilot Implementation Study: Promouvoir le traitement de sevrage tabagique fondé sur des données probantes dans les cliniques communautaires de santé mentale : résultats d'une étude pilote de mise en œuvre.

Objective: Tobacco smoking is the leading cause of preventable death among individuals with serious mental illness (SMI) but few persons with SMI are offered smoking cessation treatment. The purpose of this study was to pilot-test a multicomponent intervention to increase the delivery of evidence-based smoking cessation treatment in community mental health clinics (CMHCs).

Method: This study was carried out at five CMHCs in Maryland involving clinicians who participated in training in smoking cessation.

A disturbed communication between hypothalamic-pituitary-ovary axis and gut microbiota in female infertility: is diet to blame?

Female infertility is a multifactorial condition influenced by various genetic, environmental, and lifestyle factors. Recent research has investigated the significant impact of gut microbiome dysbiosis on systemic inflammation, metabolic dysfunction, and hormonal imbalances, which can potentially impair fertility. The gut-brain axis, a bidirectional communication system between the gut and the brain, also plays a significant role in regulating reproductive functions.

Characterizing Pathogen-Induced Changes in Black Walnut Volatile Organic Compounds Following Inoculation with Geosmithia Morbida, The Causal Agent of Thousand Cankers Disease.

Thousand cankers disease (TCD) is a pathosystem comprised of Juglandacea spp., a pathogenic fungus Geosmithia morbida, and an insect vector, the walnut twig beetle (WTB) (Pityophthorus juglandis). Of the North American Juglans species, Juglans nigra is the most susceptible to TCD and has resulted in significant decline and mortality of urban and plantation trees in the western United States.

Maytansinoids in cancer therapy: advancements in antibody-drug conjugates and nanotechnology-enhanced drug delivery systems.

Cancer remains the second leading cause of death globally, driving the need for innovative therapies. Among natural compounds, maytansinoids have shown significant promise, contributing to nearly 25% of recently approved anticancer drugs. Despite their potential, early clinical trials faced challenges due to severe side effects, prompting advancements in delivery systems such as antibody-maytansinoid conjugates (AMCs).

Treatment effects of nitrogen and phosphorus addition on foliar traits in six northern hardwood tree species.

Foliar traits can reflect fitness responses to environmental changes, such as changes in nutrient availability. Species may respond differently to these changes due to differences in traits and their plasticity. Traits and community composition together can influence forest nutrient cycling.

A network-based systems genetics framework identifies pathobiology and drug repurposing in Parkinson's disease.

Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder. However, current treatments only manage symptoms and lack the ability to slow or prevent disease progression. We utilized a systems genetics approach to identify potential risk genes and repurposable drugs for PD.

Atomically resolved imaging of radiation-sensitive metal-organic frameworks via electron ptychography.

Electron ptychography, recognized as an ideal technique for low-dose imaging, consistently achieves deep sub-angstrom resolution at electron doses of several thousand electrons per square angstrom (e/Å) or higher. Despite its proven efficacy, the application of electron ptychography at even lower doses-necessary for materials highly sensitive to electron beams-raises questions regarding its feasibility and the attainable resolution under such stringent conditions. Herein, we demonstrate the implementation of near-atomic-resolution ( ~ 2 Å) electron ptychography reconstruction at electron doses as low as ~100 e/Å, for metal-organic frameworks (MOFs), which are known for their extreme sensitivity.

Small intra-tropical long-distance migratory birds track rainy seasons across hemispheres.

The main features of long-distance migration are derived from landbirds breeding in the Northern Hemisphere. Little is known about migration within the tropics, presumably because tropical species typically move opportunistically and over shorter distances. However, such generalizations are weakened by a lack of solid data on spatial, temporal and behavioural patterns of intra-tropical migrations.