bluuebunny/crossref_metadata_2025 huggingface dataset:
What are The Best Outcome Measures for Persons with Hypermobile Ehlers-Danlos Syndrome and HSD: A Pilot Study?
Authors: Southard Veronica , Allera Arline , DiFrancisco-Donoghue Joanne
Published: April 2024

Background: Hypermobile Ehlers-Danlos, (hEDs), and Hypermobile Spectrum Disorder (HSD) are connective tissue diseases that are often clinically indistinguishable. The purpose of this study was to assess 3 outcomes for utility for persons with these diseases in terms of intrarater, interrater reliability and intertrial reliability as well as, the Health Assessment Questionnaire Disability Index (HAQ-DI) an assessment of participants perception of pain and quality of life. To assess change in vital signs and cortisol saliva measures before and after testing. Lastly, compare participants to normal. Methods: Participants attended 3 sessions within 2 weeks. Two trained examiners assessed the reliability of the two-minute walk test, (2MWT), five times sit to stand (5XSTS), grip strength on five participants. There were 10 participants, each completed the self-report, (HAQ-DI). 10 trained assessors evaluated between 1-10 of the participants for the stability of the scores between three trials. Vital signs and rate of perceived exertion (RPE) were assessed pre and post 2MWT; saliva samples were taken. Statistics: For 5 subjects the ICC (2,3) was computed for intra and interrater reliability. For 10 subjects (ICC3,3) intertrial consistency was done. Paired t tests assessed grip strength, change after 2MWT for vital signs, changes in cortisol, and assess the HAQ-DI between administrations. Pearson correlations were completed on HAQ-DI variables, RPE, saliva, and vital signs. Results: All intra and interrater reliability, intertrial agreement was found to be good to excellent. Paired t tests indicated that the HAQ-DI was stable and indicated a moderate perception of pain and reductions in quality of life. These participants showed evidence of impairments relative to normal. There were no differences in saliva cortisol levels. Conclusion: These tests appear to have utility in identification of impairments in bodily systems, activity levels and participation in these participants. Further investigation is necessary in order to establish the optimal management.
Effectiveness of Gait Training Using Body-Weight-Supported Treadmill among Patients with Stroke: A Review Study
Authors: Abul Fazal Abdullah Ibn , Islam Waliul , Tahlima Nahid , Naine Zulkar , Kibria Golam
Published: April 2024

Background: Body-weight-supported treadmill training (BWSTT) or herness system is a new approach to treat gait recovery among stroke patients. Objectives: To explore the effects of gait training using body weight supported treadmill or herness system among stroke patients. Methodology: This study aimed to explore the effectiveness of gait training using body-weight-supported treadmill among stroke patients by reviewing of the article. Five articles were reviewed in order to fulfil the purpose of this study. With a PEDro score ranging from 4 to 8, randomized controlled trial was used. Each article is analyzed carefully to find out the effectiveness of the intervention. Results: In this study found that both BWSTT and conventional overground training has beneficiary effects for recovery and had impact on parameters related to balance, mobility, and fear of falling among stroke patients. Conclusion: To determine the intensity and precise number of training sessions that should be carried out to restore normal gait, more and better study is required.
Examination of the Performance of Food Industry Enterprises Between 2010 and 2021
Authors: Földi Péter , Parádi-Dolgos Anett , Bareith Tibor
Published: April 2024

In the case of any state, the success of its corporate sector is a cardinal question for its national economy. Consequently, the issue of profitability of the corporate sector has always attracted considerable attention from experts dedicated to understanding successful economic functioning. Regarding academic research priorities, it is essential to identify the identifiable factors, mechanisms of action and trends that are important for the success of corporate growth. In the light of previous studies on the performance of the Hungarian food sector, the above findings are also confirmed, and the main focus of this research is to analyse the factors that play a significant role in stimulating the profitability of the Hungarian food industry. The relevant research period is mainly the period before, during and after the coronavirus epidemic.
Study of Bearing Structures of Buildings and Structures in the Conditions of the South of Kyrgyzstan
Authors: Rysbekova E.
Published: April 2024

The relevance of the research results presented in the article lies in the need to apply new design solutions for multi-storey residential buildings. The purpose of this work is to search for new design solutions for multi-storey residential buildings made of reinforced concrete structures in the South of Kyrgyzstan. The problems of forming a design spatial model of a multi-storey residential building were solved using pylons instead of columns with stiffening diaphragms. A spatial system was calculated using the finite element method and modern computer programs, new design solutions for a multi-storey residential building were adopted. The stress-strain states of the model from a given load are determined. The selection of the section for the structural elements of a multi-storey residential building made of reinforced concrete structures was made. The results of the study can be used in the formation of architectural and design solutions for multi-storey residential buildings.
Using Information Technology as a Means of Speech Development in Junior Schoolchildren
Authors: Khasanov N. , Nusupova K.
Published: April 2024

The rapid development of new information technologies and their implementation have left their mark on the development of the personality of the modern child. Today, a new link is being introduced into the traditional “teacher-student-textbook” scheme — a computer, and computer education is being introduced into school consciousness. One of the main parts of informatization of education is the use of information technologies in educational disciplines. According to the authors, thanks to the use of multimedia, learning becomes more visual and accessible, since the material is presented in various forms: text, audio, video.
Isolation of quinic acid from dropped Citrus reticulata Blanco fruits: its derivatization, antibacterial potential, docking studies, and ADMET profiling
Authors: Heena  , Kaushal Sonia , Kaur Vishaldeep , Panwar Harsh , Sharma Purshotam , Jangra Raman
Published: April 2024

Citrus reticulata dropped fruits are generally discarded as waste, causing environmental pollution and losses to farmers. In the present study, column chromatography has been used to isolate quinic acid (1,3,4,5-tetrahydroxycyclohexane-1-carboxylic acid) from the ethyl acetate fraction of a methanol extract of citrus fruits dropped in April. Quinic acid is a ubiquitous plant metabolite found in various plants and microorganisms. It is an important precursor in the biosynthesis of aromatic natural compounds. It was further derivatized into 3,4-o-isopropylidenequinic acid 1,5-lactone (QA1), 1,3,4,5-tetraacetoxycyclohexylaceticanhydride (QA2), and cyclohexane-1,2,3,5-tetraone (QA3). These compounds were further tested for their antibacterial potential against the foodborne pathogens Staphylococcus aureus, Bacillus spp., Yersinia enterocolitica, and Escherichia coli. QA1 exhibited maximum antibacterial potential (minimum inhibitory concentration; 80–120 μg/mL). QA1 revealed synergistic behavior with streptomycin against all the tested bacterial strains having a fractional inhibitory concentration index ranging from 0.29 to 0.37. It also caused a significant increase in cell constituent release in all the tested bacteria compared to the control, along with prominent biofilm reduction. The results obtained were further checked with computational studies that revealed the best docking score of QA1 (−6.30 kcal/mol, −5.8 kcal/mol, and −4.70 kcal/mol) against β-lactamase, DNA gyrase, and transpeptidase, respectively. The absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis revealed that the drug-like properties of QA1 had an ideal toxicity profile, making it a suitable candidate for the development of antimicrobial drugs.
The prediction of two-dimensional PbN: opened bandgap in heterostructure with CdO
Authors: Cheng Zhang , Wang Yuelei , Zheng Ruxin , Mu Weihua
Published: April 2024

The development of two-dimensional (2D) materials has received wide attention as a generation of optoelectronics, thermoelectric, and other applications. In this study, a novel 2D material, PbN, is proposed as an elemental method using the prototype of a recent reported nitride (J. Phys. Chem. C 2023, 127, 43, 21,006–21014). Based on first-principle calculations, the PbN monolayer is investigated as stable at 900 K, and the isotropic mechanical behavior is addressed by the Young’s modulus and Poisson’s ratio at 67.4 N m–1 and 0.15, respectively. The PbN monolayer also presents excellent catalytic performance with Gibbs free energy of 0.41 eV. Zero bandgap is found for the PbN monolayer, and it can be opened at about 0.128 eV by forming a heterostructure with CdO. Furthermore, the PbN/CdO is constructed by Van der Waals interaction, while the apparent potential drop and charge transfer are investigated at the interface. The PbN/CdO heterostructure also possesses excellent light absorption properties. The results provide theoretical guidance for the design of layered functional materials.
Synchronization of two electrochemical oscillators in a closed bipolar cell
Authors: Tetteh John A. , Kiss István Z.
Published: April 2024

We investigate the dynamical behavior of the oscillatory electrodissolution of nickel and hydrogen reduction reaction in a closed electrochemical bipolar cell with two nickel wires. In the bipolar setup, two-half U cells are separated by an epoxy plate with the two embedded nickel electrodes; the oxidation and reduction reactions take place at the two ends of the same wire. The electrode potential oscillations were found to be strongly synchronized with 1 mm diameter electrodes in an in-phase configuration. Because experiments in similar configurations with traditional (three-electrode) cell showed no synchronization of the oscillatory anodic nickel electrodissolution, the introduction of the cathodic side of the bipolar electrodes induced the synchronization. The results were interpreted with a model that considered the kinetically coupled cathode-anode dynamics as well as interactions on the cathode and the anode side through migration current mediated potential drops in the electrolyte. The electrical coupling strength was calculated from solution resistance and charge transfer resistance measurements. The theory correctly interpreted that the bipolar cell with large (1 mm diameter) electrodes exhibits strong coupling with synchronization, and the bipolar cell with small (0.25 mm diameter) electrodes and the traditional configuration exhibit weak coupling and thus desynchronization. The experiments demonstrate the use of bipolar electrochemical cells for the investigation of collective behavior of electrochemical processes and the proposed approach holds promise for the design of bipolar multi-electrode arrays with engineered coupling to promote sensing and information processing using microchips.
Dose–response association between Chinese visceral adiposity index and cardiovascular disease: a national prospective cohort study
Authors: Ren Yongcheng , Hu Qing , Li Zheng , Zhang Xiaofang , Yang Lei , Kong Lingzhen
Published: April 2024

Background

Chinese visceral adiposity index (CVAI) is a reliable visceral obesity index, but the association between CVAI and risk of cardiovascular disease (CVD) remains unclear. We explored the associations of CVAI with incident CVD, heart disease, and stroke and compared the predictive power of CVAI with other obesity indices based on a national cohort study.

Methods

The present study included 7,439 participants aged ≥45 years from China Health and Retirement Longitudinal Study (CHARLS). Cox regression models were applied to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Restricted cubic splines analyses were adopted to model the dose–response associations. Receiver operator characteristic (ROC) analyses were used to compare the predictive ability of different obesity indices (CVAI, visceral adiposity index [VAI], a body shape index [ABSI], conicity index [CI], waist circumference [WC], and body mass index [BMI]).

Results

During 7 years’ follow‐up, 1,326 incident CVD, 1,032 incident heart disease, and 399 stroke cases were identified. The HRs (95% CI) of CVD, heart disease, and stroke were 1.50 (1.25-1.79), 1.29 (1.05-1.57), and 2.45 (1.74-3.45) for quartile 4 versus quartile 1 in CVAI. Linear associations of CVAI with CVD, heart disease, and stroke were observed (Pnonlinear >0.05) and per-standard deviation (SD) increase was associated with 17% (HR 1.17, 1.10-1.24), 12% (1.12, 1.04-1.20), and 31% (1.31, 1.18-1.46) increased risk, respectively. Per-SD increase in CVAI conferred higher risk in participants aged<60 years than those aged ≥60 years (Pinteraction<0.05). ROC analyses showed that CVAI had higher predictive value than other obesity indices (P<0.05).

Conclusions

CVAI was linearly associated with risk of CVD, heart disease, and stroke and had best performance for predicting incident CVD. Our findings indicate CVAI as a reliable and applicable obesity index to identify higher risk of CVD.
Alzheimer’s disease as a causal risk factor for diabetic retinopathy: a Mendelian randomization study
Authors: Ouyang Fu , Yuan Ping , Ju Yaxin , Chen Wei , Peng Zijun , Xu Hongbei
Published: April 2024

Objectives

This study aims to investigate the causal relationship between Alzheimer’s Disease (AD) and Diabetic Retinopathy (DR).

Methods

Employing Mendelian Randomization (MR), Generalized Summary-data-based Mendelian Randomization (GSMR), and the MR-Steiger test, this study scrutinizes the genetic underpinnings of the hypothesized causal association between AD and DR, as well as its Proliferative DR (PDR) and Non-Proliferative DR (NPDR) subtypes. Comprehensive data from Genome-Wide Association Studies (GWAS) were analyzed, specifically AD data from the Psychiatric Genomics Consortium (71,880 cases/383,378 controls), and DR, PDR, and NPDR data from both the FinnGen consortium (FinnGen release R8, DR: 5,988 cases/314,042 controls; PDR: 8,383 cases/329,756 controls; NPDR: 3,446 cases/314,042 controls) and the IEU OpenGWAS (DR: 14,584 cases/176,010 controls; PDR: 8,681 cases/204,208 controls; NPDR: 2,026 cases/204,208 controls). The study also incorporated Functional Mapping and Annotation (FUMA) for an in-depth analysis of the GWAS results.

Results

The MR analyses revealed that genetic susceptibility to AD significantly increases the risk of DR, as evidenced by GWAS data from the FinnGen consortium (OR: 2.5090; 95% confidence interval (CI):1.2102-5.2018, false discovery rate P-value (PFDR)=0.0201; GSMR: bxy=0.8936, bxy_se=0.3759, P=0.0174), NPDR (OR: 2.7455; 95% CI: 1.3178-5.7197, PFDR=0.0166; GSMR: bxy=0.9682, bxy_se=0.3802, P=0.0126), and PDR (OR: 2.3098; 95% CI: 1.2411-4.2986, PFDR=0.0164; GSMR: bxy=0.7962, bxy_se=0.3205, P=0.0129) using DR GWAS from FinnGen consortium. These results were corroborated by DR GWAS datasets from IEU OpenGWAS. The MR-Steiger test confirmed a significant association of all identified instrumental variables (IVs) with AD. While a potential causal effect of DR and its subtypes on AD was identified, the robustness of these results was constrained by a low power value. FUMA analysis identified OARD1, NFYA, TREM1 as shared risk genes between DR and AD, suggesting a potential genetic overlap between these complex diseases.

Discussion

This study underscores the contribution of AD to an increased risk of DR, as well as NPDR and PDR subtypes, underscoring the necessity of a holistic approach in the management of patients affected by these conditions.
Effects of temporal changes in resting heart rate on future diabetes-related outcomes
Authors: Gao Lu , Wang Guo-Hong , Wan Gang , Liu Qian , Qin Ming-zhao , Fang Fang , Cui Xue-li , Li Yu-ling , Sun Fei , Zhang Xue-lian , Fu Han-jing , Yuan Shen-yuan
Published: April 2024

Background and aims

Most studies have analyzed the relationship between resting heart rate (RHR) measured at only one time point and future clinical events. The current study aims to investigate the impact of long-term RHR changes on future clinical outcomes in a decade-long cohort with type 2 diabetes mellitus (T2DM).

Methods

The two-staged follow-up involved 2,513 T2DM participants. The first stage (2008-2014) intended to identify levels and trends in RHR changes, while the second stage (2014-2018) attempted to collect new occurrence records of clinical results. Cox proportional hazards models were applied to predict hazard ratios (HRs), along with 95% confidence interval (CI) for the correlation between RHR changes and future events.

Results

There is no significant correlation between baseline RHR levels and long-term clinical events. According to the range of RHR change, compared with the stable RHR group, the adjusted HRs for cardiovascular events and all-cause death in the large increase group were 3.40 (95% CI: 1.33-8.71, p=0.010) and 3.22 (95% CI: 1.07-9.64, p=0.037), respectively. While the adjusted HRs for all-cause death and major adverse cardiac and cerebrovascular events (MACCE) in the moderate decrease group were 0.55 (95% CI: 0.31-0.96, p=0.037) and 0.51 (95% CI: 0.26-0.98, p=0.046). According to the trend of RHR, compared with the normal-normal group, the adjusted HRs for composite endpoint events and cerebrovascular events in the normal-high group were 1.64 (95% CI: 1.00-2.68, p=0.047) and 2.82 (95% CI: 1.03-7.76, p=0.043), respectively.

Conclusion

Changes in RHR had predictive value for long-term clinical events in diabetic populations. Individuals with significantly elevated RHR over a particular period of time showed an increased risk of adverse events.
Carbon neutrality in Malaysia and Kuala Lumpur: insights from stakeholder-driven integrated assessment modeling
Authors: Weber Maridee , Pressburger Leeya , Chau Loon Wai , Khan Zarrar , Waite Taryn , Westphal Michael I. , Ling Gabriel Hoh Teck , Ho Chin Siong , Evans Meredydd
Published: April 2024

Introduction: Several cities in Malaysia have established plans to reduce their CO2 emissions, in addition to Malaysia submitting a Nationally Determined Contribution to reduce its carbon intensity (against GDP) by 45% in 2030 compared to 2005. Meeting these emissions reduction goals will require a joint effort between governments, industries, and corporations at different scales and across sectors.

Methods: In collaboration with national and sub-national stakeholders, we developed and used a global integrated assessment model to explore emissions mitigation pathways in Malaysia and Kuala Lumpur. Guided by current climate action plans, we created a suite of scenarios to reflect uncertainties in policy ambition, level of adoption, and implementation for reaching carbon neutrality. Through iterative engagement with all parties, we refined the scenarios and focus of the analysis to best meet the stakeholders’ needs.

Results: We found that Malaysia can reduce its carbon intensity and reach carbon neutrality by 2050, and that action in Kuala Lumpur can play a significant role. Decarbonization of the power sector paired with extensive electrification, energy efficiency improvements in buildings, transportation, and industry, and the use of advanced technologies such as hydrogen and carbon capture and storage will be major drivers to mitigate emissions, with carbon dioxide removal strategies being key to eliminate residual emissions.

Discussion: Our results suggest a hopeful future for Malaysia’s ability to meet its climate goals, recognizing that there may be technological, social, and financial challenges along the way. This study highlights the participatory process in which stakeholders contributed to the development of the model and guided the analysis, as well as insights into Malaysia’s decarbonization potential and the role of multilevel governance.
Circulating VEGF and inflammatory bowel disease: a bidirectional mendelian randomization
Authors: Lin Haishan , Cao Bangwei
Published: April 2024

Introduction: Prior observational studies have suggested an association between circulating vascular endothelial growth factor (VEGF) levels and inflammatory bowel disease (IBD). This study sought to demonstrate the directionality of the association between circulating VEGF and particular forms of IBD as well as if there is a causal relationship between them.

Methods: We collected summary data from relevant genome-wide association studies (GWASs) to assess the validity of causality, and a two-sample bidirectional Mendelian randomization (MR) study and sensitivity testing were performed to assess the causal relationship between circulating VEGF and IBD risk, including Crohn’s disease and ulcerative colitis.

Results: Our findings revealed a direct causal link between circulating VEGF and Crohn’s disease (b 0.195, se 0.078, p < 0.013). However, neither circulating VEGF nor ulcerative colitis were shown to be causally linked (p > 0.025), nor was there proof of a reverse causal relationship from IBD to VEGF.

Discussion: In conclusion, circulating VEGF shows a cause-and-effect relationship with Crohn’s disease.
A comparative genomics study of the microbiome and freshwater resistome in Southern Pantanal
Authors: de Oliveira André R. , de Toledo Rós Bárbara , Jardim Rodrigo , Kotowski Nelson , de Barros Adriana , Pereira Ricardo H. G. , Almeida Nalvo Franco , Dávila Alberto M. R.
Published: April 2024

This study explores the resistome and bacterial diversity of two small lakes in the Southern Pantanal, one in Aquidauana sub-region, close to a farm, and one in Abobral sub-region, an environmentally preserved area. Shotgun metagenomic sequencing data from water column samples collected near and far from the floating macrophyte Eichhornia crassipes were used. The Abobral small lake exhibited the highest diversity and abundance of antibiotic resistance genes (ARGs), antibiotic resistance classes (ARGCs), phylum, and genus. RPOB2 and its resistance class, multidrug resistance, were the most abundant ARG and ARGC, respectively. Pseudomonadota was the dominant phylum across all sites, and Streptomyces was the most abundant genus considering all sites.
Exploring inflammatory bowel disease therapy targets through druggability genes: a Mendelian randomization study
Authors: Zhu Shuangjing , Lin Yunzhi , Ding Zhen
Published: April 2024

Background

Inflammatory bowel disease is an incurable group of recurrent inflammatory diseases of the intestine. Mendelian randomization has been utilized in the development of drugs for disease treatment, including the therapeutic targets for IBD that are identified through drug-targeted MR.

Methods

Two-sample MR was employed to explore the cause-and-effect relationship between multiple genes and IBD and its subtypes ulcerative colitis and Crohn’s disease, and replication MR was utilized to validate this causality. Summary data-based Mendelian randomization analysis was performed to enhance the robustness of the outcomes, while Bayesian co-localization provided strong evidential support. Finally, the value of potential therapeutic target applications was determined by using the estimation of druggability.

Result

With our investigation, we identified target genes associated with the risk of IBD and its subtypes UC and CD. These include the genes GPBAR1, IL1RL1, PRKCB, and PNMT, which are associated with IBD risk, IL1RL1, with a protective effect against CD risk, and GPX1, GPBAR1, and PNMT, which are involved in UC risk.

Conclusion

In a word, this study identified several potential therapeutic targets associated with the risk of IBD and its subtypes, offering new insights into the development of therapeutic agents for IBD.
Exploration of the core pathway of inflammatory bowel disease complicated with metabolic fatty liver and two-sample Mendelian randomization study of the causal relationships behind the disease
Authors: Wei Zhiyuan , Wang Jiangbin
Published: April 2024

Background

Inflammatory bowel disease (IBD) is often associated with complex extraintestinal manifestations. The incidence of nonalcoholic fatty liver disease (NAFLD) in IBD populations is increasing yearly. However, the mechanism of interaction between NAFLD and IBD is not clear. Consequently, this study aimed to explore the common genetic characteristics of IBD and NAFLD and identify potential therapeutic targets.

Materials and methods

Gene chip datasets for IBD and NAFLD were obtained from the Gene Expression Omnibus (GEO) database. Weighted gene co-expression network analysis (WGCNA) was performed to identify modules in those datasets related to IBD and NAFLD. ClueGO was used for biological analysis of the shared genes between IBD and NAFLD. Based on the Human MicroRNA Disease Database (HMDD), microRNAs (miRNAs) common to NAFLD and IBD were obtained. Potential target genes for the miRNAs were predicted using the miRTarbase, miRDB, and TargetScan databases. Two-sample Mendelian randomization (MR) and two-way MR were used to explore the causal relationship between Interleukin-17 (IL-17) and the risk of IBD and NAFLD using data from GWAS retrieved from an open database.

Results

Through WGCNA, gene modules of interest were identified. GO enrichment analysis using ClueGO suggested that the abnormal secretion of chemokines may be a common pathophysiological feature of IBD and NAFLD, and that the IL-17-related pathway may be a common key pathway for the pathological changes that occur in IBD and NAFLD. The core differentially expressed genes (DEGs) in IBD and NAFLD were identified and included COL1A1, LUM, CCL22, CCL2, THBS2, COL1A2, MMP9, and CXCL8. Another cohort was used for validation. Finally, analysis of the miRNAs identified potential therapeutic targets. The MR results suggested that although there was no causal relationship between IBD and NAFLD, there were causal relationships between IL-17 and IBD and NAFLD.

Conclusion

We established a comorbid model to explain the potential mechanism of IBD with NAFLD and identified the chemokine-related pathway mediated by cytokine IL-17 as the core pathway in IBD with NAFLD, in which miRNA also plays a role and thus provides potential therapeutic targets.
Interstitial lung disease: a review of classification, etiology, epidemiology, clinical diagnosis, pharmacological and non-pharmacological treatment
Authors: Althobiani Malik A. , Russell Anne-Marie , Jacob Joseph , Ranjan Yatharth , Folarin Amos A. , Hurst John R. , Porter Joanna C.
Published: April 2024

Interstitial lung diseases (ILDs) refer to a heterogeneous and complex group of conditions characterized by inflammation, fibrosis, or both, in the interstitium of the lungs. This results in impaired gas exchange, leading to a worsening of respiratory symptoms and a decline in lung function. While the etiology of some ILDs is unclear, most cases can be traced back to factors such as genetic predispositions, environmental exposures (including allergens, toxins, and air pollution), underlying autoimmune diseases, or the use of certain medications. There has been an increase in research and evidence aimed at identifying etiology, understanding epidemiology, improving clinical diagnosis, and developing both pharmacological and non-pharmacological treatments. This review provides a comprehensive overview of the current state of knowledge in the field of interstitial lung diseases.
Risk factors and metabolomics of mild cognitive impairment in type 2 diabetes mellitus
Authors: Luo Tao , Jiang Xiao , Xu Ning , Zhao Xinyu , Xie Xingjie , Xia Xiuwen , Bian XiaoLong , Liu Haixia
Published: April 2024

Objective: This study aimed to explore the risk factors, metabolic characteristics, and potential biomarkers of mild cognitive impairment in type 2 diabetes mellitus (T2DM-MCI) and to provide potential evidence for the diagnosis, prevention, and treatment of mild cognitive impairment (MCI) in patients with type 2 diabetes mellitus (T2DM).

Methods: A total of 103 patients with T2DM were recruited from the Endocrinology Department of The Second Affiliated Hospital of Dalian Medical University for inclusion in the study. The Montreal Cognitive Assessment (MoCA) was utilized to evaluate the cognitive functioning of all patients. Among them, 50 patients were categorized into the T2DM-MCI group (MoCA score < 26 points), while 53 subjects were classified into the T2DM without cognitive impairment (T2DM-NCI) group (MoCA score ≥ 26 points). Serum samples were collected from the subjects, and metabolomics profiling data were generated by Ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS). These groups were analyzed to investigate the differences in expression of small molecule metabolites, metabolic pathways, and potential specific biomarkers.

Results: Comparison between the T2DM-MCI group and T2DM-NCI group revealed significant differences in years of education, history of insulin application, insulin resistance index, insulin-like growth factor-binding protein-3 (IGFBP-3), and creatinine levels. Further binary logistic regression analysis of the variables indicated that low educational level and low serum IGFBP-3 were independent risk factor for T2DM-MCI. Metabolomics analysis revealed that differential expression of 10 metabolites between the T2DM-MCI group and T2DM-NCI group (p < 0.05 and FDR<0.05, VIP>1.5). Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment pathway analysis revealed that fatty acid degradation was the most significant pathway. Receiver operating characteristic (ROC) analysis shows that lysophosphatidylcholine (LPC) 18:0 exhibited greater diagnostic efficiency.

Conclusion: This study revealed that a shorter duration of education and lower serum IGFBP-3 levels are independent risk factors for T2DM-MCI. Serum metabolites were found to be altered in both T2DM-MCI and T2DM-NCI groups. T2DM patients with or without MCI can be distinguished by LPC 18:0. Abnormal lipid metabolism plays a significant role in the development of MCI in T2DM patients.
Postural control in gymnasts: anisotropic fractal scaling reveals proprioceptive reintegration in vestibular perturbation
Authors: Mangalam Madhur , Seleznov Ivan , Kolosova Elena , Popov Anton , Kelty-Stephen Damian G. , Kiyono Ken
Published: April 2024

Dexterous postural control subtly complements movement variability with sensory correlations at many scales. The expressive poise of gymnasts exemplifies this lyrical punctuation of release with constraint, from coarse grain to fine scales. Dexterous postural control upon a 2D support surface might collapse the variation of center of pressure (CoP) to a relatively 1D orientation—a direction often oriented towards the focal point of a visual task. Sensory corrections in dexterous postural control might manifest in temporal correlations, specifically as fractional Brownian motions whose differences are more and less correlated with fractional Gaussian noises (fGns) with progressively larger and smaller Hurst exponent H. Traditional empirical work examines this arrangement of lower-dimensional compression of CoP along two orthogonal axes, anteroposterior (AP) and mediolateral (ML). Eyes-open and face-forward orientations cultivate greater variability along AP than ML axes, and the orthogonal distribution of spatial variability has so far gone hand in hand with an orthogonal distribution of H, for example, larger in AP and lower in ML. However, perturbing the orientation of task focus might destabilize the postural synergy away from its 1D distribution and homogenize the temporal correlations across the 2D support surface, resulting in narrower angles between the directions of the largest and smallest H. We used oriented fractal scaling component analysis (OFSCA) to investigate whether sensory corrections in postural control might thus become suborthogonal. OFSCA models raw 2D CoP trajectory by decomposing it in all directions along the 2D support surface and fits the directions with the largest and smallest H. We studied a sample of gymnasts in eyes-open and face-forward quiet posture, and results from OFSCA confirm that such posture exhibits the classic orthogonal distribution of temporal correlations. Head-turning resulted in a simultaneous decrease in this angle Δθ, which promptly reversed once gymnasts reoriented their heads forward. However, when vision was absent, there was only a discernible negative trend in Δθ, indicating a shift in the angle’s direction but not a statistically significant one. Thus, the narrowing of Δθ may signify an adaptive strategy in postural control. The swift recovery of Δθ upon returning to a forward-facing posture suggests that the temporary reduction is specific to head-turning and does not impose a lasting burden on postural control. Turning the head reduced the angle between these two orientations, facilitating the release of postural degrees of freedom towards a more uniform spread of the CoP across both dimensions of the support surface. The innovative aspect of this work is that it shows how fractality might serve as a control parameter of adaptive mechanisms of dexterous postural control.
A novel variant of PLA2G6 gene related early-onset parkinsonism: a case report and literature review
Authors: Cai Dapeng , Wu Haohao , Huang Baogang , Xiao Weiwei , Du Kang
Published: April 2024

This study reported a case of early-onset parkinsonism associated with a novel variant of the PLA2G6 gene. The boy first started showing symptoms at the age of 11, with gait instability and frequent falls. As the disease progressed, his gait instability worsened, and he developed difficulties with swallowing and speaking, although there was no apparent decline in cognitive function. An MRI of the head revealed significant atrophy of the cerebellum. The initial diagnosis for the boy was early-onset parkinsonism, classified as Hoehn-Yahr grade 5.Genomic sequencing of the patient indicated that he had compound heterozygous variations in the PLA2G6 gene: c.1454G>A (p.Gly485Glu) and c.991G>T (p.Asp331Tyr). Pedigree analysis revealed that his younger brother also carried the same variant, albeit with milder symptoms. The patient's unaffected mother was found to be a carrier of the c.991G>T variant. Additionally, this study reviewed 62 unrelated families with PLA2G6 gene-related early-onset parkinsonism. The analysis showed a higher proportion of female probands, with a mean age of onset of ~23.0 years. Primary symptoms were predominantly bradykinesia and psychosis, with tremors being relatively rare. Cerebellar atrophy was observed in 41 patients (66.1%). Among the reported mutations, the most common mutation was c.991G>T, presenting in 21 families (33.9%), followed by c.2222G>A in eight families (12.9%). Other mutations were less common. Notably, the c.991G>T mutation was exclusive to Chinese families and was a prevalent mutation among this population. The initial symptoms varied significantly among patients with different mutations.
Neurofilament light chain as a biomarker for acute hepatic porphyrias
Authors: Sgobbi Paulo , Serrano Paulo de Lima , Badia Bruno de Mattos Lombardi , Farias Igor Braga , Oliveira Hélvia Bertoldo de , Barbosa Alana Strucker , Pereira Camila Alves , Moreira Vanessa de Freitas , Pinto Ícaro França Navarro , Oliveira Acary Souza Bulle , Pinto Wladimir Bocca Vieira de Rezende
Published: April 2024

Background

Acute hepatic porphyrias (AHP) represent a rare group of inherited metabolic disorders of heme biosynthesis pathway. This study aims to determine the diagnostic and prognostic value of serum neurofilament light chain (NfL) as potential biomarker for AHP.

Methods

We conducted a cross-sectional observational study to evaluate NfL levels in patients with AHP. They were divided in different groups: normal health individuals; patients with definitive diagnosis of AHP during acute episodes; patients with AHP and infrequent attacks; patients with AHP and recurrent attacks; asymptomatic individuals with positive genetic testing and urinary delta-aminolevulinic acid (ALA) and porphobilinogen (PBG) levels elevated 4 or more times (“high excretors”); asymptomatic individuals with exclusive positive genetic test; control group with Hereditary Amyloidosis related to Transthyretin with Polyneuropathy (ATTRv-PN).

Results

During acute attacks, serum NfL levels were 68 times higher compared to normal controls and disclosed a strong correlation with ALA and PBG levels; also exhibited elevated levels in patients with chronic symptoms regardless of the number of disease attacks compared to healthy controls, and at similar levels to patients with ATTRv-PN, which is a model of progressive neuropathy.

Conclusion

This study represents the first to establish NfL as a biomarker for AHP, disclosing NfL as a sensitive biomarker for axonal damage and chronic symptom occurrence. This study not only underscores that neurological damage associated with the disease in any patient, irrespective of the number of attacks, but also reinforces the progressive and profoundly debilitating nature of acute and chronic symptoms observed in individuals with AHP.
Role of composite objective nutritional indexes in patients with chronic kidney disease
Authors: Yang Bixia , Yang Yan , Liu Bicheng , Yang Min
Published: April 2024

Malnutrition persists as one of the most severe symptoms in patients with chronic kidney disease (CKD) globally. It is a critical risk factor for cardiovascular and all-cause mortality in patients with CKD. Readily available objective indicators are used to calculate composite objective nutritional assessment indexes, including the geriatric nutritional risk index, prognostic nutritional index, and controlling nutritional status score. These indexes offer a straightforward and effective method for evaluating nutritional status and predicting clinical outcomes in patients with CKD. This review presents supporting evidence on the significance of composite nutritional indexes.
Real-world outcomes on platinum-containing chemotherapy for EGFR-mutated advanced nonsquamous NSCLC with prior exposure to EGFR tyrosine kinase inhibitors
Authors: Halmos Balazs , Rai Pragya , Min Jae , Hu Xiaohan , Chirovsky Diana , Shamoun Mark , Zhao Bin
Published: April 2024

Background

Front-line therapy with an EGFR tyrosine kinase inhibitor (TKI) is the standard of care for treating patients with advanced nonsquamous NSCLC with the common sensitizing EGFR exon 19 deletion and exon 21 L858R point mutations. However, EGFR TKI resistance inevitably develops. The optimal subsequent therapy remains to be identified, although platinum-containing chemotherapy regimens are often administered. Our objectives were to describe baseline characteristics, survival, and subsequent treatment patterns for patients with advanced nonsquamous NSCLC with EGFR exon 19 deletion or L858R mutation who received a platinum-based combination regimen after front-line EGFR TKI therapy.

Methods

This retrospective study used a nationwide electronic health record-derived deidentified database to select adult patients with advanced nonsquamous NSCLC, evidence of EGFR exon 19 deletion or L858R mutation, and ECOG performance status of 0-2 who initiated platinum-containing chemotherapy, with or without concomitant immunotherapy, from 1-January-2011 to 30-June-2020 following receipt of any EGFR TKI as first-line therapy or, alternatively, a first- or second-generation EGFR TKI (erlotinib, afatinib, gefitinib, dacomitinib) as first-line therapy followed by the third-generation EGFR TKI osimertinib as second-line therapy. Data cut-off was 30-June-2022. The Kaplan-Meier method was used to estimate overall survival (OS) after initiation of pemetrexed-platinum (n=119) or any platinum-based combination regimen (platinum cohort; n=311).

Results

The two cohorts included two-thirds women (65%-66%) and 57%-58% nonsmokers; median ages were 66 and 65 years in pemetrexed-platinum and platinum cohorts, respectively. Median OS was 10.3 months (95% CI, 8.1-13.9) from pemetrexed-platinum initiation and 12.4 months (95% CI, 10.2-15.2) from platinum initiation; 12-month survival rates were 48% and 51%, respectively; 260 patients (84%) had died by the end of the study.

Conclusion

The suboptimal survival outcomes recorded in this study demonstrate the unmet need to identify more effective subsequent treatment regimens for patients with EGFR-mutated advanced nonsquamous NSCLC after EGFR TKI resistance develops.
Research on the signaling pathway and the related mechanism of traditional Chinese medicine intervention in chronic gastritis of the “inflammation-cancer transformation”
Authors: Yan-Rui Wang , Xue-Er Yan , Mao-Yu Ding , Ya-Ting Lu , Bo-Heng Lu , Miao-Jie Zhai , Li Zhu
Published: April 2024

Objective: The aim of this study is to uncover the traditional Chinese medicine (TCM) treatments for chronic gastritis and their potential targets and pathways involved in the “inflammation-cancer” conversion in four stages. These findings can provide further support for future research into TCM and its active components.

Materials and methods: The literature search encompassed PubMed, Web of Science, Google Scholar, CNKI, WanFang, and VIP, employing keywords such as “chronic gastritis”, “gastric cancer”, “traditional Chinese medicine”, “medicinal herb”, “Chinese herb”, and “natural plant”.

Results: Herbal remedies may regulate the signaling pathways linked to the advancement of chronic gastritis. Under the multi-target and multi-pathway independent or combined reaction, the inflammatory microenvironment may be enhanced, leading to repair of damaged gastric mucosal cells, buffering the progress of mucosal atrophic degeneration via the decrease of inflammatory factor expression, inhibition of oxidative stress-induced damage, facilitation of microvascular neovascularization in the gastric mucosa and regulation of the processes of gastric mucosal cell differentiation and proliferation. Simultaneously, the decreased expression of inflammatory factors may impact the expression of associated oncogenes and regulate the malignant proliferation of cells, thereby achieving the treatment and prevention objectives of gastric cancer through the reduction of cell metastasis and apoptosis.

Conclusion: Chinese medicine formulations and individual drugs can be utilised at various stages of the “inflammation-cancer” progression of chronic gastritis to prevent and treat gastric cancer in a multi-level, multi-targeted, and multi-directional fashion. This can provide guidance for the accurate application of medicines during different stages of “inflammation-cancer” transformation. New insights into the mechanism of inflammation-cancer transformation and the development of novel drugs for chronic gastritis can be gained through an extensive investigation of TCM treatment in this condition.
CFTR dysfunction leads to defective bacterial eradication on cystic fibrosis airways
Authors: Wu Min , Chen Jeng-Haur
Published: April 2024

Dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) anion channel by genetic mutations causes the inherited disease cystic fibrosis (CF). CF lung disease that involves multiple disorders of epithelial function likely results from loss of CFTR function as an anion channel conducting chloride and bicarbonate ions and its function as a cellular regulator modulating the activity of membrane and cytosol proteins. In the absence of CFTR activity, abundant mucus accumulation, bacterial infection and inflammation characterize CF airways, in which inflammation-associated tissue remodeling and damage gradually destroys the lung. Deciphering the link between CFTR dysfunction and bacterial infection in CF airways may reveal the pathogenesis of CF lung disease and guide the development of new treatments. Research efforts towards this goal, including high salt, low volume, airway surface liquid acidosis and abnormal mucus hypotheses are critically reviewed.
Cauli-Det: enhancing cauliflower disease detection with modified YOLOv8
Authors: Uddin Md. Sazid , Mazumder Md. Khairul Alam , Prity Afrina Jannat , Mridha M. F. , Alfarhood Sultan , Safran Mejdl , Che Dunren
Published: April 2024

Cauliflower cultivation plays a pivotal role in the Indian Subcontinent’s winter cropping landscape, contributing significantly to both agricultural output, economy and public health. However, the susceptibility of cauliflower crops to various diseases poses a threat to productivity and quality. This paper presents a novel machine vision approach employing a modified YOLOv8 model called Cauli-Det for automatic classification and localization of cauliflower diseases. The proposed system utilizes images captured through smartphones and hand-held devices, employing a finetuned pre-trained YOLOv8 architecture for disease-affected region detection and extracting spatial features for disease localization and classification. Three common cauliflower diseases, namely ‘Bacterial Soft Rot’, ‘Downey Mildew’ and ‘Black Rot’ are identified in a dataset of 656 images. Evaluation of different modification and training methods reveals the proposed custom YOLOv8 model achieves a precision, recall and mean average precision (mAP) of 93.2%, 82.6% and 91.1% on the test dataset respectively, showcasing the potential of this technology to empower cauliflower farmers with a timely and efficient tool for disease management, thereby enhancing overall agricultural productivity and sustainability
Taxonomy and pathogenicity of fungi associated with oak decline in northern and central Zagros forests of Iran with emphasis on coelomycetous species
Authors: Bashiri Samaneh , Abdollahzadeh Jafar
Published: April 2024

Oak decline is a complex disorder that seriously threatens the survival of Zagros forests. In an extensive study on taxonomy and pathology of fungi associated with oak decline in the central and northern part of Zagros forests, 462 fungal isolates were obtained from oak trees showing canker, gummosis, dieback, defoliation, and partial or total death symptoms. Based on inter-simple sequence repeat (ISSR) fingerprinting patterns, morphological characteristics, and sequences of ribosomal DNA (28S rDNA and ITS) and protein coding loci (acl1, act1, caM, tef-1α, rpb1, rpb2, and tub2), 24 fungal species corresponding to 19 genera were characterized. Forty percent of the isolates were placed in eight coelomycetous species from seven genera, namely, Alloeutypa, Botryosphaeria, Cytospora, Didymella, Gnomoniopsis, Kalmusia, and Neoscytalidium. Of these, four species are new to science, which are introduced here as taxonomic novelties: Alloeutypa iranensis sp. nov., Cytospora hedjaroudei sp. nov., Cytospora zagrosensis sp. nov., and Gnomoniopsis quercicola sp. nov. According to pathogenicity trials on leaves and stems of 2-year-old Persian oak (Quercus brantii) seedlings, Alternaria spp. (A. alternata, A. atra, and A. contlous), Chaetomium globosum, and Parachaetomium perlucidum were recognized as nonpathogenic. All coelomycetous species were determined as pathogenic in both pathogenicity trials on leaves and seedling stems, of which Gnomoniopsis quercicola sp. nov., Botryosphaeria dothidea, and Neoscytalidium dimidiatum were recognized as the most virulent species followed by Biscogniauxia rosacearum.