bluuebunny/crossref_metadata_2025 huggingface dataset:
Factor XI/XIa Inhibitors: What We Now Know
Authors: Lipworth Karen
Published: October 2024

The emerging class of agents targeting factor XI/XIa offers the paradigm-shifting possibility of ‘haemostasis-sparing anticoagulation’: protection from stroke and other thromboembolic events with a benign bleeding profile. With three investigational agents now into late-phase development, two presentations delivered at the European Society of Cardiology (ESC) Congress 2024, held in London, UK, have added to our knowledge of this innovative and diverse class. The first of these presentations shared the full data from the OCEANIC-AF Phase III trial, in which the small molecule factor XIa inhibitor asundexian was compared with the factor Xa inhibitor apixaban for stroke prevention in atrial fibrillation, and reviewed the probable reasons for the failure of this trial to meet its efficacy endpoint.

The second presentation was a secondary analysis from the AZALEA-TIMI 71 Phase II trial, in which the safety of the monoclonal antibody factor XI inhibitor abelacimab was compared with that of the factor Xa inhibitor rivaroxaban in patients with atrial fibrillation undergoing invasive procedures.

This article is based on a post-ESC interview with Jeffrey I. Weitz, Professor of Medicine and Biochemistry and Biomedical Sciences at McMaster University, Canada; Canada Research Chair (Tier 1) in Thrombosis and the Heart and Stroke Foundation; J.F. Mustard Chair in Cardiovascular Research; Executive Director of the Thrombosis and Atherosclerosis Research Institute (TaARI), in Hamilton, Canada; and Secretary General of the International Society on Thrombosis and Haemostasis (ISTH). It assesses the current status and future prospects of the factor XI/XIa inhibitor class in light of these recent developments.
Exploring caspase-dependent non-lethal cellular processes using Drosophila
Authors: Shinoda Natsuki , Miura Masayuki
Published: October 2024

Caspases are cysteine aspartic acid proteases conserved in animals that not only execute apoptosis, but also regulate diverse cellular processes independent of apoptosis, which are termed caspase-dependent non-lethal cellular processes (CDPs). Owing to its strong genetics to detect and manipulate caspase activity in cells of interest in vivo, Drosophila melanogaster serves as an excellent model organism for analyzing CDPs. This is further supported by the fact that apoptotic signaling, as well as CDPs and their mechanisms, are, in part, conserved in other animals. Here, we present a review to guide researchers studying CDPs using Drosophila. In this review, we provide an overview of the current understanding of apoptotic signaling, which regulates caspase activation in Drosophila as well as available genetic tools and their characteristics for detecting and manipulating caspase activity so that researchers can choose appropriate tools for their own experimental settings. We also introduce the CDPs identified in Drosophila, including a brief description of their discovery and characterization as non-lethal processes. We further describe the underlying molecular mechanisms of several well-characterized CDPs, including the regulatory mechanisms that enable non-lethal caspase activation. Finally, we introduce the use of proximity labeling techniques, especially TurboID, for studying CDPs, which facilitates the analysis of underlying molecular mechanisms. Because caspases regulate various non-lethal cellular functions, their activation is no longer considered a point of no return in cell death. Understanding CDPs will advance our understanding of the states of living and dying cells, along with the intermediate states.
Enhancing glioma treatment with 3D scaffolds laden with upconversion nanoparticles and temozolomide in orthotopic mouse model
Authors: Mishchenko Tatiana A. , Klimenko Maria O. , Guryev Evgenii L. , Savelyev Alexander G. , Krysko Dmitri V. , Gudkov Sergey V. , Khaydukov Evgeny V. , Zvyagin Andrei V. , Vedunova Maria V.
Published: October 2024

Targeted drug delivery for primary brain tumors, particularly gliomas, is currently a promising approach to reduce patient relapse rates. The use of substitutable scaffolds, which enable the sustained release of clinically relevant doses of anticancer medications, offers the potential to decrease the toxic burden on the patient’s organism while also enhancing their quality of life and overall survival. Upconversion nanoparticles (UCNPs) are being actively explored as promising agents for detection and monitoring of tumor growth, and as therapeutic agents that can provide isolated therapeutic effects and enhance standard chemotherapy. Our study is focused on the feasibility of constructing scaffolds using methacrylated hyaluronic acid with additional impregnation of UCNPs and the chemotherapeutic drug temozolomide (TMZ) for glioma treatment. The designed scaffolds have been demonstrated their efficacy as a drug and UCNPs delivery system for gliomas. Using the aggressive orthotopic glioma model in vivo, it was found that the scaffolds possess the capacity to ameliorate neurological disorders in mice. Moreover, upon intracranial co-implantation of the scaffolds and glioma cells, the constructs disintegrate into distinct segments, augmenting the release of UCNPs into the surrounding tissue and concurrently reducing postoperative damage to brain tissue. The use of TMZ in the scaffold composition contributed to restraining glioma development and the reduction of tumor invasiveness. Our findings unveil promising prospects for the application of photopolymerizable biocompatible scaffolds in the realm of neuro-oncology.
Development of novel CDK9 and CYP3A4 inhibitors for cancer therapy through field and computational approaches
Authors: Alsfouk Aisha A. , Faris Abdelmoujoud , Cacciatore Ivana , Alnajjar Radwan
Published: October 2024

Cyclin-dependent kinase 9 (CDK9) and cytochrome P450 3A4 (CYP3A4) have emerged as promising targets in the development of anticancer drugs, presenting a consistent challenge in the quest for potent inhibitors. CDK9 inhibitors can selectively target fast-growing cancer cells by disrupting transcription elongation, which in turn hinders the production of proteins essential for cell cycle progression and survivaŚ. Understanding how CYP3A4 metabolizes specific chemotherapy drugs allows for personalized treatment plans, optimizing drug dosages according to a patient’s metabolic profile. Since many cancer patients undergo combination therapies, and CYP3A4 is vital in drug metabolism, its inhibition or induction by one drug can alter the plasma levels of others, potentially leading to treatment failure or increased toxicity. Therefore, managing CYP3A4 activity is critical for effective cancer treatment. Employing a range of computational methodologies, this study systematically investigated the binding mechanisms of pyrimidine derivatives against CDK9 and CYP3A4. The field-based model demonstrated high R2 values (0.99), with Q2 (0.66), demonstrating its ability to predict in silico inhibitory activity against the target of this study. The screening process followed in this work led to the discovery of powerful new inhibitor compounds. Of the 15 new compounds designed, three have a high affinity with the target (ranging from −8 to −9 kcal/mol kcal/mol) and were singled out through docking filtration for more detailed investigation. As well as, a reference compound with a substantial pIC50 value of 8.4, serving as the foundation for the development of the new compounds, was included for comparative analysis. To elucidate the essential features of CDK9 and CYP3A4 inhibitor design, a comparative analysis was conducted between 3D-QSAR-generated contours and molecular docking conformations of ligands. Molecular dynamics simulations were carried out for a duration of 100 ns on selected docked complexes, specifically those involving novel compounds with CDK9 and CYP3A4 enzymes. Additionally, the binding free energy for these complexes was assessed using the MM/PBSA method, which evaluates the free energy landscape of protein-ligand interactions. The results of MM/PBSA highlighted the strength of the new compounds in enhancing interactions with the target protein, which favors the results of molecular docking and MD simulation. These insights contribute to a deeper understanding of the mechanisms underlying CDK9 and CYP3A4 inhibition, offering potential avenues for the development of innovative and effective CDK9 inhibitors.
Hypertensive disorders of pregnancy and stroke: a univariate and multivariate Mendelian randomization study
Authors: Qu Kang , Li Mingxi , Yu Peng , Jiang Wei , Dong Ming
Published: October 2024

Background

Hypertensive disorders of pregnancy (HDP) are associated with an increased risk of stroke later in life in multiparous women. However, causality of these associations remains unclear. This study employed 2-sample univariate and multivariate Mendelian randomization (MR) to assess the causal connection between HDP and stroke.

Methods

Genetic variants for HDP and two subtypes were identified from recent large-scale genome-wide association studies and the FinnGen consortium. Stroke summary data were obtained from the MEGASTROKE consortium. The primary analytical approach for univariate MR was the inverse variance weighting method. Sensitivity analyses incorporated methods such as MR-Egger regression, weighted median, and maximum likelihood to ascertain the robustness of the results. Additionally, multivariable MR analyses were conducted to account for potential associative effects of hypertension and type 2 diabetes.

Results

Genetically predicted HDP was associated with a high risk of large artery atherosclerosis (odds ratio [OR]=1.50, 95% confidence interval [CI]: 1.17–1.91, P=1.13×10-3) and small vessel stroke (OR=1.29, 95% CI: 1.20–1.50, P=1.52×10-3). HDP may also correlate with ischemic stroke (OR=1.13, 95% CI: 1.04–1.23, P=4.99×10-3) and stroke (OR=1.11, 95% CI: 1.03–1.20, P=8.85×10-3). An elevated risk of small vessel stroke (OR=1.20, 95% CI: 1.01–1.43, P=3.74×10-2) and large artery atherosclerosis (OR=1.22, 95% CI: 1.01–1.47, P=4.07×10-2) may be related with genetically predicted susceptibility to gestational hypertension. Genetically predicted susceptibility to preeclampsia or eclampsia may be associated with an increased risk of stroke (OR = 1.10, 95% CI: 1.02–1.19, P = 1.16×10-2) and ischemic stroke (OR = 1.10, 95% CI: 1.02–1.20, P = 1.84×10-2). Type 2 diabetes mellitus and hypertension were identified as significant factors contributing to the association between HDP and stroke.

Conclusions

This study provides genetic evidence supporting an association between HDP and increased stroke risk bolstering HDP as a cerebrovascular risk factor.
Grey wolf optimization for enhanced performance in wind power system with dual-star induction generators
Authors: Benamara Katia , Amimeur Hocine , Hamoudi Yanis , Abdolrasol Maher G. M. , Cali Umit , Ustun Taha Selim
Published: October 2024

This study investigates strategies for enhancing the performance of dual-star induction generators in wind power systems by optimizing the full control algorithm. The control mechanisms involved include the PID (Proportional-Integral-Derivative) controller for speed regulation and the PI (Proportional-Integral) controller for flux, DC-link voltage, and grid connection control. The primary objective is to optimize the entire system by fine-tuning PID and PI controllers through the application of meta-heuristic algorithms, specifically Grey Wolf Optimization (GWO) and Particle Swarm Optimization (PSO). These algorithms play a crucial role in estimating the optimal values of Kp, Ki, and Kd for the PID speed controller, as well as Kp and Ki for the PI controller used in the flux, DC-link voltage, and grid connection for wind energy conversion system based dual-star induction generator. This comprehensive optimization ensures accurate parameter tuning for optimal system performance. A comparative analysis of the optimization results has been conducted, focusing on the outcomes obtained with the GWO algorithm. The findings reveal a notable reduction in steady-state error, signifying improved stability, and an overall enhancement in the wind power system’s performance. This study contributes valuable insights into the effective application of meta-heuristic algorithms for optimizing dual-star induction generators in wind power systems.
Contamination source, health and ecological risk assessment of hazardous elements in the sediment of the Shahid Rajaee reservoir
Authors: Kachoueiyan Fatemeh , Alipour Atmianlu Pourya , Rajabi Armin , Ustaoğlu Fikret , Karbassi Abdolreza
Published: October 2024

Sediment pollution from potentially hazardous elements (PHE) generated by human activity has grown into a worldwide problem. In this regard, for the first time, surface sediment samples were obtained from six points along the Shahid Rajaee Reservoir for this investigation. Elements concentrations (Cu, Cr, Co, Mn, Fe, Pb, Ni, and Zn) were assessed using ICP-MS. Based on the individual indices (geoaccumulation index, contamination factor), all elements at all sample sites were found to be low in contamination, except Pb and Zn (at sites 1 and 2). The combined effect of PHEs in the sediment samples did not show a considerable concern, according to the synergistic indices. The health risk assessment revealed that recreational receptors were unlikely to face non-carcinogenic or carcinogenic hazards as a consequence of exposure to PHEs in sediments with unintentional ingesting and contact with the skin. The Tessier technique demonstrated that all PHEs were mostly connected with the oxidizable fraction. According to statistical study, while Cu, Co, Cr, Ni, Fe, and Mn were obtained from lithogenic sources, Pb and Zn came from natural as well as human-made sources.
Genetic heterogeneity in autosomal recessive hearing loss: a survey of Brazilian families
Authors: Antunes Larissa Nascimento , Dias Alex Marcel Moreira , Schiavo Beatriz Cetalle , Mendes Beatriz C. A. , Bertola Debora Romeo , Lezirovitz Karina , Mingroni-Netto Regina Célia
Published: October 2024

Introduction

Hearing loss is a frequent sensory impairment type in humans, with about 50% of prelingual cases being attributed to genetic factors. Autosomal recessive hearing loss (ARHL) exhibits great locus heterogeneity and is responsible for 70%–80% of hereditary nonsyndromic cases.

Methods

A total of 90 unrelated Brazilian individuals were selected for having hearing loss of presumably autosomal recessive inheritance, either born from consanguineous marriages or belonging to families with two or more affected individuals in the sibship and most cases were of normal hearing parents. In all cases, common pathogenic variants in GJB2 (c.35delG), GJB6 [del(GJB6-D13S1830) and del(GJB6-D13S1854)] and MT-RNR1 (m.1555A>G) were discarded and most were previously assessed by complete Sanger sequencing of GJB2. Their genetic material was analyzed through next-generation sequencing, targeting 99 hearing loss-related genes and/or whole exome sequencing.

Results

In 32 of the 90 probands (36,7%) causative variants were identified, with autosomal recessive inheritance confirmed in all, except for two cases due to dominant variants (SIX1 and P2RX2). Thirty-nine different causative variants were found in 24 different known hearing loss-associated genes, among which 10 variants are novel, indicating wide genetic heterogeneity in the sample, after exclusion of common pathogenic variants. Despite the genetic heterogeneity, some genes showed greater contribution: GJB2, CDH23, MYO15A, OTOF, and USH2A.

Conclusion

The present results confirmed that next-generation sequencing is an effective tool for identifying causative variants in autosomal recessive hearing loss. To our knowledge, this is the first report of next-generation sequencing being applied to a large cohort of pedigrees with presumable autosomal recessive hearing loss in Brazil and South America.
The effect of 12-week high-dose Colostrum Bovinum supplementation on immunological, hematological and biochemical markers in endurance athletes: a randomized crossover placebo-controlled study
Authors: Durkalec-Michalski Krzysztof , Główka Natalia , Podgórski Tomasz , Woźniewicz Małgorzata , Nowaczyk Paulina M.
Published: October 2024

Background

Bovine colostrum (COL) is assumed to be one of the strongest natural immune stimulants. Regular ingestion of COL may contribute to improved immune response in athletes exposed to high training loads.

Methods

Twenty-eight endurance-trained males aged 31.1 ± 10.2 years (body mass 81.9 ± 9.0 kg; height 1.82 ± 0.06 m) completed this randomized double-blind placebo(PLA)-controlled crossover study aimed at investigating the effect of 12-week COL supplementation (25gCOL·day-1) on resting (REST), exercise-induced (POST-EX), and short-term post-exercise recovery (REC; 1 h after test exercise) changes in selected saliva and blood immunoglobulins (Ig), white blood cell (WBC) count and differential; as well as blood hematological, nutritional status and muscle damage indices. The protocol assumed 4 study visits – before/after supplementation with COL (COLPRE and COLPOST) and PLA (PLAPRE and PLAPOST). During testing sessions, incremental rowing test to exhaustion and swimming-specific performance test were introduced as exercise stimuli.

Results

At COLPOST visit the secretory IgA (SIgA) concentration in saliva was significantly higher at POST-EX and REC compared to REST (p<0.05). COL supplementation had no effect on blood IgA, IgE, IgD, IgG, and IgM concentrations. Furthermore, after COL supplementation decrease of hematocrit at REC (p<0.05) was revealed.

Conclusions

12-week supplementation with 25 gCOL·day-1 in endurance-trained male athletes resulted in a favorable increase in post-exercise concentration of salivary SIgA. COL seems to be a potential stimulator of local immune defense after exercise-induced homeostasis disturbances. Nevertheless, the lack of effect on blood markers indicates the need for further research in the area of mechanisms underlying the effect of the supposed COL immunological capacity.
Cytokine production in an ex vivo model of SARS-CoV-2 lung infection
Authors: Vorobyeva Daria A. , Potashnikova Daria M. , Maryukhnich Elena V. , Rusakovich George I. , Tvorogova Anna V. , Kalinskaya Anna I. , Pinegina Natalia V. , Kovyrshina Anna V. , Dolzhikova Inna V. , Postnikov Alexander B. , Rozov Fedor N. , Sotnikova Tatiana N. , Kanner Dmitry Yu. , Logunov Denis Yu. , Gintsburg Alexander L. , Vasilieva Elena J. , Margolis Leonid B.
Published: October 2024

Introduction

The mechanisms of the SARS-CoV-2-triggered complex alterations in immune cell activation and production of cytokines in lung tissue remain poorly understood, in part because of the limited use of adequate tissue models that simulate the structure and cell composition of the lung in vivo. We developed a novel ex vivo model of SARS-CoV-2 infection of lung explants, that maintains the intact tissue composition and the viral load for up to 7–10 days. Using this model, we studied cytokine production during SARS-CoV-2 infection.

Materials and methods

Lung tissue was monitored for viability and cell composition using flow cytometry and histological analysis. SARS-CoV-2 infection was verified immunohistochemically, viral loads in tissue and culture medium were monitored by qPCR. A panel of 41 cytokines was measured in culture medium using xMAP technology.

Results

The explant lung tissue was viable and maintained viral infection that influenced the cytokine production. Elevated concentrations of G-CSF, GM-CSF, GRO-a, IFN-g, IL-6, IL-8, IP-10, MCP-3, MIP-1a, PDGF-AA, and VEGF, and decreased IL-1RA concentration were observed in infected tissue compared to non-infected tissue.

Discussion

Our results generally reflect the data obtained in COVID-19 patients. GRO-a, IFN-g, IL-6, IL-8, MCP-1, MCP-3, and RANTES correlated with the viral load, forming a distinct pro-inflammatory cluster. Thus, our lung ex vivo model faithfully reproduces some aspects of cytokine alterations in COVID-19 patients at an early disease stage, making the investigation of SARS-CoV-2 infection mechanisms more accessible and providing a potential platform for antiviral drug testing.
Analysis of lipid uptake, storage, and fatty acid oxidation by group 2 innate lymphoid cells
Authors: Roy-Dorval Audrey , Deagle Rebecca C. , Roth Frederik , Raybaud Mathilde , Ismailova Nailya , Krisna Sai Sakktee , Aboud Damon G. K. , Stegen Camille , Leconte Julien , Berberi Gabriel , Esomojumi Ademola , Fritz Jörg H.
Published: October 2024

Group 2 Innate Lymphoid Cells (ILC2) are critical drivers of both innate and adaptive type 2 immune responses, known to orchestrate processes involved in tissue restoration and wound healing. In addition, ILC2 have been implicated in chronic inflammatory barrier disorders in type 2 immunopathologies such as allergic rhinitis and asthma. ILC2 in the context of allergen-driven airway inflammation have recently been shown to influence local and systemic metabolism, as well as being rich in lipid-storing organelles called lipid droplets. However, mechanisms of ILC2 lipid anabolism and catabolism remain largely unknown and the impact of these metabolic processes in regulating ILC2 phenotypes and effector functions has not been extensively characterized. ILC2 phenotypes and effector functions are shaped by their metabolic status, and determining the metabolic requirements of ILC2 is critical in understanding their role in type 2 immune responses and their associated pathophysiology. We detail here a novel experimental method of implementing flow cytometry for large scale analysis of fatty acid uptake, storage of neutral lipids, and fatty acid oxidation in primary murine ILC2 with complementary morphological analysis of lipid storage using confocal microscopy. By combining flow cytometry and confocal microscopy, we can identify the metabolic lipid requirements for ILC2 functions as well as characterize the phenotype of lipid storage in ILC2. Linking lipid metabolism pathways to ILC2 phenotypes and effector functions is critical for the assessment of novel pharmaceutical strategies to regulate ILC2 functions in type 2 immunopathologies.
Implementing a group singing intervention for postpartum depression within the Italian health service
Authors: Lega Ilaria , Luzi Ilaria , Mastroeni Simona , Ferraro Claudia , Andreozzi Silvia , Donati Serena , Grussu Pietro , Cavazzana Valentina , Proietti Patrizia , Magliocchetti Patrizia , Monaldi Chiara , Biglia Cristina , Oreggia Rossana , Seia Catterina , Smith Calum , Warran Katey , Fietje Nils ,   The Italy and GLOBUS Music and Motherhood Groups
Published: October 2024

Background

In the United Kingdom a singing intervention for Postpartum Depression (PPD) titled “Music and Motherhood” was found to be effective. The World Health Organization Regional Office for Europe coordinated a study to assess the feasibility of implementing and adapting the intervention in other countries. In Italy, recent studies have highlighted the need to promote the availability of effective interventions for PPD in primary care.

Aim

To describe the implementation of “Music and Motherhood” within the Italian primary care services dedicated to pregnancy and postnatal care in three different geographical locations, thus providing an example of strategies for implementing an arts and health intervention in primary care that can improve health and well-being.

Methods

A 10-week group singing intervention for mothers with PPD was conducted as part of a single arm feasibility study. Data were collected through one-to-one interviews, focus groups and questionnaires from the professionals involved in the implementation and selected participating mothers. A conceptual framework including acceptability, appropriateness, feasibility, fidelity, implementation process, costs and sustainability was adopted for analysis. Number of sessions attended by mothers and implementation outcome measures for acceptability, appropriateness and feasibility, each consisting of four items rated on a 5-point Likert scale were also gathered.

Results

The intervention was found to be inclusive of women from different socio-cultural backgrounds and appropriate to the context. The group setting and the use of an arts-based intervention helped to de-medicalise the process of care maximising resources. Singing helped mothers to express their feelings and find strategies to improve interaction with their child. Attention to mothers’ needs and the co-presence of the professional singing leader and a health professional were among the key factors. The median number of sessions attended was nine out of 10. In terms of acceptability, almost 90% of the professionals were in complete agreement that they liked and approved the intervention.

Conclusion

Our study adds to the evidence that an arts and health intervention proven effective in one culture and linguistic context can be adapted to another. Collaboration among health professionals and artists in the implementation process and adequate funding are instrumental in moving from project to programme level.
Case report: Two-step lamellar keratoplasty for alkali burns
Authors: Fang Xie , Xie Zhiwen , Luo Shunrong , Xiao Xianwen , Yang Zhengwei , Lin Yuan , Wu Huping
Published: October 2024

Purpose

To report a case of a patient with ocular surface alkali burn who developed corneal perforation before entering a stable phase. This patient was treated with a custom-designed lamellar graft using a Two-Step lamellar keratoplasty (LK) after 3 months alkali burn.

Methods

This study was a case report.

Results

A 43-year-old male patient who presented with redness, pain, and decreased vision in his left eye following lime exposure. Initial treatment involved amniotic membrane transplantation and anterior chamber irrigation. However, the patient subsequently developed corneal infiltration and progressive thinning. The patient refused the corneal transplantation and ultimately underwent tarsorrhaphy. Twenty days postoperatively, the patient experienced sudden ocular pain and central corneal perforation. Considering the potential complications of conventional corneal transplantation, including stem cell deficiency, graft dissolution, and rejection, a personalized Two-Step LK was devised. Following this procedure, the patient’s vision gradually improved to 20/133 (without correction), with a good corneal condition but mild epithelial defects and edema. At the 8-month follow-up, subepithelial corneal haze was observed, but uncorrected visual acuity remained stable at 20/133 and best corrected visual acuity was up to 20/66.

Conclusion

For patients with ocular surface alkali burns who experience persistent disease progression despite early and mid-stage aggressive interventions, this study is the first to report on the use of a Two-Step LK. This approach takes into account both the “soil” factors that may lead to graft dissolution and the “seed” factors related to recipient stem cell deficiency. The results in preventing graft dissolution and maintaining postoperative corneal function are encouraging.
A prototype photoplethysmography-based cuffless device shows promising results in tracking changes in blood pressure
Authors: Hove Christine , Sæter Frode Wirum , Stepanov Alexey , Bøtker-Rasmussen Kasper Gade , Seeberg Trine M. , Westgaard Espen , Heimark Sondre , Waldum-Grevbo Bård , Hisdal Jonny , Larstorp Anne Cecilie K.
Published: October 2024

Introduction

Non-invasive cuffless blood pressure devices have shown promising results in accurately estimating blood pressure when comparing measurements at rest. However, none of commercially available or prototype cuffless devices have yet been validated according to the appropriate standards. The aim of the present study was to bridge this gap and evaluate the ability of a prototype cuffless device, developed by Aidee Health AS, to track changes in blood pressure compared to a non-invasive, continuous blood pressure monitor (Human NIBP or Nexfin) in a laboratory set up. The performance was evaluated according to the metrics and statistical methodology described in the ISO 81060-3:2022 standard. However, the present study is not a validation study and thus the study was not conducted according to the ISO 81060-3:2022 protocol, e.g., non-invasive reference and distribution of age not fulfilled.

Method

Data were sampled continuously, beat-to-beat, from both the cuffless and the reference device. The cuffless device was calibrated once using the reference BP measurement. Three different techniques (isometric exercise, mental stress, and cold pressor test) were used to induce blood pressure changes in 38 healthy adults.

Results

The mean difference (standard deviation) was 0.3 (8.7) mmHg for systolic blood pressure, 0.04 (6.6) mmHg for diastolic blood pressure, and 0.8 (7.9) mmHg for mean arterial pressure, meeting the Accuracy requirement of ISO 81060-3:2022 (≤6.0 (10.0) mmHg). The corresponding results for the Stability criteria were 1.9 (9.2) mmHg, 2.9 (8.1) mmHg and 2.5 (9.5) mmHg. The acceptance criteria for the Change requirement were achieved for the 85th percentile of ≤50% error for diastolic blood pressure and mean arterial pressure but were higher than the limit for systolic blood pressure (56% vs. ≤50%) and for all parameters for the 50th percentile (32%–39% vs. ≤25%).

Conclusions

The present study demonstrated that the cuffless device could track blood pressure changes in healthy adults across different activities and showed promising results in achieving the acceptance criteria from ISO 81060-3:2022.
Adaptation of rhizobacterial and endophytic communities in Citrus Grandis Exocarpium to long-term organic and chemical fertilization
Authors: Zhou Deyang , Yang Kaiqing , Zhang Yinhui , Liu Cancan , He Ye , Tan Jialin , Ruan Zhepu , Qiu Rongliang
Published: October 2024

Introduction

Organic fertilizers (OF) are crucial for enhancing soil quality and fostering plant growth, offering a more eco-friendly and enduring solution compared to chemical fertilizers (CF). However, few studies have systematically analyzed the effects of OF/CF on root microbiome of medicinal plants, especially in combination with active ingredients.

Methods

In this study, we investigated the composition and function of bacteria and fungi in the rhizosphere or within the root of traditional Chinese medicinal plants, Citri Grandis Exocarpium (Huajuhong), which were treated with OF or CF over 1, 3, and 5 years (starting from 2018). Additionally, we conducted metabolome analysis to evaluate the effects of different fertilizers on the medicinal properties of Huajuhong.

Results

The results indicated that extended fertilization could enhance the microbial population and function in plant roots. Notably, OF demonstrated a stronger influence on bacteria, whereas CF enhanced the cohesion of fungal networks and the number of fungal functional enzymes, and even potentially reduced the proliferation of harmful rhizosphere pathogens. By adopting distancebased redundancy analysis, we identified the key physicochemical characteristics that significantly influence the distribution of endophytes, particularly in the case of OF. In contrast, CF was found to exert a more pronounced impact on the composition of the rhizosphere microbiome. Although the application of OF resulted in a broader spectrum of compounds in Huajuhong peel, CF proved to be more efficacious in elevating the concentrations of flavonoids and polysaccharides in the fruit.

Discussion

Consequently, the effects of long-term application of OF or CF on medicinal plants is different in many ways. This research provides a guide for OF/CF selection from the perspective of soil microecology and aids us to critically assess and understand the effects of both fertilizers on the soil environment, and promotes sustainable development of organic agriculture.
Structural and functional insights from the sequences and complex domain architecture of adhesin-like proteins from Methanobrevibacter smithii and Methanosphaera stadtmanae
Authors: Gupta Anjali Bansal , Seedorf Henning
Published: October 2024

Methanogenic archaea, or methanogens, are crucial in guts and rumens, consuming hydrogen, carbon dioxide, and other fermentation products. While their molecular interactions with other microorganisms are not fully understood, genomic sequences provide information. The first genome sequences of human gut methanogens, Methanosphaera stadtmanae and Methanobrevibacter smithii, revealed genes encoding adhesin-like proteins (ALPs). These proteins were also found in other gut and rumen methanogens, but their characteristics and functions remain largely unknown. This study analyzes the ALP repertoire of M. stadtmanae and M. smithii using AI-guided protein structure predictions of unique ALP domains. Both genomes encode more than 40 ALPs each, comprising over 10% of their genomes. ALPs contain repetitive sequences, many of which are unmatched in protein domain databases. We present unique sequence signatures of conserved ABD repeats in ALPs and propose a classification based on domain architecture. Our study offers insights into ALP features and how methanogens may interact with other microorganisms.
Improving plant salt tolerance through Algoriphagus halophytocola sp. nov., isolated from the halophyte Salicornia europaea
Authors: Peng Yuxin , Cho Dong Hyun , Humaira Zalfa , Park Yu Lim , Kim Ki Hyun , Kim Cha Young , Lee Jiyoung
Published: October 2024

Salicornia europaea, commonly known as glasswort, thrives in reclaimed land and coastal areas with high salinity, demonstrating remarkable adaptation to the arid conditions of such environments. Two aerobic, Gram-stain-negative, non-motile, rod-shaped bacterial strains, designated TR-M5T and TR-M9, were isolated from the root of Salicornia europaea plants. These bacteria exhibit plant growth-promoting and salt tolerance-enhancing abilities, which have not been reported in other species of the genus. Both strains produce indole-3-acetic acid (IAA), a plant growth hormone, and synthesize proline, which functions as an osmoprotectant. Additionally, they possess gelatinase and cellulase activities. Cells grow in temperatures from 4 to 42°C (optimum 25°C), pH levels from 6.0 to 9.0 (optimum 7.0), and NaCl concentrations from 0 to 8.0% (optimum 6.0%). The average nucleotide identity and digital DNA–DNA hybridization values of strain TR-M5T with the most closely related type strains for which whole genomes are publicly available were 74.05–77.78% and 18.6–23.1%, respectively. Phylogenetic analysis of their 16S rRNA gene sequences revealed that strains TR-M5T and TR-M9 belong to the genus Algoriphagus. A. locisalis exhibited the highest similarity, sharing a sequence identity of 98.1%. The genomes of TR-M5T and TR-M9 exhibit a G + C content of 43 mol%. This study specifically focuses on the identification and characterization of strain TR-M5T as a novel species within the genus Algoriphagus, which we propose to name Algoriphagus halophytocola sp. nov., highlighting its potential role in enhancing plant growth and salt tolerance in saline environments. The type strain is TR-M5T (KCTC 92720T = GDMCC 1.3797T).
Lymphocystis viral disease impacts the diversity and functional profiles of the skin microbiome in gilthead seabream
Authors: Xavier Raquel , Pérez-Losada Marcos , Silva Sofia Marques , Lino Marilia , Faleiro Maria João , Canada Paula
Published: October 2024

Lymphocystis viral disease (LVD) is a highly transmissible disease known to affect multiple fishes worldwide. Although this disease is usually benign, mortalities can occur in cases where infection is severe or secondary infection with bacterial pathogens and parasites occur. However, little is known about the bacterial dynamics of fish with LVD or what bacterial pathogens may be responsible for secondary infections. Here we assessed the effects of LVD on the skin microbiome of gilthead seabream by comparing 30 symptomatic, asymptomatic and recovered (three weeks after infection) fish using 16S rRNA high-throughput sequencing. Our results show that LVD is associated with significant changes in microbiome structure and function. Importantly, fish pathogens like Tenacibaculum maritimum and some Vibrio species increased their abundance. Moreover, microbial metabolic activities of the commensal microbiota that may confer some protection to fish were suppressed in diseased fish. After reducing fish cage density to treat symptoms and three weeks of recovery, the abundance of pathogens was significantly reduced and microbiome functionality was recovered, although community structure remained significantly different. These results show that LVD can severely disrupt the bacterial communities of the skin of the gilthead seabream, leading to an increase in bacterial pathogens responsible for relevant diseases in gilthead seabream farms.
The impact of antibiotic induction on virulence and antibiotic resistance in Klebsiella pneumoniae: a comparative study of CSKP and CRKP strains
Authors: Chen Ke-Da , Chen Wei , Zhang Qian , Li Qingcao
Published: October 2024

Background

Klebsiella pneumoniae is an opportunistic pathogen causing nosocomial infections, classified into carbapenem-sensitive and carbapenem-resistant strains. Understanding the virulence factors and antibiotic resistance of these strains is essential for effective clinical management.

Objective

This study compared the virulence genes and antibiotic resistance profiles of 50 CSKP and 50 CRKP strains, examining their expression under antibiotic pressure and the mechanisms contributing to their pathogenicity.

Methods

Virulence genes (rmpA, rmpA2, iucA, iutA, Peg-344, ybts, iroB) were detected in both strains using polymerase chain reaction (PCR). Antibiotic susceptibility testing established minimum inhibitory concentrations (MICs) for key antibiotics. Gene expression analysis was performed with quantitative reverse transcription PCR (qRT-PCR) after 10 days of antibiotic exposure.

Results

CSKP strains exhibited significantly higher positivity rates for virulence genes compared to CRKP strains. CRKP strains predominantly expressed resistance genes KPC, SHV, and CTX-M3, whereas no resistance genes were found in CSKP. Antibiotic susceptibility tests showed increased MICs, particularly for ciprofloxacin and imipenem, following antibiotic induction. CSKP demonstrated elevated expression of rmpA and rmpA2, while CRKP showed increased expression of SHV, and KPC after antibiotic exposure.

Conclusion

This study highlights the intricate relationship between virulence and resistance in Klebsiella pneumoniae. CSKP strains show strong virulence factor expression, while CRKP strains adapt to antibiotic pressure through altered gene expression patterns. These findings underscore the urgent need for continuous surveillance and innovative therapeutic strategies to combat multidrug-resistant Klebsiella pneumoniae infections.
Post-stroke fatigue and its correlation with family functioning in patients who have experienced a first episode of stroke
Authors: Zhu Ruhuang , Huang Haiping , Yu Yueting , Bao Shaorui , Lin Na , Shu Meichun
Published: October 2024

Objective

This study aimed to analyse the relevant factors that may affect post-stroke fatigue (PSF) in patients with stroke and further explore the correlation between family functioning and PSF.

Methods

Patients who had experienced a first episode of stroke and were admitted to the Department of Neurology of the First Affiliated Hospital of Wenzhou Medical University were rigorously screened. The general data and family functioning of the patients on admission were collected, and their family adaptation, partnership, growth, affection and resolve scores and their PSF on the 5th day of admission were collected using the fatigue severity scale (FSS). Multiple linear regression analysis was then utilized to explore the factors affecting PSF in patients with stroke.

Results

A total of 220 questionnaires were distributed, and 220 were returned, with 212 valid questionnaires and a valid return rate of 96.4%. These 212 patients had a family functioning score of 6.58 ± 2.00 and an FSS score of 36.62 ± 10.96. Spearman’s correlation analysis showed negative correlations between the FSS scores and the adaptation, partnership, growth, affection, resolve and family functioning scores (r = −0.380, −0.505, −0.470, −0.303, −0.281 and −0.712, respectively; p < 0.001). Furthermore, multiple linear regression analysis showed that family functioning (β′ = −0.516), marital status (β′ = −0.244), household income (β′ = −0.185), literacy (β′ = −0.181) and activities of daily living (β′ = −0.084) were influential factors for PSF in patients with stroke (p < 0.05).

Conclusion

There is a significant negative correlation between family functioning and PSF, suggesting that better family functioning may help mitigate the severity of post-stroke fatigue. Healthcare providers should identify interventions to help patients and families address fatigue, boost disease recovery, promote patients’ physical and mental health and improve their quality of life.
Data-centric automated approach to predict autism spectrum disorder based on selective features and explainable artificial intelligence
Authors: Aldrees Asma , Ojo Stephen , Wanliss James , Umer Muhammad , Khan Muhammad Attique , Alabdullah Bayan , Alsubai Shtwai , Innab Nisreen
Published: October 2024

Autism spectrum disorder (ASD) is a neurodevelopmental condition marked by notable challenges in cognitive function, understanding language, recognizing objects, interacting with others, and communicating effectively. Its origins are mainly genetic, and identifying it early and intervening promptly can reduce the necessity for extensive medical treatments and lengthy diagnostic procedures for those impacted by ASD. This research is designed with two types of experimentation for ASD analysis. In the first set of experiments, authors utilized three feature engineering techniques (Chi-square, backward feature elimination, and PCA) with multiple machine learning models for autism presence prediction in toddlers. The proposed XGBoost 2.0 obtained 99% accuracy, F1 score, and recall with 98% precision with chi-square significant features. In the second scenario, main focus shifts to identifying tailored educational methods for children with ASD through the assessment of their behavioral, verbal, and physical responses. Again, the proposed approach performs well with 99% accuracy, F1 score, recall, and precision. In this research, cross-validation technique is also implemented to check the stability of the proposed model along with the comparison of previously published research works to show the significance of the proposed model. This study aims to develop personalized educational strategies for individuals with ASD using machine learning techniques to meet their specific needs better.
Cost-effectiveness of tax policies on promoting sustainable diets in Iran: a modeling study
Authors: Mokari-Yamchi Amin , Omidvar Nasrin , Karami Manoochehr , Tahamipour Zarandi Morteza , Eini-Zinab Hassan
Published: October 2024

Background

Implementation of food taxes may promote sustainable diets in a society. This study estimates the potential short-term impacts of taxes on sugar and sweets (SAS), sugar sweetened beverages (SSB) and hydrogenated oil and animal fats (HOAF) in Iran through a social cost-effectiveness analysis.

Methods

In this study, three tax scenarios were evaluated, including a 25% tax on SASs, a 30% tax on SSBs, and a 30% tax on HOAFs. The data from Iran’s 2019–2020 Household Income and Expenditure Survey (HIES) were utilized, and a simulated population of 1 million individuals aged over 25 years was analyzed. Population impact fraction (PIF) was calculated to estimate the averted number of cases and Disability-Adjusted Life Years (DALYs) under each policy scenario. Additionally, the study assessed water and carbon footprints, as well as all associated costs. Cost-effectiveness was evaluated through incremental cost-effectiveness ratios (ICER) and comparison with WHO-recommended thresholds.

Results

Implementation of taxes on SASs and HOAFs resulted in reductions of 1.09 and 1.08% in water footprint, as well as 0.47 and 1.05% in carbon footprint, respectively. In terms of population health, the interventions resulted in averting 343.92 DALYs (95% UI = 318.62–369.36) for the SSB tax and 1219.01 DALYs (95% UI = 1123.05–1315.77) for the tax on HOAFs. Additionally, the tax on SASs averted 1028.09 DALYs (95% UI = 947.16–1,109). All scenarios were deemed cost-effective based on the WHO threshold for ICER, with values of 0.26 billion Rials/DALY, 0.54 billion Rials/DALY, and 0.17 billion Rials/DALY, respectively.

Conclusion

The studied tax scenarios could generate substantial health gains and be cost-effective in Iran. It is recommended that policymakers consider implementing such price policies to promote healthy and sustainable diets.
Association of dietary live microbe intake with kidney stone disease in US adults: a real-world cross-sectional study
Authors: Zheng Zhongyi , Cao Xiaoming
Published: October 2024

Background

Kidney stone disease (KSD) is a common urological condition linked with hypertension, chronic kidney disease, and other health issues. Although the gut microbiome has a notable association with KSD formation, the relationship between dietary live microbes and KSD risk remains underexplored.

Methods

This study utilized data from the NHANES surveys conducted between 2007 and 2016 to analyze the association between dietary live microbe intake and KSD. Dietary intake data were obtained through 24-h dietary recall interviews conducted by trained professionals. Participants were categorized into three groups based on Sanders’ classification system of dietary live microbe intake: low, medium, and high. The intake levels were determined by estimating the live microbe content in foods. Weighted logistic regression analysis was employed to account for the complex survey design and to assess the impact of different levels of live microbe intake on KSD risk.

Results

A total of 20,380 participants were included in the study. Participants with low, medium, and high dietary microbe intake represented 33, 39, and 28% of the cohort, respectively. The adjusted odds ratios (ORs) for KSD were 0.78 (95% CI, 0.65–0.93) in the high dietary live microbe group compared to the low group (p < 0.05). Subgroup analyses revealed no significant interactions between dietary live microbe intake and gender, age, BMI, hypertension, or diabetes status.

Conclusion

Higher dietary live microbe intake group may be associated with a reduced risk of KSD. Further prospective studies are necessary to validate these findings and to elucidate the specific mechanisms and optimal intake levels of dietary microbes.