bluuebunny/crossref_metadata_2025 huggingface dataset:
Alternative splicing of pre-mRNA modulates the immune response in Holstein cattle naturally infected with Mycobacterium avium subsp. paratuberculosis
Authors: Badia-Bringué Gerard , Lavín José Luis , Casais Rosa , Alonso-Hearn Marta
Published: March 2024

Little is known about the role of alternative splicing (AS) in regulating gene expression in Mycobacteria-infected individuals in distinct stages of infection. Pre-mRNA AS consists of the removal of introns and the assembly of exons contained in eukaryotic genes. AS events can influence transcript stability or structure with important physiological consequences. Using RNA-Seq data from peripheral blood (PB) and ileocecal valve (ICV) samples collected from Holstein cattle with focal and diffuse paratuberculosis (PTB)-associated histopathological lesions in gut tissues and without lesions (controls), we detected differential AS profiles between the infected and control groups. Four of the identified AS events were experimentally validated by reverse transcription-digital droplet PCR (RT-ddPCR). AS events in several genes correlated with changes in gene expression. In the ICV of animals with diffuse lesions, for instance, alternatively spliced genes correlated with changes in the expression of genes involved in endocytosis, antigen processing and presentation, complement activation, and several inflammatory and autoimmune diseases in humans. Taken together, our results identified common mechanisms of AS involvement in the pathogenesis of PTB and human diseases and shed light on novel diagnostic and therapeutic interventions to control these diseases.
Neoadjuvant systemic therapy for hepatocellular carcinoma
Authors: Chick R. Connor , Ruff Samantha M. , Pawlik Timothy M.
Published: March 2024

Surgical resection and liver transplant remain the only curative therapies for most patients with hepatocellular carcinoma (HCC). Systemic therapy options have typically been ineffective, but recent advances, such as the combination of immune checkpoint inhibitors and targeted therapies, have shown great promise. Neoadjuvant systemic therapy in resectable or locally advanced HCC is under active investigation with encouraging results in small, early-phase trials. Many of these completed and ongoing trials include combinations of systemic therapy (e.g. immune checkpoint inhibitors, tyrosine kinase inhibitors), transarterial therapies, and radiation. Despite early successes, larger trials with evaluation of long-term oncologic outcomes are needed to determine the role of neoadjuvant systemic therapy in patients with HCC who may be eligible for curative intent surgery or transplant.
Extracellular vesicle-mediated pre-metastatic niche formation via altering host microenvironments
Authors: Li Ying , Zheng Yan , Tan Xiaojie , Du Yongxing , Wei Yingxin , Liu Shanglong
Published: March 2024

The disordered growth, invasion and metastasis of cancer are mainly attributed to bidirectional cell-cell interactions. Extracellular vesicles (EVs) secreted by cancer cells are involved in orchestrating the formation of pre-metastatic niches (PMNs). Tumor-derived EVs mediate bidirectional communication between tumor and stromal cells in local and distant microenvironments. EVs carrying mRNAs, small RNAs, microRNAs, DNA fragments, proteins and metabolites determine metastatic organotropism, enhance angiogenesis, modulate stroma cell phenotypes, restructure the extracellular matrix, induce immunosuppression and modify the metabolic environment of organs. Evidence indicates that EVs educate stromal cells in secondary sites to establish metastasis-supportive microenvironments for seeding tumor cells. In this review, we provide a comprehensive overview of PMN formation and the underlying mechanisms mediated by EVs. Potential approaches to inhibit cancer metastasis by inhibiting the formation of PMNs are also presented.
Review on structural optimization techniques for additively manufactured implantable medical devices
Authors: Peto Marinela , García-Ávila Josué , Rodriguez Ciro A. , Siller Héctor R. , da Silva Jorge Vicente Lopes , Ramírez-Cedillo Erick
Published: March 2024

Recent developments in additive manufacturing (AM) have led to significant opportunities in the design and fabrication of implantable medical devices due to the advantages that AM offers compared to conventional manufacturing, such as high customizability, the ability to fabricate highly complex shapes, good dimensional accuracy, a clean build environment, and reduced material usage. The study of structural design optimization (SDO) involves techniques such as Topology Optimization (TO), Shape Optimization (SHO), and Size Optimization (SO) that determine specific parameters to achieve the best measurable performance in a defined design space under a given set of loads and constraints. Integration of SDO techniques with AM leads to utmost benefits in designing and fabricating optimized implantable medical devices with enhanced functional performance. Research and development of various lattice structures represents a powerful method for unleashing the full potential of additive manufacturing (AM) technologies in creating medical implants with improved surface roughness, biocompatibility, and mechanical properties. Furthermore, the integration of artificial intelligence (AI) and machine learning (ML) in structural optimization has expanded opportunities to improve device performance, adaptability, and durability. The review is meticulously divided into two main sections, reflecting the predictability of the implant’s internal structure: (a) unpredictable interior topology, which explores topology-based optimization techniques, and (b) predictable inner topology, concentrating on lattice structures. The analysis of the reviewed literature highlights a common focus on addressing issues such as stress shielding, osseointegration enhancement, customization to individual needs, programmable functionalities, and weight reduction in implant designs. It emphasizes significant advances in reducing stress shielding effects, promoting osseointegration, and facilitating personalized implant creation. The review provides a detailed classification of optimization methods, with each approach scrutinized for its unique contribution to overcoming specific challenges in medical implant design, thus leading to more advanced, effective, and patient-oriented implantable devices.
Prognostic analysis of high-flow nasal cannula therapy and non-invasive ventilation in mild to moderate hypoxemia patients and construction of a machine learning model for 48-h intubation prediction—a retrospective analysis of the MIMIC database
Authors: Fu Wei , Liu Xiaoqing , Guan Lili , Lin Zhimin , He Zhenfeng , Niu Jianyi , Huang Qiaoyun , Liu Qi , Chen Rongchang
Published: March 2024

Background

This study aims to investigate the clinical outcome between high-flow nasal cannula (HFNC) and non-invasive ventilation (NIV) therapy in mild to moderate hypoxemic patients on the first ICU day and to develop a predictive model of 48-h intubation.

Methods

The study included adult patients from the MIMIC III and IV databases who first initiated HFNC or NIV therapy due to mild to moderate hypoxemia (100 < PaO2/FiO2 ≤ 300). The 48-h and 30-day intubation rates were compared using cross-sectional and survival analysis. Nine machine learning and six ensemble algorithms were deployed to construct the 48-h intubation predictive models, of which the optimal model was determined by its prediction accuracy. The top 10 risk and protective factors were identified using the Shapley interpretation algorithm.

Result

A total of 123,042 patients were screened, of which, 673 were from the MIMIC IV database for ventilation therapy comparison (HFNC n = 363, NIV n = 310) and 48-h intubation predictive model construction (training dataset n = 471, internal validation set n = 202) and 408 were from the MIMIC III database for external validation. The NIV group had a lower intubation rate (23.1% vs. 16.1%, p = 0.001), ICU 28-day mortality (18.5% vs. 11.6%, p = 0.014), and in-hospital mortality (19.6% vs. 11.9%, p = 0.007) compared to the HFNC group. Survival analysis showed that the total and 48-h intubation rates were not significantly different. The ensemble AdaBoost decision tree model (internal and external validation set AUROC 0.878, 0.726) had the best predictive accuracy performance. The model Shapley algorithm showed Sequential Organ Failure Assessment (SOFA), acute physiology scores (APSIII), the minimum and maximum lactate value as risk factors for early failure and age, the maximum PaCO2 and PH value, Glasgow Coma Scale (GCS), the minimum PaO2/FiO2 ratio, and PaO2 value as protective factors.

Conclusion

NIV was associated with lower intubation rate and ICU 28-day and in-hospital mortality. Further survival analysis reinforced that the effect of NIV on the intubation rate might partly be attributed to the other impact factors. The ensemble AdaBoost decision tree model may assist clinicians in making clinical decisions, and early organ function support to improve patients’ SOFA, APSIII, GCS, PaCO2, PaO2, PH, PaO2/FiO2 ratio, and lactate values can reduce the early failure rate and improve patient prognosis.
Modulation of growth, microcystin production, and algal-bacterial interactions of the bloom-forming algae Microcystis aeruginosa by a novel bacterium recovered from its phycosphere
Authors: Xiao Yao , Du Mijia , Deng Yang , Deng Qinglin , Wang Xin , Yang Yiwen , Zhang Binghuo , Zhang Yu-Qin
Published: March 2024

Harmful algal blooms (HABs) in natural waters are of escalating global concern due to their detrimental impact on environmental health. Emerging evidence indicates that algae-bacteria symbionts can affect HAB features, though much about this interplay remains largely unexplored. The current study isolated a new species of Mucilaginibacter (type strain JXJ CY 39T) from culture biomass of the bloom-causing Microcystis aeruginosa FACHB-905 (Maf) from Lake Dianchi, China. Strain JXJ CY 39T was an aerobic, Gram-stain-negative rod bacterium that grew at 5–38°C, pH 4.0–11.0, and 0–3.0% NaCl. Taxonomic evaluation proposed a new species, with Mucilaginibacter lacusdianchii sp. nov., as the species epithet. Experimental results revealed that strain JXJ CY 39T spurred the growth of Maf by supplying soluble phosphorus and nitrogen during cultivation, despite the unavailability of soluble phosphorus and nitrogen. Additionally, by producing the plant hormone indole-3-acetate, strain JXJ CY 39T possibly impacted Maf’s functionality. Results from co-culture experiments with other strains from Maf biomass showed possible effects of strain JXJ CY 39T on the relationship between Maf and other cohabiting bacteria, as well as microcystin toxin production characteristics. Although Maf could foster the growth of strain JXJ CY 39T by supplying organic carbon, the strain’s growth could be regulated via specific chemical compounds based on antibiotic assays. Community composition analysis disclosed that this Mucilaginibacter strain positively affected Maf’s growth and modified densities and types of bacteria linked to Maf. Overall, these results suggest that the interactions between important HAB-causing organisms and their attached bacteria are complex, dynamic, and may influence the growth characteristics of algae.
Macrolide resistance in Mannheimia haemolytica isolates associated with bovine respiratory disease from the German national resistance monitoring program GERM-Vet 2009 to 2020
Authors: Kostova Valeria , Hanke Dennis , Kaspar Heike , Fiedler Stefan , Schwarz Stefan , Krüger-Haker Henrike
Published: March 2024

Data collected from the German national resistance monitoring program GERM-Vet showed slowly increasing prevalence of macrolide resistance among bovine respiratory disease (BRD)-associated Pasteurellacae from cattle over the last decade. The focus of this study was to analyze the genetic basis of antimicrobial resistance (AMR) and the prevalence of multidrug-resistance (MDR)-mediating integrative and conjugative elements (ICEs) in 13 German BRD-associated Mannheimia haemolytica isolates collected between 2009 and 2020 via whole-genome sequencing. Antimicrobial susceptibility testing (AST) was performed via broth microdilution according to the recommendations of the Clinical and Laboratory Standards Institute for the macrolides erythromycin, tilmicosin, tulathromycin, gamithromycin, tildipirosin, and tylosin as well as 25 other antimicrobial agents. All isolates either had elevated MICs or were resistant to at least one of the macrolides tested. Analysis of whole-genome sequences obtained by hybrid assembly of Illumina MiSeq and Oxford Nanopore MinION reads revealed the presence of seven novel Tn7406-like ICEs, designated Tn7694, and Tn7724- Tn7729. These ICEs harbored the antimicrobial resistance genes erm(T), mef (C), mph(G), floR, catA3, aad(3“)(9), aph(3‘)-Ia, aac(3)-IIa, strA, strB, tet(Y), and sul2 in different combinations. In addition, mutational changes conferring resistance to macrolides, nalidixic acid or streptomycin, respectively, were detected among the M. haemolytica isolates. In addition, four isolates carried a 4,613-bp plasmid with the β-lactamase gene blaROB − 1. The detection of the macrolide resistance genes erm(T), mef (C), and mph(G) together with other resistance genes on MDR-mediating ICEs in bovine M. haemolytica may explain the occurrence of therapeutic failure when treating BRD with regularly used antimicrobial agents, such as phenicols, penicillins, tetracyclines, or macrolides. Finally, pathogen identification and subsequent AST is essential to ensure the efficacy of the antimicrobial agents applied to control BRD in cattle.
Streptomyces tagetis sp. nov., a chromomycin producing bacteria isolated from the roots of Tagetes patula
Authors: Chhetri Geeta , Kim Myeong Ji , Kim Inhyup , Tran Duc V. H. , Kim Young-Woo , Kim Hyun Woo , Seo Taegun
Published: March 2024

A novel halotolerant actinobacterium, designated as RG38T, capable of producing black extracellular melanin pigment on SP2 agar, was isolated from the roots of Tagetes patula. Comparative analysis of the 16S rRNA gene sequence revealed the highest similarity to Streptomyces collinus NBRC 12759T (99.3%). Phylogenetic analysis showed that strain RG38T clustered within the genus Streptomyces forming a monophyletic cluster with its close relatives. The average nucleotide identity (ANI), digital DNA–DNA hybridization (dDDH), and amino-acid identity (AAI) values between strain RG38T and related species within the genus Streptomyces were below the standard threshold for prokaryotic species delineation. The DNA G + C content of the strain RG38T was determined to be 73.3%. The genome size measured 7,150,598 bp comprising 17 contigs and encompassed 6,053 protein coding genes. AntiSMASH analysis of the whole genome revealed 35 putative biosynthetic gene clusters (BGCs) responsible for various secondary metabolites. Among these clusters, two gene clusters exhibited 100% similarity to the chromomycin A3, albaflavenone, and anthracimycin, respectively. These compounds were reported to possess significant anticancer and antibacterial activities. LC–MS-based analysis, coupled with further isolation studies, confirmed the production of chromomycins A2 (1), A3 (2), and their derivatives, along with their antibiotic activities. These findings underscore the potential of this novel strain as a novel resource for the discovery of diverse antimicrobial compounds. This study is the first to report an antimicrobial compound producing Streptomyces species isolated from medicinal plant T. patula. Based on a polyphasic study, the strain RG38T isolated from an unexplored habitat with a high potential for new natural products represents a novel species within the genus Streptomyces. Accordingly, we propose the name Streptomyces tagetis sp. nov. for this novel species, with the type strain is RG38T (=KCTC 49624T = TBRC 15113T).
Distinct microbiota assembly and functional patterns in disease-resistant and susceptible varieties of tobacco
Authors: Yang Luhua , Guo Yuan , Yang Hui , Li Shun , Zhang Yunzeng , Gao Cheng , Wei Tian , Hao Likai
Published: March 2024

The plant microbiota is believed to be an accessory genome that extends plant functions, forming holobionts together with the host plant. Plant disease resistance, therefore, is inextricably linked with plant microbiota, which play important roles in plant growth and health. To explore the relationship between plant microbiota and disease resistance, we investigated the tobacco microbiome of two varieties with contrasting disease-resistance levels to bacterial wilt and black shank diseases. Comparative microbiome analysis indicated that the resistant variety assembled a distinct microbiota with higher network complexity and diversity. While Pseudomonas and Ensifer, which contain biocontrol and beneficial members, were enriched in the rhizosphere of the resistant variety, Ralstonia, a genus including the known causative pathogen, was enriched in the susceptible variety. Metagenome sequencing revealed that biocontrol functions, such as hydrogen cyanide synthase, pyochelin biosynthesis, and arthrofactin-type cyclic lipopeptide synthetase, were more abundant in the resistant variety. Further analysis indicated that contigs encoding the corresponding genes were mostly assigned to Pseudomonas. Among all the metagenome-assembled genomes, positive selection was suggested in the genome assigned to Pseudomonas only in the rhizosphere of the resistant variety. The search of biosynthetic gene clusters in the Pseudomonas genome revealed a non-ribosomal peptide synthetase, the compound of which was brabantamide A, with known antimicrobial activity. Collectively, our study suggests that the plant microbiota might be involved in microbe-mediated disease resistance. Particularly, our results highlight Pseudomonas in the rhizosphere of the disease-resistant variety as a promising biocontrol candidate. Our study may facilitate further screening of bacterial isolates and the targeted design of microbial communities.
Elastic modulus of cadaveric acetabular labrum correlates with ultrashort echo time (UTE) apparent spin-spin (T2*) and spin-lattice (T1) relaxation times
Authors: Moazamian Dina , Hananouchi Takehito , Shaterian Mohammadi Hamidreza , Tayarani Alireza , Dorthé Erik W. , D'lima Darryl , Jerban Saeed
Published: March 2024

Introduction

The acetabulum labrum plays a critical role in hip function. Medical imaging techniques for measuring changes in labral properties due to its degeneration may help improve our knowledge of its role in hip osteoarthritis (OA). This study aimed to explore the correlation between the mechanical properties of the acetabulum labrum and ultrashort echo time (UTE) MRI properties.

Material and method

Acetabular labrum specimens were dissected from 12 fresh-frozen human cadaveric hip joints (64.6 ± 11.6 years old at the time of death, 7 female). UTE Cones sequences were used to measure apparent spin-spin (T2*) and spin-lattice (T1) relaxation times using a knee coil at 3 T in a clinical MR scanner. The stiffness and the elastic modulus (E) of the specimens were measured before MRI scans using uniaxial tensile tests. Spearman's rank correlation coefficients of Tendons' UTE-T2* and -T1 with their mechanical properties were calculated.

Results

The human labrum specimen elastic modulus showed a significant inverse correlation with UTE-T2* (R = −0.66, P < 0.01) and with UTE-T1 (R = −0.56, P = 0.05). The stiffness of the specimens showed significant inverse correlations with UTE-T2* (R = −0.53, P = 0.01) and UTE-T1 (R = −0.63, P = 0.02).

Conclusion

This study highlighted the potential of UTE-MRI techniques for the mechanical assessment of the acetabular labrum. UTE-MRI may improve labrum degeneration detection and monitoring, which requires further investigations.
A narrative review on the application of artificial intelligence in renal ultrasound
Authors: Xu Tong , Zhang Xian-Ya , Yang Na , Jiang Fan , Chen Gong-Quan , Pan Xiao-Fang , Peng Yue-Xiang , Cui Xin-Wu
Published: March 2024

Kidney disease is a serious public health problem and various kidney diseases could progress to end-stage renal disease. The many complications of end-stage renal disease. have a significant impact on the physical and mental health of patients. Ultrasound can be the test of choice for evaluating the kidney and perirenal tissue as it is real-time, available and non-radioactive. To overcome substantial interobserver variability in renal ultrasound interpretation, artificial intelligence (AI) has the potential to be a new method to help radiologists make clinical decisions. This review introduces the applications of AI in renal ultrasound, including automatic segmentation of the kidney, measurement of the renal volume, prediction of the kidney function, diagnosis of the kidney diseases. The advantages and disadvantages of the applications will also be presented clinicians to conduct research. Additionally, the challenges and future perspectives of AI are discussed.
Acute urinary retention due to corpus cavernosum penile metastasis from lung adenocarcinoma after targeted therapy: a case report and review of the literature
Authors: Yan Wei , Fu Hui , Liu Huiqun , Liu Zhentian , Qi Xueliang , Chen Tanxiu
Published: March 2024

Background

Metastasis in penile corpus cavernosum from adenocarcinoma of lung is a rare but fatal disease, which was reported in cases without series studies. It causes various clinical symptoms seriously affecting the quality of life.

Case presentation

A 72-year-old male smoker patient, who had a history of adenocarcinoma of lung after targeted therapy 36 months before, was admitted to Jiangxi Cancer Hospital because of presenting with aggressive dysuria and penis pain for one hour. A Foley catheter was inserted into the patient’s bladder with difficulty. Immediately do a bladder puncture. Emergency pelvic computed tomography (CT): a soft tissue nodule of 1.1 cm×1.4 cm was found in the cavernous area of the middle part of the penis, and the proximal urethra was dilated with a wide diameter of about 1.5 cm. The diagnosis of metastatic lung adenocarcinoma from the primary was made by CT-guided biopsy.

Conclusion

The penis may be a site of metastasis from primary lung cancer, especially for old patient. Metastasis to the penis usually indicates that the primary lung cancer is at an advanced stage and the prognosis is very poor. More research is necessary to understand the underlying mechanism of adenocarcinoma of lung metastasis.
Long-term outcomes of liver transplantation for biliary atresia and results of policy changes: over 20 years of follow-up experience
Authors: Kwon Yiyoung , Ahn Yoon Ji , Yang Jaehun , Kim Eun Sil , Choe Yon Ho , Lee Sanghoon , Kim Mi Jin
Published: March 2024

Objective

Biliary atresia (BA) patients develop chronic liver disease after the Kasai operation and are eventually indicated for liver transplantation (LT). The purposes of this study were to analyze long-term outcomes after LT and risk factors that affect complications to reduce graft failure.

Study design

Overall, 145 pediatric patients who underwent LT between June 1996 and June 2020 after a diagnosis of BA were included. We performed a retrospective analysis of medical records and evaluated patient and graft survival, cumulative incidence of complications, risk factors, and the results of policy changes.

Results

Patient and graft survival rates in over 20 years were 95.8% and 91.0%, respectively. Post-transplantation lymphoproliferative disease was frequently observed in the early period of immunosuppression within the first 1–2 years after LT. The incidence of cholangitis and rejection steadily increased over time. Weight-to-portal vein size was evaluated as a risk factor for cholangitis and bile duct strictures (OR = 12.82, p = 0.006 and OR = 16.54, p = 0.015, respectively). When evaluated using 2013 as a reference point, the split graft indication was expanded and the group that received LT after 2013 had a significantly lower survival over time compared with that of the group that received LT before 2013 (p = 0.006).

Conclusion

This study revealed time differences in prevalence of complications. The evaluation of weight-to-duct or vessel size is a more important factor in considering complications than the graft-to-recipient weight ratio. Survival outcomes may have been altered by a policy change that affects the donor type ratio in transplantation.
Referent data for investigations of upper limb accelerometry: harmonized data from three cohorts of typically-developing children
Authors: Lang Catherine E. , Hoyt Catherine R. , Konrad Jeffrey D. , Bell Kayla R. , Marrus Natasha , Bland Marghuretta D. , Lohse Keith R. , Miller Allison E.
Published: March 2024

Aim

The rise of wearable sensing technology shows promise for addressing the challenges of measuring motor behavior in pediatric populations. The current pediatric wearable sensing literature is highly variable with respect to the number of sensors used, sensor placement, wearing time, and how data extracted from the sensors are analyzed. Many studies derive conceptually similar variables via different calculation methods, making it hard to compare across studies and clinical populations. In hopes of moving the field forward, this report provides referent upper limb wearable sensor data from accelerometers on 25 variables in typically-developing children, ages 3–17 years.

Methods

This is a secondary analysis of data from three pediatric cohorts of children 3–17 years of age. Participants (n = 222) in the cohorts wore bilateral wrist accelerometers for 2–4 days for a total of 622 recording days. Accelerometer data were reprocessed to compute 25 variables that quantified upper limb movement duration, intensity, symmetry, and complexity. Analyses examined the influence of hand dominance, age, gender, reliability, day-to-day stability, and the relationships between variables.

Results

The majority of variables were similar on the dominant and non-dominant sides, declined slightly with age, and were not different between boys and girls. ICC values were moderate to excellent. Variation within individuals across days generally ranged from 3% to 32%. A web-based R shiny object is available for data viewing.

Interpretation

With the use of wearable movement sensors increasing rapidly, these data provide key, referent information for researchers as they design studies, and analyze and interpret data from neurodevelopmental and other pediatric clinical populations. These data may be of particularly high value for pediatric rare diseases.
A pathway to strengthening open science: comments on the draft South African Ethics in Health Research Guidelines
Authors: Gooden Amy
Published: March 2024

The recently releaseddraft South African Ethics in Health Research Guidelines: Principles, Processes and Structures(Draft Guidelines) by the National Health Research Ethics Council recognize open data and provide guiding principles for this in the context of health research in South Africa. While its inclusion is a positive development, there is room for improvement. Although the Draft Guidelines leverage theDraft National Policy on Data and Cloud, it lacks incorporation of other relevant government policies, notably theDraft National Open Science Policy, and fails to sufficiently detail the principles of open science and open access. This limited scope and lack of comprehensive definition and detailed guidance present challenges for researchers in conducting ethical and responsible health research in South Africa. It constrains the Draft Guidelines from fully aligning with national imperatives and from fostering African-centric approaches. To address these issues, it is recommended that the Draft Guidelines integrate broader policies and principles, enhance clarity through comprehensive definitions, provide detailed guidance on open access, and promote African-centric approaches. Implementing these solutions will strengthen the Draft Guidelines, aligning them with national visions of open science, and thereby harnessing the full potential of South Africa’s diverse scientific community in advancing health research.
Chemico-pharmacological evaluation of the methanolic leaf extract of Catharanthus ovalis: GC–MS/MS, in vivo, in vitro, and in silico approaches
Authors: Shahriar Saimon , Shermin Samia Akter , Hasnat Hasin , Hossain Faisal , Han Aixia , Geng Peiwu , Alam Safaet , Mamun Abdullah Al
Published: March 2024

Introduction: Natural plant-based medicines have gained popularity recently as a major source of inventive, risk-free, and more potent secondary bioactive compounds with medicinal potential. Catharanthus ovalis is a perennial shrub containing various indole alkaloids cultivated extensively for local medical purposes.

Methods: This research is conducted to identify the phytocompounds present in the leaves of C. ovalis and its central and peripheral analgesic, thrombolytic, and membrane-stabilizing activities through tail immersion, acetic acid-induced writhing, human blood clot lysis, and erythrocyte lysis by heat and hypotonic solution methods, respectively.

Results and discussion: A total of 39 compounds were identified using GC–MS/MS techniques, including hexadecanoic acid, methyl ester (56.749%), methyl stearate (29.782%), carvacrol and its TBDMS derivative (12.586%), and 9-octadecenoic acid, methyl ester, (E)-] (9.297%) presented in high quantity. The highest tail immersion latency was observed for the 600 mg/kg extract of C. ovalis crude extract. Both 400 and 600 mg/kg doses of C. ovalis crude extract exhibited prominent peripheral analgesic activity. The maximum thrombolytic effect was observed by DCM soluble fraction extract by inhibiting 54.87% of the clot. However, the aqueous-soluble fraction of this extract manifested an excellent membrane-stabilizing effect by showing 73.98% and 87.51% hemolysis against heat- and hypotonic-induced hemolysis, respectively. Some of the compounds were identified as active agents against different receptors related to these diseases, which supported the findings of in vitro and in vivo tests.

Conclusion: Further investigation needs to be conducted to specify and identify the exact mechanism of action of these compounds.
Silencing of the PHLDA1 leads to global proteome changes and differentiation pathways of human neuroblastoma cells
Authors: Bugara Beata , Durbas Małgorzata , Kudrycka Maja , Malinowska Agata , Horwacik Irena , Rokita Hanna
Published: March 2024

Neuroblastoma (NB) is the most common extracranial pediatric solid tumor originating from the abnormal development of cells of the sympathoadrenal lineage of the neural crest. Targeting GD2 ganglioside (GD2), a glycolipid expressed on neuroblastoma cells, with GD2 ganglioside-recognizing antibodies affects several pivotal signaling routes that drive or influence the malignant phenotype of the cells. Previously performed gene expression profiling helped us to identify the PHLDA1 (pleckstrin homology-like domain family A member 1) gene as the most upregulated gene in the IMR-32 human neuroblastoma cells treated with the mouse 14G2a monoclonal antibody. Mass spectrometry-based proteomic analyses were applied to better characterize a role of PHLDA1 protein in the response of neuroblastoma cells to chimeric ch14.18/CHO antibody. Additionally, global protein expression profile analysis in the IMR-32 cell line with PHLDA1 silencing revealed the increase in biological functions of mitochondria, accompanied by differentiation-like phenotype of the cells. Moreover, mass spectrometry analysis of the proteins co-immunoprecipitated using anti-PHLDA1-specific antibody, selected a group of possible PHLDA1 binding partners. Also, a more detailed analysis suggested that PHLDA1 interacts with the DCAF7/AUTS2 complex, a key component of neuronal differentiation in vitro. Importantly, our results indicate that PHLDA1 silencing enhances the EGF receptor signaling pathway and combinatory treatment of gefitinib and ch14.18/CHO antibodies might be beneficial for neuroblastoma patients. Data are available via ProteomeXchange with the identifier PXD044319.
Spatiotemporal metabolic responses to water deficit stress in distinct leaf cell-types of poplar
Authors: Balasubramanian Vimal Kumar , Veličković Dušan , Rubio Wilhelmi Maria Del Mar , Anderton Christopher R. , Stewart C. Neal , DiFazio Stephen , Blumwald Eduardo , Ahkami Amir H.
Published: March 2024

The impact of water-deficit (WD) stress on plant metabolism has been predominantly studied at the whole tissue level. However, plant tissues are made of several distinct cell types with unique and differentiated functions, which limits whole tissue ‘omics’-based studies to determine only an averaged molecular signature arising from multiple cell types. Advancements in spatial omics technologies provide an opportunity to understand the molecular mechanisms underlying plant responses to WD stress at distinct cell-type levels. Here, we studied the spatiotemporal metabolic responses of two poplar (Populus tremula× P. alba) leaf cell types -palisade and vascular cells- to WD stress using matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI). We identified unique WD stress-mediated metabolic shifts in each leaf cell type when exposed to early and prolonged WD stresses and recovery from stress. During water-limited conditions, flavonoids and phenolic metabolites were exclusively accumulated in leaf palisade cells. However, vascular cells mainly accumulated sugars and fatty acids during stress and recovery conditions, respectively, highlighting the functional divergence of leaf cell types in response to WD stress. By comparing our MALDI-MSI metabolic data with whole leaf tissue gas chromatography-mass spectrometry (GC-MS)-based metabolic profile, we identified only a few metabolites including monosaccharides, hexose phosphates, and palmitic acid that showed a similar accumulation trend at both cell-type and whole leaf tissue levels. Overall, this work highlights the potential of the MSI approach to complement the whole tissue-based metabolomics techniques and provides a novel spatiotemporal understanding of plant metabolic responses to WD stress. This will help engineer specific metabolic pathways at a cellular level in strategic perennial trees like poplars to help withstand future aberrations in environmental conditions and to increase bioenergy sustainability.
Correlations of religious beliefs with anxiety and depression of Chinese adolescents
Authors: Li Lejun , Liu Xiliang , Wang Pingping , Qu Miao , Xiu Meihong
Published: March 2024

Objective

This study was designed to investigate the prevalence of religious belief and its relationship with psychiatric symptoms among Chinese adolescents.

Methods

This study recruited 11,603 adolescents in Grades 7-9 from March 21 to 31, 2020 in five cities in China. The religious beliefs of adolescents were collected by asking whether they held religious beliefs and what type of religious beliefs they held. The Patient Health Questionnaire-9 (PHQ-9) and the Generalized Anxiety Disorder-7 Scale (GAD-7) were used to assess depressive and anxiety symptoms in all adolescents. Demographics, religious beliefs, and mental health status were collected through the professional version of Wenjuanxing.

Results

Of 11,069 valid questionnaires collected, 847 (7.7%) reported holding religious beliefs. Adolescents with religious beliefs showed significantly more severe symptoms of depression and anxiety compared to those without religious beliefs (both p<0.05). Logistic regression analysis revealed that religious belief was a risk factor for symptoms of depression (OR = 1.37, 95%CI: 1.16-1.61, p < 0.001) and anxiety (OR = 1.49, 95%CI: 1.23-1.79, p < 0.001) after controlling age, gender, and parental marital status.

Conclusions

Our findings suggest that religiousness in adolescents was associated with a higher likelihood of depression/more intense depressive symptoms. In addition, religious Chinese adolescents should be provided with more resources to help them cope with mental health concerns.
Staff perspectives on poor mental health in secondary school students: an increasing problem handled with insufficient resources
Authors: Svensson Åsa , Warne Maria
Published: March 2024

Introduction

An increasing number of schools are recognizing the importance of addressing students' mental health based on the association with educational outcomes and long-term health. The school organization and the members of the school staff play important but, in several ways, challenging roles in this work. The purpose of this study was to explore views of staff from schools and school health services on mental ill health among students and their own role in detecting and managing it.

Methods

A qualitative study was conducted in a sparsely populated municipality in northern Sweden. In total, 40 participants from three secondary schools and the school health services participated either in focus groups or individual interviews. Participants were teachers, assistants, school nurses, school counselors and psychologists. Data were analyzed using thematic analysis.

Results

The analysis revealed the main theme Student mental ill health: an increasing problem handled with insufficient resources and two subthemes, i.e., Uncertainty in interpreting students' signs of mental ill health and the need to clarify roles and establish a supportive organization.

Conclusions

It was concluded that school staff were uncertain regarding how to interpret signs of mental ill health among students and required better knowledge and more resources to help students with mental ill health. A clearer organization and consensus regarding support for students with mental ill health were also necessary in light of the division of responsibilities between school staff and the school health services.
Predictors of adherence in Austrian employees during the COVID-19 pandemic: results of an online survey
Authors: Avian Alexander , Könczöl Clemens , Kubicek Bettina , Spary-Kainz Ulrike , Siebenhofer Andrea
Published: March 2024

Background

Since the beginning of the pandemic in December 2019, Coronavirus disease 2019 (COVID-19) has been a significant challenge to health care systems throughout the world. The introduction of measures to reduce the incidence of infection had a significant impact on the workplace. Overall, companies played a key and adaptive role in coping with the pandemic.

Methods

Cross-sectional data from an online-survey of 1,183 employees conducted during the COVID-19 pandemic in spring 2021 in Austria were used in the analyses. The influence of health beliefs (e.g., perceived severity), modifying factors (e.g., age) and time-dependent factors (e.g., corona fatigue) on individual adherence were evaluated. The conception of the questionnaire was based on the health belief model.

Results

The majority of respondents were female (58.3%), worked in companies with more than 250 employees (56.6%) and had been to an academic secondary school or had a university degree (58.3%). Overall, employees were adherent to most of the measures at their company (>80%), except for wearing FFP-2 masks when they were travelling in a car with coworkers (59.3, 95%CI 51.3–66.7%). Overall adherence was associated with high ratings for the meaningfulness of testing (OR: 2.06 95%CI: 1.00–4.22; p = 0.049), the extent to which social norms govern behavior (OR: 6.61 95%CI: 4.66–9.36; p < 0.001), lower perceived difficulties associated with the adoption of health-promoting measures (OR: 0.37 95%CI: 0.16–0.82; p = 0.015) and lower corona fatigue (OR: 0.23 95%CI: 0.10–0.52; p < 0.001). Adherence to four single measures was influenced by different predictors. The most important predictors (important for the adherence to three out of four single measures) were social norms and corona fatigue.

Conclusion

The importance attached to testing and social norms, as well as lower perceived barriers to health-promoting measures and low levels of corona fatigue all increase overall adherence to Covid-19 protective measures in companies. Strategies to improve adherence should be adapted depending on the aim (to raise overall adherence or adherence to individual measures) and on the group of persons that is being targeted.
Radiation transport methods in star formation simulations
Authors: Wünsch Richard
Published: March 2024

Radiation transport plays a crucial role in star formation models, as certain questions within this field cannot be accurately addressed without taking it into account. Given the high complexity of the interstellar medium from which stars form, numerical simulations are frequently employed to model the star formation process. This study reviews recent methods for incorporating radiation transport into star formation simulations, discussing them in terms of the used algorithms, treatment of radiation frequency dependence, the interaction of radiation with the gas, and the parallelization of methods for deployment on supercomputers. Broadly, the algorithms fall into two categories: i) moment-based methods, encompassing the flux-limited diffusion approximation, M1 closure, and variable Eddington tensor methods, and ii) methods directly solving the radiation transport equation, including forward and reverse ray tracing, characteristics-based methods, and Monte Carlo techniques. Beyond discussing advantages and disadvantages of these methods, the review also lists recent radiation hydrodynamic codes implemented the described methods.
Enhanced viability and stability of the Lactobacillus reuteri DSM 17938 probiotic strain following microencapsulation in pea and rice protein-inulin conjugates
Authors: Mudgil Priti , Alkaabi Fatima , Khan Hina , Javed Miral , Hajamohideen Abdul Razack , Hamed Fatallah , Maqsood Sajid
Published: March 2024

Probiotics, which offer various health benefits can face challenges in terms of stability during food processing, storage, and gastrointestinal digestion. Therefore, this study aimed to improve the stability and survival of probiotics during various processing conditions and storage. To address this issue, the study was designed to microencapsulate Lactobacillus reuteri DSM 17938 within plant proteins (specifically rice protein (RP) and pea protein (PeP)) and their Maillard reaction conjugated with inulin by spray-drying. The encapsulation efficiency (EE%), stability during storage and temperature, and the viability after simulated gastrointestinal digestion of the microcapsules were examined. The results demonstrate that individual proteins exhibited lower EE%; however, the Maillard conjugates showed increased EE%, with RC (rice protein conjugates) displaying a higher EE% (96.99%) than PC (pea protein conjugates) (92.87%) (p < 0.05). Fourier Transform Infrared Spectroscopy verified the interaction between different functional groups of the proteins and Maillard conjugated and indicated the successful encapsulation of Lactobacillus reuteri DSM 17938 cells. The results also suggested that RC-encapsulated probiotic cells exhibited maximum survival upon gastrointestinal transit, with a decline of only 1.24 and 1.52 log CFU/g after gastric and complete simulated gastrointestinal digestion, respectively. The viability of probiotics encapsulated with RC and PeC showed improvement compared to those encapsulated with RP and PeP, particularly during refrigerated and room temperature storage, thermal challenge, and simulated gastrointestinal transit. Overall, these findings suggest that plant proteins and prebiotic inulin conjugates could serve as promising new encapsulation matrices for the encapsulation of probiotics in food applications.
Assessing electrogenetic activation via a network model of biological signal propagation
Authors: Chun Kayla , VanArsdale Eric , May Elebeoba , Payne Gregory F. , Bentley William E.
Published: March 2024

Introduction:Molecular communication is the transfer of information encoded by molecular structure and activity. We examine molecular communication within bacterial consortia as cells with diverse biosynthetic capabilities can be assembled for enhanced function. Their coordination, both in terms of engineered genetic circuits within individual cells as well as their population-scale functions, is needed to ensure robust performance. We have suggested that “electrogenetics,” the use of electronics to activate specific genetic circuits, is a means by which electronic devices can mediate molecular communication, ultimately enabling programmable control.

Methods:Here, we have developed a graphical network model for dynamically assessing electronic and molecular signal propagation schemes wherein nodes represent individual cells, and their edges represent communication channels by which signaling molecules are transferred. We utilize graph properties such as edge dynamics and graph topology to interrogate the signaling dynamics of specific engineered bacterial consortia.

Results:We were able to recapitulate previous experimental systems with our model. In addition, we found that networks with more distinct subpopulations (high network modularity) propagated signals more slowly than randomized networks, while strategic arrangement of subpopulations with respect to the inducer source (an electrode) can increase signal output and outperform otherwise homogeneous networks.

Discussion:We developed this model to better understand our previous experimental results, but also to enable future designs wherein subpopulation composition, genetic circuits, and spatial configurations can be varied to tune performance. We suggest that this work may provide insight into the signaling which occurs in synthetically assembled systems as well as native microbial communities.
Mechanism of Qingchang compound against coccidiosis based on network pharmacology-molecular docking
Authors: Yan Zhiqiang , Chen Chunlin , Zhai Shaoqin , Tang Hongmei , Zhu Maixun , Yu Yuandi , Zheng Hua
Published: March 2024

The aim of this study was to investigate the anti-Eimeria tenella mechanism of Qingchang Compound (QCC) and provide a basis for its clinical application. The active ingredients, active ingredient-disease intersection targets, and possible pathways of QCC for the treatment of chicken coccidiosis were analyzed, the binding ability of pharmacodynamic components and target proteins was determined by network pharmacology and the molecular docking, and a model of infection with coccidiosis was constructed to verify and analyze the mechanism of action of QCC against coccidiosis. Among the 57 components that met the screening conditions, the main bioactive components were quercetin, dichroine, and artemisinin, with IL-1β, IL-6, IL-10, IFN-γ, and IL-8 as the core targets. Simultaneously, the KEGG signaling pathway of QCC anti-coccidiosis in chickens was enriched, including cytokine-cytokine receptor interactions. The results showed that the main pharmacodynamic components of QCC and the core targets could bind well; artemisinin and alpine possessed the largest negative binding energies and presented the most stable binding states. In addition, in vivo studies showed that QCC reduced blood stool in chickens with coccidiosis, restored cecal injury, and significantly reduced the mRNA and protein expression levels of IL-1β, IL-10, and IFN-γ in ceca (p < 0.01). Our results suggest that the main active ingredients of QCC are artemisinin and alpine and its mechanism of action against coccidiosis may be related to the reduction of the inflammatory response by acting on specific cytokines.