Neonatal administration of ATCC 202195 with or without fructooligosaccharide in Bangladesh: a placebo-controlled randomized trial.

Unlabelled: ATCC 202195 (LP202195) plus fructooligosaccharide (FOS) for 7 days was previously shown to colonize the infant intestine up to 6 months of age and reduced sepsis rates among young infants in rural India. In a phase 2 randomized controlled trial in Dhaka, Bangladesh ( = 519), neonatal administration of LP202195 for 1 or 7 days, with or without FOS, increased LP202195 stool abundance from 14 to 60 days of age, versus placebo. Abundance progressively declined in the post-administration period and did not persist beyond 2 months of age.

Head Circumference Versus Length and Weight Deficits up to 2 Years of Age in Bangladesh.

Infant undernutrition, defined by length- and weight-based indices, is common in low- and middle-income countries (LMICs), but corresponding deficits in head size have received less attention. In a cohort of term newborns in Dhaka, Bangladesh, we compared the severity of deficits (vs. World Health Organization Growth Standards) in head circumference (HC), length and weight at birth and every 3 months until 2 years of age (n range across timepoints: 843-920).

Height-Age as An Alternative to Height-For-Age z-Scores to Assess the Effect of Interventions on Child Linear Growth in Low- and Middle-Income Countries.

Background: Assessments of the efficacy of interventions to improve child growth are often based on differences in mean height-for-age -scores (HAZ) and stunting (HAZ<-2) in randomized controlled trials (RCTs). However, this approach does not account for children's starting skeletal age and does not enable assessment of the extent to which interventions optimized linear growth.

Objectives: The objectives of this study were to develop and apply a new method using height-age to express linear growth effects in RCTs.

Reassessing the Photochemical Upcycling of Polystyrene Using Acridinium Salts.

Polystyrene (PS) is a commodity plastic recalcitrant to chemical recycling or upcycling processes. Approaches aimed at deconstructing PS by photocatalytic means struggle to generate high-energy species capable of cleaving the robust C-H and C-C bonds of PS. We show that 9-mesityl-10-methylacridinium perchlorate (MA) is capable of upcycling various grades of PS substrates into up to 40 % benzoic acid (BAc), formic acid (FA) and small proportions of acetophenone (ACP), under visible light (456 nm) or through solar radiation.

A comprehensive study of SARS-CoV-2 main protease (Mpro) inhibitor-resistant mutants selected in a VSV-based system.

Nirmatrelvir was the first protease inhibitor specifically developed against the SARS-CoV-2 main protease (3CLpro/Mpro) and licensed for clinical use. As SARS-CoV-2 continues to spread, variants resistant to nirmatrelvir and other currently available treatments are likely to arise. This study aimed to identify and characterize mutations that confer resistance to nirmatrelvir.

The contributions of fertility during adolescence to disability across the life-course: hypothesized causal pathways, research gaps, and future directions.

Context: Robust associations have been identified between fertility during adolescence and the disablement process, including pathologies, impairments, functional limitations and disability. Limited theoretical or empirical research considers how and why such relationships exist generally or with the individual associated components of disablement.

Objective: To consolidate and critically evaluate literature to describe testable, theory-based hypotheses to guide future research on the mechanisms by which fertility during adolescence contributes to disablement.

7-Amino-[1,2,4]triazolo[1,5-a][1,3,5]triazines as CK1δ inhibitors: Exploring substitutions at the 2 and 5-positions.

CK1δ is a serine-threonine kinase involved in several pathological conditions including neuroinflammation and neurodegenerative disorders like Alzheimer's disease, Parkinson's disease, and Amyotrophic Lateral Sclerosis. Specifically, it seems that an inhibition of CK1δ could have a neuroprotective effect in these conditions. Here, a series of [1,2,4]triazolo[1,5-a][1,3,5]triazines were developed as ATP-competitive CK1δ inhibitors.

Another string to your bow: machine learning prediction of the pharmacokinetic properties of small molecules.

Introduction: Prediction of pharmacokinetic (PK) properties is crucial for drug discovery and development. Machine-learning (ML) models, which use statistical pattern recognition to learn correlations between input features (such as chemical structures) and target variables (such as PK parameters), are being increasingly used for this purpose. To embed ML models for PK prediction into workflows and to guide future development, a solid understanding of their applicability, advantages, limitations, and synergies with other approaches is necessary.

Association of maternal, obstetric, fetal, and neonatal mortality outcomes with Lady Health Worker coverage from a cross-sectional survey of >10,000 households in Gilgit-Baltistan, Pakistan.

Pakistan has among the highest rates of maternal, perinatal, and neonatal mortality globally. Many of these deaths are potentially preventable with low-cost, scalable interventions delivered through community-based health worker programs to the most remote communities. We conducted a cross-sectional survey of 10,264 households during the baseline phase of a cluster randomized controlled trial (cRCT) in Gilgit-Baltistan, Pakistan from June-August 2021.

An integrated newborn care kit (iNCK) to save newborn lives and improve health outcomes in Gilgit Baltistan (GB), Pakistan: study protocol for a cluster randomized controlled trial.

Background: Ongoing high neonatal mortality rates (NMRs) represent a global challenge. In 2021, of the 5 million deaths reported worldwide for children under five years of age, 47% were newborns. Pakistan has one of the five highest national NMRs in the world, with an estimated 39 neonatal deaths per 1,000 live births.

Associations between human milk oligosaccharides and infant growth in a Bangladeshi mother-infant cohort.

Background: We aimed to estimate associations between human milk oligosaccharides (HMOs) and infant growth (length-for-age (LAZ) and weight-for-length (WLZ) z-scores) at 12 months postnatal age.

Methods: In this secondary analysis of data from a maternal vitamin D trial in Dhaka, Bangladesh (N = 192), absolute concentrations of HMOs were measured in 13 ± 1 week(s) postpartum milk samples, infant anthropometric measurements were obtained soon after birth and at 12 months postpartum, and infant feeding was classified during 6 months postpartum. Associations between individual HMOs or HMO groups and LAZ or WLZ were estimated by multivariable linear regression adjusting for infant feeding pattern, maternal secretor status, and other potential confounders.

Federated Learning in Computational Toxicology: An Industrial Perspective on the Effiris Hackathon.

approaches have acquired a towering role in pharmaceutical research and development, allowing laboratories all around the world to design, create, and optimize novel molecular entities with unprecedented efficiency. From a toxicological perspective, computational methods have guided the choices of medicinal chemists toward compounds displaying improved safety profiles. Even if the recent advances in the field are significant, many challenges remain active in the on-target and off-target prediction fields.

Molecular Modeling Unveils the Effective Interaction of B-RAF Inhibitors with Rare B-RAF Insertion Variants.

The Food and Drug Administration (FDA) has approved MAPK inhibitors as a treatment for melanoma patients carrying a mutation in codon V600 of the BRAF gene exclusively. However, BRAF mutations outside the V600 codon may occur in a small percentage of melanomas. Although these rare variants may cause B-RAF activation, their predictive response to B-RAF inhibitor treatments is still poorly understood.

Sequential chiral induction between organic and inorganic supramolecular helical assemblies for the formation of chiral carbon dots.

Self-organised helical bilayers of dicationic gemini surfactants confined in helical silica nanospace were transformed to carbon dots (CDots) pyrolysis. These water-dispersible CDots exhibit electronic absorption spanning the UV and visible range and possess symmetrical circular dichroism (CD) signals, the sign of which depends on the handedness of the helices.

Adolescent childbirth and mobility disability among women ages 15-49: an analysis of population health surveys from 14 low-income and middle-income countries.

Objectives: Adolescent childbirth is associated with older adult adverse health outcomes that negatively affect mobility function, but these associations have not been studied globally in large samples of reproductive-age women. This study examines the association between age at first childbirth and mobility disability in national surveys from low-income and middle-income countries, and hypotheses that adolescent childbirth is associated with mobility disability.

Design: Cross-sectional analysis.

A novel systematic pipeline for increased predictability and explainability of growth patterns in children using trajectory features.

Objective: Longitudinal patterns of growth in early childhood are associated with health conditions throughout life. Knowledge of such patterns and the ability to predict them can lead to better prevention and improved health promotion in adulthood. However, growth analyses are characterized by significant variability, and pattern detection is affected by the method applied.

Correction: Bassani, D.; Moro, S. Past, Present, and Future Perspectives on Computer-Aided Drug Design Methodologies. 2023, , 3906.

In the published publication [...

Redox-active ions unlock substitutional doping in halide perovskites.

Electrical doping of metal halide perovskites (MPHs) is a key step towards the use of this efficient and cost-effective semiconductor class in modern electronics. In this work, we demonstrate n-type doping of methylammonium lead iodide (CHNHPbI) by the post-fabrication introduction of Sm. The ionic radius of the latter is similar to that of Pb and can replace it without altering the perovskite crystal lattice.

Strong circularly polarized luminescence intramolecular excited-state symmetry-breaking charge separation.

-1,2-di(1-pyrenylamino)cycloxexane was found to display circularly polarized excimer emission ( = 0.016) both in polar and non-polar solvents that is assigned to charge separation symmetry breaking on the basis of its large transition state dipole moment (12.1 D).

"Dual Anta-Inhibitors" of the A Adenosine Receptor and Casein Kinase CK1delta: Synthesis, Biological Evaluation, and Molecular Modeling Studies.

Based on a screening of a chemical library of A adenosine receptor (AR) antagonists, a series of di- and tri-substituted adenine derivatives were synthesized and tested for their ability to inhibit the activity of the enzyme casein kinase 1 delta (CK1δ) and to bind adenosine receptors (ARs). Some derivatives, here called "dual anta-inhibitors", demonstrated good CK1δ inhibitory activity combined with a high binding affinity, especially for the AAR. The -methyl-(2-benzimidazolyl)-2-dimethyamino-9-cyclopentyladenine (, IC = 0.

Past, Present, and Future Perspectives on Computer-Aided Drug Design Methodologies.

The application of computational approaches in drug discovery has been consolidated in the last decades. These families of techniques are usually grouped under the common name of "computer-aided drug design" (CADD), and they now constitute one of the pillars in the pharmaceutical discovery pipelines in many academic and industrial environments. Their implementation has been demonstrated to tremendously improve the speed of the early discovery steps, allowing for the proficient and rational choice of proper compounds for a desired therapeutic need among the extreme vastness of the drug-like chemical space.

Are Two Riboses Better Than One? The Case of the Recognition and Activation of Adenosine Receptors.

Traditionally, molecular recognition between the orthosteric site of adenosine receptors and their endogenous ligand occurs with a 1 : 1 stoichiometry. Inspired by previous mechanistic insights derived from supervised molecular dynamics (SuMD) simulations, which suggested an alternative 2 : 1 binding stoichiometry, we synthesized BRA1, a bis-ribosyl adenosine derivative, tested its ability to bind to and activate members of the adenosine receptor family, and rationalized its activity through molecular modeling.

Chiral Binaphthalene Building Blocks for Self-Assembled Nanoscale CPL Emitters.

The introduction of biuret hydrogen-bonding sites onto chiral binaphthalene-based chromophores was investigated as a route to sub-micron-sized, vesicle-like aggregates endowed with chiroptical properties. The synthesis was conducted from the corresponding chiral 4,4'-dibromo-1,1'-bis(2-naphthol) via Suzuki-Miyaura coupling to afford luminescent chromophores whose emission spectrum could be tuned from blue to yellow-green through extension of the conjugation. For all compounds, the spontaneous formation of hollow spheres with a diameter of ca.