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WWII and the evolution of US federal research funding
Many fundamental innovation policies were developed during World War II that persist in some form to this day
The experimental study on multimodal ultrasound evaluation of changes in the rabbit gastrocnemius muscle after acute cold exposure and peritoneal lavage treatment
A dietary switch promotes sensory neuron–dependent cancer-associated cachexia
Sickness behaviors are common in cancer-associated cachexia and affect up to half of lung cancer patients. We demonstrate that among the most common cancer mutations, loss of liver kinase B1 ( Lkb1 ) promotes the development of cachexia in preclinical models of lung cancer. In an effort to improve caloric intake with an obesogenic high-fat diet, we paradoxically observed worsened cachexia-associated sickness. We found that local production of prostaglandin E2 (PGE 2 ), rather than circulating factors, promotes sickness and that genetic, dietary, and pharmacological inhibition of tumor-derived PGE 2 suppresses sickness and cachexia. Notably, we demonstrate that lung sensory neuron abrogation prevents PGE 2 -dependent cachexia. Our study establishes localized tumor-derived signals to sensory neurons, rather than circulating factors, as drivers of cachexia and highlights a previously unknown role of the peripheral nervous system in cancer cachexia.
Phase transition and optical bistability in a cold Rydberg Rb sample observed via absorption spectroscopy
Stop the biodiversity sampling arms race
Spatially resolved proteomic landscape unveils the molecular dichotomy of distal stenosis and proximal dilation in pediatric type Ia congenital biliary dilatation
Why have a revered physicist’s papers been retracted?
Springer Nature has removed two studies by quantum mechanics pioneer Max Planck. A bot may be to blame
Region-of-interest histopathology with fine-tuned CNNs enables colorectal cancer grading and pathologic stage estimation
Abstract While AI-based diagnostic support using whole slide images of pathological specimens has advanced in recent years, the development of systems that work with small biopsy specimens remains underexplored. In this study, we evaluated 1.5-mm-diameter colorectal cancer tissue microarray cores to estimate histological grade, to predict the resection-assigned pathological T (pT) category from microscopic morphology, and to estimate pathological TNM stage. We fine-tuned multiple ImageNet-pretrained convolutional neural network (CNN) backbones (ResNet, WideResNet, DenseNet, MobileNet, and EfficientNet) and evaluated individual models and ensemble learning. A maximum area under the curve for two-class classification of tumor histological grade was 0.991 across CNNs. A Nemenyi multiple-comparison test indicated significant differences in performance across tumor grading task definitions. Furthermore, the models predicted early versus advanced pT category (resection-assigned) with a maximum AUC of 0.888, and the Nemenyi test again indicated differences across task definitions. Early versus advanced pathological stage was separated with a maximum AUC of 0.721. Gradient-weighted class activation mapping visualization confirmed that the CNN model focused on histological features characteristic of Grade 3 tumors, such as tumor budding and poorly differentiated clusters, validating its classification performance. These results suggest that pathologist-selected biopsy-scale region of interests (ROIs) enable robust grading and pT-associated risk stratification with modest computational requirements, although they do not directly measure anatomical depth of invasion. They also suggest the potential of CNN-based diagnostic support systems as practical tools for treatment planning that can be implemented with limited computational resources, including constrained image data and storage capacity.
Observation of disorder-free localization using a (2+1)D lattice gauge theory on a quantum processor
Disorder-induced phenomena in quantum many-body systems pose a challenge for analytical and numerical approaches at relevant time and system scales. To reduce the cost of disorder sampling, we investigated quantum circuits initialized in states that form tunable superpositions over all disorder configurations, which in lattice gauge theories can be interpreted as superpositions over gauge sectors. On the experimentally accessible timescales, we observed localization in the absence of disorder in one and two dimensions: Perturbations failed to diffuse despite fully disorder-free evolution and initial states. However, entropy measurements revealed that superposition-prepared states fundamentally differ from those obtained by direct disorder sampling. Leveraging superposition, we propose an algorithm with a polynomial speedup in sampling disorder configurations, a long-standing challenge in many-body localization studies.
Plasma biomarkers in ischemia and reperfusion in acute occlusion of the superior mesenteric artery: a rat model study
Institutionalizing AI diplomacy in Africa
Long-term alterations in serum metabolite profiles in women with a history of preeclampsia -FINNCARE study
Abstract Preeclampsia (PE) is a multifaceted pregnancy condition which increases the risk of cardiometabolic diseases later in life. Long-term follow-up data on metabolome utilizing novel metabolomic techniques are needed to gain insights into metabolism after PE and non-PE pregnancies for identifying potential areas of investigation that could assist in predicting and managing future health risks. The objective of the current study was to characterize long-term metabolome in women with and without a history of PE. Non-targeted metabolomics (liquid chromatography–mass spectrometry, LC–MS) was applied to determine whether the metabolomic profile of fasting serum samples differed between PE ( n = 101) and control ( n = 52) women 11.6 ± 1.1 years (mean ± SD) after pregnancy. Statistical analyses, including linear models and correlation analyses, were conducted to identify differences in metabolite abundances and associations with clinical variables. Women with a history of PE exhibited higher levels of acylcarnitines, specific dipeptides, and amino acids such as citrulline, aspartic acid and glutamic acid. They also had increased levels of certain steroids compared to control women. Conversely, lower levels of dicarboxylic acids, phospholipids, and specific amino acids like histidine and asparagine were observed in PE women. Correlation analysis revealed associations between metabolites and clinical variables such as body mass index, fat percentage and blood pressure, particularly in PE women. This study provides a unique long-term follow-up of metabolic alterations in women with a history of PE and several of the identified metabolites have previously been linked to cardiometabolic pathways, including mitochondrial dysfunction and endothelial function. Some of the observed metabolite alterations were associated with higher BMI and adiposity, particularly in women with prior PE, indicating that both pregnancy-related factors and metabolic comorbidities may influence the metabolomic profile.
Ecology of the gut microbiome
Microbial competition can be harnessed to prevent and cure deadly diseases
Intention to take COVID-19 vaccine and its predictors among adult residents of Jimma town, Oromia, South West Ethiopia
Membrane protein solubilization and structure determination using de novo–designed proteins
Developing therapies and vaccines against integral membrane proteins is hindered by their extensive hydrophobic surfaces, which complicate production and structural analysis. Here, we describe a general deep learning–based design approach for solubilizing native membrane proteins while preserving their sequence, fold, active-site, and ligand-binding properties. Genetically encoded de novo protein WRAPs [water-soluble RFdiffused amphipathic proteins] surround the lipid-interacting hydrophobic surfaces, rendering them thermostable and water-soluble without the need for detergents. We design WRAPs for both monomeric and oligomeric beta-barrel outer membrane proteins and helical multipass transmembrane proteins. A 2.95-angstrom-resolution cryo–electron microscopy structure of WRAPed mycobacterial porin demonstrates that WRAPs can be used for the structural determination of membrane proteins in solution. As a step toward syphilis vaccine development, we generated soluble versions of Treponema pallidum antigens.
A comparative study of seasonal irrigation demand and actual water supply in the Kaleshwaram project command area
Abstract This paper assesses seasonal and spatial mismatch between irrigation water demands and water supply in the Kaleshwaram Lift Irrigation Scheme (KLIS) command area, India where inflows dependent on the monsoon seasons, high evapotranspiration, timing of canal-release, and planting schemes have a combined effect on irrigation reliability. Based on multi-year occurrences data, which covers climate-data between 2000 and 2023, groundwater-observations data between 2015 and 2023, reservoir and canal-operation data between 2019 and 2023, and crops/land-use data between 2022 and 2023, the study generates a monthly water-balance framework, here variables specific periods were used according to the verified data availability. Digital Elevation Model (DEM)-based Geographic Information System (GIS) preprocessing was combined with the results of CROPWAT and Soil and Water Assessment Tool (SWAT) to estimate the reference evapotranspiration (ET 0), crop evapotranspiration (ET c), effective rainfall, runoff, recharge, and soil-moisture change. The available supply was estimated by using an addition of canal release, reservoir- operation values, ground water contribution, and contribution of return-flow. These findings indicate that irrigation takes up the largest portion of the annual water needs with about 98.4% of total yearly needs i.e. 1650 Mm 3 of the total 1677 Mm 3 . The gross supply available was around 730 Mm 3 which could only satisfy about 43.5% of the overall demand leaving behind an annual unfulfilled demand of around 947 Mm 3 , which would cater to almost 56.5% of the aggregate demand. The greatest demand was at April-May where it was approximately 197–212 Mm 3 /month, or 11.8–12.7% annual demand during this period. None of the months had over supply and highest monthly loss was in the months of March–May corresponding to a range of approximately 102–127 Mm 3 monthly which only constituted about 10.8–13.4% of the annual loss in that year. The seasonal interpretation shows that the periods of water-stress are peak three months pre-monsoon and Rabi (spring) and Kharif (autumn) depend heavily on storage of the reservoir, efficient rainfall distribution, and timing of the canals. The results prove that annual supply volumes cannot be considered the only factors of KLIS performance, monthly alignment of crop-water demand and monsoon recharge with the performance of the storage and the canal delivery plays a vital role. The research offers application evidence on how to better reservoir rule curves, canal-sort, conjunctive ground water utilization, crop-arrangement and deficit-irrigation techniques in monsoon-based command regions that are semi-arid.
Making time
Flies seek out darkness to restart their biological clocks
Quality-by-design optimized reversed phase-high performance liquid chromatography method for quantification of everolimus in bulk drug and nanoparticle-based formulations
Abstract Everolimus, a potent mTORC1 inhibitor used in various oncological and immunological indications, requires precise quantitative analysis due to its narrow therapeutic window and susceptibility to pharmacokinetic variability. This study aimed to develop and validate a robust, sensitive, and cost-effective reverse-phase high-performance liquid chromatography method for EVR quantification in bulk drugs, marketed formulations, and nanoparticle-based delivery systems. A systematic analytical Quality by Design approach was utilized to facilitate method development and ensure method optimization. Critical method variables were identified through one-factor-at-a-time screening and subsequently optimized using a Box–Behnken Design. Thirty-seven experimental runs were evaluated to model their effects on retention time, tailing factor, theoretical plates, and peak area. The QbD-optimized chromatographic conditions, 85% ACN and 15% water, 0.85 mL/min flow rate, 50 °C column temperature, and 20 µL injection volume, detection wavelength was 278 nm yielded a high composite desirability (0.759) and produced sharp, well-resolved EVR peaks. Method validation was performed in accordance with ICH Q2(R2) guidelines, and results were found within the accepted limits. Linearity range was found to be from 100 ng/mL to 10,000 ng/mL, the coefficient of determination was 0.9965, and LOD and LOQ was found to be 50 ng/mL and 100 ng/mL, respectively. Overall, the developed RP-HPLC method is sensitive, reproducible, and suitable for routine quantification of EVR in pharmaceutical formulations and nanoformulations, providing a practical alternative to liquid chromatography with tandem mass spectrometry in resource-limited analytical settings.
The missing thriftiness
Host-microbial coevolution and its influence on human health