A novel rapalog shows improved safety vs. efficacy in a human organoid model of polycystic kidney disease.

The mammalian target of rapamycin (mTOR) pathway is a therapeutic target in polycystic kidney disease (PKD), but mTOR inhibitors such as everolimus have failed to show efficacy at tolerated doses in clinical trials. Here, we introduce AV457, a novel rapalog developed to reduce side effects, and assess its dose-dependent safety and efficacy versus everolimus in PKD1 and PKD2 human kidney organoids, which form cysts in a PKD-specific way. Both AV457 and everolimus reduce cyst growth over time.

Paediatric strategy forum for medicinal product development in diffuse midline gliomas in children and adolescents ACCELERATE in collaboration with the European Medicines Agency with participation of the Food and Drug Administration.

Fewer than 10 % of children with diffuse midline glioma (DMG) survive 2 years from diagnosis. Radiation therapy remains the cornerstone of treatment and there are no medicinal products with regulatory approval. Although the biology of DMG is better characterized, this has not yet translated into effective treatments.

The impact of climate change on Korea's agricultural sector under the national self-sufficiency policy.

Evolving environmental conditions due to climate change have brought about changes in agriculture, which is required for human life as both a source of food and income. International trade can act as a buffer against potential negative impacts of climate change on crop yields, but recent years have seen breakdowns in global trade, including export bans to improve domestic food security. For countries that rely heavily on imported food, governments may institute policies to protect their agricultural industry from changes in climate-induced crop yield changes and other countries' potential trade restrictions.

Antiviral Mx proteins have an ancient origin and widespread distribution among eukaryotes.

Mx proteins, first identified in mammals, encode potent antiviral activity against a wide range of viruses. Mx proteins arose within the Dynamin superfamily of proteins (DSP), which mediate critical cellular processes, such as endocytosis and mitochondrial, plastid, and peroxisomal dynamics. Despite their crucial role, the evolutionary origins of Mx proteins are poorly understood.

Improving Social Determinants of Health via the Workplace.

: Social determinants of health (SDOH), such as food security and healthcare access, are key to maintaining and improving health. Publicly funded safety-net programs, such as Medicaid and the Supplemental Nutrition Assistance Program, address SDOH. Many low-wage employees are program-eligible, but there are substantial participation gaps.

Distributed lag models for retrospective cohort data with application to a study of built environment and body weight.

Distributed lag models (DLMs) estimate the health effects of exposure over multiple time lags prior to the outcome and are widely used in time series studies. Applying DLMs to retrospective cohort studies is challenging due to inconsistent lengths of exposure history across participants, which is common when using electronic health record databases. A standard approach is to define subcohorts of individuals with some minimum exposure history, but this limits power and may amplify selection bias.

Proximal remote sensing: an essential tool for bridging the gap between high-resolution ecosystem monitoring and global ecology.

A new proliferation of optical instruments that can be attached to towers over or within ecosystems, or 'proximal' remote sensing, enables a comprehensive characterization of terrestrial ecosystem structure, function, and fluxes of energy, water, and carbon. Proximal remote sensing can bridge the gap between individual plants, site-level eddy-covariance fluxes, and airborne and spaceborne remote sensing by providing continuous data at a high-spatiotemporal resolution. Here, we review recent advances in proximal remote sensing for improving our mechanistic understanding of plant and ecosystem processes, model development, and validation of current and upcoming satellite missions.

The MASCC COG-IMPACT: An unmet needs assessment for cancer-related cognitive impairment impact developed by the Multinational Association of Supportive Care in Cancer.

Purpose: Cancer-related cognitive impairment (CRCI) can have a profound impact on the lives of cancer survivors. A multitude of subjective and objective assessment tools exist to assess the presence and severity of CRCI. However, no purpose-built tool exists to assess the unmet needs of cancer survivors directly relating to CRCI.

Species Differences in the Biotransformation of Aflatoxin B1: Primary Determinants of Relative Carcinogenic Potency in Different Animal Species.

It has been known since the early days of the discovery of aflatoxin B1 (AFB1) that there were large species differences in susceptibility to AFB1. It was also evident early on that AFB1 itself was not toxic but required bioactivation to a reactive form. Over the past 60 years there have been thousands of studies to delineate the role of ~10 specific biotransformation pathways of AFB1, both phase I (oxidation, reduction) and phase II (hydrolysis, conjugation, secondary oxidations, and reductions of phase I metabolites).

Streamlining the Journey of Research Into Clinical Practice: Making Your Patients and Practice Flourish Evaluation and Treatment of Pyogenic Spondylodiscitis of the Spine: AO Spine Knowledge Forum Trauma and Infection.

Study Design: Literature Review with clinical recommendations.

Objective: To highlight impactful studies on pyogenic spondylodiscitis (PS), identified by the AO Spine Knowledge Forum Trauma and Infection, with recommendations for their integration into clinical practice.

Methods: Five influential studies on PS that have the potential to shape current practice in spinal infections were selected and reviewed.

Development of RT-PCR Assays for Simple Detection and Identification of Sabin Virus Contaminants in the Novel Oral Poliovirus Vaccines.

Background/objectives: Conventional live oral poliovirus vaccines (OPVs) effectively prevent poliomyelitis. These vaccines are derived from three attenuated Sabin strains of poliovirus, which can revert within the first week of replication to a neurovirulent phenotype, leading to sporadic cases of vaccine-associated paralytic poliomyelitis (VAPP) among vaccinees and their contacts. A novel OPV2 vaccine (nOPV2) with enhanced genetic stability was developed recently; type 1 and type 3 nOPV strains were engineered using the nOPV2 genome as a backbone by replacing the capsid precursor polyprotein (P1) with that of Sabin strains type 1 and type 3, respectively.

The Role of Partnerships in Supporting COVID-19 Vaccine Uptake Among Migrants: A Qualitative Case Study from Tamil Nadu and Punjab, India.

Background: During the COVID-19 pandemic, migrant populations remained under-immunized due to limited access to health care, language barriers, and vaccine hesitancy. The USAID-funded MOMENTUM Routine Immunization Transformation and Equity project supported the government in collaborating with various local health and non-health partners to identify and vaccinate migrants. This case study examines the roles of project partners and the strategies each entity implemented to increase COVID-19 vaccine uptake among migrants, as well as the perceptions regarding the effectiveness of these strategies.

Safety, Tolerability, and Immunogenicity of the Invaplex Vaccine Co-Administered with the dmLT Adjuvant in Dutch and Zambian Adults: Study Protocol for a Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation Phase Ia/b Clinical Trial.

Background: Shigella infections remain endemic in places with poor sanitation and are a leading cause of diarrheal mortality globally, as well as a major contributor to gut enteropathy and stunting. There are currently no licensed vaccines for shigellosis but it has been estimated that an effective vaccine could avert 590,000 deaths over a 20-year period. A challenge to effective Shigella vaccine development has been the low immunogenicity and protective efficacy of candidate Shigella vaccines in infants and young children.

Mid-Infrared High-Power InGaAsSb/AlGaInAsSb Multiple-Quantum-Well Laser Diodes Around 2.9 μm.

Antimonide laser diodes, with their high performance above room temperature, exhibit significant potential for widespread applications in the mid-infrared spectral region. However, the laser's performance significantly degrades as the emission wavelength increases, primarily due to severe quantum-well hole leakage and significant non-radiative recombination. In this paper, we put up an active region with a high valence band offset and excellent crystalline quality with high luminescence to improve the laser's performance.

Controlled Capture of Magnetic Nanoparticles from Microfluidic Flows by Ferromagnetic Antidot and Dot Nanostructures.

The capture of magnetic nanoparticles (MNPs) is essential in the separation and detection of MNPs for applications such as magnetic biosensing. The sensitivity of magnetic biosensors inherently depends upon the distribution of captured MNPs within the sensing area. We previously demonstrated that the distribution of MNPs captured from evaporating droplets by ferromagnetic antidot nanostructures can be controlled via an external magnetic field.

Serious Bacterial Infections and Hepatitis C Virus Among People Who Inject Drugs: A Syndemic or Intertwined Epidemics?

Limited research has examined the possible synergistic interrelationships between serious bacterial infections (SBIs) of the heart (i.e., endocarditis), bone, spine, brain, or joints (e.

Safety and Efficacy of Incorporating Actellic 300 CS into Soil Wall Plaster for Control of Malaria Vectors in Rural Northeastern Uganda.

Indoor residual spraying (IRS) and the use of insecticide-treated bednets for malaria vector control have contributed substantially to a reduction in malaria disease burden. However, these control tools have important shortcomings including being donor-dependent, expensive, and often failing because of insufficient uptake. We assessed the safety and efficacy of a user-friendly, locally tailored malaria vector control approach dubbed "Hut Decoration for Malaria Control" (HD4MC) based on the incorporation of a WHO-approved insecticide, Actellic 300 CS, into a customary hut decoration practice in rural Uganda where millions of the most vulnerable and malaria-prone populations live in mud-walled huts.

Mapping Drug-Resistant Tuberculosis Treatment Outcomes in Hunan Province, China.

Background: Drug-resistant tuberculosis (DR-TB) remains a major public health challenge in China, with varying treatment outcomes across different regions. Understanding the spatial distribution of DR-TB treatment outcomes is crucial for targeted interventions to improve treatment success in high-burden areas such as Hunan Province. This study aimed to map the spatial distribution of DR-TB treatment outcomes at a local level and identify sociodemographic and environmental factors associated with poor treatment outcomes in Hunan Province, China.

Maternal Birth Satisfaction Relating to Intraoperative and Early Postpartum Skin-to-Skin Contact with the Neonate During Caesarean Birth: An Integrative Review.

: Mothers and their newborns experiencing caesarean birth often receive delayed or interrupted skin-to-skin care (SSC) despite the intervention being well recognised as beneficial to both mother and baby, with no associated risk for increased morbidity or mortality. Maternal birth satisfaction is recognised as an indicator of quality maternity care; however, most of the research has focused on early intraoperative SSC initiation and breastfeeding outcomes. : To collate and synthesise evidence for maternal satisfaction of intraoperative and early postpartum SSC during and immediately following caesarean birth.

: Co-Design of a Novel Approach for Engaging People with Dementia in Physical Activity.

Background: Promoting physical activity among people living with dementia is critical to maximise physical, cognitive and social benefits; yet the lack of knowledge, skills and confidence among health professionals, informal care partners and people with dementia deters participation. As the initial phase of a larger feasibility study, co-design was employed to develop a new model of community care, to facilitate the physical activity participation of older people living with mild dementia.

Methods: Co-design methodology was utilised with nine stakeholders (with experience in referring to or providing physical activity programs and/or contributing to policy and program planning) over three workshops plus individual interviews with four care partners of people with dementia.

Sensitivity to the Demethylation Inhibitor Difenoconazole Among Baseline Populations of Various spp. Causing Blue Mold of Apples and Pears.

Difenoconazole (DIF), a demethylation inhibitor fungicide, was registered in 2016 for the control of postharvest diseases of pome fruits. In this study, 162 isolates from ( = 31) and 13 other "non-" spp., i.

Simulation of a Reverse Electrodialysis-Absorption Refrigeration Integration System for the Efficient Recovery of Low-Grade Waste Heat.

The absorption refrigeration system (ARS) stands as a remarkable device that is capable of efficiently harnessing low-grade thermal energy and converting it into cooling capacity. The reverse electrodialysis (RED) system harvests the salinity gradient energy embedded in two solutions of different concentrations into electricity. An innovative RED-ARS integration system is proposed that outputs cooling capacity and electric energy, driven by waste heat.

Imaging Flow Cytometric Identification of Chromosomal Defects in Paediatric Acute Lymphoblastic Leukaemia.

Acute lymphoblastic leukaemia is the most common childhood malignancy that remains a leading cause of death in childhood. It may be characterised by multiple known recurrent genetic aberrations that inform prognosis, the most common being hyperdiploidy and t(12;21) . We aimed to assess the applicability of a new imaging flow cytometry methodology that incorporates cell morphology, immunophenotype, and fluorescence in situ hybridisation (FISH) to identify aneuploidy of chromosomes 4 and 21 and the translocation .

The Multifactorial Memory Questionnaire and Quality of Life: A Longitudinal Study in Parkinson's Disease.

Background/objectives: Objective memory decline is associated with poor quality of life (QOL) in Parkinson's disease (PD, but it is unclear what role perception of memory (metamemory) plays. The Multifactorial Memory Questionnaire (MMQ) measures metamemory and is proposed to have a three-factor structure, but the factor structure of the MMQ in PD has not been explored. The current study examined (i) the factor structure of the MMQ in PD and (ii) the relationship between the metamemory and QOL in PD.

Experimental Biomechanics of Neonatal Brachial Plexus Avulsion Injuries Using a Piglet Model.

Background: A brachial plexus avulsion occurs when the nerve root separates from the spinal cord during birthing trauma, such as shoulder dystocia or a difficult vaginal delivery. A complete paralysis of the affected levels occurs post-brachial plexus avulsion. Despite being reported in 10-20% of brachial plexus birthing injuries, it remains poorly diagnosed during the acute stages of injury, leading to poor intervention approaches.