MMRT: MultiMut Recursive Tree for predicting functional effects of high-order protein variants from low-order variants.

Protein sequences primarily determine their stability and functions. Mutations may occur at one, two, or three positions at the same time (low-order variants) or at multiple positions simultaneously (high-order variants), which affect protein functions. So far, low-order variants, such as single variants, double variants, and triple variants, have been well-studied through high-throughput experimental scanning techniques and computational prediction methods.

Relating Solute-Membrane Electrostatic Interactions to Solute Permeability in Reverse Osmosis Membranes.

Despite the widespread use of reverse osmosis (RO) membranes in water desalination, the role of solute-membrane interactions in solute transport remains complex and relatively not well understood. This study elucidates the relationship between solute-membrane electrostatic interactions and solute permeability in RO membranes. The transport of salt and neutral molecules through charged polyamide (PA) and uncharged cellulose triacetate (CTA) RO membranes was examined.

Quality of life in heart failure. The heart of the matter. A scientific statement of the Heart Failure Association and the European Association of Preventive Cardiology of the European Society of Cardiology.

For most patients with chronic, progressive illnesses, maintaining good quality of life (QoL), with preserved functional capacity, is just as crucial as prolonging survival. Patients with heart failure (HF) experience much worse QoL and effort intolerance than both the general population and people with other chronic conditions, since they present a range of physical and psychological symptoms, including shortness of breath, chest discomfort, fatigue, fluid congestion, trouble with sleeping, and depression. These symptoms reduce patients' capacity for daily social and physical activity.

A steric gate prevents mutagenic dATP incorporation opposite 8-oxo-deoxyguanosine in mitochondrial DNA polymerases.

Reactive oxygen species (ROS) generate DNA lesions that alter genome integrity. Among those DNA lesions, 7,8-dihydro-8-oxo-2'-deoxyguanosine (8-oxodG) is particularly mutagenic. 8-oxodG efficiently incorporates deoxycytidine monophosphate (dCMP) and deoxyadenosine monophosphate (dAMP) via base pairing mediated by its anti and syn conformations, respectively.

Genome-wide selection scans in Mexican Indigenous populations reveal recent signatures of pathogen and diet adaptation.

Whole genome scans for natural selection signatures across Mexican Indigenous (MI) Populations remain underrepresented in the literature. Here, we conducted the first comparative analysis of genetic adaptation in MI populations using whole genome sequencing (WGS) data from 76 individuals representing 27 different ethnic groups in Mexico. We divided the cohort into Northern, Central, and Southern populations and identified signals of natural selection within and across populations.

Fetal exposure to gestational diabetes severity and postnatal infant feeding in the first year of life associated with preadolescent obesity: a prospective cohort.

Objective: This study sought to evaluate the distinct impact of fetal exposure to gestational diabetes (GDM) severity, as well as the impact of infant breastfeeding (BF) and sugary beverage intake, on preadolescent overweight and obesity, accounting for other established risk factors.

Methods: This analysis included 850 mother-infant dyads exposed to GDM who reported monthly infant BF duration and intensity, as well as sugary beverage intake (sugar-sweetened beverages [SSB] and 100% fruit juice [FJ]) during the first year of life, BMI measured at ages 6 to 11 years, and GDM severity variables (i.e.

EXPRESS: Exploring Novel Non-Opioid Pathways and Therapeutics for Pain Relief.

The opioid crisis has highlighted the urgent need for alternative pain management strategies. This review explores novel non-opioid targets and pathways involved in pain modulation, highlighting advancements in understanding and therapeutic potential. Pain, a multifaceted phenomenon with nociceptive, neuropathic, and inflammatory components, involves intricate molecular signaling cascades.

Efficacy of human papillomavirus vaccines in the prevention of male genital diseases: a systematic review.

Objectives: To evaluate the results of randomised controlled trials (RCTs) regarding the efficacy of human papillomavirus (HPV) vaccination in preventing male genital-related diseases.

Methods: A systematic search of English language literature using PubMed, Scopus, and Cochrane Library was performed in April 2024 according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol.

Results: Evidence from four RCTs (including 7008 male participants) support the efficacy of the quadrivalent HPV vaccine in preventing genital warts and persistent HPV infection in HPV-naïve men.

Establishing a Common Lexicon for Circulating Tumor DNA Analysis and Molecular Residual Disease: Insights From the BLOODPAC Consortium.

The use of a liquid biopsy to assess molecular residual disease (MRD) of solid tumors holds significant promise for improving outcomes for patients with cancer. Liquid biopsies are a minimally invasive approach for the identification of circulating tumor biomarkers through a simple blood sample. Assays capable of detecting MRD through analysis of circulating tumor DNA (ctDNA) are rapidly evolving for clinical study applications and therapeutic interventions.

Biofilm Dispersal and Wound Infection Clearance With Preclinical Debridement Agents.

Biofilms complicate wound care by causing recurrent infections that are often resistant to debridement and are highly antibiotic-tolerant. We investigated whether the addition of a biofilm dispersal agent could improve the efficacy of debridement. The previous studies have indicated that a glycoside hydrolase cocktail of alpha-amylase and cellulase can act as a potent biofilm dispersal agent.

Sex-specific attenuation of constant light-induced memory impairment and Clock gene expression in brain in hepatic Npas2 knockout mice.

NPAS2 (Neuronal PAS Domain Protein 2) is a component of the core circadian clock and the coordinated activity between central brain and peripheral liver clock proteins postulated to be instrumental for linking behaviour and metabolism. We investigated a conditional liver-specific knockout mouse model (Npas2-/- or cKO) to explore its function in activity, circadian rhythms and cognition (novel object recognition-NOR). Circadian rhythms showed no genotype differences.

Aryl halide cross-coupling via formate-mediated transfer hydrogenation.

Transfer hydrogenation is widely practised across all segments of chemical industry, yet its application to aryl halide reductive cross-coupling is undeveloped because of competing hydrogenolysis. Here, exploiting the distinct reactivity of Pd species, an efficient catalytic system for the reductive cross-coupling of activated aryl bromides with aryl iodides via formate-mediated hydrogen transfer is described. These processes display orthogonality with respect to Suzuki and Buchwald-Hartwig couplings, as pinacol boronates and anilines are tolerated and, owing to the intervention of chelated intermediates, are effective for challenging 2-pyridyl systems.

Improved linear growth after routine zinc supplementation in preterm very low birth weight infants.

Background: This study was designed (1) to compare growth, morbidity and mortality in < 33-week gestational age (GA) (very preterm, VPT) or very low birth weight (BW < 1500 grams, VLBW) infants before (Epoch-1) and after implementing routine enteral zinc (Zn) supplementation (Epoch-2) to meet recommendations, and (2) to assess serum Zn levels and associated variables.

Methods: Single-center prospective cohort of 826 infants. The primary outcome was the change (Δ) in Z-scores of accurate length (Δlength), weight and head circumference from birth to discharge home.

Low responsiveness of machine learning models to critical or deteriorating health conditions.

Background: Machine learning (ML) based mortality prediction models can be immensely useful in intensive care units. Such a model should generate warnings to alert physicians when a patient's condition rapidly deteriorates, or their vitals are in highly abnormal ranges. Before clinical deployment, it is important to comprehensively assess a model's ability to recognize critical patient conditions.

Study-phase reinstatement predicts subsequent recall.

Can the brain improve the retrievability of an experience after it has occurred? Systems consolidation theory proposes that item-specific cortical reactivation during post-encoding rest periods facilitates the formation of stable memory representations, a prediction supported by neural evidence in humans and animals. Such reactivation may also occur on shorter timescales, offering a potential account of classic list memory phenomena but lacking in support from neural data. Leveraging the high temporal specificity of intracranial electroencephalography (EEG), we investigate spontaneous reactivation of previously experienced items during brief intervals between individual encoding events.

AI-guided framework for the design of materials and devices for magnetic-tunnel-junction-based true random number generators.

Emerging devices, such as magnetic tunnel junctions, are key for energy-efficient, performant future computing systems. However, designing devices with the desirable specification and performance for these applications is often found to be time-consuming and non-trivial. Here, we investigate the design and optimization of spin-orbit torque and spin transfer torque magnetic tunnel junction models as the probabilistic devices for true random number generation.

Loss of Socs2 improves molecular responses to IFNα in a mouse model of myeloproliferative neoplasms driven by JAK2-V617F.

Therapy with pegylated interferon alpha (pegIFNα) can induce a deep molecular response in a subset of patients with myeloproliferative neoplasms (MPN). Here we investigated the role of Socs2, a negative regulator of cytokine signaling, in modulating the response to pegIFNα in a JAK2-V617F mouse model of MPN. Deleting Socs2 in JAK2-V617F mice resulted in increased sensitivity to cytokines, without causing significant alterations in the MPN phenotype.

Longitudinal multi-omics in alpha-synuclein Drosophila model discriminates disease- from age-associated pathologies in Parkinson's disease.

Parkinson's disease (PD) starts decades before symptoms appear, usually in the later decades of life, when age-related changes are occurring. To identify molecular changes early in the disease course and distinguish PD pathologies from aging, we generated Drosophila expressing alpha-synuclein (αSyn) in neurons and performed longitudinal bulk transcriptomics and proteomics on brains at six time points across the lifespan and compared the data to healthy control flies as well as human post-mortem brain datasets. We found that translational and energy metabolism pathways were downregulated in αSyn flies at the earliest timepoints; comparison with the aged control flies suggests that elevated αSyn accelerates changes associated with normal aging.

Management of corneal injuries in spaceflight and recommendations for planetary missions.

In February 1968, NASA purchased 400 antigravity ballpoint pens from the Fisher Pen Company for the Apollo Program to prevent potential harm to astronauts and equipment. Mechanical pencils previously used in microgravity posed risks like eye injuries from floating fragments penetrating the cornea. The cornea is vulnerable to abrasions, perforations, and chemical burns in such environments, affecting crewmembers aboard the International Space Station (ISS).

Microbiota and metabolite-based prediction tool for colonic polyposis with and without a known genetic driver.

Despite extensive investigations into the microbiome and metabolome changes associated with colon polyps and colorectal cancer (CRC), the microbiome and metabolome profiles of individuals with colonic polyposis, including those with (Gene-pos) and without (Gene-neg) a known genetic driver, remain comparatively unexplored. Using colon biopsies, polyps, and stool from patients with Gene-pos adenomatous polyposis ( = 9), Gene-neg adenomatous polyposis ( = 18), and serrated polyposis syndrome (SPS,  = 11), we demonstrated through 16S rRNA sequencing that the mucosa-associated microbiota in individuals with colonic polyposis is representative of the microbiota associated with small polyps, and that both Gene-pos and SPS cohorts exhibit differential microbiota populations relative to Gene-neg polyposis cohorts. Furthermore, we used these differential microbiota taxa to perform linear discriminant analysis to differentiate Gene-neg subjects from Gene-pos and from SPS subjects with an accuracy of 89% and 93% respectively.

Reimagining Dearomatization: Arenophile-Mediated Single-Atom Insertions and π-Extensions.

ConspectusDearomatization of simple aromatics serves as one of the most direct strategies for converting abundant chemical feedstocks into three-dimensional value-added products. Among such transformations, cycloadditions between arenes and alkenes have historically offered effective means to construct complex polycyclic architectures. However, traditionally harsh conditions, such as high-energy UV light irradiation, have greatly limited the scope of this transformation.

Optimizing Postoperative Anticoagulation Regimen To Improve Lower Extremity Free Flap Outcomes.

Purpose: Free flap reconstruction for lower extremity (LE) trauma has a higher failure rate than free flaps in other anatomic regions. Post-operative anticoagulation and antiplatelet therapy may influence LE free flap outcomes, but an optimal regimen has not been established. This study aims to evaluate complication rates associated with different anticoagulation and antiplatelet protocols in LE free flap reconstruction.

Alpha-frequency stimulation strengthens coupling between temporal fluctuations in alpha oscillation power and default mode network connectivity.

Alpha (8-12 Hz) oscillations and default mode network (DMN) activity dominate the brain's intrinsic activity in the temporal and spatial domains, respectively. They are thought to play crucial roles in the spatiotemporal organization of the complex brain system. Relatedly, both have been implicated, often concurrently, in diverse neuropsychiatric disorders, with accruing electroencephalogram/magnetoencephalogram (EEG/MEG) and functional magnetic resonance imaging (fMRI) data linking these two neural activities both at rest and during key cognitive operations.

The Salient Aroma Hypothesis: host plant specialization is linked with plant volatile availability in Lepidoptera.

Host plant use in Lepidoptera has been a primary focus in studies of ecological specialization, and multiple factors are likely to be involved in shaping the evolution of diet breadth. Here, we first describe the Salient Aroma Hypothesis, suggesting that the availability of chemical information, particularly host-associated aromas, plays a critical role in shaping dietary specialization. According to the Salient Aroma Hypothesis, herbivores active during periods when chemical information is abundant, particularly during the daytime hours when plant aromas are hypothesized to be more prevalent, are more likely to evolve specialized diets.