bluuebunny/crossref_metadata_2025 huggingface dataset:
Immune tolerance and the prevention of autoimmune diseases essentially depend on thymic tissue homeostasis
Authors: Shirafkan Fatemeh , Hensel Luca , Rattay Kristin
Published: March 2024

The intricate balance of immune reactions towards invading pathogens and immune tolerance towards self is pivotal in preventing autoimmune diseases, with the thymus playing a central role in establishing and maintaining this equilibrium. The induction of central immune tolerance in the thymus involves the elimination of self-reactive T cells, a mechanism essential for averting autoimmunity. Disruption of the thymic T cell selection mechanisms can lead to the development of autoimmune diseases. In the dynamic microenvironment of the thymus, T cell migration and interactions with thymic stromal cells are critical for the selection processes that ensure self-tolerance. Thymic epithelial cells are particularly significant in this context, presenting self-antigens and inducing the negative selection of autoreactive T cells. Further, the synergistic roles of thymic fibroblasts, B cells, and dendritic cells in antigen presentation, selection and the development of regulatory T cells are pivotal in maintaining immune responses tightly regulated. This review article collates these insights, offering a comprehensive examination of the multifaceted role of thymic tissue homeostasis in the establishment of immune tolerance and its implications in the prevention of autoimmune diseases. Additionally, the developmental pathways of the thymus are explored, highlighting how genetic aberrations can disrupt thymic architecture and function, leading to autoimmune conditions. The impact of infections on immune tolerance is another critical area, with pathogens potentially triggering autoimmunity by altering thymic homeostasis. Overall, this review underscores the integral role of thymic tissue homeostasis in the prevention of autoimmune diseases, discussing insights into potential therapeutic strategies and examining putative avenues for future research on developing thymic-based therapies in treating and preventing autoimmune conditions.
Evolutionary insights and functional diversity of gasdermin family proteins and homologs in microorganisms
Authors: Wang Shule , Ma Tingbo , Xia Xiaoyi , Zhang Leiliang
Published: March 2024

The gasdermin protein family and its homologs in microorganisms have gained significant attention due to their roles in programmed cell death, immune defense, and microbial infection. This review summarizes the current research status of gasdermin proteins, their structural features, and functional roles in fungi, bacteria, and viruses. The review presents evolutionary parallels between mammalian and microbial defense systems, highlighting the conserved role of gasdermin proteins in regulating cell death processes and immunity. Additionally, the structural and functional characteristics of gasdermin homologs in microorganisms are summarized, shedding light on their potential as targets for therapeutic interventions. Future research directions in this field are also discussed to provide a roadmap for further investigation.
Programmable mechanical metamaterials: basic concepts, types, construction strategies—a review
Authors: Liu Chenyang , Zhang Xi , Chang Jiahui , Lyu You , Zhao Jianan , Qiu Song
Published: March 2024

Metamaterials have been a hot topic over the past 2 decades, involving scientific research directions in materials, engineering, and physics. Among them, programmable mechanical metamaterials are an emerging class of metamaterials that offer intelligent programming and control of diverse mechanical properties, such as stiffness, damping, thermal expansion, and shape memory behavior. Meanwhile, it can be rationally designed to have specific geometric architectures and programming strategies in response to different types of external stimuli, such as temperature, electric and magnetic fields, and mechanical loads. These intelligent mechanical properties have a wide range of potential applications due to their uniqueness and controllability, including soft robotics, adaptive structures, and wearable devices. Thus, the programming strategies to achieve them are particularly critical. Combined with related programmable thinking concepts, this paper briefly reviews programming strategies for programmable mechanical metamaterials, including geometric, structural, and external driving force programming. Meanwhile, this paper presents the principles of programming strategies classified according to different programmable mechanical properties (e.g., programmable stiffness, deformation, multistability) and looks ahead to the challenges and opportunities for future research.
Sex-differences in COPD: from biological mechanisms to therapeutic considerations
Authors: Milne Kathryn M. , Mitchell Reid A. , Ferguson Olivia N. , Hind Alanna S. , Guenette Jordan A.
Published: March 2024

Chronic obstructive pulmonary disease (COPD) is a heterogeneous respiratory condition characterized by symptoms of dyspnea, cough, and sputum production. We review sex-differences in disease mechanisms, structure-function-symptom relationships, responses to therapies, and clinical outcomes in COPD with a specific focus on dyspnea. Females with COPD experience greater dyspnea and higher morbidity compared to males. Imaging studies using chest computed tomography scans have demonstrated that females with COPD tend to have smaller airways than males as well as a lower burden of emphysema. Sex-differences in lung and airway structure lead to critical respiratory mechanical constraints during exercise at a lower absolute ventilation in females compared to males, which is largely explained by sex differences in maximum ventilatory capacity. Females experience similar benefit with respect to inhaled COPD therapies, pulmonary rehabilitation, and smoking cessation compared to males. Ongoing re-assessment of potential sex-differences in COPD may offer insights into the evolution of patterns of care and clinical outcomes in COPD patients over time.
Regulatory effect of Ganoderma lucidum and its active components on gut flora in diseases
Authors: Qin Xinjie , Fang Zinan , Zhang Jinkang , Zhao Wenbo , Zheng Ni , Wang Xiaoe
Published: March 2024

Driven by the good developmental potential and favorable environment at this stage, Ganoderma lucidum is recognized as a precious large fungus with medicinal and nutritional health care values. Among them, polysaccharides, triterpenoids, oligosaccharides, trace elements, etc. are important bioactive components in G. lucidum. These bioactive components will have an impact on gut flora, thus alleviating diseases such as hyperglycemia, hyperlipidemia and obesity caused by gut flora disorder. While numerous studies have demonstrated the ability of G. lucidum and its active components to regulate gut flora, a systematic review of this mechanism is currently lacking. The purpose of this paper is to summarize the regulatory effects of G. lucidum and its active components on gut flora in cardiovascular, gastrointestinal and renal metabolic diseases, and summarize the research progress of G. lucidum active components in improving related diseases by regulating gut flora. Additionally, review delves into the principle by which G. lucidum and its active components can treat or assist treat diseases by regulating gut flora. The research progress of G. lucidum in intestinal tract and its potential in medicine, health food and clinical application were fully explored for researchers.
Magnesium oxide nanoparticles reduce clubroot by regulating plant defense response and rhizosphere microbial community of tumorous stem mustard (Brassica juncea var. tumida)
Authors: Liao Jingjing , Yuan Zitong , Wang Xiangmei , Chen Tingting , Qian Kun , Cui Yuanyuan , Rong Anping , Zheng Chunyang , Liu Yuanxiu , Wang Diandong , Pan Limei
Published: March 2024

Clubroot, caused by Plasmodiophora brassicae, is a major disease that significantly impairs the yield of cruciferous crops and causes significant economic losses across the globe. The prevention of clubroot, especially in tumorous stem mustard (without resistant varieties), are is limited and primarily relies on fungicides. Engineered nanoparticles have opened up new avenues for the management of plant diseases, but there is no report on their application in the prevention of clubroot. The results showed that the control efficacy of 500 mg/L MgO NPs against clubroot was 54.92%. However, when the concentration was increased to 1,500 and 2,500 mg/L, there was no significant change in the control effect. Compared with CK, the average fresh and dry weight of the aerial part of plants treated with MgO NPs increased by 392.83 and 240.81%, respectively. Compared with the F1000 treatment, increases were observed in the content of soil available phosphorus (+16.72%), potassium (+9.82%), exchangeable magnesium (+24.20%), and water-soluble magnesium (+20.64%) in the 1,500 mg/L MgO NPs treatment. The enzyme-linked immune sorbent assay (ELISA) results showed that the application of MgO NPs significantly increased soil peroxidase (POD, +52.69%), alkaline protease (AP, +41.21%), alkaline phosphatase (ALP, +79.26%), urease (+52.69%), and sucrase (+56.88%) activities; And also increased plant L-phenylalanine ammonla-lyase (PAL, +70.49%), polyphenol oxidase (PPO, +36.77%), POD (+38.30%), guaiacol peroxidase (POX, +55.46%) activities and salicylic acid (SA, +59.86%) content. However, soil and plant catalase (CAT, −27.22 and − 19.89%, respectively), and plant super oxidase dismutase (SOD, −36.33%) activities were significantly decreased after the application of MgO NPs. The metagenomic sequencing analysis showed that the MgO NPs treatments significantly improved the α-diversity of the rhizosphere soil microbial community. The relative abundance of beneficial bacteria genera in the rhizosphere soil, including Pseudomonas, Sphingopyxis, Acidovorax, Variovorax, and Bosea, was significantly increased. Soil metabolic functions, such as oxidative phosphorylation (ko00190), carbon fixation pathways in prokaryotes (ko00720), indole alkaloid biosynthesis (ko00901), and biosynthesis of various antibiotics (ko00998) were significantly enriched. These results suggested that MgO NPs might control clubroot by promoting the transformation and utilization of soil nutrients, stimulating plant defense responses, and enriching soil beneficial bacteria.
Intercropping changed the soil microbial community composition but no significant effect on alpha diversity
Authors: Liu Jiaying , Zhang Weixi , Teng Chao , Pang Zhongyi , Peng Yanhui , Qiu Jian , Lei Jiawei , Su Xiaohua , Zhu Wenxu , Ding Changjun
Published: March 2024

Introduction

Enhancing the planning of the forest-agricultural composite model and increasing the efficiency with which forest land is utilized could benefit from a thorough understanding of the impacts of intercropping between forests and agriculture on soil physicochemical properties and microbial communities.

Methods

Populus cathayana × candansis cv. Xinlin No.1 and Glycine max intercrop soils, along with their corresponding monocrops, were used in this study’s llumina high-throughput sequencing analysis to determine the composition and diversity of soil bacterial and fungal communities.

Results

The findings indicated that intercropping considerably raised the soil’s total phosphorus content and significantly lowered the soil’s carbon nitrogen ratio when compared to poplar single cropping. Furthermore, the total carbon and nitrogen content of soil was increased and the soil pH was decreased. The sequencing results showed that intercropping had no significant effect on soil alpha diversity. Intercropping could increase the composition of fungal community and decrease the composition of bacterial community in poplar soil. At the phylum level, intercropping significantly increased the relative abundance of four dominant phyla, i.e., Patescibacteria, Proteobacteria, Patescibacteria and Deinococcus-Thermus. And the relative abundances of only two dominant phyla were significantly increased. It was found that soil total phosphorus and available phosphorus content had the strongest correlation with soil bacterial community diversity, and soil pH had the strongest correlation with soil fungal community diversity.

Discussion

The results of this study were similar to those of previous studies. This study can serve as a theoretical foundation for the development of a poplar and black bean-based forest-agricultural complex management system in the future.
Quality assessment of glucose measurement with regard to epidemiology and clinical management of diabetes mellitus in Germany
Authors: Luppa Peter B. , Zeller Michael , Pieper Marija , Kaiser Patricia , Weiss Nathalie , Vierbaum Laura , Freckmann Guido
Published: March 2024

Background:

During the last decade, Germany has seen an increased prevalence and a redistribution from undetected to diagnosed diabetes mellitus. Due to this substantial epidemiological development, the number of people with documented type 2 diabetes was 8.7 million in 2022. An estimated two million undiagnosed subjects are to be added. Beyond that, the life expectancy of diabetic subjects is increasing due to more responsive health systems in terms of care. Possible reasons include improved screening of at-risk individuals, the introduction of HbA1c for diagnosis in 2010, and the higher use of risk scores. Additionally, quality aspects of the laboratory methodology should be taken into consideration.

Methods:

Epidemiology and clinical management of diabetes in Germany are presented in the light of publications retrieved by a selective search of the PubMed database. Additionally, the data from German external quality assessment (EQA) surveys for the measurands glucose in plasma and HbA1c in whole blood, reviewed from 2010 until 2022, were evaluated. Above this, data concerning the analytical performance of near-patient glucometer devices, according to the ISO norm 15197:2013, were analyzed.

Results:

Two laboratory aspects are in good accordance with the observation of an increase in the diabetes mellitus prevalence when retrospectively reviewing the period 2010 to 2022: First, the analytical performance according to the ISO norm 15197:2013 of the glucometer devices widely used by patients with diabetes for the glucose self-testing, has improved during this period. Secondly, concerning the EQA program of INSTAND, the number of participating laboratories raised significantly in Germany. The spreads of variations of the specified results for plasma glucose remained unchanged between 2010 and 2022, whereas for HbA1c a significant decrease of the result scattering could be observed.

Conclusion:

These retrospectively established findings testify to an excellent analytical quality of laboratory diagnostics for glucose and HbA1c throughout Germany which may be involved in a better diagnosis and therapy of previously undetected diabetes mellitus.
Platelet-activating factor receptor (PAFR) regulates neuronal maturation and synaptic transmission during postnatal retinal development
Authors: Dalmaso Barbara , Liber Andre Mauricio Passos , Ventura Dora Fix , Jancar Sonia , Del Debbio Carolina Beltrame
Published: March 2024

Introduction

Platelet-activating factor (PAF), PAF receptor (PAFR), and PAF- synthesis/degradation systems are involved in essential CNS processes such as neuroblast proliferation, differentiation, migration, and synaptic modulation. The retina is an important central nervous system (CNS) tissue for visual information processing. During retinal development, the balance between Retinal Progenitor Cell (RPC) proliferation and differentiation is crucial for proper cell determination and retinogenesis. Despite its importance in retinal development, the effects of PAFR deletion on RPC dynamics are still unknown.

Methods

We compared PAFR knockout mice (PAFR−/−) retinal postnatal development proliferation and differentiation aspects with control animals. Electrophysiological responses were analyzed by electroretinography (ERG).

Results and discussion

In this study, we demonstrate that PAFR−/− mice increased proliferation during postnatal retinogenesis and altered the expression of specific differentiation markers. The retinas of postnatal PAFR−/− animals decreased neuronal differentiation and synaptic transmission markers, leading to differential responses to light stimuli measured by ERG. Our findings suggest that PAFR signaling plays a critical role in regulating postnatal RPC cell differentiation dynamics during retinal development, cell organization, and neuronal circuitry formation.
IgLON5 autoimmunity in a patient with Creutzfeldt–Jakob disease: case report and review of literature
Authors: Li Xiaofeng , Chen Yimin , Zhang Le , Zhang Wei , Li Bin , Baizabal-Carvallo José Fidel , Song Xingwang
Published: March 2024

Objective

We present the case of a patient with clinical and imaging features of sporadic Creutzfeldt–Jakob disease (sCJD) and positive IgLON5 antibodies (Abs) in the serum and CSF.

Case report

A 66-year-old Chinese man presented to the hospital with a stroke-like episode, followed by rapidly progressive cognitive decline, mutism, and parkinsonism. The MRI results showed a cortical ribboning sign in diffusion-weighted MRI, periodic triphasic waves with a slow background in EEG, and positive protein 14–3-3 in CSF. There were matching IgLON5 Abs in the serum and CSF. A literature review showed positive autoimmune encephalitis Abs or autoimmune inflammatory disease between 0.5 and 8.6% among patients with clinical suspicion of CJD, most commonly anti-voltage-gated potassium channel (VGKC) complex and anti-N-methyl-D-aspartate receptor (NMDAR) Abs; however, IgLON5 autoimmunity in CJD has been rarely reported. This is an intriguing association as both conditions have been associated with brain deposits of phosphorylated tau protein.

Conclusion

IgLON5 Abs may be observed in patients with a diagnosis of CJD; it is unknown whether a synergistic effect of IgLON5 Abs with CJD exists, increasing neurodegenerative changes.
Participation of calcium-permeable AMPA receptors in the regulation of epileptiform activity of hippocampal neurons
Authors: Zinchenko Valery Petrovich , Teplov Ilia Yu. , Kosenkov Artem Mikhailovich , Gaidin Sergei Gennadievich , Kairat Bakytzhan Kairatuly , Tuleukhanov Sultan Tuleukhanovich
Published: March 2024

Introduction

Epileptiform activity is the most striking result of hyperexcitation of a group of neurons that can occur in different brain regions and then spread to other sites. Later it was shown that these rhythms have a cellular correlate in vitro called paroxysmal depolarization shift (PDS). In 13–15 DIV neuron-glial cell culture, inhibition of the GABA(A) receptors induces bursts of action potential in the form of clasters PDS and oscillations of intracellular Ca2+ concentration ([Ca2+]i). We demonstrate that GABAergic neurons expressing calcium-permeable AMPA receptors (CP-AMPARs) as well as Kv7-type potassium channels regulate hippocampal glutamatergic neurons’ excitability during epileptiform activity in culture.

Methods

A combination of whole-cell patch-clamp in current clamp mode and calcium imaging microscopy was used to simultaneously register membrane potential and [Ca2+]i level. To identify GABAergic cell cultures were fixed and stained with antibodies against glutamate decarboxylase GAD 65/67 and neuron-specific enolase (NSE) after vital [Ca2+]i imaging.

Results and discussion

It was shown that CP-AMPARs are involved in the regulation of the PDS clusters and [Ca2+]i pulses accompanied them. Activation of CP-AMPARs of GABAergic neurons is thought to cause the release of GABA, which activates the GABA(B) receptors of other GABAergic interneurons. It is assumed that activation of these GABA(B) receptors leads to the release of beta-gamma subunits of Gi protein, which activate potassium channels, resulting in hyperpolarization and inhibition of these interneurons. The latter causes disinhibition of glutamatergic neurons, the targets of these interneurons. In turn, the CP-AMPAR antagonist, NASPM, has the opposite effect. Measurement of membrane potential in GABAergic neurons by the patch-clamp method in whole-cell configuration demonstrated that NASPM suppresses hyperpolarization in clusters and individual PDSs. It is believed that Kv7-type potassium channels are involved in the control of hyperpolarization during epileptiform activity. The blocker of Kv7 channels, XE 991, mimicked the effect of the CP-AMPARs antagonist on PDS clusters. Both drugs increased the duration of the PDS cluster. In turn, the Kv7 activator, retigabine, decreased the duration of the PDS cluster and Ca2+ pulse. In addition, retigabine led to deep posthyperpolarization at the end of the PDS cluster. The Kv7 channel is believed to be involved in the formation of PDS, as the channel blocker reduced the rate of hyperpolarization in the PDS almost three times. Thus, GABAergic neurons expressing CP-AMPARs, regulate the membrane potential of innervated glutamatergic neurons by modulating the activity of postsynaptic potassium channels of other GABAergic neurons.
Association of taurine intake with changes in physical fitness among community-dwelling middle-aged and older Japanese adults: an 8-year longitudinal study
Authors: Domoto Takashi , Kise Kazuyoshi , Oyama Yukiko , Furuya Kanae , Kato Yuki , Nishita Yukiko , Kozakai Rumi , Otsuka Rei
Published: March 2024

Introduction

Taurine has diverse valuable biological functions, including antioxidant activity and regulation of osmotic pressure. Maintaining physical fitness from middle age is important for healthy life expectancy. Although taurine administration improves muscle endurance and strength, its role in maintenance remains unclear. We aimed to clarify the longitudinal taurine intake association with fitness changes.

Methods

Participants comprised men and women aged ≥40 years who participated in the third (2002–2004; Baseline) and seventh (2010–2012; Follow-up) waves of the National Institute for Longevity Sciences-Longitudinal Study of Aging (NILS-LSA) and completed a 3-day dietary weights recording survey at baseline. A table of taurine content was prepared for 751 foods (including five food groups: Seaweed; Fish and shellfish; Meat; Eggs; and Milk and dairy products) from the Standard Tables of Food Composition in Japan (1,878 foods) 2010. Four physical fitness items (knee extension muscle strength, sit-and-reach, one-leg standing with eyes closed, and maximum walking speed) were measured at baseline and follow-up. We analyzed the association of taurine intake with physical fitness change, employing a general linear model (GLM) and trend tests for baseline taurine intake and follow-up fitness change. Adjustments included baseline variables: sex, age, height, weight, educational level, self-rated health, smoking status, depressive symptoms, and clinical history.

Results

The estimated average daily taurine intake (standard deviation) was 207.5 (145.6) mg/day at the baseline. When examining the association with the four physical fitness parameters, higher taurine intake positively increased the change in knee extension muscle strength (T1; 0.1, T2; 0.8, T3; 1.1 (kgf) GLM, p < 0.05; p for trend <0.05) and reduced the decline in knee extension muscle strength in the subgroup analysis of participants aged ≥65 years (T1: −1.9, T2: −1.7, T3: −0.4 kgf; GLM p < 0.05, p for trend <0.05). No relationship was found between taurine intake and the remaining three fitness factors.

Conclusion

Estimation of taurine intake showed that dietary taurine intake potentially contributes to the maintenance of knee extension muscle strength over 8 years among Japanese community-dwelling middle-aged and older individuals. This is the first study to investigate the association of dietary taurine intake with muscle strength.
Intrahousehold empowerment gaps and dietary diversity in China
Authors: Huang Yanfang , Yang Yuying , Nie Fengying , Jia Xiangping
Published: March 2024

Objective

This article analyzes the relationship between intrahousehold empowerment gaps and food and nutrition security using quantitative data collected through a household survey organized by the Agricultural Information Institute, Chinese Academy of Agricultural Sciences (CAAS-AII), in 2023.

Methods

Based on empowerment theory, this study measured the relative empowerment of spouses from the Abbreviated Women's Empowerment in Agriculture Index (A-WEAI).

Results

From the micro-level evidence of 468 rural households, this study found that intrahousehold empowerment gaps harm the diversity of household diets. In particular, reducing gender gaps in access to resources, leadership, and income can help diversify household diets. However, data on the impact of shortening the difference in working hours between wives and husbands for the benefit of food safety are yet to be conclusive. Additionally, gender gaps in the group of non-coresident mothers-in-law and non-migrants hurt household food security.

Conclusion

The paper also provides further justification for policies and interventions that aim to improve women's bargaining position in the household.
Virtual reality as a non-medical tool in the treatment of anxiety, pain, and perception of time in children in the maintenance phase of acute lymphoblastic leukemia treatment
Authors: Velasco-Hidalgo Liliana , González-Garay Alejandro , Segura-Pacheco Blanca Angélica , Esparza-Silva Ana Luisa , Cuéllar Mendoza Miguel Enrique , Ochoa-Drucker Cecilia , Campos-Ugalde Sofía , Bernabé-Gaspar Luis Eduardo , Zapata-Tarrés Marta
Published: March 2024

Introduction

Management of pediatric cancer patients involves invasive procedures such as punctures, injections, catheter placements, and chemotherapy which can generate fatigue, nausea, vomiting, anxiety, and pain. Virtual Reality (VR) is a nonpharmacological intervention classified as a cognitive-behavioral method to relieve symptoms.

Methods

We designed a crossover protocol and included 20 patients between 9 and 12 years old; ten were male. All patients had acute lymphoblastic leukemia diagnosis and were treatedwith St. Jude’s XV protocol in the maintenance phase. Pain and anxiety were measured with validated scales in the pediatric population.

Results

Although we used a small group of patients, we found statistical difference in the reduction of anxiety and perception of time.

Discussion

These results open a window to non-pharmacological treatments and show a strategy to improve quality of life in children inside the hospital.
Pyroptosis-related gene signature for predicting gastric cancer prognosis
Authors: Khamis Salem Saeed Saad , Lu Jianhua , Yi Yongdong , Rao Shangrui , Sun Weijian
Published: March 2024

Gastric cancer (GC) is a prevalent form of malignancy characterized by significant heterogeneity. The development of a specific prediction model is of utmost importance to improve therapy alternatives. The presence of H. pylori can elicit pyroptosis, a notable carcinogenic process. Furthermore, the administration of chemotherapeutic drugs is often employed as a therapeutic approach to addressing this condition. In the present investigation, it was observed that there were variations in the production of 17 pyroptosis-regulating proteins between stomach tissue with tumor development and GC cells. The predictive relevance of each gene associated with pyroptosis was assessed using the cohort from the cancer genome atlas (TCGA). The least absolute shrinkage and selection operator (LASSO) was utilized to enhance the outcomes of the regression approach. Patients with gastric cancer GC in the cohort from the TCGA were categorized into low-risk or high-risk groups based on their gene expression profiles. Patients with a low risk of gastric cancer had a higher likelihood of survival compared to persons classified as high risk (P<0.0001). A subset of patients diagnosed with GC from a Genes Expression Omnibus (GEO) cohort was stratified according to their overall survival (OS) duration. The statistical analysis revealed a higher significance level (P=0.0063) regarding OS time among low-risk individuals. The study revealed that the GC risk score emerged as a significant independent prognostic factor for OS in patients diagnosed with GC. The results of Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) research revealed that genes associated with a high-risk group had significantly elevated levels of immune system-related activity. Furthermore, it was found that the state of immunity was diminished within this particular group. The relationship between the immune response to cancer and pyroptosis genes is highly interconnected, suggesting that these genes have the potential to serve as prognostic indicators for GC.
Antineoplastic effect of compounds C14 and P8 on TNBC and radioresistant TNBC cells by stabilizing the K-Ras4BG13D/PDE6δ complex
Authors: Carrión-Estrada Dayan A. , Aguilar-Rojas Arturo , Huerta-Yepez Sara , Montecillo-Aguado Mayra , Bello Martiniano , Rojo-Domínguez Arturo , Arechaga-Ocampo Elena , Briseño-Díaz Paola , Meraz-Ríos Marco Antonio , Thompson-Bonilla María del Rocío , Hernández-Rivas Rosaura , Vargas Miguel
Published: March 2024

Introduction

Breast cancer (BC) is the leading cause of cancer-related deaths among women, with triple-negative breast cancer (TNBC) representing one of the most aggressive and treatment-resistant subtypes. In this study, we aimed to evaluate the antitumor potential of C14 and P8 molecules in both TNBC and radioresistant TNBC cells. These compounds were chosen for their ability to stabilize the complex formed by the overactivated form of K-Ras4BG13D and its membrane transporter (PDE6δ).

Methods

The antitumor potential of C14 and P8 was assessed using TNBC cell lines, MDA-MB-231, and the radioresistant derivative MDA-MB-231RR, both carrying the K-Ras4B>
G13D mutation. We investigated the compounds' effects on K-Ras signaling pathways, cell viability, and tumor growth in vivo.

Results

Western blotting analysis determined the negative impact of C14 and P8 on the activation of mutant K-Ras signaling pathways in MDA-MB-231 and MDA-MB-231RR cells. Proliferation assays demonstrated their efficacy as cytotoxic agents against K-RasG13D mutant cancer cells and in inducing apoptosis. Clonogenic assays proven their ability to inhibit TNBC and radioresistant TNBC cell clonogenicity. In In vivo studies, C14 and P8 inhibited tumor growth and reduced proliferation, angiogenesis, and cell cycle progression markers.

Discussion

These findings suggest that C14 and P8 could serve as promising adjuvant treatments for TNBC, particularly for non-responders to standard therapies. By targeting overactivated K-Ras and its membrane transporter, these compounds offer potential therapeutic benefits against TNBC, including its radioresistant form. Further research and clinical trials are warranted to validate their efficacy and safety as novel TNBC treatments.
NUP214 fusion genes in acute leukemias: genetic characterization of rare cases
Authors: Brunetti Marta , Andersen Kristin , Spetalen Signe , Lenartova Andrea , Osnes Liv Toril Nygård , Vålerhaugen Helen , Heim Sverre , Micci Francesca
Published: March 2024

Introduction

Alterations of the NUP214 gene (9q34) are recurrent in acute leukemias. Rearrangements of chromosomal band 9q34 targeting this locus can be karyotypically distinct, for example t(6;9)(p22;q34)/DEK::NUP214, or cryptic, in which case no visible change of 9q34 is seen by chromosome banding.

Methods

We examined 9 cases of acute leukemia with NUP214 rearrangement by array Comparative Genomic Hybridization (aCGH), reverse-transcription polymerase chain reaction (RT-PCR), and cycle sequencing/Sanger sequencing to detect which fusion genes had been generated.

Results

The chimeras DEK::NUP214, SET::NUP214, and NUP214::ABL1 were found, only the first of which can be readily detected by karyotyping.

Discussion

The identification of a specific NUP214 rearrangement is fundamental in the management of these patients, i.e., AMLs with DEK::NUP214 are classified as an adverse risk group and might be considered for allogenic transplant. Genome- and/or transcriptome-based next generation sequencing (NGS) techniques can be used to screen for these fusions, but we hereby present an alternative, step-wise procedure to detect these rearrangements.
Children with non-central nervous system tumors treated with platinum-based chemotherapy are at risk for hearing loss and cognitive impairments
Authors: L’Hotta Allison J. , Spence Anne , Varughese Taniya E. , Felts Kara , Hayashi Susan S. , Jones-White Megan , LaFentres Emily , Lieu Judith E. C. , Hayashi Robert J. , King Allison A.
Published: March 2024

Background

Childhood cancer survivors (CCS) with chemotherapy induced sensorineural hearing loss (SNHL) are at risk for neurocognitive impairments. The purpose of this study was to determine the relationship between SNHL and cognitive function among CCS.

Procedure

Inclusion: non-CNS solid tumor diagnosis; history of platinum chemotherapy (cisplatin and/or carboplatin); 8–17 years of age; off anti-cancer treatment for ≥6 months; and English speaking. Exclusion: history of intrathecal chemotherapy, cranial radiation, or baseline neurocognitive disorder. Participants completed the NIH Toolbox Cognition Battery at enrollment. T-tests were used to compare participants with normal hearing to those with hearing loss and the total sample with established Toolbox normative data (mean: 50; SD: 10).

Results

Fifty-seven individuals enrolled; 52 completed full cognitive testing. Participants were on average 12.2 years of age and 7.0 years since treatment completion. Twenty-one participants (40%) received cisplatin, 27 (52%) carboplatin, and 4 (8%) received both. Fifteen participants (29%) demonstrated SNHL based on the better ear. CCS, regardless of the presence or absence of SNHL, demonstrated significantly lower mean cognitive skills compared to the normative sample in attention, executive function, language- vocabulary and oral reading, processing speed, and fluid, crystallized and total composite scores (all p < 0.01). Participants with SNHL had significantly lower crystallized composite (vocabulary, oral reading) than those with normal hearing (41.9 vs. 47.2, p < 0.05, Cohen's d = 0.62).

Conclusions

CCS at risk for platinum induced hearing loss but without cranial radiation or intrathecal chemotherapy exposure demonstrate impaired cognitive skills and those with SNHL demonstrate lower crystallized composite scores.
Skin-to-skin transfer from the delivery room to the neonatal unit for neonates of 1,500g or above: a feasibility and safety study
Authors: M’Rini Meline , De Doncker Loïc , Huet Emilie , Rochez Céline , Kelen Dorottya
Published: March 2024

Objective

Immediate skin-to-skin contact (SSC) is already standard care for healthy term newborns, but its use for term or preterm newborns requiring admission to neonatal intensive care unit (NICU) with or without respiratory support is challenging. This study aimed to assess the safety and feasibility of SSC during the transfer of newborn infants, using a new purpose-built mobile shuttle care-station, called “Tandem”.

Material and methods

A monocentric prospective observational study was conducted at the tertiary referral center of the Université libre de Bruxelles in Brussels, Belgium after ethical approval by Hopital Erasme's Ethics Committee (ClinicalTrials.gov ID: NCT06198478). Infants born with a birth weight above 1,500 g were included. Following initial stabilization, infants were placed in SSC with one of their parents and transferred to the NICU using the Tandem.

Results

Out of 65 infants initially included, 64 (98.5%) were successfully transported via SSC using the Tandem. One transfer was not successful due to last minute parental consent withdrawal. The median (range) duration of continuous skin-to-skin contact after birth was 120 min (10–360). SSC transfers were associated with gradually decreasing heart rate (HR) values, stable oxygen saturation levels (SpO2), and no increase in median fraction of inspired oxygen (FiO2). Heatloss was predominantly observed during initial setup of SSC. There was no significant difference in the occurrence of tachycardia, desaturation or hypothermia between preterm and term neonates. No equipment failures compromising the transfer were recorded.

Conclusion

Skin-to-skin transfer of infants with a birthweight of equal or above 1,500 g using the Tandem shuttle is feasible and associated with stable physiological parameters. This method facilitates early bonding and satisfies parents.

Clinical Trial Registration

ClinicalTrials.gov (NCT06198478).
Profile and challenges of interdisciplinary physics
Authors: Mantegna R. N.
Published: March 2024

We discuss profile and challenges of interdisciplinary physics. We start discussing the current definition of physics. We therefore focus on the type of experimental settings observed in different branches of physics. We recall how the term predictability has changed over the last century and we comment on the effects of data deluge in science and society. Lastly we present a few examples of current profile and challenges of interdisciplinary physics.
Causal relationship between physical activity and platelet traits: a Mendelian randomization study
Authors: Jia Mingyuan , Wang Zhiyong , Hu Fengting
Published: March 2024

Introduction: The purpose of this study was to discuss the causal relationship between physical activity and platelet traits.

Methods: A dataset from a large-scale European physical activity and platelet traits was collected by using Mendelian randomization of the study. For the analysis, the inverse variance weighting method, weighted median and MR-Egger were used to estimate causal effects. The sensitivity analyses were also performed using Cochran’s Q test, funnel plots and Leave-one-out analysis.

Results: Light DIY, other exercises, strenuous sports, walking for pleasure were significantly associated with a decrease in platelet crit. But none of the heavy /light DIY was associated with increase in platelet crit. Other exercises and strenuous sports were associated with decrease in platelet count.

Conclusion: Some types of physical activity have a causal relationship with platelet crit and platelet count. However, the types of physical activity we studied have not supported a causal relationship with mean platelet volume and platelet distribution width.
Effect of a novel dwarfing mutant site on chromosome 4B on agronomic traits in common wheat
Authors: Hao Jiamin , Zhao Zhangchen , Fu Xiaoge , Zhao Yujiao , Ateeq Muhammad , Mou Liming , Han Yong , Liu Yangbin , Yin Yongan , Zotova Lyudmila , Serikbay Dauren , Fan Chunyan , Hu Yin-Gang , Chen Liang
Published: March 2024

The introduction of dwarfing genes triggered a wave of “green revolution”. A number of wheats dwarfing genes have been reported in previous studies, and only a small fraction of these have been applied to production practices. Therefore, the development of novel dwarfing genes for wheat is of great value. In this study, a novel dwarfing site, Rht-yz, identified in the Yanzhan mutation, is located on chromosome 4B (30-33MB) and its mechanism of action is different from that of Rht-B1b (C-T mutation), but whether it affects the Rht-B1a (TraesCS4B02G043100) or other genes is unclear. Exogenously applied GA3 experiments showed that Rht-yz is one of the gibberellin-insensitive dwarf genes. The effects of the dwarf gene Rht-yz on agronomic traits in wheat were evaluated in the field using Yanzhan, Yanzhan mutations, F2:3 and F3:4 lines. The results showed that Rht-yz improved lodging resistance by reducing plant height, increasing diameter, wall thickness and mechanical strength of the basal stem. In terms of yield traits, Rht-yz had negative effects on tiller number plant-1, biomass plant-1 and yield plant-1, but had no significant effect on harvest index, 1000-kernel weight and spike traits. In addition, Rht-yz significantly increased crude protein, wet gluten and starch content. Therefore, the rational use of the new dwarfing site Rht-yz has potential and value in dwarf wheat breeding.
The struggle within dual systems of government: dealing with conflict between traditional leaders and ward councilors in the greater Giyani Municipality in South Africa
Authors: Muchaku Shadreck , Magaiza Grey
Published: March 2024

Introduction

Current frameworks of conflict resolution have shown only partial success, particularly in the context of local municipalities where conflicts persist. There is a pressing need for context-specific framework that address leadership conflicts while fostering peace.

Methods

To address the lack of progress in resolving conflicts, this study identifies major challenges undermining the assimilation and implementation of objectively informed conflict resolution strategies. A purposive sampling method was employed to select 33 respondents from the Greater Giyani Municipality. Data were collected through semistructured interviews and analyzed using statistically established matrix scoring procedures. ATLAS.ti software was utilized for data analysis.

Results

Without claiming to be exhaustive, this paper highlights examples of externalities that threaten the coexistence of the dual system of governance in South African communities, with a focus on leadership conflict and unsustainable peace. Factors contributing to conflict escalation include capacity constraints, lack of inclusive, bias, divisive decision-making and contested court decisions.

Discussion

The study underscores the importance of addressing these challenges to foster effective conflict resolution. It emphasizes the need for the scientific community to provide critical information necessary for responding effectively to these challenges.

Conclusion

To enhance conflict resolution in local municipalities, it is imperative to develop context-specific frameworks that address underlying challenges and promote sustainable peace. This requires concerted efforts from both researchers and practitioners to provide the necessary insights and strategies for resolution.
Implementing machine learning techniques for continuous emotion prediction from uniformly segmented voice recordings
Authors: Diemerling Hannes , Stresemann Leonie , Braun Tina , von Oertzen Timo
Published: March 2024

Introduction

Emotional recognition from audio recordings is a rapidly advancing field, with significant implications for artificial intelligence and human-computer interaction. This study introduces a novel method for detecting emotions from short, 1.5 s audio samples, aiming to improve accuracy and efficiency in emotion recognition technologies.

Methods

We utilized 1,510 unique audio samples from two databases in German and English to train our models. We extracted various features for emotion prediction, employing Deep Neural Networks (DNN) for general feature analysis, Convolutional Neural Networks (CNN) for spectrogram analysis, and a hybrid model combining both approaches (C-DNN). The study addressed challenges associated with dataset heterogeneity, language differences, and the complexities of audio sample trimming.

Results

Our models demonstrated accuracy significantly surpassing random guessing, aligning closely with human evaluative benchmarks. This indicates the effectiveness of our approach in recognizing emotional states from brief audio clips.

Discussion

Despite the challenges of integrating diverse datasets and managing short audio samples, our findings suggest considerable potential for this methodology in real-time emotion detection from continuous speech. This could contribute to improving the emotional intelligence of AI and its applications in various areas.
Changes in mental health levels among Chinese athletes from 1995 to 2023
Authors: Xi Yue , Liu Fengbo , Yang Jian
Published: March 2024

Objective

In recent years, with the increasing intensity of sports competition and social pressure, the issue of mental health among athletes have gradually attracted attention. Understanding the changing trends of athletes’ mental health is of great significance for formulating effective intervention measures and safeguarding the mental health of athletes.

Methods

A total of 306 articles were accumulated from September to November 2023 by selecting literature from databases that measured the mental health of Chinese athletes using the Symptom Checklist-90 (SCL-90). Based on the screening criteria, 28 articles (N = 4,227) were finally included. A cross-sectional historical meta-analysis of these 28 studies using the SCL-90 between 1995 and 2023 was conducted. Based on cross-sectional historical meta-analysis methods, specific statistical methods, such as correlation and regression analyses, were used to examine trends over time in the scores of the nine SCL-90 factors measured by the athletes in the studies, as well as athlete type and gender differences.

Results

(1) Athletes’ scores on the depression, hostility, phobic anxiety, and paranoid ideation factors gradually increased with the change of era, and the explanation rate of the variation of each factor by era ranged from 18.8 to 27.2%; (2) During the period from 1995 to 2023, the mental health of athletes in China gradually deteriorated on the factors of depression, hostility, and phobic anxiety, the rate of change was rapid, with a medium to large magnitude (0.28–0.42); (3) The scores of female athletes on the depression and psychoticism factors scores showed a significant upward trend, while male mental health scores for each factor did not improve significantly over the years; (4) College athletes’ scores on the depression, anxiety, hostility, phobic anxiety, paranoid ideation, and psychoticism factors showed an upward trend as the years changed.

Conclusion

Chinese athletes’ mental health has been on a downward trend for the past 28 years, which needs to be a cause for concern.
Improvement of social functioning in patients with first-episode schizophrenia using blonanserin treatment: a prospective, multi-centre, single-arm clinical trial
Authors: Gao Tianqi , Deng Hong , Sheng Jianhua , Wu Bin , Liu Zhening , Yang Fude , Wang Lina , Hu Shaohua , Wang Xijin , Li Haiyun , Pu Chengcheng , Yu Xin
Published: March 2024

Objectives

This clinical trial primarily aimed to investigate the effects of blonanserin on social functioning in patients with first-episode schizophrenia.

Methods

In this prospective, multi-centre, single-arm clinical trial study, blonanserin (flexible oral dose ranging from 8mg to 24mg per day) was given 26 weeks. Outcome measures included the Personal and Social Performance (PSP) scale for evaluating social functioning, the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB) for measuring neurocognitive performance, and the Positive and Negative Syndrome Scale (PANSS) for assessing symptom severity. The primary endpoint was social function improvement evaluated by PSP scale at the end of blonanserin treatment. And the secondary endpoint was to validate the efficacy and neurocognitive effects of blonanserin. Adverse drug reactions (ADRs) were also recorded and analysed.

Results

A total of 96 patients with first-episode schizophrenia were recruited and proceeded to analysis. Fifty-one participants (53.1%) completed the PSP scale measurements at baseline and week 26. Following 26 weeks of blonanserin treatment, all outcome measurements demonstrated significant improvement during the follow-up period. Notably, PSP scores exhibited a continuous increase up to 68.1% ± 103.7% at the end of the treatment (46.6 ± 14.6 at baseline, 69.4 ± 17.4 at week 26, p<0.001), indicating positive effects on social functioning that were already noticeable by week 8.

Conclusion

Blonanserin treatment exhibited favourable effects on social functioning in individuals with first-episode schizophrenia. The results suggest that blonanserin was effective treatment options for patients with schizophrenia encountering functional impairments.