bluuebunny/crossref_metadata_2025 huggingface dataset:
A twist of the tail in turning maneuvers of bird-inspired drones
Authors: Phan Hoang-Vu , Floreano Dario
Published: November 2024

A banked turn is a common flight maneuver observed in birds and aircraft. To initiate the turn, whereas traditional aircraft rely on the wing ailerons, most birds use a variety of asymmetric wing-morphing control techniques to roll their bodies and thus redirect the lift vector to the direction of the turn. Nevertheless, when searching for prey, soaring raptors execute steady banked turns without exhibiting observable wing movements apart from the tail twisting around the body axis. Although tail twisting can compensate for adverse yaw, functioning similarly to the vertical tail in aircraft, how raptors use only tail twisting to perform banked turns is still not well understood. Here, we developed and used a raptor-inspired feathered drone to find that the proximity of the tail to the wings causes asymmetric wing-induced flows over the twisted tail and thus lift asymmetry, resulting in both roll and yaw moments sufficient to coordinate banked turns. Moreover, twisting the tail induces a nose-up pitch moment that increases the angle of attack of the wings, thereby generating more lift to compensate for losses caused by the banking motion. Flight experiments confirm the effectiveness of tail twist to control not only low-speed steady banked turns but also high-speed sharp turns by means of coordinated tail twist and pitch with asymmetric wing shape morphing. These findings contribute to the understanding of avian flight behaviors that are difficult to study in controlled laboratory settings and provide effective control strategies for agile drones with morphing aerial surfaces.
Inactivation of checkpoint kinase 1 (Chk1) during parvovirus minute virus of mice (MVM) infection inhibits cellular homologous recombination repair and facilitates viral genome replication
Authors: Etingov Igor , Pintel David J.
Published: November 2024

During infection, the autonomous parvovirus minute virus of mice (MVM) induces cellular DNA breaks and localizes to such sites, which presumably affords an environment beneficial for genome replication. MVM replication also benefits from the DNA damage response (DDR) mediated by the ataxia-telangiectasia mutated (ATM) kinase, while the ataxia telangiectasia and Rad-3 related (ATR) arm of the DDR is disabled, which prevents activation of its primary target, checkpoint kinase 1 (Chk1). We find here that Chk1 inactivation strongly correlates with dephosphorylation of one of its targets, RAD51, known to play a pivotal role in homologous recombination repair (HRR), thus leading to substantial inhibition of DNA repair in infected cells. We demonstrate colocalization of replicating MVM DNA with cellular double-strand breaks (DSBs) during infection, and show that an agent that exogenously induces cellular DSBs significantly increases viral DNA replication levels, establishing a role for cellular genome damage in facilitating virus DNA replication. Additionally, overexpression of active Chk1 during MVM infection was found to re-establish the activating phosphorylation of RAD51 Thr 309, significantly suppress infection-induced reduction of HRR efficiency with a concomitant increase in cellular genome DSBs, and reduce viral DNA replication levels. Thus, we conclude that during infection, MVM inhibition of Chk1 activation enhances viral replication, at least in part, by inhibiting cellular HRR.

IMPORTANCE

The autonomous parvovirus minute virus of mice (MVM) has a compact DNA genome encoding a minimum number of proteins. During infection, it induces cellular DNA damage and both utilizes and modifies the subsequent cellular DNA damage response (DDR) in various ways to facilitate its replication. One of MVM’s activities in this regard is to inhibit one of the primary arms of the DDR, the ataxia telangiectasia and Rad-3 related (ATR) pathway, which prevents activation of checkpoint kinase 1 (Chk1), a key protein involved in controlling the cellular DDR and preserving genome integrity. We show that prevention by MVM of Chk1 activation leads to inhibition of homologous recombination repair (HRR) of cellular DNA, which helps sustain viral replication. This work illuminates another way in which autonomous parvoviruses adjust the cellular environment for their replicative advantage.
Antibiotic resistant bacteria survive treatment by doubling while shrinking
Authors: Campey Adrian , Łapińska Urszula , Chait Remy , Tsaneva-Atanasova Krasimira , Pagliara Stefano
Published: November 2024

Many antibiotics that are used in healthcare, farming, and aquaculture end up in environments with different spatial structures that might promote heterogeneity in the emergence of antibiotic resistance. However, the experimental evolution of microbes at sub-inhibitory concentrations of antibiotics has been mainly carried out at the population level which does not allow capturing single-cell responses to antibiotics. Here, we investigate and compare the emergence of resistance to ciprofloxacin in
Escherichia coli
in well-mixed and structured environments using experimental evolution, genomics, and microfluidics-based time-lapse microscopy. We discover that resistance to ciprofloxacin and cross-resistance to other antibiotics is stronger in the well-mixed environment due to the emergence of target mutations, whereas efflux regulator mutations emerge in the structured environment. The latter mutants also harbor sub-populations of persisters that survive high concentrations of ciprofloxacin that inhibit bacterial growth at the population level. In contrast, genetically resistant bacteria that display target mutations also survive high concentrations of ciprofloxacin that inhibit their growth via population-level antibiotic tolerance. These resistant and tolerant bacteria keep doubling while shrinking in size in the presence of ciprofloxacin and regain their original size after antibiotic removal, which constitutes a newly discovered phenotypic response. This new knowledge sheds light on the diversity of strategies employed by bacteria to survive antibiotics and poses a stepping stone for understanding the link between mutations at the population level and phenotypic single-cell responses.

IMPORTANCE

The evolution of antimicrobial resistance poses a pressing challenge to global health with an estimated 5 million deaths associated with antimicrobial resistance every year globally. Here, we investigate the diversity of strategies employed by bacteria to survive antibiotics. We discovered that bacteria evolve genetic resistance to antibiotics while simultaneously displaying tolerance to very high doses of antibiotics by doubling while shrinking in size.
Complete genome sequence of
Sporosarcina pasteurii
type strain DSM33
Authors: Tuttle Matthew J. , Stamps Blake W. , Chodkowski John L. , Mechan-Llontop Marco E. , Shade Ashley , Hung Chia-Suei , Gupta Maneesh K. , Carter Michael S.
Published: November 2024

Here, we present the complete genome sequence of
Sporosarcina pasteurii
type strain DSM33, a model organism for microbially induced calcium carbonate precipitation. This genome consists of a single 3.3-Mb chromosome and is an improvement upon draft
S. pasteurii
genome sequences currently available in public databases.
Neutrophil prime unique transcriptional responses in intestinal organoids during infection with nontyphoidal
Salmonella enterica
serovars
Authors: Lawrence Anna-Lisa E. , Berger Ryan P. , Hill David R. , Huang Sha , Yadagiri Veda K. , Bons Brooke , Fields Courtney , Knight Jason S. , Wobus Christiane E. , Spence Jason R. , Young Vincent B. , Abuaita Basel H. , O'Riordan Mary X.
Published: November 2024

Nontyphoidal strains of
Salmonella enterica
are a major cause of foodborne illnesses, and infection with these bacteria results in inflammatory gastroenteritis. Polymorphonuclear leukocytes (PMNs), also known as neutrophils, are a dominant immune cell type found at the site of infection in
Salmonella-
infected individuals, but how they regulate infection outcome is not well understood. Here, we used a co-culture model of primary human PMNs and human intestinal organoids to probe the role of PMNs during infection with two of the most prevalent
Salmonella
serovars:
Salmonella enterica
serovar Enteritidis and Typhimurium. Using a transcriptomics approach, we identified a dominant role for PMNs in mounting differential immune responses including production of pro-inflammatory cytokines, chemokines, and antimicrobial peptides. We also identified specific gene sets that were induced by PMNs in response to Enteritidis or Typhimurium infection. By comparing host responses to these serovars, we uncovered differential regulation of host metabolic pathways particularly induction of cholesterol biosynthetic pathways during Typhimurium infection and suppression of RNA metabolism during Enteritidis infection. Together, these findings provide insight into the role of human PMNs in modulating different host responses to pathogens that cause similar disease in humans.

IMPORTANCE

Nontyphoidal serovars of
Salmonella enterica
are known to induce robust recruitment of polymorphonuclear leukocytes (PMNs) in the gut during early stages of infection, but the specific role of PMNs in regulating infection outcome of different serovars is poorly understood. Due to differences in human infection progression compared to small animal models, characterizing the role of PMNs during infection has been challenging. Here, we used a co-culture model of human intestinal organoids with human primary PMNs to study the role of PMNs during infection of human intestinal epithelium. Using a transcriptomics approach, we define PMN-dependent reprogramming of the host response to
Salmonella
, establishing a clear role in amplifying pro-inflammatory gene expression. Additionally, the host response driven by PMNs differed between two similar nontyphoidal
Salmonella
serovars. These findings highlight the importance of building more physiological infection models to replicate human infection conditions to study host responses specific to individual pathogens.
Investigation of choroidal vascular alterations in eyes with myopia using ultrawidefield optical coherence tomography angiography
Authors: Tang Xiangcheng , Liang Jia , Luo Lishi , Yuan Fanglan , Zhao Keming , Zhuo Xiaohua , Li Wangting , Wang Jiantao , Zhang Shaochong , Zeng Kun
Published: November 2024

Background/aims

The study aims to evaluate choroidal vascular changes in younger patients with myopia using ultrawidefield swept-source optical coherence tomography angiography (SS-OCTA).

Methods

Overall, 724 eyes of 362 participants (177 males, 185 females, age: 32.43±6.20 years) underwent SS-OCTA imaging (24×20 mm). The eyes were divided into normal, low myopia (LM), moderate myopia (MM), high myopia and superhigh myopia groups according to the spherical equivalent refraction (SER). Changes in choroidal vascular thickness (ChVT) and density (ChVD) in nine grids of the fundus were analysed using the latest version of the built-in analysis software.

Results

Axial length (AL) showed a negative correlation with SER (r=0.822, p=0.000); ChVT and ChVD showed a negative correlation with AL (p≤0.001) in all nine grids. In group analysis, compared with normal eyes, myopia affects ChVT earlier than ChVD, as observed in the LM and MM groups, respectively. The decrease in ChVT was most evident in the macular grid (β= −34.20, p=0.000), whereas the decrease in ChVD was most evident in the optic disc grid (β= −2.19, p=0.001).

Conclusion

Myopia has a significant impact on choroidal vascular structure, resulting in spatiotemporal differences. Using SS-OCTA with a new version of the built-in analysis software and a study with a larger sample cohort may aid in providing more authentic information on choroidal vascular changes in eyes with myopia.
TNFR2 blockade promotes antitumoral immune response in PDAC by targeting activated Treg and reducing T cell exhaustion
Authors: Debesset Anais , Pilon Caroline , Meunier Sylvain , Cuelenaere-Bonizec Orianne , Richer Wilfrid , Thiolat Allan , Houppe Claire , Ponzo Matteo , Magnan Jeanne , Caron Jonathan , Caudana Pamela , Tosello Boari Jimena , Baulande Sylvain , To Nhu Han , Salomon Benoit Laurent , Piaggio Eliane , Cascone Ilaria , Cohen José Laurent
Published: November 2024

Background

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers, highly resistant to standard chemotherapy and immunotherapy. Regulatory T cells (Tregs) expressing tumor necrosis factor α receptor 2 (TNFR2) contribute to immunosuppression in PDAC. Treg infiltration correlates with poor survival and tumor progression in patients with PDAC. We hypothesized that TNFR2 inhibition using a blocking monoclonal antibody (mAb) could shift the Treg-effector T cell balance in PDAC, thus enhancing antitumoral responses.

Method

To support this hypothesis, we first described TNFR2 expression in a cohort of 24 patients with PDAC from publicly available single-cell analysis data. In orthotopic and immunocompetent mouse models of PDAC, we also described the immune environment of PDAC after immune cell sorting and single-cell analysis. The modifications of the immune environment before and after anti-TNFR2 mAb treatment were evaluated as well as the effect on tumor progression.

Results

Patients with PDAC exhibited elevated TNFR2 expression in Treg, myeloid cells and endothelial cells and lower level in tumor cells. By flow cytometry and single-cell RNA-seq analysis, we identified two Treg populations in orthotopic mouse models: Resting and activated Tregs. The anti-TNFR2 mAb selectively targeted activated tumor-infiltrating Tregs, reducing T cell exhaustion markers in CD8+T cells. However, anti-TNFR2 treatment alone had limited efficacy in activating CD8+T cells and only slightly reduced the tumor growth. The combination of the anti-TNFR2 mAb with agonistic anti-CD40 mAb promoted stronger T cell activation, tumor growth inhibition, and improved survival and immunological memory in PDAC-bearing mice.

Conclusion

Our data suggest that combining a CD40 agonist with a TNFR2 antagonist represents a promising therapeutic strategy for patients with PDAC.
Distributive justice, best options and organ markets: a reply to Semrau
Authors: Albertsen Andreas
Published: November 2024

How important is it, morally speaking, that banning the sale of organs removes the best option available to would-be organ sellers? According to a widespread argument called the best option argument, this is very important. In a recent article I criticised such reasoning, drawing on considerations of distributive justice. Luke Semrau has argued that I have misunderstood the best option argument. In this article, I respond to Semrau’s criticism and elaborate on my original argument.
Associations between objectively measured nighttime sleep duration, sleep timing, and sleep quality and body composition in toddlers in the Guelph Family Health Study
Authors: Ribey Sarah C.S. , Coyle-Asbil Hannah J. , Osojnicki Katarina , Coyle-Asbil Bridget , Vallis Lori Ann , Darlington Gerarda , Duncan Alison M. , Ma David W.L. , Haines Jess , Buchholz Andrea C.
Published: November 2024

The prevalence of child obesity is a worldwide public health concern. Good sleep quality is associated with reduced adiposity in older children and adults. More research is needed in younger children to help mitigate risk of obesity. In addition, we aimed to address limitations found in previous studies such as relying on subjective measures, or only including one parameter of sleep, using only one body composition parameter, and/or not adjusting for relevant covariates. This cross-sectional study examined baseline data from 48 toddlers aged 1 to <3 years enrolled in the Guelph Family Health Study. Nighttime sleep duration (total sleep time; TST), sleep timing (sleep onset and offset time), and sleep quality (wake after sleep onset; WASO) were measured using 24 h accelerometry for 7 consecutive days. Height, body weight, and waist circumference were measured, and BMI z-scores and waist-to-height ratios were calculated. Percent fat mass and fat mass index were calculated using bioelectrical impedance analysis. Linear regression models were used to estimate associations between sleep parameters and body composition outcomes, with adjustments for relevant covariates (age, sex, household income, screen time, energy intake, physical activity, household stress). Nighttime sleep onset time was positively associated with waist-to-height ratio ([Formula: see text] = 0.004, p = 0.04). Sleep offset time was negatively associated with BMI z-score ([Formula: see text] = −0.48, p = 0.02). TST and WASO were not associated with any body composition outcome. Building healthy sleep habits may prevent childhood obesity; longitudinal research in a larger sample is warranted. This study was registered on ClinicalTrials.gov (NCT02939261).
Field investigation on the performance of low-carbon MgO-carbonated composite piles for ground treatments
Authors: Liu Yi-Zhao , Liu Song-Yu , Li Hong-Jiang , Du Guang-Yin , Zhang Chao-Zhe , Sun Jia-Wei
Published: November 2024

Carbonation technology using MgO and CO2 has been considered a rapid, effective, and environmentally friendly method for improving weak soils, mainly applied in shallow foundation treatments. This study introduced a novel MgO-carbonated composite pile (MCP) technique developed by injecting CO2 through a gas-permeable pipe pile into a MgO-mixing column for carbonation and solidification and its applications in weak subgrade treatments. Several field tests were carried out to study the characteristics of MCP as well as the performance of the MCP-reinforced foundations, including carbonation reaction temperature monitoring, pore-water pressure monitoring, standard penetration tests (SPTs), unconfined compressive strength (UCS) tests, static load tests, and subgrade deformation monitoring. Results showed vigorous and uniform carbonation within the MgO-mixing column, confirming the feasibility of constructing large-diameter MgO-mixing columns. The distribution, evolution, and affected zone of excess pore-water pressure induced by MCP installation were determined. The MCP exhibited good pile quality, with average SPT blow count and UCS value of 39 and 1021 kPa, respectively. MCP’s bearing capacity was superior to prestressed high-strength concrete pipe piles, with ultimate vertical and lateral bearing capacities of 1920 and 119 kN, respectively. The MCP-reinforced foundation exhibited a small settlement of 54.5 mm under embankment loads. Life cycle assessment indicated significant carbon reduction benefits for MCP, with 44.7% lower carbon emissions compared to traditional composite piles.
A scoping review of strengths-based drinking water policies in Indigenous communities in Canada, the United States, New Zealand, and Australia
Authors: Lyeo Joonsoo S. , Samim Yagana , Decter Kate , Agarwal Nehul , Liberda Eric N. , Haines Sarah R. , Spence Nicholas D.
Published: November 2024

The Indigenous Peoples of Australia, Canada, New Zealand, and the United States have faced a shared history of disenfranchisement under settler-colonial paradigms. One consequence of this marginalization has been the widespread deprivation of secure access to safe drinking water in Indigenous communities. To date, much of the literature on Indigenous drinking water access has taken a deficit-based approach, focusing on the factors that are “lacking” from Indigenous communities. Deficit-based approaches have been criticized for perpetuating cycles of negative experiences, fostering dependency within the target community, and leading to interventions that are unsustainable and limited in scope. In contrast, this scoping review comprised a strengths-based investigation of successful Indigenous drinking water policy in Australia, Canada, New Zealand, and the United States. Through this review of the gray literature published from 2000 to 2024, we identified methods for measuring the success of Indigenous drinking water policies; common features of Indigenous drinking water policies said to be successful; and external factors which have been found to contribute to the success of Indigenous drinking water policies. The subsequent thematic analysis revealed a need to leverage the assets within Indigenous communities, drawing upon the strengths inherent to traditional knowledge systems and cultural practices, by involving Indigenous Peoples as key stakeholders in the development of drinking water policy. There is an opportunity for policymakers to engage in an iterative process that considers the larger problems we have identified in this review, as well as the community-specific concerns of the Indigenous groups being served.
Ginsenoside Rh4 Ameliorates Cisplatin-Induced Intestinal Toxicity via PGC-1α-Mediated Mitochondrial Autophagy and Apoptosis Pathways
Authors: Liu Wei , Sun Meng , Wang Wen-Ting , Song Jian , Wang Chun-Mei , Mou Neng-Yan , Shao Tian-Qi , Zhang Zhi-Hong , Wang Meng-Yang , Sun Hai-Ming
Published: November 2024

Cisplatin-evoked profound gastrointestinal symptomatology is one of the most common side effects of chemotherapy drugs, causing further gastrointestinal cell and intestinal mucosal injury. Ginsenoside Rh4 (G-Rh4), an active component extracted from red ginseng, possesses beneficial anti-oxidative and anti-apoptosis effects. This study aimed to assess the effectiveness of pharmacological intervention with G-Rh4 mitigating intestinal toxicity evoked by cisplatin in a murine model and in IEC-6 cells in vitro. Following oral administration for 10 days, G-Rh4 (10[Formula: see text]mg/kg and 20[Formula: see text]mg/kg) significantly increased the indicators of diamine oxidase (DAO) affected by cisplatin (20[Formula: see text]mg/kg) in mice, and histopathological analysis further indicated that G-Rh4 could effectively improve intestinal tissue morphology, as well as the expression of peroxisome proliferator-activated receptor-gamma coactivator 1 [Formula: see text] (PGC-1[Formula: see text] pathway and autophagy-related proteins. Moreover, in vitro experiments demonstrated that G-Rh4 exerted a concentration-dependent increase in cell viability, while also inhibiting cytotoxicity and abnormal rise of reactive oxygen species (ROS). Notably, ROS also activate PGC-1[Formula: see text] protein and mediate the occurrence of mitochondrial autophagy and apoptosis pathways. The molecular docking approach was employed to dock G-Rh4 with PGC-1[Formula: see text] and AMPK, revealing a binding energy of [Formula: see text]7.3[Formula: see text]kcal/mol and [Formula: see text]8.1[Formula: see text]kcal/mol and indicating a tight interaction between the components and the target. G-Rh4 could reduce the expression of autophagy-related protein p62/p53, reduce the accumulation of autophagy products, and promote the flow of autophagy. In conclusion, G-Rh4 exerted protective effects against cisplatin-induced intestinal toxicity, at least partially through PGC-1[Formula: see text]-mediated autophagy and apoptosis.
Does Energy Consumption Affect the Environment and Economic Growth: Evidence from Emerging Economies
Authors: Shivani Shivani
Published: November 2024

The relationship between economic growth, energy consumption, and carbon emissions has been extensively studied within the Environmental Kuznets Curve (EKC) framework. However, much of the existing literature focuses on the direct effects of energy consumption on the economic growth-carbon emission nexus, often overlooking the potential moderating influences of different energy sources. Thus, this study fills this gap by investigating the moderating effect of renewable energy consumption on the relationship between economic growth and carbon emissions in emerging economies using panel data methods. The study presents evidence supporting the existence of the EKC, indicating that economic growth negatively impacts the environment until a certain threshold of income is reached. Moreover, our results indicate that renewable energy weakens the relationship between economic growth and carbon emissions. This suggests that the adoption of renewable energy can help mitigate the negative environmental impacts of economic growth. Based on the findings, it is recommended that emerging countries should prioritize the integration of renewable energy into their energy mix, reduce dependence on fossil fuels, and promote economic growth strategies that align with environmental goals.
Hybrid machine learning techniques based on genetic algorithm for heart disease detection
Authors: Kumar Ankur , Dhanka Sanjay , Singh Jaspreet , Ali Khan Asim , Maini Surita
Published: November 2024

This research study addresses the critical global health issue of heart disease (HD), emphasizing the importance of early detection for improving recovery outcomes. The authors have applied various machine learning (ML) algorithms, including logistic regression (LR), linear discriminant analysis (LDA), Gaussian naive bayes (GNB), support vector machine (SVM), and XGBoost (XGB) to classify the Statlog and Cleveland HD datasets. Performance metrics such as accuracy, precision, recall, F1-score, specificity, and Cohen’s kappa have been evaluated across these HD records. This study conducted two experiments: one using default ML classifiers and another with a hybrid genetic algorithm ML (GA-ML) model. The GA has been employed as a feature selector (FS), significantly enhancing the performance of each default classifier by selecting 9 out of 13 features. Notably, the GA-XGB model achieved the highest performance with an accuracy of 94.83%, precision of 93.33%, sensitivity of 96.55%, F1-score of 94.52%, specificity of 93.10%, Cohen’s kappa of 0.90, a positive likelihood ratio (LR[Formula: see text]) of 14, a negative likelihood ratio (LR-) of 0.037, and a diagnostic odds ratio (DOR) of 378 on the combined HD dataset. These results have been validated using a 10-fold cross-validation technique. A comparative analysis has been conducted with default ML classifiers, hybrid GA-ML classifiers, and state-of-the-art methods. The results of the GA-ML models confirm the superiority of the proposed method, offering valuable insights into advancing early detection strategies and improving heart health care outcomes.
Evaluation of rapidly mutating Y-short tandem repeats in distinguishing genetic variations
Authors: Ullah Muhammad Farhat , Khan Muhammad Ramzan , Ijaz Khan M.
Published: November 2024

The Y chromosome contains short tandem repeats (STRs) that have numerous applications, including forensic investigations, male identification for legal purposes, and population genetics. However, commercially available Y-STR tests have limitations in their ability to differentiate closely linked male individuals in forensic genetics. Recent studies have shown that rapidly mutating (RM) Y-STRs offer significantly greater haplotype diversity across worldwide populations than conventional Y-STRs, although some RM Y-STR loci are not included in current commercial kits. This research aimed to evaluate the effectiveness of RM Y-STR haplotype frequencies in distinguishing individuals with genetic variations in the Gilgit population and other Pakistani populations. The study involved analyzing several RM Y-STRs in 56 unrelated Gilgit men and 21 other Pakistani populations. Statistical analysis showed that most of the loci maintained haplotype values, while some varied in certain cases. The results indicated that RM Y-STRs were highly effective in distinguishing genetic differences among the Gilgit population and other Pakistani populations, as evidenced by the gene diversity (GD), average GD and discrimination capacity (DC), match probability (MP), and power discrimination (PD) values calculated for the set of various RM Y-STRs in Table  1 for the Gilgit population and in Table  2 for other Pakistani populations. These findings highlight the potential of RM Y-STRs in forensic genetics and population genetics research and underscore the importance of including a diverse set of loci to maximize the discriminatory power of genetic markers. Further research could explore the utility of RM Y-STRs in other populations and their potential for use in other applications beyond forensic investigations and male identification.
Deep Learning Applied to Diffusion-weighted Imaging for Differentiating Malignant from Benign Breast Tumors without Lesion Segmentation
Authors: Iima Mami , Mizuno Ryosuke , Kataoka Masako , Tsuji Kazuki , Yamazaki Toshiki , Minami Akihiko , Honda Maya , Imanishi Keiho , Takada Masahiro , Nakamoto Yuji
Published: November 2024

Deep learning models, particularly small two-dimensional convolutional neural networks, showed good performance in differentiating between benign and malignant breast tumors using diffusion-weighted MRI, compared with breast radiologists.
The Promising Potential of Ezh1 Inhibition as a Therapeutic Strategy Against Dengue Infections
Authors: Liu Danping , Tan Ningxin , Chi Peidong , Huang Junqi
Published: November 2024

The investigation of enhancer of zeste homolog 1 (Ezh1) in the context of dengue infection immunity has been limited, necessitating further exploration to elucidate its precise role and underlying mechanisms during infections. To address this gap, we generated Ezh1 knockout mice and obtained bone marrow and spleen samples from both Ezh1 knockout mice and wild‐type (WT) counterparts. Leveraging RNA sequencing (RNA‐seq) analysis, we identified the enrichment of genes associated with the interleukin‐17 (IL‐17) signaling pathway among the differentially expressed genes (DEGs) in the spleens of male Ezh1 knockout mice when compared to WT mice. Furthermore, our results revealed that Ezh1 knockout not only curtailed the viral load in dengue virus (DENV) infections but also suppressed the expression of pivotal cytokines, including interleukin‐9 (IL‐9) and IL‐17. Additionally, utilizing high‐parameter flow cytometry, we observed alterations in the immune cell phenotype within the spleens linked to Ezh1 gene knockout. Specifically, Ezh1 knockout inhibited the expressions of programmed cell death protein 1 (PD‐1), lymphocyte‐activation gene 3 (LAG‐3), and cluster of differentiation 86 (CD86). Additionally, we noted a reduction in cluster of differentiation 62L (CD62L) expression in neutrophils following DENV infection. Our comprehensive findings collectively underscore the significant role of Ezh1 in DENV infection, suggesting that targeting Ezh1 could offer a promising antiviral strategy.
Ethnopharmacological Perspective for Treatment of Epilepsy: An Updated Review
Authors: Kalra Sunishtha , Bhatia Saurabh , Harrasi Ahmed Al , Mohan Syam , Sachdeva Himanshu , Sharma Divya , Budhwar Vikas , Choudhary Manjusha , Malik Rohit
Published: November 2024

Plants have been used as healing agents since humanity began. This review presents the plant profiles inhabiting the world regarding their traditional usage by various tribes/ethnic groups for the treatment of epilepsy. The bibliographic investigation was carried out by analyzing standard reference textbooks, Science Direct, Google Scholar, Scopus, Medline, Web of Science, and PubMed databases. Search terms and keywords used for the search were epilepsy, medicinal plants for epilepsy, herbal remedies used in the treatment of epilepsy, and traditional antiepilepsy medication. This review article was prepared by including the biological names of plants/their parts/extracts/compounds/doses/models/results. Further, experimentally explored 15 potential medicinal plants have also been explored in detail. The present review was prepared by including 114 plants from 3 books, 83 research, and 59 review articles. This review indicates that the list of medicinal plants presented in this review might be useful to researchers for preliminary screening of potential antiepileptic agents.
Nurse‐Led Telephone Program for Nonadherent to Treatment Type 2 Diabetics With Comorbid Depression: A Cost‐Consequence and Budget Impact Analysis
Authors: Gómez-Barrera Manuel , Lozano-Del Hoyo María Luisa , Roy Juan Francisco , Fernández-Rodrigo María Teresa , Gómez-Torres Piedad , Blázquez-Ornat Isabel , Pérez-Calahorra Sofía , Samaniego Diaz de Corcuera Maria Esther , Ferrer-López Emilia , Ramón-Arbués Enrique
Published: November 2024

Objective: To estimate the efficiency of a nurse‐led telephone program for nonadherent to treatment Type 2 diabetics with comorbid depression (TELE‐DD program).

Design: Secondary analysis of cost‐consequence and budget impact, utilizing data from a randomized clinical trial conducted in the primary healthcare setting. The target population consisted of Type 2 diabetic patients with comorbid depression who were nonadherent to their pharmacological treatment.

Method: The average cost per controlled patient (glycated hemoglobin < 7%) and the incremental cost‐effectiveness ratio were calculated. Similarly, the budgetary impact over 1 year of implementing this program in the region of reference of the randomized clinical trial was assessed.

Results: The number of controlled patients is higher in the TELE‐DD group at 6, 12, and 18 months. The average cost per controlled patient was higher in the TELE‐DD group than in the control group at 6 months (€160.31 vs. €49.79), but lower at 12 (€150.09 vs. €179.59) and 18 months (€209.22 vs. €376.88). The incremental cost‐effectiveness ratio at 6, 12, and 18 months was €254.47, €143.65, and €177.46, respectively. The budget impact analysis revealed that implementing the TELE‐DD program would result in a reduction of €721,940.68 in expenditure for the funder in the first year of application.

Conclusions: A nurse‐led telephone program for nonadherent Type 2 diabetics with comorbid depression is an efficient option in the management of healthcare resources. These results highlight the role of nursing in chronic patient management and the efficient use of healthcare resources.

Trial Registration: ClinicalTrials.gov Identifier: NCT04097483.
KAST Improves Airway Inflammation in Allergic Asthma via GATA3/ILC2
Authors: Di Kuan , Liu Lanying
Published: November 2024

This study aimed to investigate the effects of KAST in asthma and its underlying mechanisms by combining network pharmacology and bioinformatic methods. Based on the TCMSP and HERB databases, we found the active compounds and targets of KAST. We integrated results from three databases, GeneCards, OMIM, and TTD, to search for asthma targets. We constructed a PPI network to better understand the interaction between proteins and selected core proteins. GO enrichment analysis was used to find functional changes in the target from three aspects: molecular function, cellular component, and biological process involved. The KEGG was used to uncover the signaling pathways of these targets. We screened differential genes through the GEO database and used a weighted gene coexpression network analysis to find gene modules closely related to asthma and further construct a core PPI network. Active compounds and core proteins were assessed using molecular docking. In total, 107 active compounds and 564 potential targets were identified. GO and KEGG pathway enrichment analyses showed that the role of KAST was closely related to inflammation, cell cycle, endocrine resistance, and PI3K/AKT signaling pathways. The core PPI network revealed five core targets. Molecular docking revealed a good binding ability between the active compound and the core protein. Experiments have confirmed that KAST can regulate the expression of IL33 in lung tissue and the expression of GATA3 in ILC2 and improve airway inflammation in asthma. KAST has various components and targets and can improve asthma systematically through various pathways. This study will lay the foundation for further study of its mechanism of action.
Refractory HIV‐Associated Guillain–Barré Syndrome Responsive to Antiretroviral Therapy: A Case Report
Authors: Coyle Sean , Cormack Ian Sutherland
Published: November 2024

Guillain–Barré Syndrome (GBS) is an acute polyneuropathy commonly preceded by infection, with growing recognition of the human immunodeficiency virus (HIV) as a trigger. We present a case of a 44‐year‐old male with HIV‐associated GBS refractory to intravenous immunoglobulin (IVIG) therapy, who achieved remission upon starting highly active antireroviral therapy (HAART). There remains a lack of consensus on the management of this condition across the spectrum of disease, and the interplay between the therapeutic options is poorly understood. This report aims to add to the current body of knowledge on this rare condition and highlight the need for retrospective analysis of the currently available literature.
The Evaluation of the Relationship Between Coronary Ectasia and Trimethylamine N‐Oxide
Authors: Sari Hasan , Alsancak Yakup , Gurbuz Ahmet Seyfeddin , Keskin Oznur , Tatar Sefa , Duzenli Mehmet Akif
Published: November 2024

Introduction: It is now known that the microbiota is far beyond the microbial communities living in certain parts of our body and functions like a metabolic organ. In addition, the microbiota, through its metabolites, is involved in the pathophysiology or progression of a wide range of diseases, from atherosclerotic diseases to metabolic diseases and even neurological diseases. Among these metabolites, trimethylamine n‐oxide metabolite has been shown to be particularly effective in atherosclerotic heart diseases.

Materials and Methods: A total of 155 patients, who underwent coroner angiography for stable angina were included in the study. Of these patients, 81 patients with coronary artery ectasia (patient group) and 74 patients without coronary artery ectasia (control group) were evaluated for trimethylamine n‐oxide metabolite.

Results: Statistically significantly higher trimethylamine n‐oxide metabolite levels were observed in the coronary artery ectasia group compared to the control group.

Conclusion: The significantly higher trimethylamine n‐oxide levels in patients with coronary artery ectasia without coronary artery disease suggest that the microbiota and its metabolites independently play a role in the pathophysiology or progression of vascular remodeling or endothelial dysfunctions. Also, its effect on the endothelial surface may depend on the threshold value.
Supplementary Notes from St. Jude Survivorship Portal: Sharing and Analyzing Large Clinical and Genomic Datasets from Pediatric Cancer Survivors
Authors: Matt Gavriel Y. , Sioson Edgar , Shelton Kyla , Wang Jian , Lu Congyu , Zaldivar Peraza Airen , Gangwani Karishma , Paul Robin , Reilly Colleen , Acić Aleksandar , Liu Qi , Sandor Stephanie R. , McLeod Clay , Patel Jaimin , Wang Fan , Im Cindy , Wang Zhaoming , Sapkota Yadav , Wilson Carmen L. , Bhakta Nickhill , Ness Kirsten K. , Armstrong Gregory T. , Hudson Melissa M. , Robison Leslie L. , Zhang Jinghui , Yasui Yutaka , Zhou Xin
Published: November 2024

Supplementary Notes
Venetoclax-Based Combination Regimens in Acute Myeloid Leukemia
Authors: Goulart Hannah , Kantarjian Hagop , Pemmaraju Naveen , Daver Naval , DiNardo Courtney D. , Rausch Caitlin R. , Ravandi Farhad , Kadia Tapan M.
Published: November 2024

Incorporation of the B-cell lymphoma 2 inhibitor venetoclax into the treatment of acute myeloid leukemia (AML) has been transformative. Initially studied in combination with low-intensity therapy in older adults and those ineligible for intensive therapy, venetoclax has proven to be efficacious and tolerable in this setting. Recently, venetoclax has been investigated in combination with more intensive regimens. However, these approaches come with a myriad of dosing strategies and questions surrounding the practicality of venetoclax administration. In this study, we provide an overview of the incorporation of venetoclax into AML treatment and a discussion of practical considerations and areas of unmet need.

Significance:

In recent years, there has been tremendous interest surrounding the integration of venetoclax into both non-intensive and intensive chemotherapy regimens for AML. However, with this increasing utilization of venetoclax, considerable questions surrounding key issues such as dosing strategies and the practicality of venetoclax administration have arisen. This review highlights the evolution of venetoclax-based regimens in AML and provides a commentary on notable practical considerations when utilizing this agent.
Posttraumatic Stress Disorder and the Risk of Heart Failure Hospitalizations Among Individuals With Coronary Artery Disease
Authors: Almuwaqqat Zakaria , Liu Chang , Ko Yi-An , Elon Lisa , Moazzami Kasra , Wang Maggie , Murrah Nancy , Shallenberger Lucy , Lewis Tené T. , Shah Amit J. , Raggi Paolo , Bremner J. Douglas , Quyyumi Arshed A. , Vaccarino Viola
Published: November 2024

BACKGROUND:

Posttraumatic stress disorder (PTSD) is associated with maladaptive dysregulation of stress response systems, which could lead to an increased risk of heart failure. We investigated whether PTSD was independently associated with first and recurrent heart failure hospitalizations in the setting of coronary artery disease.

METHODS:

Individuals with stable coronary artery disease and without heart failure at baseline were enrolled in 2 parallel prospective cohort studies in metropolitan Atlanta, GA. Participants underwent a structured clinical interview to assess their lifetime history of PTSD. Current PTSD symptoms were assessed using the PTSD symptom checklist. Participants were followed up for a median time of 4.9 years. The primary end point was first or recurrent hospitalization for heart failure. Secondary end points included cardiovascular death and nonfatal myocardial infarction with and without hospitalization for heart failure. Survival analysis for repeated events was used to assess the association of PTSD with adverse events.

RESULTS:

We studied 736 individuals with a mean age of 60±10 years; 36% were Black, and 35% were women. In total, 69 (9.4%) patients met the criteria for PTSD. Having a PTSD diagnosis was associated with the primary end point of first or recurrent heart failure hospitalizations, with a hazard ratio of 4.4 (95% CI, 2.6–7.3). The results were minimally attenuated after adjusting for demographic and clinical factors (hazard ratio, 3.7 [95% CI, 2.1–6.3]). Similarly, a 10-point increase in the PTSD symptom checklist score was associated with a 30% (95% CI, 10%–50%) increase in heart failure hospitalizations. PTSD was not associated with an end point of cardiovascular death or nonfatal myocardial infarction, which excluded hospitalizations due to heart failure.

CONCLUSIONS:

Among patients with coronary artery disease, PTSD is associated with incident and recurrent heart failure hospitalizations. Future research is needed to investigate whether PTSD management can reduce the risk of heart failure.
The Emergence of Chunking Structures with Hierarchical RNN
Authors: Wu Zijun , Deshmukh Anup Anand , Wu Yongkang , Lin Jimmy , Mou Lili
Published: November 2024

In Natural Language Processing (NLP), predicting linguistic structures, such as parsing and chunking, has mostly relied on manual annotations of syntactic structures. This article introduces an unsupervised approach to chunking, a syntactic task that involves grouping words in a non-hierarchical manner. We present a Hierarchical Recurrent Neural Network (HRNN) designed to model word-to-chunk and chunk-to-sentence compositions. Our approach involves a two-stage training process: pretraining with an unsupervised parser and finetuning on downstream NLP tasks. Experiments on multiple datasets reveal a notable improvement of unsupervised chunking performance in both pretraining and finetuning stages. Interestingly, we observe that the emergence of the chunking structure is transient during the neural model’s downstream-task training. This study contributes to the advancement of unsupervised syntactic structure discovery and opens avenues for further research in linguistic theory.1
Spectral graph model for fMRI: A biophysical, connectivity-based generative model for the analysis of frequency-resolved resting-state fMRI
Authors: Raj Ashish , Sipes Benjamin S. , Verma Parul , Mathalon Daniel H. , Biswal Bharat , Nagarajan Srikantan
Published: November 2024

Resting-state functional MRI (rs-fMRI) is a popular and widely used technique to explore the brain’s functional organization and to examine whether it is altered in neurological or mental disorders. The most common approach for its analysis targets the measurement of the synchronized fluctuations between brain regions, characterized as functional connectivity (FC), typically relying on pairwise correlations in activity across different brain regions. While hugely successful in exploring state- and disease-dependent network alterations, these statistical graph theory tools suffer from two key limitations. First, they discard useful information about the rich frequency content of the fMRI signal. The rich spectral information now achievable from advances in fast multiband acquisitions is consequently being underutilized. Second, the analyzed FCs are phenomenological without a direct neurobiological underpinning in the underlying structures and processes in the brain. There does not currently exist a complete generative model framework for whole brain resting fMRI that is informed by its underlying biological basis in the structural connectome. Here we propose that a different approach can solve both challenges at once: the use of an appropriately realistic yet parsimonious biophysics-informed signal generation model followed by graph spectral (i.e., eigen) decomposition. We call this model a spectral graph model (SGM) for fMRI, using which we can not only quantify the structure–function relationship in individual subjects, but also condense the variable and individual-specific repertoire of fMRI signal’s spectral and spatial features into a small number of biophysically interpretable parameters. We expect this model-based analysis of rs-fMRI that seamlessly integrates with structure can be used to examine state and trait characteristics of structure–function relationships in a variety of brain disorders.
Neural processing of rhythmic speech by children with developmental language disorder (DLD): An EEG study
Authors: Keshavarzi Mahmoud , Richards Susan , Feltham Georgia , Parvez Lyla , Goswami Usha
Published: November 2024

Sensitivity to rhythmic and prosodic cues in speech has been described as a precursor of language acquisition. Consequently, atypical rhythmic processing during infancy and early childhood has been considered a risk factor for developmental language disorders. Despite many behavioural studies, the neural processing of rhythmic speech has not yet been explored in children with developmental language disorder (DLD). Here, we utilise EEG to investigate the neural processing of rhythmic speech by 9-year-old children with and without DLD. In the current study, we investigate phase entrainment, angular velocity, power, event related potentials (ERPs), phase-amplitude coupling (PAC), and phase-phase coupling (PPC) at three frequency bands selected on the basis of the prior literature, delta, theta, and low gamma. We predicted a different phase of entrainment in the delta band in children with DLD, and also greater theta power, atypical cross-frequency coupling, and possibly atypical gamma-band responses. Contrary to prediction, children with DLD demonstrated significant and equivalent phase entrainment in the delta and theta bands to control children. However, only the control children showed significant phase entrainment in the low gamma band. The children with DLD also exhibited significantly more theta and low gamma power compared to the control children, and there was a significant gamma-band difference in angular velocity between the two groups. Finally, group resultant phase analyses showed that low-frequency phase (delta and theta) affected gamma oscillations differently by group. These EEG data show important differences between children with and without DLD in the neural mechanisms underpinning the processing of rhythmic speech. The findings are discussed in terms of auditory theories of DLD, particularly Temporal Sampling theory.