Browse Articles

More continuity than change following the Black Death epidemic in medieval Cambridge

Abstract The Black Death epidemic of Yersinia pestis (1347-50 CE) killed about half the population of England, and many historical changes have been ascribed to it. But we still know surprisingly little about how the epidemic actually affected people’s daily lives. This study reports results from a broad bioarchaeological study, with 18 skeletal and molecular indicators from 336 adults from Cambridge, England (940–1561 CE). Results reveal two major findings. First, although the epidemic killed millions, no dramatic changes in skeletal indicators of health and lifestyle are directly ascribable to the epidemic. Most indicators either remained stable, or changed in response to other known historical trends. Traumatic though the plague was, it did not transform medieval people’s health and lifeways radically. Secondly, there were important long-term health trends beginning before the Black Death, notably a decline in stature. This may be due to a general 14th -century environmental and economic deterioration which left the population more vulnerable to novel epidemic diseases.

In vitro investigation of Datura innoxia phytocompounds against Mycobacterium tuberculosis H37Ra strain in association with in silico studies

Abstract Tuberculosis (TB) is a recurrent and progressive bacterial disease caused by Mycobacterium tuberculosis (Mtb), posing a significant challenge globally due to its drug resistance. This study focuses on identifying natural phytocompounds from the plant Datura innoxia (leaves), which is well known for its biologically active metabolites. Initially, the current study employed in vitro analysis of 20 phytocompounds, revealing that the natural compound 9, o-vanillin, exhibited the best minimal inhibitory concentration (MIC) which was 12.5 µg/mL, and minimal bactericidal concentration (MBC) was 50 µg/mL, all other phytocompounds showing remarkable antitubercular activity against the Mtb H37Ra strain. The molecular docking and simulation also validated the strong affinity and stable binding interactions between compound 9 and target protein kinase. The pharmacokinetic analysis highlighted the suitable oral bioavailability and no significant CYP450 inhibition for the lead compound 9, reducing the risk for drug-drug interactions. Moreover, the density functional theory analysis of lead compound 9 demonstrated optimal molecular properties, further contributing to the chemical stability and reactivity. Therefore, these results suggest that D. innoxia contains the potent phytocompound o-vanillin, which possesses antitubercular activity and can potentially be used as a drug against TB. However, future studies will focus on in vivo validation and formulation development for clinical applications.

HIV vaccine candidate ΔV1gp120 formulated in ALFQA adjuvant augments mucosal immunity in female macaques

Abstract Simian or Human immunodeficiency virus (SIV or HIV) vaccines based on V1-deleted envelope virus-like particles, delivered by the DNA/ALVAC platforms, followed by the ΔV1gp120 boost formulated in Alum, protect 50% and 80% of macaques from mucosal infection with SIVmac251 or Simian-Human immunodeficiency virus, respectively. Adding the Army Liposome Formulation + QS21 (ALFQ) adjuvant to the ΔV1gp120+Alum boost (ALFQA) may enhance protective immune responses. Here, we show that ALFQA protects 58% of female macaques from infection following eleven exposures to SIVmac251, achieving 79% vaccine efficacy. The ALFQA vaccine regimen augments mucosal CD73+CD163+ M2-like macrophages and NKp44+ innate lymphoid cells (ILCs), while reducing NKG2A-NKP44- cells producing interferon-γ. Antibody-Dependent Cellular Cytotoxicity (ADCC) targeting helical V2, and mucosal tolerogenic dendritic cells-10 (DC-10) and envelope-specific interleukin-17+ NKp44+ ILCs, correlate with decreased risk of infection. Plasma proteome analysis links vaccine efficacy to lymphotoxin-α, mucosal DC-10, and chemokine (C-C motif) ligand-8, a chemokine produced mainly by M2-macrophages. These data support the role of pro-resolution immunity in protection afforded by the V1-deleted SIV and HIV immunogens. The Combined Long-term Efferocytosis and ADCC Responses (CLEAR) phase I HIV-vaccine trial is designed to test the safety and immunogenicity of the Alum and ALFQA adjuvants in combination with V1-deleted HIV immunogens in humans.

Impact of the type of bacteria on high-density lipoprotein cholesterol level during sepsis

Characterization of brain microstructural abnormalities in spasmodic dysphonia using diffusion kurtosis imaging

Constructing artificial neurons with functional parameters comprehensively matching biological values

Imbalanced data classification using graph based transformation

Occurrence of potentially toxic metals in Turkish cheese with dietary intake and health risk assessment

GM-CSF-dependent CD301b+ mouse lung dendritic cells confer tolerance to inhaled allergens

Abstract The severity of allergic asthma is driven by the balance between allergen-specific T regulatory (Treg) and T helper (Th)2 cells. However, it is unclear whether specific subsets of conventional dendritic cells (cDCs) promote the differentiation of Tregs. We have identified a subset of lung resident type 2 cDCs (cDC2s) that display high levels of CD301b and have potent Treg-inducing activity ex vivo. Single-cell RNA sequencing and adoptive transfer experiments show that during allergic sensitization, many CD301b + cDC2s transition in a stepwise manner to CD200 + cDC2s that selectively promote Th2 differentiation. GM-CSF augments the development and maintenance of CD301b + cDC2s in vivo, and also selectively expands Treg-inducing CD301b + cDC2s derived from bone marrow. Upon their adoptive transfer to recipient mice, lung-derived CD301b + cDC2s confer immunological tolerance to inhaled allergens. Thus, GM-CSF maintains lung homeostasis by increasing numbers of Treg-inducing CD301b + cDC2s.

Immediate effect of physical activity on gut motility in healthy adults

Abstract Constipation is a prevalent condition that negatively impacts health and quality of life. Inadequate physical activity is a known contributing factor, often associated with reduced gut motility. However, the physiological mechanism linking physical activity and constipation remains unclear. Particularly research on the immediate effects of physical activity on peristalsis is scarce. Therefore, we aimed to elucidate this mechanism by examining the immediate effects of physical activity on gut motility in healthy adults. Twenty-one participants were instructed to walk on a treadmill for 20 min. Bowel sounds were assessed at rest and at intervals up to 15 min after walking. Bowel sounds were used as indirect markers of gut motility. We calculated the sum of the absolute signal amplitudes of bowel sounds, the percentage of bowel sounds duration, and number of discrete bowel sounds, which have been proposed as indices of gut motility. All the indices increased significantly 1–2 min post-exercise compared to resting values. This increase may be attributed to changes in the autonomic nervous system and local reflexes caused by biomechanical oscillations. In addition, gut motility activation might explain the effects of physical activity intervention on constipation and offer insights into its potential role in managing the condition.

S-ketamine relieves neuropathic pain by inhibiting microglia phagocytosis of the perineuronal nets

A Bayesian decision support system for automated insulin doses in adults with type 1 diabetes on multiple daily injections: a randomized controlled trial

Abstract Achieving optimal glycemic control remains challenging for many individuals with type 1 diabetes using multiple daily injections. We report results from a 12-week, open-label, randomized controlled trial evaluating a decision support system (DSS) consisting of a mobile application and a titration algorithm that provides weekly basal and prandial insulin recommendations. Eighty-four adults with type 1 diabetes and suboptimal glycemic control (HbA1c ≥ 7.5%) are randomized 1:1 to receive the DSS or a non-adaptive bolus calculator (control), alongside Freestyle Libre glucose sensors. The primary endpoint is change in HbA1c from baseline; secondary endpoints include additional glycemic and insulin-related metrics. The DSS reduces mean HbA1c from 8.6% (SD 1.1) to 8.1% (0.8) (p = 0.0002), while the control reduces HbA1c from 8.6% (1.0) to 8.5% (1.0) (p = 0.22); yielding a treatment effect of –0.40% (95% CI: –0.75 to –0.051; p = 0.025). There are no reported severe hypoglycemia or diabetic ketoacidosis events. Our DSS improves HbA1c in this population without compromising safety. ClinicalTrials.gov: NCT04123054 .

The hidden diversity of Saudi Arabian Red Sea octocorals revealed through a morpho-molecular assessment across bathymetric and latitudinal gradients

Burden of subarachnoid hemorrhage in Asia and ARIMA model prediction trends from 1990 to 2021

Abstract Subarachnoid hemorrhage (SAH) is a rare but serious stroke subtype that accounts for approximately 5% of all strokes. This study analyzed SAH epidemiology in Asia from 1990 to 2021 using the Global Burden of Disease (GBD) 2021 data. This study assessed the burden of SAH in Asia using four indicators: incidence, prevalence, mortality, and disability-adjusted life years (DALYs). An autoregressive integrated moving average (ARIMA) model was used to conduct a long-term trend analysis and forecast the changing trends of various indicators from 2022 to 2041. Between 1990 and 2021, the age-standardized incidence rates (ASIR) of SAH in Asia increased and then decreased, while the age-standardized prevalence rates (ASPR), age-standardized mortality rates (ASMR), and age-standardized disability-adjusted life years rates (ASDR) of SAH continued to decline. The Arima model predictions suggest that Asian age-standardized rates will typically show a decreasing trend over the next 20 years, except for the ASIR, which shows an increasing trend. Over the next 20 years, the ASIR of SAH in Asia is expected to increase. The ASPR, ASMR, and ASDR were expected to show decreasing trends. The burden of SAH in older patients remains high, highlighting the need to strengthen the health management of the older population.

Genetic controllers for enhancing the evolutionary longevity of synthetic gene circuits in bacteria

Abstract Engineered gene circuits often degrade due to mutation and selection, limiting their long-term utility. Here we present designs for genetic controllers which maintain synthetic gene expression over time. Using a multi-scale “host-aware" computational framework, which captures interactions between host and circuit expression, mutation, and mutant competition, we evaluate several controller architectures based on three metrics for evolutionary stability: total protein output, duration of stable output, and half-life of production. We propose a number of designs with varying inputs (e.g., output per cell, growth rate) and actuation methods (transcriptional vs. post-transcriptional regulation). We find post-transcriptional controllers generally outperform transcriptional ones, but no single design optimizes all goals. Negative autoregulation prolongs short term performance, while growth-based feedback extends functional half-life. We propose three biologically feasible, multi-input controllers that improve circuit half-life over threefold without requiring coupling the process to an essential gene or a genetic kill switch.

Adaptive immune responses associated with the progression of premalignant lesions to colorectal cancer

Next-generation COVID-19 detection using a metasurface biosensor with machine learning-enhanced refractive index sensing

Molecular mechanisms of SLC30A10-mediated manganese transport

Integrative effects of different mulching practices and Azospirillum brasilense on wheat growth, physiology, and soil health under drought stress

Abstract Azospirillum brasilense, a plant growth-promoting rhizobacterium that plays a vital role in sustainable wheat production by enhancing nutrient uptake, improving stress tolerance, and reducing reliance on chemical fertilizers. This study aimed to investigate the integrative effects of Azospirillum brasilense inoculation and different mulching practices on the growth, physiology, and soil health of wheat (Triticum aestivum L.) under drought stress, particularly during the critical booting stage. The primary research question focused on identifying whether these combined treatments could mitigate drought-induced damage and enhance plant performance. The experimental was consisted of 9 treatments, including T0 (control: no mulch, no drought, no soil microbes), T1 (drought stress at the booting stage (DB)), T2 (DB + A. brasilense), T3 (DB + wheat straw mulch), T4 (DB + rice husk mulch), T5 (DB + plastic mulch), T6 (DB + A. brasilense + wheat straw mulch), T7 (DB + A. brasilense + rice husk mulch), and T8 (DB + A. brasilense + plastic mulch) with randomized complete block design having three replications. Various growth, yield, physiological, and soil nutrient parameters were assessed. Data analysis included ANOVA, cluster heatmap, and principal component analysis (PCA) to evaluate treatment impacts. Drought stress significantly reduced plant height (34.24%), 1000-grain weight (49.05%), and photosynthetic pigments. However, treatments combining A. brasilense with organic mulches (T6: wheat straw and T7: rice husk) substantially improved plant biomass, photosynthetic rate (up to 24.67%), stomatal conductance (7.54%), and soil nutrient uptake. T6 showed the highest increase in chlorophyll a (118.74%) and grain weight (78.78%) compared to drought alone. PCA and heatmap analyses revealed strong clustering of treatments, highlighting T6 as the most effective strategy. The combination of A. brasilense and organic mulching (especially wheat straw) effectively mitigated drought stress in wheat by enhancing physiological resilience, nutrient uptake, and soil health. The demonstrated benefits suggest that incorporating bio-inoculants with locally available mulching materials can be scaled up as a practical intervention for climate-smart agriculture.

Effectiveness of traditional augmentation methods for rebar counting using UAV imagery with Faster R-CNN and YOLOv10-based transformer architectures

Abstract Accurate inspection of Reinforced Concrete (RC) structures requires precise rebar counting. Although deep-learning object detectors can extract this information from drone imagery, their effectiveness depends on large, diverse, and well-labeled datasets. Image augmentation can increase data variability, yet its impact on Unmanned Aerial Vehicles (UAVs)-based rebar counting has been underexplored. This study systematically evaluates ten augmentation methods—brightness, contrast, perspective, rotation, scale, shearing, translation, blurring, a probabilistic sampling policy, and a sum of techniques composition—using Faster R-CNN and YOLOv10 across six backbones (ResNet-101, ResNet-152, MobileNetV3; ViT, PVT, Swin Transformer). Performance is reported using AP50, AP50:95, and exact-count accuracy. Results show that augmentation efficacy is both architecture and metric-dependent. The best test-set configuration is YOLOv10–PVT with shearing, which achieves AP50 = 87.71%, AP50:95 = 68.53%, and rebar-count accuracy = 86.27%—improvements of + 5.92, + 9.07, and + 5.99 percentage points, respectively, over the PVT original baseline. A probabilistic sampling policy provides consistent, policy-level gains over original data and approaches the best single transform (especially with a magnitude ramp), whereas indiscriminate a sum of techniques application does not reliably outperform the top single augmentation.