bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of potential therapeutic targets for COVID-19 through a structural-based similarity approach between SARS-CoV-2 and its human host proteins
Authors: Tasneem Alvea , Sultan Armiya , Singh Prithvi , Bairagya Hridoy R. , Almasoudi Hassan Hussain , Alhazmi Abdulfattah Yahya M. , Binshaya Abdulkarim S. , Hakami Mohammed Ageeli , Alotaibi Bader S. , Abdulaziz Eisa Alaa , Alolaiqy Abdulaziz Saleh I. , Hasan Mohammad Raghibul , Dev Kapil , Dohare Ravins
Published: February 2024

Background: The COVID-19 pandemic caused by SARS-CoV-2 has led to millions of deaths worldwide, and vaccination efficacy has been decreasing with each lineage, necessitating the need for alternative antiviral therapies. Predicting host–virus protein–protein interactions (HV-PPIs) is essential for identifying potential host-targeting drug targets against SARS-CoV-2 infection.

Objective: This study aims to identify therapeutic target proteins in humans that could act as virus–host-targeting drug targets against SARS-CoV-2 and study their interaction against antiviral inhibitors.

Methods: A structure-based similarity approach was used to predict human proteins similar to SARS-CoV-2 (“hCoV-2”), followed by identifying PPIs between hCoV-2 and its target human proteins. Overlapping genes were identified between the protein-coding genes of the target and COVID-19-infected patient’s mRNA expression data. Pathway and Gene Ontology (GO) term analyses, the construction of PPI networks, and the detection of hub gene modules were performed. Structure-based virtual screening with antiviral compounds was performed to identify potential hits against target gene-encoded protein.

Results: This study predicted 19,051 unique target human proteins that interact with hCoV-2, and compared to the microarray dataset, 1,120 target and infected group differentially expressed genes (TIG-DEGs) were identified. The significant pathway and GO enrichment analyses revealed the involvement of these genes in several biological processes and molecular functions. PPI network analysis identified a significant hub gene with maximum neighboring partners. Virtual screening analysis identified three potential antiviral compounds against the target gene-encoded protein.

Conclusion: This study provides potential targets for host-targeting drug development against SARS-CoV-2 infection, and further experimental validation of the target protein is required for pharmaceutical intervention.
Mining of disease-resistance genes in Crocus sativus based on transcriptome sequencing
Authors: Ye Dongdong , Zhang Siwei , Gao Xiankui , Li Xiujuan , Jin Xin , Shi Min , Kai Guoyin , Zhou Wei
Published: February 2024

Introduction:Crocus sativus L. has an important medicinal and economic value in traditional perennial Chinese medicine. However, due to its unique growth characteristics, during cultivation it is highly susceptible to disease. The absence of effective resistance genes restricts us to breed new resistant varieties of C. sativus.

Methods: In present study, comprehensive transcriptome sequencing was introduced to explore the disease resistance of the candidate gene in healthy and corm rot-infected C. sativus.

Results and discussion: Totally, 43.72 Gb of clean data was obtained from the assembly to generate 65,337 unigenes. By comparing the gene expression levels, 7,575 differentially expressed genes (DEGs) were primarily screened. A majority of the DEGs were completely in charge of defense and metabolism, and 152 of them were annotated as pathogen recognition genes (PRGs) based on the PGRdb dataset. The expression of some transcription factors including NAC, MYB, and WRKY members, changed significantly based on the dataset of transcriptome sequencing. Therefore, this study provides us some valuable information for exploring candidate genes involved in the disease resistance in C. sativus.
Molecular characterization, expression pattern and immunologic function of CD82a in large yellow croaker (Larimichthys crocea)
Authors: Liu Yue , Bai Yulin , Chen Sijing , Pu Fei , Li Yaxian , Chi Hongshu , Zheng Zaiyu , Xu Peng , Zhou Tao
Published: February 2024

Visceral white spot disease (VWND) caused by Pseudomonas plecoglossicida poses a major threat to the sustainable development of large yellow croaker (Larimichthys crocea) aquaculture. Genome-wide association analysis (GWAS) and RNA-seq research indicated that LcCD82a play an important role in resistance to visceral white spot disease in L. crocea, but the molecular mechanism of LcCD82a response to P. plecoglossicida infection is still unclear. In this study, we cloned and validated the Open Reading Frame (ORF) sequence of LcCD82a and explored the expression profile of LcCD82a in various tissues of L.crocea. In addition, two different transcript variants (LcCD82a-L and LcCD82a-S) of LcCD82a were identified that exhibit alternative splicing patterns after P. plecoglossicida infection, which may be closely related to the immune regulation during pathogenetic process of VWND. In order to explore the function of LcCD82a, we purified the recombinant protein of LcCD82a-L and LcCD82a-S. The bacterial agglutination and apoptosis function analysis showed that LcCD82a may involve in extracellular bacterial recognition, agglutination, and at the same time participate in the process of antigen presentation and induction of cell apoptosis. Collectively, our studies demonstrate that LcCD82a plays a crucial role in regulating apoptosis and antimicrobial immunity.
Role and therapeutic targets of P2X7 receptors in neurodegenerative diseases
Authors: Zheng Huiyong , Liu Qiang , Zhou Siwei , Luo Hongliang , Zhang Wenjun
Published: February 2024

The P2X7 receptor (P2X7R), a non-selective cation channel modulated by adenosine triphosphate (ATP), localizes to microglia, astrocytes, oligodendrocytes, and neurons in the central nervous system, with the most incredible abundance in microglia. P2X7R partake in various signaling pathways, engaging in the immune response, the release of neurotransmitters, oxidative stress, cell division, and programmed cell death. When neurodegenerative diseases result in neuronal apoptosis and necrosis, ATP activates the P2X7R. This activation induces the release of biologically active molecules such as pro-inflammatory cytokines, chemokines, proteases, reactive oxygen species, and excitotoxic glutamate/ATP. Subsequently, this leads to neuroinflammation, which exacerbates neuronal involvement. The P2X7R is essential in the development of neurodegenerative diseases. This implies that it has potential as a drug target and could be treated using P2X7R antagonists that are able to cross the blood-brain barrier. This review will comprehensively and objectively discuss recent research breakthroughs on P2X7R genes, their structural features, functional properties, signaling pathways, and their roles in neurodegenerative diseases and possible therapies.
Age and growth estimates for the nurse shark (Ginglymostoma cirratum) over 17 years in Bimini, The Bahamas
Authors: Fadool Baylie A. , Bostick Kylie G. , Brewster Lauran R. , Hansell Alexander C. , Carlson John K. , Smukall Matthew J.
Published: February 2024

Age and growth estimates are essential for life history modeling in elasmobranchs and are used to inform accurate conservation and management decisions. The nurse shark (Ginglymostoma cirratum) is abundant in coastal waters of the Atlantic Ocean, yet many aspects of their life history remain relatively understudied, aside from their reproductive behavior. We used mark-recapture data of 91 individual G. cirratum from Bimini, The Bahamas, from 2003 to 2020, to calculate von Bertalanffy (vB) growth parameters, empirical growth rate, and age derived from the resulting length-at-age estimates. The Fabens method for estimating growth from mark-recapture methods was applied through a Bayesian framework using Markov chain Monte Carlo (MCMC) methods. This provided growth parameters with an asymptotic total length (L∞) of 303.28 cm and a growth coefficient (k) of 0.04 yr-1. The average growth rate for G. cirratum was approximately 8.68 ± 6.00 cm yr-1. This study also suggests that the previous maximum age for G. cirratum is likely underestimated, with the oldest individual predicted to be 43 years old. Our study is the first to present vB growth parameters and a growth curve for G. cirratum. It indicates that this species is slow-growing and long-lived, which improves our understanding of their life history.
Bifidobacterium species viability in dairy-based probiotic foods: challenges and innovative approaches for accurate viability determination and monitoring of probiotic functionality
Authors: Sibanda Thulani , Marole Tlaleo Azael , Thomashoff Ursula Louise , Thantsha Mapitsi S. , Buys Elna M.
Published: February 2024

Bifidobacteriumspecies are essential members of a healthy human gut microbiota. Their presence in the gut is associated with numerous health outcomes such as protection against gastrointestinal tract infections, inflammation, and metabolic diseases. Regular intake ofBifidobacteriumin foods is a sustainable way of maintaining the health benefits associated with its use as a probiotic. Owing to their global acceptance, fermented dairy products (particularly yogurt) are considered the ideal probiotic carrier foods. As envisioned in the definition of probiotics as “live organisms,” the therapeutic functionalities ofBifidobacteriumspp. depend on maintaining their viability in the foods up to the point of consumption. However, sustainingBifidobacteriumspp. viability during the manufacture and shelf-life of fermented dairy products remains challenging. Hence, this paper discusses the significance of viability as a prerequisite forBifidobacteriumspp. probiotic functionality. The paper focuses on the stress factors that influenceBifidobacteriumspp. viability during the manufacture and shelf life of yogurt as an archetypical fermented dairy product that is widely accepted as a delivery vehicle for probiotics. It further expounds theBifidobacteriumspp. physiological and genetic stress response mechanisms as well as the methods for viability retention in yogurt, such as microencapsulation, use of oxygen scavenging lactic acid bacterial strains, and stress-protective agents. The report also explores the topic of viability determination as a critical factor in probiotic quality assurance, wherein, the limitations of culture-based enumeration methods, the challenges of species and strain resolution in the presence of lactic acid bacterial starter and probiotic species are discussed. Finally, new developments and potential applications of next-generation viability determination methods such as flow cytometry, propidium monoazide–quantitative polymerase chain reaction (PMA-qPCR), next-generation sequencing, and single-cell Raman spectroscopy (SCRS) methods are examined.
A biofertilizing fungal endophyte of cranberry plants suppresses the plant pathogen Diaporthe
Authors: Thimmappa Bhagya C. , Salhi Lila Naouelle , Forget Lise , Sarrasin Matt , Bustamante Villalobos Peniel , Henrissat Bernard , Lang B. Franz , Burger Gertraud
Published: February 2024

Fungi colonizing plants are gaining attention because of their ability to promote plant growth and suppress pathogens. While most studies focus on endosymbionts from grasses and legumes, the large and diverse group of ericaceous plants has been much neglected. We recently described one of the very few fungal endophytes promoting the growth of the Ericaceae Vaccinium macrocarpon (American cranberry), notably the Codinaeella isolate EC4. Here, we show that EC4 also suppresses fungal pathogens, which makes it a promising endophyte for sustainable cranberry cultivation. By dual-culture assays on agar plates, we tested the potential growth suppression (or biocontrol) of EC4 on other microbes, notably 12 pathogenic fungi and one oomycete reported to infect not only cranberry but also blueberry, strawberry, tomato plants, rose bushes and olive trees. Under greenhouse conditions, EC4 protects cranberry plantlets infected with one of the most notorious cranberry-plant pathogens, Diaporthe vaccinii, known to cause upright dieback and berry rot. The nuclear genome sequence of EC4 revealed a large arsenal of genes potentially involved in biocontrol. About ∼60 distinct clusters of genes are homologs of secondary metabolite gene clusters, some of which were shown in other fungi to synthesize nonribosomal peptides and polyketides, but in most cases, the exact compounds these clusters may produce are unknown. The EC4 genome also encodes numerous homologs of hydrolytic enzymes known to degrade fungal cell walls. About half of the nearly 250 distinct glucanases and chitinases are likely involved in biocontrol because they are predicted to be secreted outside the cell. Transcriptome analysis shows that the expression of about a quarter of the predicted secondary-metabolite gene clusters and glucan and chitin-degrading genes of EC4 is stimulated when it is co-cultured with D. vaccinii. Some of the differentially expressed EC4 genes are alternatively spliced exclusively in the presence of the pathogen, altering the proteins’ domain content and subcellular localization signal, thus adding a second level of proteome adaptation in response to habitat competition. To our knowledge, this is the first report of Diaporthe-induced alternative splicing of biocontrol genes.
Feedback control of collective dynamics in an oscillator population with time-dependent connectivity
Authors: Rosenblum Michael
Published: February 2024

We present a numerical study of pulsatile feedback-based control of synchrony level in a highly-interconnected oscillatory network. We focus on a nontrivial case when the system is close to the synchronization transition point and exhibits collective rhythm with strong amplitude modulation. We pay special attention to technical but essential steps like causal real-time extraction of the signal of interest from a noisy measurement and estimation of instantaneous phase and amplitude. The feedback loop’s parameters are tuned automatically to suppress synchrony. Though the study is motivated by neuroscience, the results are relevant to controlling oscillatory activity in ensembles of various natures and, thus, to the rapidly developing field of network physiology.
Correlation between inflammatory markers over time and disease severity in status epilepticus: a preliminary study
Authors: Shi Xiangsong , Zhang Xiulin , Song Sumeng , Pan Heyue , Huang Chengbing , Sun Taipeng , Wang Shouyong , Xu Jianyang
Published: February 2024

Objectives

Convulsive status epilepticus (CSE) is a major subtype of status epilepticus that is known to be closely associated with systemic inflammation. Some important inflammatory biomarkers of this disorder include the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), systemic immune inflammation index (SII), and pan-immune inflammation value (PIV). This study aimed to determine the NLR, PLR, MLR, SII, and PIV levels before and after treatment in adult patients with CSE and investigated the relationship of these parameters with disease severity.

Methods

This retrospective study analyzed data from 103 adult patients with CSE and 103 healthy controls. The neutrophil, monocyte, platelet, and lymphocyte counts, as well as the NLR, PLR, MLR, SII, and PIV, were compared in adult patients with CSE during acute seizures (within 2 h of admission) and after treatment relief (1–2 weeks of complete seizure control). Furthermore, multivariate linear regression analysis investigated the relationship between NLR, PLR, MLR, SII, and PIV with the Status Epilepticus Severity Score (STESS).

Results

The data revealed significant differences (p < 0.05) in neutrophils, monocytes, lymphocytes, NLR, PLR, MLR, SII, and PIV between adult patients with CSE during acute seizures and after treatment relief. The average neutrophil count was high during acute seizures in the patient group and decreased after remission. In contrast, the average lymphocyte count was lower after remission (p < 0.05). Furthermore, significant differences (p < 0.05) were observed in monocytes, lymphocytes, platelets, NLR, PLR, MLR, and PIV levels between adult patients with CSE after remission and the healthy control group. Multivariate linear regression analysis showed no significant correlation between NLR, PLR, MLR, SII, and PIV with STESS.

Conclusion

The results of this study indicated that adult patients with CSE experienced a transient systemic inflammatory response during acute seizures, which gradually returned to baseline levels after remission. However, there was a lack of robust clinical evidence correlating the severity of adult CSE and systemic inflammatory response.
Machine learning-based prediction of mild cognitive impairment among individuals with normal cognitive function
Authors: Zhu Xia Wei , Liu Si Bo , Ji Chen Hua , Liu Jin Jie , Huang Chao
Published: February 2024

Background

Previous studies mainly focused on risk factors in patients with mild cognitive impairment (MCI) or dementia. The aim of the study was to provide basis for preventing MCI in cognitive normal populations.

Methods

The data came from a longitudinal retrospective study involving individuals with brain magnetic resonance imaging scans, clinical visits, and cognitive assessment with interval of more than 3 years. Multiple machine-learning technologies, including random forest, support vector machine, logistic regression, eXtreme Gradient Boosting, and naïve Bayes, were used to establish a prediction model of a future risk of MCI through a combination of clinical and image variables.

Results

Among these machine learning models; eXtreme Gradient Boosting (XGB) was the best classification model. The classification accuracy of clinical variables was 65.90%, of image variables was 79.54%, of a combination of clinical and image variables was 94.32%. The best result of the combination was an accuracy of 94.32%, a precision of 96.21%, and a recall of 93.08%. XGB with a combination of clinical and image variables had a potential prospect for the risk prediction of MCI. From clinical perspective, the degree of white matter hyperintensity (WMH), especially in the frontal lobe, and the control of systolic blood pressure (SBP) were the most important risk factor for the development of MCI.

Conclusion

The best MCI classification results came from the XGB model with a combination of both clinical and imaging variables. The degree of WMH in the frontal lobe and SBP control were the most important variables in predicting MCI.
Experiences and perceptions of people with celiac disease, food allergies and food intolerance when dining out
Authors: Figueroa-Gómez Ximena , Oliveras-López María Jesus , Rodríguez Silva Juan Manuel , Poyanco Marcelo , López Herminia , Araya Magdalena
Published: February 2024

Introduction

Eating out is a common practice in modern society. Celiac disease (CeD) and food allergy (FA) are among the most common conditions responsible for adverse reactions to food. Despite their different origins, both require treatment with restrictive diets (avoidance of gluten and/or specific allergens) and this results posing similar challenges when eating out. Our objective was to learn about the experiences/perceptions of consumers with CeD and FA when dining out, as well as the challenges they face in food service environments.

Methods

An ad hoc questionnaire was used to record consumer perceptions, food service characteristics and resulting adverse reactions.

Results

377 individuals living in Santiago, Chile, provided complete information and were analyzed (160 CeD, 105 FA). 301 participants (79.8%) declared eating out, 33.6% reported experiencing an adverse reaction at least once while eating out. 94.4% of the 377 participants believed that the serving staff had little or no knowledge about his/her condition. Consumers reporting symptoms as severe adverse reactions were more common among celiac than allergic patients (p < 0.001).

Discussion

The study showed no significant differences based on consumer-related characteristics (p:NS). The consequences of eating out did not vary based on individual’s data, including diagnosis, age, frequency of eating out, adverse reactions experienced, or intensity. These findings suggest that the most important determinants of risk associated with eating out are characteristics of the food service, like availability of information, staff training, and establishment’s facilities like equipment available, exclusive utensils for customers with special dietary needs and kitchen and bathrooms organization.
Trends of serum 25(OH) vitamin D and association with cardiovascular disease and all-cause mortality: from NHANES survey cycles 2001–2018
Authors: Hu Changlun , Yang Mei
Published: February 2024

Background

The focus of this survey is on survey data for adults aged 20 and above, covering nine survey cycles from 2001 to 2018. Additionally, the present study explored the correlation between vitamin D concentrations and both cardiovascular disease (CVD) and all-cause mortality.

Objective

The objectives of this study were to evaluate the trend of changes in the serum 25(OH)D concentration changes in US adults during the survey period, the prevalence of vitamin D deficiency, and the current status of vitamin D dietary intake and supplementation.

Methods

In-home health interviews were performed using meticulously designed questionnaires that gathered information on demographic details, socioeconomic conditions, dietary patterns, and overall health status. Health assessments were conducted in specially designed mobile centers.1

Results

Survey data from 2001 to 2018 revealed a rise in serum 25(OH)D levels, from a weighted mean (95% CI) of 65.6 (63.8–67.4) nmol/L during 2001–2002 to 73.5 (70.4–76.5) nmol/L during 2017–2018, among US adults, while overall vitamin D deficiency rates remained stable (p = 0.152). Notably, in adults aged 20–39, 25(OH)D levels decreased (p = 0.002 for trend), and 25(OH)D deficiency increased (p = 0.003 for trend), especially among those with low incomes (deficiency >30%). Upon multivariable adjustment, an L-shaped relationship was found between serum 25(OH)D concentrations and both CVD and all-cause mortality (p < 0.001 for nonlinearity), as corroborated by sensitivity analyses.

Conclusion

From 2001 to 2018, US adults experienced a significant increase in their serum 25(OH) D concentration. However, subgroups of individuals, including young adults and individuals with lower socioeconomic status, exhibited a heightened risk of 25(OH)D deficiency. Furthermore, an L-shaped relationship was found between 25(OH)D concentration and both all-cause and CVD mortality among US adults.
Contemporary preclinical mouse models for pediatric rhabdomyosarcoma: from bedside to bench to bedside
Authors: Martynov Illya , Dhaka Lajwanti , Wilke Benedikt , Hoyer Paul , Vahdad M. Reza , Seitz Guido
Published: February 2024

Background

Rhabdomyosarcoma (RMS) is the most common pediatric soft-tissue malignancy, characterized by high clinicalopathological and molecular heterogeneity. Preclinical in vivo models are essential for advancing our understanding of RMS oncobiology and developing novel treatment strategies. However, the diversity of scholarly data on preclinical RMS studies may challenge scientists and clinicians. Hence, we performed a systematic literature survey of contemporary RMS mouse models to characterize their phenotypes and assess their translational relevance.

Methods

We identified papers published between 01/07/2018 and 01/07/2023 by searching PubMed and Web of Science databases.

Results

Out of 713 records screened, 118 studies (26.9%) were included in the qualitative synthesis. Cell line-derived xenografts (CDX) were the most commonly utilized (n = 75, 63.6%), followed by patient-derived xenografts (PDX) and syngeneic models, each accounting for 11.9% (n = 14), and genetically engineered mouse models (GEMM) (n = 7, 5.9%). Combinations of different model categories were reported in 5.9% (n = 7) of studies. One study employed a virus-induced RMS model. Overall, 40.0% (n = 30) of the studies utilizing CDX models established alveolar RMS (aRMS), while 38.7% (n = 29) were embryonal phenotypes (eRMS). There were 20.0% (n = 15) of studies that involved a combination of both aRMS and eRMS subtypes. In one study (1.3%), the RMS phenotype was spindle cell/sclerosing. Subcutaneous xenografts (n = 66, 55.9%) were more frequently used compared to orthotopic models (n = 29, 24.6%). Notably, none of the employed cell lines were derived from primary untreated tumors. Only a minority of studies investigated disseminated RMS phenotypes (n = 16, 13.6%). The utilization areas of RMS models included testing drugs (n = 64, 54.2%), studying tumorigenesis (n = 56, 47.5%), tumor modeling (n = 19, 16.1%), imaging (n = 9, 7.6%), radiotherapy (n = 6, 5.1%), long-term effects related to radiotherapy (n = 3, 2.5%), and investigating biomarkers (n = 1, 0.8%). Notably, no preclinical studies focused on surgery.

Conclusions

This up-to-date review highlights the need for mouse models with dissemination phenotypes and cell lines from primary untreated tumors. Furthermore, efforts should be directed towards underexplored areas such as surgery, radiotherapy, and biomarkers.
The Pain Intervention & Digital Research Program: an operational report on combining digital research with outpatient chronic disease management
Authors: Fu Melanie , Shen Joanna , Gu Cheryl , Oliveira Ellina , Shinchuk Ellisha , Isaac Hannah , Isaac Zacharia , Sarno Danielle L. , Kurz Jennifer L. , Silbersweig David A. , Onnela Jukka-Pekka , Barron Daniel S.
Published: February 2024

Chronic pain affects up to 28% of U.S. adults, costing ∼$560 billion each year. Chronic pain is an instantiation of the perennial complexity of how to best assess and treat chronic diseases over time, especially in populations where age, medical comorbidities, and socioeconomic barriers may limit access to care. Chronic disease management poses a particular challenge for the healthcare system's transition from fee-for-service to value and risk-based reimbursement models. Remote, passive real-time data from smartphones could enable more timely interventions and simultaneously manage risk and promote better patient outcomes through predicting and preventing costly adverse outcomes; however, there is limited evidence whether remote monitoring is feasible, especially in the case of older patients with chronic pain. Here, we introduce the Pain Intervention and Digital Research (Pain-IDR) Program as a pilot initiative launched in 2022 that combines outpatient clinical care and digital health research. The Pain-IDR seeks to test whether functional status can be assessed passively, through a smartphone application, in older patients with chronic pain. We discuss two perspectives—a narrative approach that describes the clinical settings and rationale behind changes to the operational design, and a quantitative approach that measures patient recruitment, patient experience, and HERMES data characteristics. Since launch, we have had 77 participants with a mean age of 55.52, of which n = 38 have fully completed the 6 months of data collection necessitated to be considered in the study, with an active data collection rate of 51% and passive data rate of 78%. We further present preliminary operational strategies that we have adopted as we have learned to adapt the Pain-IDR to a productive clinical service. Overall, the Pain-IDR has successfully engaged older patients with chronic pain and presents useful insights for others seeking to implement digital phenotyping in other chronic disease settings.
Neurodegeneration: can metabolites from Eremurus persicus help?
Authors: Cavalloro Valeria , Marchesi Nicoletta , Linciano Pasquale , Rossi Daniela , Campagnoli Lucrezia Irene Maria , Fossati Alice , Ahmed Karzan Mahmood , Malacrida Alessio , Miloso Mariarosaria , Mazzeo Giuseppe , Abbate Sergio , Longhi Giovanna , Ambrosio Francesca Alessandra , Costa Giosuè , Alcaro Stefano , Pascale Alessia , Martino Emanuela , Collina Simona
Published: February 2024

The number of patients affected by neurodegenerative diseases is increasing worldwide, and no effective treatments have been developed yet. Although precision medicine could represent a powerful tool, it remains a challenge due to the high variability among patients. To identify molecules acting with innovative mechanisms of action, we performed a computational investigation using SAFAN technology, focusing specifically on HuD. This target belongs to the human embryonic lethal abnormal visual-like (ELAV) proteins and plays a key role in neuronal plasticity and differentiation. The results highlighted that the molecule able to bind the selected target was (R)-aloesaponol-III-8-methyl ether [(R)-ASME], a metabolite extracted from Eremurus persicus. Notably, this molecule is a TNF-α inhibitor, a cytokine involved in neuroinflammation. To obtain a suitable amount of (R)-ASME to confirm its activity on HuD, we optimized the extraction procedure. Together with ASME, another related metabolite, germichrysone, was isolated. Both ASME and germichrysone underwent biological investigation, but only ASME confirmed its ability to bind HuD. Given the multifactorial nature of neurodegenerative diseases, we decided to investigate ASME as a proteasome activator, being molecules endowed with this kind of activity potentially able to counteract aggregations of dysregulated proteins. ASME was able to activate the considered target both in enzymatic and cellular assays. Therefore, ASME may be considered a promising hit in the fight against neurodegenerative diseases.
Modeling the SDF-1/CXCR4 protein using advanced artificial intelligence and antagonist screening for Japanese anchovy
Authors: Yahiro Issei , Barnuevo Kyle Dominic Eguid , Sato Oga , Mohapatra Sipra , Toyoda Atsushi , Itoh Takehiko , Ohno Kaoru , Matsuyama Michiya , Chakraborty Tapas , Ohta Kohei
Published: February 2024

SDF-1/CXCR4 chemokine signaling are indispensable for cell migration, especially the Primordial Germ Cell (PGC) migration towards the gonadal ridge during early development. We earlier found that this signaling is largely conserved in the Japanese anchovy (Engraulis japonicus, EJ), and a mere treatment of CXCR4 antagonist, AMD3100, leads to germ cell depletion and thereafter gonad sterilization. However, the effect of AMD3100 was limited. So, in this research, we scouted for CXCR4 antagonist with higher potency by employing advanced artificial intelligence deep learning-based computer simulations. Three potential candidates, AMD3465, WZ811, and LY2510924, were selected and in vivo validation was conducted using Japanese anchovy embryos. We found that seven transmembrane motif of EJ CXCR4a and EJ CXCR4b were extremely similar with human homolog while the CXCR4 chemokine receptor N terminal (PF12109, essential for SDF-1 binding) was missing in EJ CXCR4b. 3D protein analysis and cavity search predicted the cavity in EJ CXCR4a to be five times larger (6,307 Å³) than that in EJ CXCR4b (1,241 Å³). Docking analysis demonstrated lower binding energy of AMD3100 and AMD3465 to EJ CXCR4a (Vina score −9.6) and EJ CXCR4b (Vina score −8.8), respectively. Furthermore, we observed significant PGC mismigration in microinjected AMD3465 treated groups at 10, 100 and 1 × 105 nM concentration in 48 h post fertilized embryos. The other three antagonists showed various degrees of PGC dispersion, but no significant effect compared to their solvent control at tested concentrations was observed. Cumulatively, our results suggests that AMD3645 might be a better candidate for abnormal PGC migration in Japanese anchovy and warrants further investigation.
Impact of cognitive reserve on bipolar disorder: a systematic review
Authors: Matsumoto Kazuki , Hamatani Sayo
Published: February 2024

Background

Cognitive reserve (CR) is a complex concept that includes premorbid IQ, years of education, and exposure to neuropsychological stimuli through work and leisure. Previous studies have suggested that CR has a positive impact on several aspects of bipolar disorder. Synthesizing the evidence to date is an important work in providing directions for future studies. The objectives of this systematic review to summary impact of CR on onsetting, relapsing bipolar episodes, buffering cognitive dysfunctions, and maintaining quality of life (QOL) in bipolar disorder.

Methods

Two researchers independently reviewed selected paper from three database as PubMed, PsychINFO, and Web of Science. The search keywords were “bipolar disorder” and “cognitive reserve.” The selected studies were classified as the levels of evidence according to the criteria of the Oxford Center for Evidence- Based Medicine. The results of the selected studies were summarized according to the objectives.

Results

Thrity six studies were included in this review. People with high CR may have fewer bipolar episodes and alleviate cognitive impairments and dysfunction. CR may keep the functional level in patients with bipolar disorder.

Conclusion

The results of this systematic review suggest that CR may be involved in preventing relapse of bipolar episodes and may alleviate cognitive dysfunction. However, effect on prevention of onset-risk and relapse of bipolar episodes need further investigation in prospective studies.

Systematic review registration

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021270293, the protocol was registered with PROSERO (CRD42021270293).
Electroacupuncture versus Escitalopram for mild to moderate Post-Stroke Depression: A randomized non-inferiority trial
Authors: Ma Feixiang , Cao Guiping , Lu Lu , Zhu Yingling , Li Wanlang , Chen Li
Published: February 2024

Objective

To explore the efficacy of electroacupuncture in treating post-stroke depression (PSD) by modulating the inflammatory response pathway.

Methods

One hundred and fifty participants with mild or moderate PSD were randomly divided into 75 cases each in the electroacupuncture group (EA group) and escitalopram group (ESC group). In the EA group, 30 sessions of electroacupuncture were performed on the Baihui (GV 20), Yintang (GV 29), and the ipsilateral Taichong (LR 3) and Hegu (LI 4), simultaneous oral placebo for 40 days. The ESC group received oral escitalopram oxalate tablets 10mg to 20mg for 40 days, plus 30 sessions of sham electroacupuncture. The effectiveness of the treatment was evaluated by the Hamilton Depression Scale (HAMD-17), Self-Depression Scale (SDS), Modified Barthel Index Score (MBI), and the serum levels of IL-1β, IL-6, IL-10, TNF-α, and INF-γ.

Results

There was no statistically significant difference in the baseline data, HAMD-17, SDS, MBI scores, and serum IL-1β, IL-6, IL-10, TNF-α, and INF-γ levels between the two groups of participants before the intervention (P >0.05). After treatment, HAMD-17 and SDS scores continued to decrease and MBI scores continued to increase in both groups. The differences were statistically significant at the 6th week and baseline, the 10th week and baseline, and the 10th week and the 6th week (all P <0.001). The differences in HAMD-17, SDS, and MBI scores between the two groups at the 6th week were not statistically significant (P=0.110, 0.115, 0.516, respectively); HAMD-17 scores and SDS scores in the EA group were lower than those in the ESC group at the 10th week, and the differences were statistically significant (P=0.002,0.026, respectively). In the 6th week, the serum levels of pro-inflammatory factors such as IL-1β, IL-6, TNF-α, and INF-γ were significantly lower in both groups compared with the baseline, while the level of anti-inflammatory factor IL-10 was significantly higher. The difference between the pre-and post-intervention intra-group comparisons was statistically significant (P <0.001), and the difference between the inter-group comparisons was not statistically significant (P >0.05). No serious adverse events occurred throughout the trial. Both therapies could safely and effectively improve HAMD-17, SDS, and MBI scores and modulate neuroinflammatory responses in PSD participants. After the treatment was stopped, some parameters were better in the EA group than the ESC group in a short time.

Conclusion

Electroacupuncture is an effective, alternative to escitalopram for the treatment of mild-to-moderate PSD.

Clinical trial registration

Chinese Clinical Trial Registry (ChiCTR2300072576).
Safety risk assessment of subway shield construction under-crossing a river using CFA and FER
Authors: He Kuang , Cui Tianlin , Cheng Jianhua , Huang Yanlong , Li Hujun , Chen Huihua , Yang Ke
Published: February 2024

Numerous subway projects are planned by China's city governments, and more subways can hardly avoid under-crossing rivers. While often being located in complex natural and social environments, subway shield construction under-crossing a river (SSCUR) is more susceptible to safety accidents, causing substantial casualties, and monetary losses. Therefore, there is an urgent need to investigate safety risks during SSCUR. The paper identified the safety risks during SSCUR by using a literature review and experts' evaluation, proposed a new safety risk assessment model by integrating confirmatory factor analysis (CFA) and fuzzy evidence reasoning (FER), and then selected a project to validate the feasibility of the proposed model. Research results show that (a) a safety risk list of SSCUR was identified, including 5 first-level safety risks and 38 second-level safety risks; (b) the proposed safety risk assessment model can be used to assess the safety risk of SSCUR; (c) safety inspection, safety organization and duty, quicksand layer, and high-pressure phreatic water were the high-level risks, and the onsite total safety risk was at the medium level; (d) management-type safety risks, environment-type safety risks, and personnel-type safety risks have higher expected utility values, and manager-type safety risks were expected have higher risk-utility values when compared to worker-type safety risks. The research can enrich the theoretical knowledge of SSCUR safety risk assessment and provide references to safety managers for conducting scientific and effective safety management on the construction site when a subway crosses under a river.
Factors affecting advance directives completion among older adults in Korea
Authors: Choi Seunghye , Ko Hana
Published: February 2024

Objective

Advance directives (ADs) provide an opportunity for patients to enhance the quality of their end-of-life care and prepare for a dignified death by deciding treatment plans. The purpose of this study was to explore the multiple factors that influence the advance directives completion among older adults in South Korea.

Methods

This was a secondary analysis of a cross-sectional study of 9,920 older adults. The differences in ADs based on subjects’ sociodemographic characteristics, health-related characteristics, and attitude toward death were tested using the chi-squared and t-test. A multinomial logistic regression model was used to identify the influencing factor of ADs.

Results

The number of chronic diseases, number of prescribed medications, depression, insomnia, suicide intention, and hearing, vision, or chewing discomfort were higher in the ADs group compared to the non-ADs group. The influencing factors of the signing of ADs included men sex, higher education level, exercise, death preparation education, lower awareness of dying-well, and experience of fracture.

Conclusion

Information dissemination regarding ADs should be promoted and relevant authorities should consider multiple options to improve the physical and psychological health of older adults, as well as their attitude toward death to increase the ADs completion rate.
Detecting the corruption of online questionnaires by artificial intelligence
Authors: Lebrun Benjamin , Temtsin Sharon , Vonasch Andrew , Bartneck Christoph
Published: February 2024

Online questionnaires that use crowdsourcing platforms to recruit participants have become commonplace, due to their ease of use and low costs. Artificial intelligence (AI)-based large language models (LLMs) have made it easy for bad actors to automatically fill in online forms, including generating meaningful text for open-ended tasks. These technological advances threaten the data quality for studies that use online questionnaires. This study tested whether text generated by an AI for the purpose of an online study can be detected by both humans and automatic AI detection systems. While humans were able to correctly identify the authorship of such text above chance level (76% accuracy), their performance was still below what would be required to ensure satisfactory data quality. Researchers currently have to rely on a lack of interest among bad actors to successfully use open-ended responses as a useful tool for ensuring data quality. Automatic AI detection systems are currently completely unusable. If AI submissions of responses become too prevalent, then the costs associated with detecting fraudulent submissions will outweigh the benefits of online questionnaires. Individual attention checks will no longer be a sufficient tool to ensure good data quality. This problem can only be systematically addressed by crowdsourcing platforms. They cannot rely on automatic AI detection systems and it is unclear how they can ensure data quality for their paying clients.
Valuing the contribution of sport volunteering to subjective wellbeing: evidence from eight European countries
Authors: Kokolakakis Themistocles , Schoemaker Jelle , Lera-Lopez Fernando , de Boer Willem , Čingienė Vilma , Papić Alma , Ahlert Gerd
Published: February 2024

Introduction

Volunteering is a prominent and integral aspect of the activities undertaken by sports clubs in Europe. However, even with its growing importance, quantifying the monetary worth of this nonmarket activity, in terms of wellbeing, can present certain difficulties. Traditional approaches to valuing volunteering (i.e., replacement and opportunity cost approaches) do not fully capture the value of volunteering to individuals, as they do not consider the intangible benefits that individuals may derive from their participation.

Methods

This research provides added value to the monetisation of volunteering in sport by applying the wellbeing valuation approach (WVA) for the first time to a cross-sectional data in eight European countries. A double instrumental variable approach was developed to correct for unobservable variables that may influence the pairs: income and subjective wellbeing (SWB), and volunteering and SWB. This allows to estimate the causal impact of volunteering and income on SWB more accurately and assign a reasonable monetary value to this non-market activity.

Results

The results, based on a sample size of 1,091, show an income compensation for a volunteer, devoting on average 8.7 hours during a four-week period of €16 to €50 per hour, equivalent to between € 1,700 and € 5,200 per year, depending on the nationality of the volunteer.

Discussion

With these estimations insights into the value of volunteering in sports are provided, contributing to a better understanding of how this activity can be valued and supported. By recognising and accurately valuing the contributions of volunteers, sport organizations and policymakers can develop more effective strategies for promoting and supporting volunteering in sports.
Optimizing ensembles machine learning, genetic algorithms, and multivariate modeling for enhanced prediction of maize yield and stress tolerance index
Authors: Azrai Muhammad , Aqil Muhammad , Andayani N. N. , Efendi Roy , Suarni  , Suwardi  , Jihad Muhammad , Zainuddin Bunyamin , Salim  , Bahtiar  , Muliadi Ahmad , Yasin Muhammad , Hannan Muhammad Fitrah Irawan , Rahman  , Syam Amiruddin
Published: February 2024

The frequent occurrence of drought, halting from unpredictable climate-induced weather patterns, presents significant challenges in breeding drought-tolerant maize to identify adaptable genotypes. The study explores the optimization of machine learning (ML) to predict both the grain yield and stress tolerance index (STI) of maize under normal and drought-induced stress. In total, 35 genotypes, comprising 31 hybrid candidates and four commercial varieties, were meticulously evaluated across three normal and drought-treated sites. Three popular ML were optimized using a genetic algorithm (GA) and ensemble ML to enhance data capture. Additionally, a Multi-trait Genotype-Ideotype Distance (MGIDI) was also involved to identify superior maize hybrids well-suited for drought conditions. The results highlight that the ensemble meta-models optimized by grid search exhibit robust performance with high accuracy across the testing datasets (R2 = 0.92 for grain yield and 0.82 for STI). The RF optimized by GA algorithm demonstrates slightly lower performance (R2 = 0.91 for grain yield and 0.79 for STI), surpassing the predictive performance of individual SVM-GA and KNN-GA models. Selection of the best-performing hybrids indicated that out of the six hybrids with the highest STI values, both the ensemble and MGIDI can accurately predict four hybrids, namely H06, H10, H13, and H35. Thus, combining ML with MGIDI enables researchers to discern traits for each genotype and holds promise for advancing the field of drought-tolerant maize breeding and expediting the development of resilient varieties.
An evaluation of the physiological uptake range of 18F-fluoro-2-deoxy-D-glucose in normal ovaries of seven dogs using positron emission tomography/computed tomography
Authors: Choi Jinyoung , Chae Yeon , Kang Byeong-Teck , Lee Sungin
Published: February 2024

Introduction

This study evaluated the physiological uptake range of 18F-fluoro-2-deoxy-D-glucose (18F-FDG) in the normal ovaries of seven dogs using positron emission tomography/computed tomography (PET/CT).

Materials and methods

The dogs were subjected to general anesthesia and were positioned in ventral recumbency for PET/CT scans. The dosage of 18F-FDG ranged from 0.14 to 0.17 mCi/kg and was administered intravenously followed by 0.9% NaCl flushing; PET/CT images of each dog were obtained precisely 60 min after the injection of 18F-FDG. The regions of interest were drawn manually, and standardized uptake values (SUV) were calculated to evaluate the 18F-FDG uptake in each ovary. The maximum and mean SUVs (SUV max and SUV mean) for all the ovaries of the dogs were then computed.

Results

The range of SUV max and SUV mean of the normal ovaries of the dogs were 1.28–1.62 and 1.07–1.31 (mean ± standard deviation), respectively.

Conclusion

This is the first study to investigate the normal 18F-FDG uptake baseline data of normal canine ovaries using PET/CT scans. These data will help clinicians in identifying malignant tumors before anatomical changes in the ovary through PET/CT scans.
Exploration of Polyphenols Extracted from Cytisus Plants and Their Potential Applications: A Review
Authors: Ferreira-Sousa Diana , Genisheva Zlatina , Rodríguez-Yoldi María Jesús , Gullón Beatriz , Costa Carlos E. , Teixeira José A. , Botelho Cláudia M. , Ferreira-Santos Pedro
Published: February 2024

The increasing world population means an increased demand for sustainable processes and products related to foods, particularly those with added health benefits. Plants can be an alternative source of nutritional and biofunctional ingredients. Cytisus plants are an underexploited bioresource, currently prevalent in the Mediterranean Basin and western Asia. This manuscript addresses the processing potential of Cytisus plants for the development of added-value products, including food formulations, food packaging, cosmetics, and therapeutic applications. Most research has reported that Cytisus spp. are a promising source of inexpensive bioactive polyphenol compounds. Cytisus flowers should be considered and exploited as raw materials for the development of new food ingredients (antioxidants, preservatives, additives, etc.), nutraceuticals, or even direct therapeutic agents (anticancer, antibacterial, etc.). In order to evaluate the socioeconomic effect of these underutilized plants, more research is needed to assess their valorization for therapeutic and dietary possibilities, as well as the economic impact.