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Transcriptome and DNA methylation analysis of the goat pineal gland during puberty
Discordance, accuracy and reproducibility study of pathologists’ diagnosis of melanoma and melanocytic tumors
Abstract Accurate melanoma diagnosis is crucial for patient outcomes and reliability of AI diagnostic tools. We assess interrater variability among eight expert pathologists reviewing histopathological images and clinical metadata of 792 melanoma-suspicious lesions prospectively collected at eight German hospitals. Moreover, we provide access to the largest panel-validated dataset featuring dermoscopic and histopathological images with metadata. Complete agreement is achieved in 53.5% of cases (424/792), and a majority vote ( ≥ five pathologists) in 90.9% (720/792). Considerable discordance is observed for non-invasive melanomas (complete agreement in only 10/73 cases). The expert panel disagrees with the local pathologists’ and dermatologists’ diagnoses in 14.9% and 33.5% of cases, respectively. This variability highlights the diagnostic challenges of early-stage melanomas and the need to reconsider how ground truth is established in routine care and AI research. Including at least two pathologists or virtual panels may contribute to more consistent diagnostic results.
Evaluating and upgrading the performance of a bridge network structure with Rayleigh distribution lifetimes
In this work, bridge network model with Rayleigh distribution lifetimes is used. Two main techniques are calculated to upgrade this model: reduction and redundancy techniques. In order to compare the effectiveness of the various approaches, the survival function, the mean time to failure and gamma-fractiles for the original and upgraded model are calculated. Finally, we analyze comprehensively a computer simulation example to distingue between the methods. The numerical simulations were done in Mathematica which indicated that the upgraded system performs better than the original one and the best technique is by cold duplication.
Investigating the impact of Multiwalled Carbon Nanotubes exposure on enzymatic activities and histopathological variations in Swiss albino mice
Energy and climate policy implications on the deployment of low-carbon ammonia technologies
Abstract The economic feasibility of low-carbon ammonia production pathways, such as steam methane reforming with carbon capture and storage, biomass gasification, and electrolysis, is assessed under various policy frameworks, including subsidies, carbon pricing, and renewable hydrogen regulations. Here, we show that employing a stochastic techno-economic analysis at the plant level and a net present value approach under the US Inflation Reduction Act reveals that carbon capture and biomass pathways demonstrate strong economic potential due to cost-effectiveness and minimal public support needs. Conversely, the electrolytic pathway faces significant economic challenges due to higher costs and lower efficiency. We conclude that efficient decarbonization of ammonia production requires adapting the Haber-Bosch process for variable bioenergy quality, ensuring safe CO 2 transport and storage, advancing research to lower costs and improve efficiency in renewable energy and storage technologies, as well as creating a technologically neutral policy framework.
Establishing thresholds for swing transparency at the knee during gait to inform exoskeleton design
Knee exoskeletons have been developed to assist, stabilize, or improve human movement or recovery. However, exoskeleton designers must implement transparency (i.e., get out of the way) modes during the swing phase of locomotor tasks to avoid impeding movement. The problem is that it is not understood how sensitive people are to small knee torques or what level of knee impedance is acceptable (sufficiently transparent) during swing phase. Here, we (i) characterized the biomechanical consequences of knee stiffness and damping during swing, and (ii) leveraged user perceptions of being impeded and toe clearance to define transparency thresholds, below which the participants were sufficiently unimpeded during the swing phase of gait. We conducted a series of human subject experiments that involved walking and stair ascent/descent while wearing a modified knee brace with five stiffness values ranging from 0 to 4 Nm/rad and five damping values ranging from 0 to 0.77 Nm/rad/s. We measured changes to lower limb kinematics, knee flexor muscle activity, and participants’ perception of being impeded during swing. Kinematics, muscle activity, and perceived impedance all changed in response to added stiffness and damping. For stiffness, we found the median transparency thresholds for walking and stairs to be 1.76 Nm/rad and 2.95 Nm/rad, respectively, which corresponds to peak knee moments during swing of around 2.3 and 5 Nm. For damping, we found the median transparency threshold for walking and stairs to be about the same, 0.29 Nm/rad/s, which corresponds to peak knee moments during swing of around 2.3 Nm. These values provide useful benchmarks for defining quantitative design requirements for knee exoskeletons intended for locomotor activities.
Exploration of linear and interpretable models for quantification of cell parameters via contactless short-wave infrared hyperspectral sensing
Multidimensional free shape-morphing flexible neuromorphic devices with regulation at arbitrary points
The impact of health risk communication on self-perceived health and worry of targeted groups: Lessons from the Swedish COVID-19 response
Background The Swedish COVID-19 strategy aimed to protect vulnerable groups through targeted measures, categorizing individuals aged 70 and above as high-risk. This study examines the impact of such group-based risk assessments on subjective health and virus-related concerns among older adults. Methods We analyzed survey data from the SOM Institute for 68- to 71-year-olds in 2019 (N = 684) and 2020 (N = 726). Using ordered logit regression, we compared perceived health and virus-related concerns between individuals just below (68–69 years) and just above (70–71 years) the high-risk age threshold, controlling for demographic factors. Results In 2020, 70-year-olds reported significantly lower perceived health compared to their 69-year-old peers, a difference not observed in 2019. Furthermore, 70-year-olds exhibited significantly higher virus-related concerns than their slightly younger counterparts. These patterns persisted when expanding the analysis to include individuals aged 68 and 71. Conclusion Our findings suggest that the Swedish COVID-19 strategy, while aimed at protecting individuals aged 70 and over, may have inadvertently increased perceived vulnerability and health concerns within this group. Conversely, those just below the high-risk age threshold reported better health and lower virus-related concerns, highlighting potential unintended psychological consequences of age-based risk communication.
Curcumin mimics of potential chemoprevention with NQO1 induction properties
Abstract Chemoprevention is one of the accessible strategies for preventing, delaying or reversing cancer processing utilizing chemical intervention of carcinogenesis. NAD(P)H quinone oxidoreductase 1 (NQO1) is a xenobiotic metabolizing cytosolic enzyme/protein with important functional properties towards oxidation stress, supporting its ability in detoxification/chemoprotective role. A set of 3,5-diylidene-4-piperidones (as curcumin mimics) bearing alkyl sulfonyl group were synthesized with potential NQO1 induction properties. Compounds 5ab (R = 2-MeOC6H4, R’ = Me) and 5ac (R = 2-MeOC6H4, R’ = Et) are the most promising agents synthesized (% induction of NQO1 = 51.562, 45.793) relative to that of 4’-bromoflavone (4’-BF, reference standard) at 10 µM. LPS-induced iNOS production in RAW264.7 macrophages of the most promising agents discovered (5ab and 5ac) displayed concentration-dependent with comparable activities to the reference anti-inflammatory drug indomethacin. Molecular modeling studies (including QSAR, molecular docking and molecular dynamics) were accessed supporting the observed biological profiles.
Structural basis for metal ion transport by the human SLC11 proteins DMT1 and NRAMP1
Abstract Iron and manganese are essential nutrients whose transport across membranes is catalyzed by members of the SLC11 family. In humans, this protein family contains two paralogs, the ubiquitously expressed DMT1, which is involved in the uptake and distribution of Fe2+ and Mn2+, and NRAMP1, which participates in the resistance against infections and nutrient recycling. Despite previous studies contributing to our mechanistic understanding of the family, the structures of human SLC11 proteins and their relationship to functional properties have remained elusive. Here we describe the cryo-electron microscopy structures of DMT1 and NRAMP1 and relate them to their functional properties. We show that both proteins catalyze selective metal ion transport coupled to the symport of H+, but additionally also mediate uncoupled H+ flux. Their structures, while sharing general properties with known prokaryotic homologs, display distinct features that lead to stronger transition metal ion selectivity.
Exploration and verification of the therapeutic mechanism of shenfu injection in sepsis-induced myocardial injury
Background Shenfu injection (SFI), derived from a traditional Chinese medicine (TCM) prescription, is an effective drug for the treatment of sepsis-induced myocardial injury (SIMI) with good efficacy, but its exact therapeutic mechanism remains unclear. Methods SwissTargetPrediction and GeneCards database were used to obtain relevant targets for SFI and SIMI. STRING 11.5 and MCODE were used to analyse potential therapeutic targets for SFI. DAVID 6.8 database was used to perform enrichment analysis. In addition, the SIMI model was constructed by cecal ligation and puncture (CLP) on Sprague Dawley rats and the related protein expression levels were verified by AutoDock Vina 1.1.2 and experiment. Results SFI has a total of 10 main active compounds and treats SIMI through 52 potential targets, among which LGALS3, STAT3, FGF1, and AKT1 were the core targets for treatment. Based on enrichment analysis, STAT3, FGF1, and AKT1 in the core targets were experimentally validated. The experimental results showed that SFI effectively ameliorated the inflammatory response and myocardial injury and inhibited apoptosis in SIMI. And SFI improved SIMI by decreasing caspase-9, STAT3 and phospho-AKT1 (p-AKT1) expression, and enhancing FGF1 expressions. Conclusions This study showed that SFI effectively reduced the expression of caspase-9, STAT3 and p-AKT1, enhanced the expression of FGF1, reduced the inflammatory response, inhibited apoptosis and attenuated cardiac injury to SIMI.
How knee muscles and ground reaction forces shape knee buckling and ankle push-off in neuromuscular simulations of human walking
Abstract Ankle push-off is important for efficient, human-like walking, and many prosthetic devices mimic push-off using motors or elastic elements. The knee is extended throughout the stance phase and begins to buckle just before push-off, with timing being crucial. However, the exact mechanisms behind this buckling are still unclear. We use a predictive neuromuscular simulation to investigate whether active muscles are required for knee buckling and to what extent ground reaction forces (GRFs) drive it. In a systematic parameter search, we tested how long the knee muscles vastus (VAS), gastrocnemius (GAS), and hamstrings could be deactivated while maintaining a stable gait with impulsive push-off. VAS deactivation up to 35% of the gait cycle resulted in a dynamic gait with increased ankle peak power. GAS deactivation up to 20% of the gait cycle was detrimental to gait efficiency and showed reduced ankle peak power. At the start of knee buckling, the GRF vector is positioned near the knee joint’s neutral axis, assisting in knee flexion. However, this mechanism is likely not enough to drive knee flexion independently. Our findings contribute to the biomechanical understanding of ankle push-off, with applications in prosthetic and bipedal robotic design, and fundamental research on human gait mechanics.
Fermented foods affect the seasonal stability of gut bacteria in an Indian rural population
Abstract The effect of fermented foods on healthy human gut microbiota structure and function, particularly its seasonal preference and frequent long-term consumption, has been largely uncharacterised. Here, we assess the gut microbiota and metabolite composition of 78 healthy Indian agrarian individuals who differ in the intake of fermented milk and soybean products by seasonal sampling during hot-humid summer, autumn and dry winter. Here we show that, seasonal shifts between the Prevotella- and Bifidobacterium/Ruminococcus-driven community types, or ecological states, and associated fatty acid derivatives, with a bimodal change in Bacteroidota community structure during summer, particularly in fermented milk consumers. Our results associate long-term fermented food consumption with reduced gut microbiota diversity and bacterial load. We identify taxonomic groups that drive the seasonal fluctuation and associated shifts between the two ecological states in gut microbiota. This understanding may pave the way towards developing strategies to sustain a healthy and resilient gut microbiota through dietary interventions.
Prohibiting Babel—A call for professional remote interpreting services in pre-operation anaesthesia information
Introduction Language barriers within clinical settings pose a threat to patient safety. As a potential impediment to understanding, they hinder the process of obtaining informed consent and uptake of critical medical information. This study investigates the impact of the current use of interpreters, with a particular focus on of engaging laypersons as interpreters, rather than professional interpreters potentially affecting patient safety. A further objective is to explore the reliability of phone-based telemedicine in terms of the retention of important medical facts. Methods In three groups (N per group = 30), we compared how using lay or professional interpreters affected non-German speaking patients’ subjectively perceived understanding (understood vs. not understood) and recollection (recollected vs. not recollected) of information about general anaesthesia. Proficient German speaking patients served as the control group. Statistical analyses ( χ 2 tests and binomial) were calculated to show differences between and within the groups. Results All three groups indicated similar, high self-reported levels of having understood the medical information provided. This was in stark contrast to the assessed objective recollection data. In the lay interpreter group, recollection of anaesthesia facts was low; only around half of participants recalled specific facts. For patients supported by professional interpreters, their recollection of facts about anaesthesia was significantly enhanced and elevated to the same level of the control group (fluent in German). Moreover, for these patients, providing information by means of phone-based telemedicine before anaesthesia yielded high levels of understanding and recollection of anaesthesia facts. Conclusion Phone-based telemedicine is a safe and reliable method of communication in the professional interpreter group and German speaking control group, but not in the lay interpreter group. Compared to lay interpreters, professional interpreters significantly improve patients’ uptake of critical information about general anaesthesia, thus highlighting the importance of professional interpreters for patient safety and informed consent.
Single-cell profiling transcriptomic reveals cellular heterogeneity and cellular crosstalk in breast cancer lymphatic node, bone, and brain metastases
High-throughput method characterizes hundreds of previously unknown antibiotic resistance mutations
Abstract A fundamental obstacle to tackling the antimicrobial resistance crisis is identifying mutations that lead to resistance in a given genomic background and environment. We present a high-throughput technique – Quantitative Mutational Scan sequencing (QMS-seq) – that enables quantitative comparison of which genes are under antibiotic selection and captures how genetic background influences resistance evolution. We compare four E. coli strains exposed to ciprofloxacin, cycloserine, or nitrofurantoin and identify 812 resistance mutations, many in genes and regulatory regions not previously associated with resistance. We find that multi-drug and antibiotic-specific resistance are acquired through categorically different types of mutations, and that minor genotypic differences significantly influence evolutionary routes to resistance. By quantifying mutation frequency with single base pair resolution, QMS-seq informs about the underlying mechanisms of resistance and identifies mutational hotspots within genes. Our method provides a way to rapidly screen for resistance mutations while assessing the impact of multiple confounding factors.