bluuebunny/crossref_metadata_2025 huggingface dataset:
Faculty perception of online education: considerations for the post-pandemic world
Authors: Ahmed Vian , Anane Chiraz , Alzaatreh Ayman , Saboor Sara
Published: November 2023

In the post-COVID era, academic institutions adapted curricula, utilizing aspects of the online delivery in full or partially. Consequently, this research focuses on identifying the factors that influence faculty perceptions of effective online delivery in higher education and comparing them with students’ perceptions. The study involves semi-structured interviews with 15 faculty members at a renowned university to gain insights into their online teaching experiences during the pandemic. Additionally, 51 faculty members participated in a survey using the Relative Importance Index (RII) method to determine the most significant practices impacting online delivery. The results indicate that the most concerning factor for faculty during online delivery is facilitating students’ engagement and interactions in class, with an RII of 0.94. Controlling academic dishonesty during assessments receives a relatively lower concern with an RII of 0.67. Making lectures interactive is identified as the most challenging practice for faculty. Comparing the findings with students’ perceptions based on previous studies, both groups emphasize the significance of effective communication, interaction, and the use of technology. Faculty prioritize the delivery and organization of lectures, while students focus on engagement and interactive elements. Faculty value organization and relevance in assignments, while students emphasize instructor qualities and responsiveness.
Low-carbon optimal operation of the integrated energy system considering integrated demand response
Authors: Ji Xiu , Li Meng , Li Meiyue , Han Huanhuan
Published: November 2023

In order to further reduce the carbon emission level of the integrated energy system and improve the system operation economy, a low-carbon economic dispatch strategy for the integrated energy system considering comprehensive demand response is proposed. First, based on the composition and operating characteristics of the integrated energy system, two demand response models, price-based and substitution-based, are established. Secondly, based on the ladder-type carbon trading mechanism and the green certificate trading mechanism, a green certificate-carbon trading mechanism model is designed to construct a ladder-type carbon trading mechanism model. A comprehensive energy system low-carbon economic dispatch model with the lowest system operating cost is composed of carbon transaction costs, energy purchase costs, operation and maintenance costs, green certificate trading income and wind and light abandonment costs. Finally, through simulation experiments, this paper is verified the effectiveness of the proposed model is analyzed, and the impact of demand response sensitivity and ladder-type carbon trading mechanism parameters on system dispatch results is analyzed.
Common variants in toll-like receptor family genes and risk of gastric cancer: a systematic review and meta-analysis
Authors: Al Othaim Ayoub , Al-Hawary Sulieman Ibraheem Shelash , Alsaab Hashem O. , Almalki Sami G. , Najm Mazin A. A. , Hjazi Ahmed , Alsalamy Ali , Firras Almulla Abbas , Alizadeh Hamzeh
Published: November 2023

Background: An increasing number of studies have suggested the relationship between single-nucleotide polymorphisms (SNPs) in toll-like receptor (TLR) genes and gastric cancer (GC) susceptibility; however, the available evidence is contradictory. This meta-analysis aimed to comprehensively evaluate whether the SNPs within the TLR family are related to GC development.

Methods: PubMed, Scopus, and China National Knowledge Infrastructure (CNKI) were systematically searched up to May 2023 to obtain the pertinent publications. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were applied to examine the associations using the random-effects model.

Results: A total of 45 studies with 25,831 participants (cases: 11,308; controls: 14,523) examining the relation of 18 different SNPs in the TLR family to GC were analyzed. Variations in TLR-4 rs4986790, TLR-4 rs4986791, TLR-5 rs5744174, and TLR-9 rs187084 were significantly associated with increased risk of GC in different genetic models. No significant association was detected for TLR-2-196 to -174de (Delta22), TLR-2 rs3804100, TLR-4 rs11536889, TLR-4 rs11536878, TLR-4 rs2770150, TLR-4 rs10116253, TLR-4 rs1927911, TLR-4 rs10983755, TLR-4 rs10759932, TLR-4 rs1927914, and TLR-10 rs10004195.

Conclusion: These findings indicate that variations in TLR-4, TLR-5, and TLR-9 genes were found to be potential risk factors for GC.
Deep computational phenotyping of genomic variants impacting the SET domain of KMT2C reveal molecular mechanisms for their dysfunction
Authors: Jorge Salomão Dória , Chi Young-In , Mazaba Jose Lizarraga , Haque Neshatul , Wagenknecht Jessica , Smith Brian C. , Volkman Brian F. , Mathison Angela J. , Lomberk Gwen , Zimmermann Michael T. , Urrutia Raul
Published: November 2023

Introduction: Kleefstra Syndrome type 2 (KLEFS-2) is a genetic, neurodevelopmental disorder characterized by intellectual disability, infantile hypotonia, severe expressive language delay, and characteristic facial appearance, with a spectrum of other distinct clinical manifestations. Pathogenic mutations in the epigenetic modifier type 2 lysine methyltransferase KMT2C have been identified to be causative in KLEFS-2 individuals.

Methods: This work reports a translational genomic study that applies a multidimensional computational approach for deep variant phenotyping, combining conventional genomic analyses, advanced protein bioinformatics, computational biophysics, biochemistry, and biostatistics-based modeling. We use standard variant annotation, paralog annotation analyses, molecular mechanics, and molecular dynamics simulations to evaluate damaging scores and provide potential mechanisms underlying KMT2C variant dysfunction.

Results: We integrated data derived from the structure and dynamics of KMT2C to classify variants into SV (Structural Variant), DV (Dynamic Variant), SDV (Structural and Dynamic Variant), and VUS (Variant of Uncertain Significance). When compared with controls, these variants show values reflecting alterations in molecular fitness in both structure and dynamics.

Discussion: We demonstrate that our 3D models for KMT2C variants suggest distinct mechanisms that lead to their imbalance and are not predictable from sequence alone. Thus, the missense variants studied here cause destabilizing effects on KMT2C function by different biophysical and biochemical mechanisms which we adeptly describe. This new knowledge extends our understanding of how variations in the KMT2C gene cause the dysfunction of its methyltransferase enzyme product, thereby bearing significant biomedical relevance for carriers of KLEFS2-associated genomic mutations.
Characterization of the microRNA408-LACCASE5 module as a regulatory axis for photosynthetic efficiency in Medicago ruthenica: implications for forage yield enhancement
Authors: Zhang Yutong , Yan Wei , Qiao Yu , Gao Xia , Tang Fang , Gao Cuiping , Shi Fengling
Published: November 2023

Medicago ruthenica is closely related to Medicago sativa, a commonly cultivated forage. Characterized by its high tolerance to environmental stress, M. ruthenica is a valuable genetic resource. However, low yield limits its large-scale utilization. Leaf morphology, an important agronomic trait, is closely related to forage yield and photosynthetic efficiency. In the presented study, “Correlation of Leaf Morphology and Photosynthetic Performance with Forage Yield in Medicago ruthenica: The Underlying Molecular Mechanisms,” comprehensive data analysis revealed a significant positive association between leaf width and leaf area with forage yield in Medicago ruthenica (p < 0.05). The specific cultivar “Mengnong No.1 (MN No.1) had a large leaf area, and its physiological parameters related to photosynthetic characteristics were superior. Anatomical examination revealed that the leaves of MN No.1 had strong palisade tissue and compact cell structure. Subsequent investigations, utilizing small RNA and transcriptome sequencing, discerned critical miRNA-target gene networks that underpin the high photosynthetic efficiency in M. ruthenica. A total of 63 differentially expressed miRNAs (DEMs) were identified, inclusive of several well-characterized miRNAs such as miR408, miR171, and miR398. These miRNAs were predicted to target 55 genes (mRNAs), of which 6 miRNA-target gene pairs, particularly those involving miR408and miR171, exhibited inverse expression patterns. Among the six postulated miRNA-target gene pairs, the targeted cleavage of LACCASE5 (LAC5) by miR408 was conclusively validated through degradome sequencing, with the cleavage site pinpointed between the 9th and 10th nucleotides from the 5′end of miR408 via the 5′-RLM-RACE assay. Therefore, it is posited that the miR408-MrLAC5 module constitutes a central mechanism in fostering high photosynthetic efficiency in M. ruthenica. Moreover, these findings also provide valuable information for further study of the regulatory genes and miRNA functions of forage yield in legume forage.
Circulating cell-free nucleic acids of plasma in human aging, healthy aging and longevity: current state of knowledge
Authors: Tessier Nicolas P. , Hardy Lise M. , Deleuze Jean-François , How-Kit Alexandre
Published: November 2023

Circulating cell-free nucleic acids (ccfNAs) of plasma are a remarkable source of genetic, epigenetic and transcriptomic materials originating from different cells, tissues and organs of an individual. They have been increasingly studied over the past decade as they can carry several important pieces of information about the health status of an individual, which makes them biomarkers of choice for non-invasive diagnosis of numerous diseases and health conditions. However, few studies have investigated variations of plasma ccfNAs in healthy subjects, particularly in relation to aging, healthy aging and longevity, despite the great variability of these biological processes among individuals. Here, we reviewed several studies that focused on the analysis of circulating cell-free DNA (ccfDNA) and microRNAs (ccfmiRNAs) during aging and in the elderly, including some on exceptionally long-lived individuals, i.e., centenarians. After a brief overview of the types, origins and functions of plasma ccfNAs, we described the variations of both ccfDNA and ccfmiRNAs during aging as well as the identification of several potential ccfDNA-based and ccfmiRNA-based biomarkers of aging, healthy aging and/or longevity. We finally highlighted some prospects offered by ccfNAs for the understanding and improvement of healthy aging and longevity.
Altered intestinal microbiota enhances adenoid hypertrophy by disrupting the immune balance
Authors: Liu Wenxin , Jiang Huier , Liu Xiling , Zheng Yue , Liu Yanan , Pan Fen , Yu Fangyuan , Li Zhi , Gu Meizhen , Du Qingqing , Li Xiaoyan , Zhang Hong , Han Dingding
Published: November 2023

Introduction

Adenoid hypertrophy (AH) is a common upper respiratory disorder in children. Disturbances of gut microbiota have been implicated in AH. However, the interplay of alteration of gut microbiome and enlarged adenoids remains elusive.

Methods

119 AH children and 100 healthy controls were recruited, and microbiome profiling of fecal samples in participants was performed using 16S rRNA gene sequencing. Fecal microbiome transplantation (FMT) was conducted to verify the effects of gut microbiota on immune response in mice.

Results

In AH individuals, only a slight decrease of diversity in bacterial community was found, while significant changes of microbial composition were observed between these two groups. Compared with HCs, decreased abundances of Akkermansia, Oscillospiraceae and Eubacterium coprostanoligenes genera and increased abundances of Bacteroides, Faecalibacterium, Ruminococcus gnavus genera were revealed in AH patients. The abundance of Bacteroides remained stable with age in AH children. Notably, a microbial marker panel of 8 OTUs were identified, which discriminated AH from HC individuals with an area under the curve (AUC) of 0.9851 in the discovery set, and verified in the geographically different validation set, achieving an AUC of 0.9782. Furthermore, transfer of mice with fecal microbiota from AH patients dramatically reduced the proportion of Treg subsets within peripheral blood and nasal-associated lymphoid tissue (NALT) and promoted the expansion of Th2 cells in NALT.

Conclusion

These findings highlight the effect of the altered gut microbiota in the AH pathogenesis.
Association of retinal vessel pathology and brain atrophy in relapsing-remitting multiple sclerosis
Authors: Romahn Eva Feodora , Wiltgen Tun , Bussas Matthias , Aly Lilian , Wicklein Rebecca , Noll Christina , Berthele Achim , Dehmelt Vera , Mardin Christian , Zimmer Claus , Korn Thomas , Hemmer Bernhard , Kirschke Jan S. , Mühlau Mark , Knier Benjamin
Published: November 2023

Background

Optical coherence tomography angiography (OCTA) allows non-invasive assessment of retinal vessel structures. Thinning and loss of retinal vessels is evident in eyes of patients with multiple sclerosis (MS) and might be associated with a proinflammatory disease phenotype and worse prognosis. We investigated whether changes of the retinal vasculature are linked to brain atrophy and disability in MS.

Material and methods

This study includes one longitudinal observational cohort (n=79) of patients with relapsing-remitting MS. Patients underwent annual assessment of the expanded disability status scale (EDSS), timed 25-foot walk, symbol digit modalities test (SDMT), retinal optical coherence tomography (OCT), OCTA, and brain MRI during a follow-up duration of at least 20 months. We investigated intra-individual associations between changes in the retinal architecture, vasculature, brain atrophy and disability. Eyes with a history of optic neuritis (ON) were excluded.

Results

We included 79 patients with a median disease duration of 12 (interquartile range 2 - 49) months and a median EDSS of 1.0 (0 - 2.0). Longitudinal retinal axonal and ganglion cell loss were linked to grey matter atrophy, cortical atrophy, and volume loss of the putamen. We observed an association between vessel loss of the superficial vascular complex (SVC) and both grey and white matter atrophy. Both observations were independent of retinal ganglion cell loss. Moreover, patients with worsening of the EDSS and SDMT revealed a pronounced longitudinal rarefication of the SVC and the deep vascular complex.

Discussion

ON-independent narrowing of the retinal vasculature might be linked to brain atrophy and disability in MS. Our findings suggest that retinal OCTA might be a new tool for monitoring neurodegeneration during MS.
A high-fat diet protects C57BL/6 mice from Plasmodium berghei ANKA infection in an experimental malaria study
Authors: Soares Sara Malaguti Andrade , Gualberto Ana Cristina Moura , da Costa Augusto Cesar , Gonçalves Diego Assis , Gameiro Jacy
Published: November 2023

Introduction

It is well known that dietary changes have a significant impact on the immune system, and modifications in lipid balance may contribute to disease progression in several cases. Malaria is still a major global health concern, and the development of the disease has already been linked to the host’s nutritional status, so it’s critical to understand how environmental factors, such as dietary variations, can influence the outcome of infection. We therefore investigated the effect of a short-term diet in a murine model of experimental cerebral malaria.

Methods

For this, male C57BL/6 mice were fed a high fat diet containing 60% of the calories from lipids for 5 days. Following this period, the animals were infected with Plasmodium berghei ANKA, and parasitemia, survival, and neurological scores were compared. Considering that one of the first elimination routes of the intracellular parasite is oxidative stress, the antioxidant N-acetylcysteine was administered to assess whether the protection would be reversed.

Results and discussion

Animals fed a hyperlipidic diet reacted the same way to infection even after NAC administration. Unlike the control group, which died after eight days of infection with roughly 7% parasitized red blood cells, the hyperlipidic diet group was resistant to infection, with no clinical signs and no increase in blood parasitemia. Several proinflammatory cytokines such as TNF-α IFN-γ and IL-6 were increased in the spleen of both infected groups, regardless of their diet. The provision of a high-fat diet to mice for as little as 5 days completely prevents Plasmodium berghei ANKA infection in C57BL/6 mice, while the treatment of an antioxidant failed to reverse the parasite protection.
Presence of tissue schistosomiasis in KwaZulu-Natal, South Africa: a retrospective histopathologic review
Authors: Mwazha Absalom , Nhlonzi Gamalenkosi Bonginkosi , Kjetland Eyrun Floerecke
Published: November 2023

Background

Schistosomiasis affects many parts of the human body including those not usually accessible during routine clinical follow-up. We investigated the presence of schistosomiasis in routine tissue specimens sent to the only public histopathology laboratory in KwaZulu-Natal, South Africa.

Methods

The catchment area for the Department of Anatomical Pathology constitutes 11 million people in 10 districts. We retrospectively reviewed all the histopathology reports for occurrence of schistosomiasis between 1 January 2015 and 30 June 2020.

Results

Schistosomiasis was identified in the appendix, uterine cervix, urinary bladder, lung, liver, fallopian tubes and prostate. During the study period, 725 cases had a diagnosis of schistosomiasis confirmed on histopathology, which equals 0.3% of the total number of specimens sent to the laboratory. Female genital schistosomiasis represented 49.1% (356/725) of the schistosomiasis cases of which 25.1% (182) were from the uterine cervix and 24% (174) from the fallopian tubes. The appendix had 39.7% (289) of all the cases of schistosomiasis. Other organs were urinary bladder (4.4%, 32), lung (3.2%, 23) and liver (2.6%, 19). There were two cases of schistosomiasis in the prostate and four cases in the anorectal region. The main three indications for taking biopsies were acute appendicitis, cervical intraepithelial neoplasia, and sterilization. Majority of the schistosomiasis cases (312) were from eThekwini/Durban metropolitan district, however this represented only 1.2% (312/25 111) of the specimens received from eThekwini/Durban. The districts with the highest percentage positive cases were uMkhanyakude (43/965, 4.5%), followed by Ugu (129/5 251, 2.6%), and King Cetshwayo districts (132/5 360, 2.5%).

Conclusion

Clinicians in the KwaZulu-Natal public health sector hospitals did not suspect schistosomiasis when they submitted patient samples for histopathological investigations. The study indicates the prevalence and the diversity of the body organs affected by schistosomiasis.
Interactive effects of temperature and nitrogen on the physiology of kelps (Nereocystis luetkeana and Saccharina latissima)
Authors: Fales Robin J. , Weigel Brooke L. , Carrington Emily , Berry Helen D. , Dethier Megan N.
Published: November 2023

Kelp forest declines have been linked to warming ocean temperatures worldwide. Ocean warming rarely occurs in isolation, so multiple stressor studies are necessary to understand the physiological responses of kelp to climate change. The canopy-forming bull kelp, Nereocystis luetkeana, is going locally extinct in areas of the Salish Sea that are seasonally warm and nutrient poor, while the understory kelp, Saccharina latissima, persists at those sites. Further, nitrogen availability can alter physiological responses of kelps to temperature stress, including alleviating warming stress. We compared the physiological responses of kelp sporophytes to high temperature stress and nitrogen limitation between two populations of N. luetkeana with different environmental histories (warm and nutrient poor vs. cold and nutrient rich) and between two species, N. luetkeana and S. latissima. Using laboratory mesocosms, we tested the interactive effects of short term (8-9 day) exposure of kelp blades to different temperatures: low (9, 13°C), moderate (15, 16°C), and warm (21°C) at two different nitrogen concentrations: low (1-3 μM) vs. high (>10 μM). We examined a wide array of physiological responses: blade growth, photosynthesis, respiration, photosynthetic yield, nutrient uptake, and tissue C:N. Both kelp species responded negatively to elevated temperatures, but not to low nitrogen levels. Blades of both species showed signs of metabolic stress and reduced growth in the warmest temperature treatment (21°C), at both high and low nitrogen levels, suggesting that N. luetkeana and S. latissima are susceptible to thermal stress over short time periods. Populations of N. luetkeana from warm, nutrient poor and cool, nutrient rich areas were equally susceptible to the effects of ocean warming. Our results suggest that nutrient additions may actually reduce kelp performance at supra-optimal temperatures, and a thorough understanding of kelp responses to coastal temperature and nutrient dynamics is needed to guide conservation and restoration actions.
IgG4-related diseases involving pleura: a case report and literature review
Authors: Zuo Anli , Liu Xinyi , Guo Zihan , Jiang Yunxiu , Lu Degan
Published: November 2023

Immunoglobulin G4-related disease (IgG4-RD) is a systemic fibro-inflammatory disease with the potential to involve virtually all organs, including the pancreas, kidneys, lungs, and pleura, amongst others. IgG4-RD pleural involvement may cause diverse complications such as pleural effusion, pleural thickening, pleural nodules, and additional lesions, which can be presented in many clinical diseases. However, isolated cases of pleurisy are still rare in IgG4-RD. We report a 72-year-old patient who was admitted to our hospital with cough, expectoration, and fatigue. He had a right-sided pleural effusion, and the tissue evaluation of the pleural biopsy by medical thoracoscopy met the diagnostic criteria of IgG4-RD. His serum IgG4 levels were elevated and he was finally diagnosed with IgG4-RD pleural involvement. He was subsequently started on prednisone 40 mg daily and his pleural effusion was almost disappeared 2 weeks later. This paper reported a case of IgG4-RD who had exclusive involvement of the pleura and highlighted the significance of considering IgG4-RD as a potential diagnosis in patients with unexplained pleural effusion.
Development and validation of a nomogram for predicting low birth weight among pregnant women who had antenatal care visits at Debre Markos Comprehensive and Specialized Hospital, Ethiopia
Authors: Fente Bezawit Melak , Tesema Getayeneh Antehunegn , Gudayu Temesgen Worku , Asaye Mengstu Melkamu
Published: November 2023

Background

Birth weight is a crucial factor linked to a newborn’s survival and can also affect their future health, growth, and development. Earlier, researchers focused on exploring maternal and fetal factors contributing to low birth weight. However, in recent years, there has been a shift toward effectively predicting low birth weight by utilizing a combination of variables. This study aims to develop and validate a nomogram for predicting low birth weight in Ethiopia.

Methods

A retrospective follow-up study was conducted, and a total of 1,120 pregnant women were included. Client charts were selected using a simple random sampling technique. Data were extracted using a structured checklist prepared on the KoboToolbox (Cambridge, Massachusetts in the United States) and exported to STATA version 14 (Computing Resource Center in California) and R version 4.2.2 (University of Auckland, New Zealand) for data management and analysis. A nomogram was developed based on a binary logistic model, and its performance was assessed by discrimination power and calibration. Internal validation was performed using bootstrapping. To evaluate the clinical impact, decision curve analysis was applied.

Results

The nomogram included gestational age, hemoglobin, primigravida, unplanned pregnancy, and preeclampsia. The AUROC of the predicted nomogram was 84.3%, and internal validation was 80.1%. The calibration plot indicated that the nomogram was well calibrated. The model was found to have clinical benefit.

Conclusion

The nomogram demonstrates strong discrimination performance and can predict low birth weight clinically. As a result, it can be used in clinical practice, which will help clinicians in making quick and personalized predictions simply and rapidly, enabling the early identification and medical intervention. For broader applicability, the nomogram must be externally validated.
Alcohol consumption and the risk of liver disease: a nationwide, population-based study
Authors: Moon Sang Yi , Son Minkook , Kang Yeo Wool , Koh Myeongseok , Lee Jong Yoon , Baek Yang Hyun
Published: November 2023

Introduction

Although most patients with alcohol-related liver disease (ALD) have a history of prolonged and heavy drinking, there is no clear threshold defining the level of alcohol consumption that leads to ALD. We aimed to evaluate the correlation between average alcohol consumption and the risk of liver disease and to determine the threshold for clinically significant alcohol consumption.

Materials and methods

Using the Korean National Health Insurance database, we identified participants who underwent a health-screening program in 2010 and 2011 and retrospectively analyzed their data until 2019. To diagnose and categorize the extracted participants, we used the International Classification of Diseases version 10 and Fatty Liver Index. The primary outcome was to determine the incidence of newly diagnosed liver-related diseases during the observation period and compare the incidence of liver-related diseases among non-drinkers and drinkers based on the amount of alcohol consumption.

Results

A total of 53,006 patients were enrolled and followed-up for a median of 8.4 years, during which 1,509 cases of liver-related diseases occurred. The participants were divided into five groups: no alcohol consumption (n = 31,359), 1st quartile (n = 5,242), 2nd quartile (n = 5,704), 3rd quartile (n = 5,337), and 4th quartile (n = 5,364). The corresponding number of glasses of alcohol consumed per week for each quantile (Q1, Q2, Q3, and Q4) was labeled 2.5 ± 1.1 standard units (1 standard unit = 8 g alcohol), 5.4 ± 1.9 standard units, 11.5 ± 3.3 standard units, and 27.9 ± 18.2 standard units, respectively. Compared with non-drinkers, the risk of liver-related disease was found to be higher in Q1 drinkers (adjusted hazard ratio [aHR], 1.09; 95% CI, 0.90–1.33), Q2 drinkers (aHR, 1. 10; 95% CI, 0.91–1.32), Q3 drinkers (aHR, 1.33; 95% CI, 1.11–1.59), and Q4 drinkers (aHR, 1.47; 95% CI, 1.24–1.75).

Conclusion

We report that our study has shown that drinking more than 11.5 ± 3.3 standard units/week (92 ± 26.4 g/week) significantly increases the risk of developing liver-related diseases. Therefore, as a preventive measure to reduce the risk of developing liver disease, alcohol consumption should be limited beyond traditionally recommended levels.
Associations between microstructural tissue changes, white matter hyperintensity severity, and cognitive impairment: an intravoxel incoherent motion imaging study
Authors: Lin Huihua , Dai Xiaomin , Su Jiawei , Yang Shengsheng , Zheng Yonghong , Ma Mingping , Yu Shun
Published: November 2023

Introduction

White matter hyperintensities (WMHs) are a common age- and vascular risk factor-related disease and have been recognized to play an important role in cognitive impairment. However, it is still unclear what the mechanism of this effect is. In this study, intravoxel incoherent motion (IVIM) was employed to assess the microvasculature and parenchymal microstructure changes of WMHs and explore their relationship with cognitive function.

Methods

Forty-nine WMH patients and thirty-one healthy controls underwent IVIM imaging, a diffusion technique that provides parenchymal diffusivity D, intravascular diffusivity D*, and perfusion fraction f . The IVIM dual exponential model parameters were obtained in specific regions of interest, including deep white matter hyperintensities (DWMHs), periventricular white matter hyperintensities (PWMHs), and normal-appearing white matter (NAWM). The independent-sample t-test or Mann–Whitney U-test was utilized to compare IVIM parameters between patients and controls. The Kruskal–Wallis test or one-way analysis of variance was used to compare IVIM parameters among DWMH, PWMH, and NAWM for patients. The Wilcoxon two-sample test or independent-sample t-test was used to assess the differences in IVIM parameters based on the severity of WMH. The multivariate linear regression analysis was conducted to explore the factors influencing cognitive scores.

Results

WMH patients exhibited significantly higher parenchymal diffusivity D than controls in DWMH, PWMH, and NAWM (all p < 0.05). IVIM parameters in the three groups (DWMH, PWMH, and NAWM) were significantly different for patients (all p < 0.001). The severe WMH group had a significantly higher parenchymal diffusivity D (DWMH and PWMH) than mild WMH (both p < 0.05). The multiple linear regression analysis identified D in DWMH and PWMH as influencing cognitive function scores (all p < 0.05).

Conclusion

IVIM has the potential to provide a quantitative marker of parenchymal diffusivity for assessing the severity of WMH and may serve as a quantitative marker of cognitive dysfunction in WMH patients.
Experimental verification and identifying biomarkers related to insomnia
Authors: Wang Qianfei , Liu Dong , Gao Tianci , Tao Yulei , Li Xin , Liu Yuan , Liu Zhiliang , Mei Jianqiang , Chen Fenqiao
Published: November 2023

Introduction

Insomnia is the most common form of sleep deprivation (SD) observed in clinics. Although there are differences between insomnia and SD, they have similar symptoms and the same animal model. Currently, there is a lack of microarray data on insomnia. Therefore, for now, we are going to apply the SD data to insomnia. Although many studies have explained the possible mechanisms associated with insomnia, no previous studies have considered the key genes associated with insomnia or the relationship between insomnia and immune cells. In this study, we analyzed the relationship between key genes and immune cells by identifying biomarkers for the diagnosis of insomnia. Next, we verified the efficacy of these biomarkers experimentally.

Methods

First, we downloaded four microarrays (GSE11755, GSE12624, GSE28750, and GSE48080) from the Gene Expression Omnibus (GEO) database, which included data from 239 normal human blood samples and 365 blood specimens from patients with SD. Then, we analyzed two groups of differentially expressed genes (DEGs) and used Support Vector Machine Recursive Feature Elimination (SVM-RFE) analysis and the Least Absolute Shrinkage and Selection Operator (LASSO) regression model to investigate these key genes. Next, we used CIBERSORT to investigate the composition of 22 immune cell components of key genes in SD patients. Finally, the expression levels of key biomarkers in sleep-deprived patients were examined by quantitative real-time polymerase chain reaction (qRT-PCR).

Results

A total of 50 DEGs were identified: six genes were significantly upregulated, and 44 genes were significantly downregulated. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that Salmonella infection, NOD-like receptor (NLR) signaling pathway, Kaposi sarcoma-associated herpesvirus infection, and Th17 cell differentiation were significant. Based on machine learning, we identified C2CD2L, SPINT2, APOL3, PKNOX1, and A2M as key genes for SD; these were confirmed by receiver operating characteristic (ROC) analysis. Immune cell infiltration analysis showed that C2CD2L, SPINT2, APOL3, PKNOX1, and A2M were related in different degrees to regulatory T cells (Tregs), follicular T helper cells, CD8 cells, and other immune cells. The qRT-PCR experiments confirmed that the expression levels of C2CD2L concurred with the results derived from machine learning, but PKNOX1 and APOL3 did not.

Discussion

In summary, we identified a key gene (C2CD2L) that may facilitate the development of biomarkers for insomnia.
Relationships among gut microbes, the interleukin family, and hypertension: a mediation Mendelian randomization study
Authors: Zhao Shiyao , Zhang Jing , Ding Fuxia , Sun Shougang
Published: November 2023

Purpose

Observational studies have increasingly recognized the influence of gut microbes on blood pressure modulation. Despite these findings, a direct causal link between gut flora and hypertension remains unestablished due to inherent confounders and the challenges of reverse causality in observational research. In this study, we sought to elucidate the causal relationship between specific gut flora and hypertension and its intermediary mediators.

Methods

We employed a two-sample Mendelian randomization (MR) and mediation MR analysis, analyzing 211 species of gut bacteria, with a focus on the interleukin family as potential mediators and hypertension as the primary outcome. The central methodological technique was inverse variance-weighted estimation, supplemented by various other estimators.

Results

Our findings revealed that two bacterial species positively correlated with hypertension risk, while five exhibited a negative association. Further validation was conducted using sensitivity analyses. Notably, our mediation MR results suggest interleukin-1 receptor type 2 (IL-1R2) as a mediator for the effect of the genus Clostridium innocuum group on hypertension, accounting for a mediation proportion of 14.07% [mediation effect: (b = 0.0007, 95%CI: 0.0002–0.0011); proportion mediation = 14.07% (4.26–23.40%)].

Conclusion

Our research confirms a genetic causal relationship between specific gut microbes and hypertension, emphasizing the potential mediating role of interleukin-1 receptor type 2 (IL-1R2) and offering insights for clinical hypertension interventions.
Risk factors associated with multiple organ damage in childhood-onset systemic lupus erythematosus
Authors: Puengpipattrakul Thanaporn , Lerkvaleekul Butsabong , Pirojsakul Kwanchai , Vilaiyuk Soamarat
Published: November 2023

Objective

Previous studies have shown that approximately 39%–65% of patients with childhood-onset systemic lupus erythematosus (cSLE) have damage in at least one organ. Data on risk factors for organ damage in cSLE remain limited, especially in Asian populations. This study was conducted to evaluate the incidence of cSLE and identify the risk factors for accumulated organ damage in patients with cSLE.

Methods

This was a retrospective study. Patients aged <18 years who were diagnosed with cSLE between 2008 and 2020 were enrolled. Information on baseline characteristics, treatment, and disease activity assessed using the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) was collected from diagnosis until the most recent visits were reviewed from medical records. Disease damage was measured using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI).

Results

A total of 134 patients with a mean age at diagnosis of 11.2 ± 2.9 years were enrolled. The median duration of treatment was 4.7 (interquartile range 2.8–7.1) years. Forty patients (29.9%) had irreversible organ damage (SDI > 1) with an incidence rate of 5.7 events per 100 person-years. The most frequent type of organ damage was ocular (11.1%), followed by musculoskeletal (8.9%) and neurological (7.4%). High disease activity at diagnosis (SLEDAI-2K ≥ 12) (odds ratio [OR] 3.19, 95% confidence interval [CI] 1.32–7.68), infection (OR 3.73, 95% CI 1.60–8.67), and mycophenolate mofetil use (OR 3.62, 95% CI 1.45–9.03) were predictors of organ damage. The median time to disease damage in patients with SLEDAI-2K scores ≥12 at diagnosis was 6.5 years (95% CI 5.77–7.36; P = 0.004).

Conclusion

Physicians should be aware of organ damage in patients with cSLE, particularly those with high disease activity at initial presentation, those who are receiving mycophenolate mofetil therapy, and those with an infection.
Pricing and reimbursement mechanisms for advanced therapy medicinal products in 20 countries
Authors: Rejon-Parrilla Juan Carlos , Espin Jaime , Garner Sarah , Kniazkov Stanislav , Epstein David
Published: November 2023

Introduction: Advanced Therapy Medicinal Products are a type of therapies that, in some cases, hold great potential for patients without an effective current therapeutic approach but they also present multiple challenges to payers. While there are many theoretical papers on pricing and reimbursement (P&R) options, original empirical research is very scarce. This paper aims to provide a comprehensive international review of regulatory and P&R decisions taken for all ATMPs with centralized European marketing authorization in March 2022.

Methods: A survey was distributed in July 2022 to representatives of 46 countries.

Results: Responses were received from 20 countries out of 46 (43.5%). 14 countries reimbursed at least one ATMP. Six countries in this survey reimbursed no ATMPs.

Conclusion: Access to ATMPs is uneven across the countries included in this study. This arises from regulatory differences, commercial decisions by marketing authorization holders, and the divergent assessment processes and criteria applied by payers. Moving towards greater equality of access will require cooperation between countries and stakeholders, for example, through the WHO Regional Office for Europe’s Access to Novel Medicines Platform.
Inhibitory effect of napabucasin on arbidol metabolism and its mechanism research
Authors: Nie Jingjing , Xia Hailun , Liu Ya-Nan , Yu Yige , Xu Ren-Ai
Published: November 2023

As a broad-spectrum antiviral, and especially as a popular drug for treating coronavirus disease 2019 (COVID‐19) today, arbidol often involves drug–drug interactions (DDI) when treating critical patients. This study established a rapid and effective ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) method to detect arbidol and its metabolite arbidol sulfoxide (M6-1) levels in vivo and in vitro. In this study, a 200 μL incubation system was used to study the inhibitory effect of the antitumor drug napabucasin on arbidol in vitro, with IC50 values of 2.25, 3.91, and 67.79 μM in rat liver microsomes (RLMs), human liver microsomes (HLMs), and CYP3A4.1, respectively. In addition, we found that the mechanism of inhibition was non-competitive inhibition in RLM and mixed inhibition in HLM. In pharmacokinetic experiments, it was observed that after gavage administration of 48 mg/kg napabucasin and 20 mg/kg arbidol, napabucasin inhibited the metabolism of arbidol in vivo and significantly changed the pharmacokinetic parameters of arbidol, such as AUC(0-t) and AUC(0-∞), in rats. We also found that napabucasin increased the AUC(0-t) and AUC(0-∞) of M6-1, the main metabolite of arbidol. This study provides a reference for the combined use of napabucasin and arbidol in clinical practice.
The Feynman chessboard model in 3 + 1 dimensions
Authors: Ord G. N.
Published: November 2023

The chessboard model was Feynman’s adaptation of his path integral method to a two-dimensional relativistic domain. It is shown that chessboard paths encode information about the contiguous pairs of paths in a spacetime plane, as required by discrete worldlines in Minkowski space. The application of coding by pairs in a four-dimensional spacetime is then restricted by the requirements of the Lorentz transformation, and the implementation of these restrictions provides an extension of the model to 4D, illuminating the relationship between relativity and quantum propagation.
Elucidation of the evolutionary history of Stipa in China using comparative transcriptomic analysis
Authors: Sha Na , Li Zhiyong , Sun Qiang , Han Ying , Tian Li , Wu Yantao , Li Xing , Shi Yabo , Zhang Jinghui , Peng Jiangtao , Wang Lixin , Dang Zhenhua , Liang Cunzhu
Published: November 2023

Phylogenetic analysis provides crucial insights into the evolutionary relationships and diversification patterns within specific taxonomic groups. In this study, we aimed to identify the phylogenetic relationships and explore the evolutionary history of Stipa using transcriptomic data. Samples of 12 Stipa species were collected from the Qinghai-Tibet Plateau and Mongolian Plateau, where they are widely distributed, and transcriptome sequencing was performed using their fresh spikelet tissues. Using bidirectional best BLAST analysis, we identified two sets of one-to-one orthologous genes shared between Brachypodium distachyon and the 12 Stipa species (9397 and 2300 sequences, respectively), as well as 62 single-copy orthologous genes. Concatenation methods were used to construct a robust phylogenetic tree for Stipa, and molecular dating was used to estimate divergence times. Our results indicated that Stipa originated during the Pliocene. In approximately 0.8 million years, it diverged into two major clades each consisting of native species from the Mongolian Plateau and the Qinghai-Tibet Plateau, respectively. The evolution of Stipa was closely associated with the development of northern grassland landscapes. Important external factors such as global cooling during the Pleistocene, changes in monsoonal circulation, and tectonic movements contributed to the diversification of Stipa. This study provided a highly supported phylogenetic framework for understanding the evolution of the Stipa genus in China and insights into its diversification patterns.
Self-regulatory employability attributes and competency: the strengthening role of grit
Authors: Ismail Sadika , Potgieter Ingrid L. , Coetzee Melinde
Published: November 2023

Introduction

This study examines grit as psychological mindsets that explain the link between self-regulatory employability attributes and perceived employability competency expectations in a sample of South African adults (N = 308).

Methods

A quantitative, cross-sectional research design approach was used to collect primary data.

Results

Results of a mediation analysis through structural equation modelling revealed grit as an important mechanism to strengthen the association between employability attributes (career agility, cultural ingenuity, proactive career resilience) and employability competency expectations (autonomy/leadership skills and personal employability qualities).

Discussion

This study makes an important contribution to the role of learning and training through understanding the role of grit in enhancing prospects of employability. This study further adds to the grit literature, highlighting the role that grit plays in the contemporary employment context. Practical implications include supportive practices that strengthen individual workers’ grit when confronted with the turbulent changes of today’s work world.
Clinical case report: considerable improvement of severe and difficult-to-treat obsessive-compulsive disorder with comorbid depression under treatment with esketamine and concomitant psychotherapy
Authors: Kaltenboeck Alexander , Foerster Elisa , Strafner Sabrina , Demal Ulrike , Mossaheb Nilufar , Friedrich Fabian
Published: November 2023

A 28-year-old man was admitted to our psychiatric ward with severe obsessive-compulsive disorder (OCD) and comorbid depression. At intake, obsessive-compulsive symptoms were present most time of the day and were related to an intense fear of causing interpersonal misunderstandings. Various treatment attempts, including cognitive-behavioural therapy (CBT) with exposure and response prevention (ERP), selective serotonin reuptake inhibitors, clomipramine, and add-on antipsychotics were either ineffective and/or were not tolerated, and the patient’s condition worsened progressively. Following an in-depth multidisciplinary team discussion and a shared decision-making process, an off-label treatment trial with esketamine and concomitant psychotherapy was started. The patient received 10 esketamine + psychotherapy sessions over a period of about 2 months, followed by two maintenance sessions in about 3-week intervals. After this, he was discharged into regular outpatient care where he continued to receive maintenance esketamine treatment every 4–6 weeks and, independent of this, individual CBT. Following the establishment of esketamine with concurrent psychotherapy, the patient exhibited a remarkable clinical improvement. Obsessive-compulsive symptoms showed a clear and sustained response (Y-BOCS before treatment >35, Y-BOCS at week 8 = 23, Y-BOCS at week 26 = 14). Paralleling this, depressive symptoms also decreased (MADRS before treatment = 47, MADRS at week 9 = 12, MADRS at week 26 = 3). At a naturalistic follow-up at week 66, obsessive-compulsive symptoms were still mild (Y-BOCS = 13), and depression was still in remission (MADRS < 6). This clinical case suggests that (es)ketamine plus concomitant psychotherapy may hold promise as a therapeutic strategy for difficult-to-treat OCD and depression and its full clinical potential should be evaluated in more comprehensive future studies.
Assessment of knowledge, attitudes, and practices regarding menstruation and menstrual hygiene among early-reproductive aged women in Bangladesh: a cross-sectional survey
Authors: Siddique Abu Bakkar , Deb Nath Sudipto , Mubarak Mahfuza , Akter Amena , Mehrin Sanjida , Hkatun Mst Jemi , Parvine Liza Antara , Amin M. Ziaul
Published: November 2023

Background

Poor menstrual hygiene practices during menstruation increases the risk of reproductive tract infections, absenteeism, and negative impact on school performance. Despite being a global problem, there is a lack of knowledge and misconceptions about menstrual hygiene among women of all ages, especially in developing countries like Bangladesh. The study aims to assess the knowledge, attitudes, and practices toward menstrual hygiene among early reproductive-aged women in Bangladesh to help policymakers and planners take effective initiatives.

Methodology

A cross-sectional survey was conducted between July and December 2022 in Dhaka, Rajshahi, Chittagong, Sylhet, and Barisal regions of Bangladesh. A convenience sampling technique was utilized to recruit a total of 1,214 participants (100% female; mean age: 22.87 ± 2.64 years). A semi-structured questionnaire including informed consent, socio-demographic information, as well as questions regarding knowledge (6-item), attitudes (7-item), and practices (6-item) toward menstruation and menstrual hygiene practices, was used to conduct the survey. All analyses were performed using the STATA (Version 15.0) and Statistical Package for the Social Sciences (SPSS version 25.0).

Result

The mean scores of the knowledge, attitudes, and practices were 4.9 ± 1.51 (out of 6), 12.58 ± 1.58 (out of 14), and 8.80 ± 1.87 (out of 12), respectively. The higher scores of knowledge, attitudes, and practices were significantly associated with several socio-demographic and menstruation-related factors (education, family type, type of menstruation, duration of menstruation, etc.).

Conclusion

This study identified several key factors associated with improved knowledge, attitudes, and practices related to menstrual hygiene, including higher education levels, student status, younger age, non-alcohol consumption, and regular menstrual cycles. To enhance menstrual hygiene practices among women, it is crucial to implement targeted interventions that address knowledge disparities and tackle social and environmental influences.