bluuebunny/crossref_metadata_2025 huggingface dataset:
Single-Cell RNA sequencing investigation of female-male differences under PAD conditions
Authors: Sánchez Marrero Gloriani , Villa-Roel Nicolas , Li Feifei , Park Christian , Kang Dong-Won , Hekman Katherine E. , Jo Hanjoong , Brewster Luke P.
Published: September 2023

Peripheral arterial disease (PAD) is an age-related medical condition affecting mostly muscular arteries of the limb. It is the 3rd leading cause of atherosclerotic morbidity. The mechanical environment of endothelial cells (ECs) in PAD is characterized by disturbed blood flow (d-flow) and stiff extracellular matrices. In PAD, the stiffness of arteries is due to decreased elastin function and increased collagen content. These flow and stiffness parameters are largely missing from current models of PAD. It has been previously proven that ECs exposed to d-flow or stiff substrates lead to proatherogenic pathways, but the effect of both, d-flow and stiffness, on EC phenotype has not been fully investigated. In this study, we sought to explore the effect of sex on proatherogenic pathways that could result from exposing endothelial cells to a d-flow and stiff environment. We utilized the scRNA-seq tool to analyze the gene expression of ECs exposed to the different mechanical conditions both in vitro and in vivo. We found that male ECs exposed to different mechanical stimuli presented higher expression of genes related to fibrosis and d-flow in vitro. We validated our findings in vivo by exposing murine carotid arteries to d-flow via partial carotid artery ligation. Since women have delayed onset of arterial stiffening and subsequent PAD, this work may provide a framework for some of the pathways in which biological sex interacts with sex-based differences in PAD.
Digital twin for healthcare systems
Authors: Vallée Alexandre
Published: September 2023

Digital twin technology is revolutionizing healthcare systems by leveraging real-time data integration, advanced analytics, and virtual simulations to enhance patient care, enable predictive analytics, optimize clinical operations, and facilitate training and simulation. With the ability to gather and analyze a wealth of patient data from various sources, digital twins can offer personalized treatment plans based on individual characteristics, medical history, and real-time physiological data. Predictive analytics and preventive interventions are made possible by machine learning algorithms, allowing for early detection of health risks and proactive interventions. Digital twins can optimize clinical operations by analyzing workflows and resource allocation, leading to streamlined processes and improved patient care. Moreover, digital twins can provide a safe and realistic environment for healthcare professionals to enhance their skills and practice complex procedures. The implementation of digital twin technology in healthcare has the potential to significantly improve patient outcomes, enhance patient safety, and drive innovation in the healthcare industry.
Experimental study on shear mechanical properties of improved loess based on rubber particle incorporation and EICP technology
Authors: Chen Yong , Chai Shaoqiang , Cai Dongbo , Wang Wei , Li Xianpeng , Liu Jinhao
Published: September 2023

Loess is often not suitable for direct use as a roadbed or building foundation due to its collapsibility, and it needs to be improved by adding curing agents. Taking the loess in Xi’an area as the research object, the reinforcement of loess was carried out using waste tire rubber particles and Enzyme Induced Carbonate Precipitation (EICP) technology. The change of shear strength and shear strength index of improved soil with rubber content and rubber particle size under different strengthening conditions was analyzed, and the strengthening mechanism was also expounded. The results show that rubber powder can improve the shear strength of loess to a certain extent, and the combination of EICP technology can increase the strength of improved loess by nearly 50%. In addition, rubber particles have a certain inhibitory effect on EICP, and the shear strength growth rate decreases with the increase of rubber content. When the rubber particle size is 1–2 mm, the shear strength growth rate is the highest. It is suggested that when adding rubber particles or adding rubber particles combined with EICP technology is used to improve loess, the rubber particle size should be selected as 1–2 mm, and the content is about 10%. The test results can provide a scientific basis for the reduction of geologic disasters in loess areas, and at the same time can provide a non-polluting way for the disposal of waste tires.
Fostering future music teachers' professional skills: developing a signature pedagogy using e-learning
Authors: Karkina Svetlana , Mena Juanjo , Valeeva Roza , Yarmakeev Iskander , Dyganova Elena , Bhullar Mandeep
Published: September 2023

Introduction

The emergency crisis due to the COVID-19 pandemic caused noticeable changes that stimulated the transition to the new normal based on the digitalization of our systems. In this regard, the revision of learning tools in higher education exposes new challenges and requires the development and implementation of digital technologies. Fostering future music teachers' professional skills needs designing of online resources that provide close student–teacher interaction, as well as the engagement of students and regulation of their professional music practice. Based on the theory of Shulman, the signature pedagogy in music education was developed and implemented in an e-learning environment by a small private online course. The aim of the research was stated: How and which students' music teacher professional skills are affected in the process of e-learning based on the signature approach? The research was conducted at Kazan Federal University. During the educational process students studied the professional practicum.

Methods

Totally, 124 students from 1st to 4th academic level had taken part in the experimental work in the academic year 2021–2022. All of them studied bachelor programs for future music teacher as full- or part-time regime and studied the online course in MOODLE during the experiment. A combination of online tasks which cover all the types of the music teacher‘ professional activities was suggested. Considering the aim of the research, the multi-case study research methodology was chosen, using a mixed method approach, resourcing mainly to questionnaire, interview, documental analysis, and observation as data gathering methods, and descriptive statistical analysis, as data analysis techniques.

Results

The main results demonstrate the effectiveness of the developed online course that allowed to significantly foster students' music teacher professional skills.

Discussion

The investigation of the efficiency of using e-learning for training future music teachers' professional skills was carried out in this study. To improve future music teachers' skills according to the features of the professional field, a signature pedagogy approach was suggested. The contribution of the paper brings the detail characteristic of the signature pedagogy in music education, and the way of its implementation by the means of online tools.
Survival outcomes of low-risk papillary thyroid carcinoma at different risk levels: a corollary for active surveillance
Authors: Ding Wu , Ruan Guodong , Lin Yingli , Zhu Jianming , Li Zhian , Ye Dengfeng
Published: September 2023

Background

This study aims to compare the outcomes of active surveillance (AS) in low-risk papillary thyroid carcinoma (PTC) patients with different tumor sizes and lymph node metastasis status, in order to establish appropriate management strategies. By analyzing these results, this study provides valuable insights for the effective management of such patients, addressing the issues and challenges associated with AS in practical clinical practice.

Methods

The study utilized the SEER database supported by the National Cancer Institute of the United States, extracting data of PTC diagnosed between 2000 and 2015. Statistical analyses were conducted using inverse probability weighting (IPTW) and propensity score matching (PSM), including Kaplan-Meier survival curves and Cox regression models, to evaluate the impact of different tumor sizes and lymph node metastasis status on thyroid cancer-specific survival (TCSS).

Results

A total of 57,000 PTC patients were included, with most covariates having standardized mean differences below 10% after IPTW and PSM adjustments. The TCSS of PTC with a diameter smaller than 13mm is significantly better than that of tumors with a diameter larger than 13mm, regardless of the presence of lymph node metastasis. Among PTC cases with a diameter smaller than 13mm, the TCSS of patients is similar, regardless of the presence of lymph node metastasis. However, in PTC cases with a diameter larger than 13mm, the presence of lateral neck lymph node metastasis (N1b stage) significantly impacts the TCSS, although the absolute impact on TCSS rate is minimal.

Conclusion

The treatment strategy of AS is safe for patients with T1a stage papillary thyroid microcarcinoma (PTMC). However, for patients with T1b stage, if the tumor diameter exceeds 13mm or there is lymph node metastasis in the lateral neck region, the TCSS will be significantly affected. Nevertheless, the absolute impact on survival is relatively small.
Non-syndromic enlarged vestibular aqueduct caused by novel compound mutations of the SLC26A4 gene: a case report and literature review
Authors: Huang Yunhua , Li Linlin , Pan Liqiu , Ling Xiaoting , Wang Chenghan , Huang Chaoyu , Huang Yifang
Published: September 2023

Enlarged vestibular aqueduct is an autosomal genetic disease mainly caused by mutations in the SLC26A4 gene and includes non-syndromic and syndromic types. This study aimed to identify genetic defects in a Chinese patient with non-syndromic enlarged vestibular aqueduct (NSEVA) and to investigate the impact of variants on the severity of non-syndromic enlarged vestibular aqueduct. A male patient with NSEVA, aged approximately 6 years, was recruited for this study. The clinical characteristics and results of auxiliary examinations, including laboratory and imaging examinations, were collected, and 127 common hereditary deafness genes were detected by chip capture high-throughput sequencing. Protein structure predictions, the potential impact of mutations, and multiple sequence alignments were analyzed in silico. Compound heterozygote mutations c.1523_1528delinsAC (p.Thr508Asnfs*3) and c.422T>C (p.Phe141Ser) in the SLC26A4 gene were identified. The novel frameshift mutation c.1523_1528delinsAC produces a severely truncated pendrin protein, and c.422T>C has been suggested to be a disease-causing mutation. Therefore, this study demonstrates that the novel mutation c.1523_1528delinsAC in compound heterozygosity with c.422T>C in the SLC26A4 gene is likely to be the cause of NSEVA. Cochlear implants are the preferred treatment modality for patients with NSEVA and severe-to-profound sensorineural hearing loss Genetic counseling and prenatal diagnosis are essential for early diagnosis. These findings expand the mutational spectrum of SLC26A4 and improve our understanding of the molecular mechanisms underlying NSEVA.
The prognostic value of whole-genome DNA methylation in response to Leflunomide in patients with Rheumatoid Arthritis
Authors: Chen Yulan , Wang Qiao , Liu Haina , Jin Lei , Feng Xin , Dai Bingbing , Chen Meng , Xin Fangran , Wei Tingting , Bai Bingqing , Fan Zhijun , Li Jiahui , Yao Yuxin , Liao Ruobing , Zhang Jintao , Jin Xiangnan , Fu Lingyu
Published: September 2023

Objective

Although Leflunomide (LEF) is effective in treating rheumatoid arthritis (RA), there are still a considerable number of patients who respond poorly to LEF treatment. Till date, few LEF efficacy-predicting biomarkers have been identified. Herein, we explored and developed a DNA methylation-based predictive model for LEF-treated RA patient prognosis.

Methods

Two hundred forty-five RA patients were prospectively enrolled from four participating study centers. A whole-genome DNA methylation profiling was conducted to identify LEF-related response signatures via comparison of 40 samples using Illumina 850k methylation arrays. Furthermore, differentially methylated positions (DMPs) were validated in the 245 RA patients using a targeted bisulfite sequencing assay. Lastly, prognostic models were developed, which included clinical characteristics and DMPs scores, for the prediction of LEF treatment response using machine learning algorithms.

Results

We recognized a seven-DMP signature consisting of cg17330251, cg19814518, cg20124410, cg21109666, cg22572476, cg23403192, and cg24432675, which was effective in predicting RA patient’s LEF response status. In the five machine learning algorithms, the support vector machine (SVM) algorithm provided the best predictive model, with the largest discriminative ability, accuracy, and stability. Lastly, the AUC of the complex model(the 7-DMP scores with the lymphocyte and the diagnostic age) was higher than the simple model (the seven-DMP signature, AUC:0.74 vs 0.73 in the test set).

Conclusion

In conclusion, we constructed a prognostic model integrating a 7-DMP scores with the clinical patient profile to predict responses to LEF treatment. Our model will be able to effectively guide clinicians in determining whether a patient is LEF treatment sensitive or not.
Quantitative approaches for decoding the specificity of the human T cell repertoire
Authors: Ghoreyshi Zahra S. , George Jason T.
Published: September 2023

T cell receptor (TCR)-peptide-major histocompatibility complex (pMHC) interactions play a vital role in initiating immune responses against pathogens, and the specificity of TCRpMHC interactions is crucial for developing optimized therapeutic strategies. The advent of high-throughput immunological and structural evaluation of TCR and pMHC has provided an abundance of data for computational approaches that aim to predict favorable TCR-pMHC interactions. Current models are constructed using information on protein sequence, structures, or a combination of both, and utilize a variety of statistical learning-based approaches for identifying the rules governing specificity. This review examines the current theoretical, computational, and deep learning approaches for identifying TCR-pMHC recognition pairs, placing emphasis on each method’s mathematical approach, predictive performance, and limitations.
Immunomodulatory properties of the lymphatic endothelium in the tumor microenvironment
Authors: Viúdez-Pareja Cristina , Kreft Ewa , García-Caballero Melissa
Published: September 2023

The tumor microenvironment (TME) is an intricate complex and dynamic structure composed of various cell types, including tumor, stromal and immune cells. Within this complex network, lymphatic endothelial cells (LECs) play a crucial role in regulating immune responses and influencing tumor progression and metastatic dissemination to lymph node and distant organs. Interestingly, LECs possess unique immunomodulatory properties that can either promote or inhibit anti-tumor immune responses. In fact, tumor-associated lymphangiogenesis can facilitate tumor cell dissemination and metastasis supporting immunoevasion, but also, different molecular mechanisms involved in LEC-mediated anti-tumor immunity have been already described. In this context, the crosstalk between cancer cells, LECs and immune cells and how this communication can shape the immune landscape in the TME is gaining increased interest in recent years. In this review, we present a comprehensive and updated report about the immunomodulatory properties of the lymphatic endothelium within the TME, with special focus on primary tumors and tumor-draining lymph nodes. Furthermore, we outline emerging research investigating the potential therapeutic strategies targeting the lymphatic endothelium to enhance anti-tumor immune responses. Understanding the intricate mechanisms involved in LEC-mediated immune modulation in the TME opens up new possibilities for the development of innovative approaches to fight cancer.
Immunotherapy: a promising approach for glioma treatment
Authors: Yasinjan Feroza , Xing Yang , Geng Huayue , Guo Rui , Yang Lei , Liu Ziling , Wang Hong
Published: September 2023

Gliomas are the most prevalent primary malignant brain tumors worldwide, with glioblastoma (GBM) being the most common and aggressive type. Despite two decades of relentless pursuit in exploring novel therapeutic approaches for GBM, there is limited progress in improving patients’ survival outcomes. Numerous obstacles impede the effective treatment of GBM, including the immunosuppressive tumor microenvironment (TME), the blood-brain barrier, and extensive heterogeneity. Despite these challenges, immunotherapies are emerging as a promising avenue that may offer new hope for the treatment of gliomas. There are four main types of immunotherapies for gliomas, immune checkpoint blockades, chimeric antigen receptor T-cell therapies, vaccines, and oncolytic viruses. In addition, gene therapy, bispecific antibody therapy, and combine therapy are also briefly introduced in this review. The significant role of TME in the process of immunotherapies has been emphasized in many studies. Although immunotherapy is a promising treatment for gliomas, enormous effort is required to overcome the existing barriers to its success. Owing to the rapid development and increasing attention paid to immunotherapies for gliomas, this article aims to review the recent advances in immunotherapies for gliomas.
Compensatory growth and production economics of Silver pompano, Trachinotus blochii (Lacepede, 1801), fingerlings stunted by feed and space deprivation
Authors: P. P. Suresh Babu , A. Anuraj , M. T. Shilta , Ebeneezar Sanal , P. Shinoj , K. Raghu Ramudu , N. D. Praveen , N. G. Vaidya , Pal Mahendra , I. Boby , K. K. Anikuttan , A. Gopalakrishnan
Published: September 2023

The effect of stunting by feed and space deprivation on compensatory growth (CG) in Silver pompano,Trachinotus blochii, was investigated. A commercial pellet feed (45% protein and 10% fat) was fed two times a day, throughout the entire experiment. The 270-day experiment consisted of an initial 60-day stunting phase and a 60-day post-stunting phase carried out in 4 × 2 × 2 m3galvanized iron (GI) rectangular cages, and a 150-day grow-out phase carried out in 3-m diameter circular GI cages. During the stunting phase, the normal fish (in triplicates) were stocked at lower stocking density (17 fish/m3) and fed at 10% of body weight (BW), while stunted fish (one replication) were stocked at about three times higher stocking density (56 fish/m3) and fed at a three times lower feeding rate (3% of BW). The stunted and normal fish were reared in triplicates during the post-stunting phase, at uniform stocking density (15 fish/m3) with feeding at a higher rate (10% of BW) for stunted fish and normal feeding rate (8% of BW) was adopted for normal fish. During the grow-out stage, each replication from the post-stunting phase was shifted to 3-m circular cages with the same feeding rates. The lag in growth in stunted fish (5.56 g against 9.43 ± 0.13 g of normal) during the stunting phase was compensated during the post-stunting phase (36.88 ± 2.23 g against 38.13 ± 1.48 g of normal) by higher feeding rate. There were no significant (p> 0.05) differences in final harvest, biometry, morphometry, dressing yield, carcass nutritional composition, and serum biochemical markers at the end of grow-out stage. Because of the significant difference (p< 0.05) in the total feed provided (5.2 kg for stunted fish against 22.8 kg for normal fish) and the lesser unit cost for the production of stunted fingerling (USD 0.087 for stunted fish against USD 0.106 for normal), the farming of stunted fish brought about a higher net operational revenue and benefit:cost ratio.
Synthesis of novel acylated and esterified ciprofloxacin derivatives as efficient anticancer and antimicrobial agents
Authors: Alasadi Gheith M. , Al-Obaidi Zaid
Published: September 2023

Nowadays, various factors enhance the resistance of some microbes to antibiotics. Irrational antibiotic use is considered an example of such factors. Therefore, the synthesis and reporting of heterocyclic compounds with multiple biological properties are of considerable value. Ciprofloxacin is an antibiotic used to treat infections. New amidification and esterification derivatives of ciprofloxacin were synthesized. Their structure was identified and confirmed using both proton and carbon-13 nuclear magnetic resonance, mass spectrometry, and elemental analysis. With the employment of MTT (3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyl-terazoliumbromide) methods, in vitro anticancer activity was evaluated. The utilization of clinical and laboratory standards institute (CLSI) instructions was involved in the in vitro antimicrobial activity evaluation of the newly synthesized derivatives. In terms of anticancer activity, cell proliferation, viability, and IC50, as well as antimicrobial activities, IZD (Inhibition Zone Diameter), MIC (Minimum Inhibitory Concentrations), MBC (Minimum Bactericidal Concentrations), and MFC (Minimum Fungicidal Concentration) were measured and reported. The lowest cell proliferation and viability and IC50 for 2,3-dihydroxypropyl 1-cyclopropyl-6-fluoro-4-oxo-7-(piperazin-1-yl)-1,4-dihydroquinoline-3-carboxylate (compound 5) were observed to be 27.12% and 7.83 μg/mL. In antimicrobial activity, the lowest MIC for 2,3-dihydroxypropyl 7-(4-benzoylpiperazin-1-yl)-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylate (compound 6c) was observed to be 2 μg/mL (against Proteus mirabilis) and the lowest MIC for 1-cyclopropyl-6-fluoro-7-(4-(4-(methylthio)benzoyl)piperazin-1-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (compound 3d) was observed to be 32 μg/mL (against Candida albicans, Aspergillus fumigatus). The effects were compared with commercially available drugs, and it was observed that some derivatives have the same efficacy as abemaciclib, which is used to treat breast cancer. Some derivatives were more effective than Cefazolin and Tolnaftate, well-known antibiotics and antifungals, respectively. Finally, a fairly clear relationship between the structure of the derivatives and their biological effectiveness was observed.
Seismic behavior of steel-reinforced high-strength concrete composite beams with bonded tendons
Authors: He Jinjin , Jiang Liangqin , Ji Jing , Zhang Zhanbin , Chu Xuan , Hong Yigang , Zhang Huiling
Published: September 2023

To study the seismic behavior of steel-reinforced high-strength concrete composite beams with bonded tendons (PSRHSCBs) under low cyclic loading, 13 PSRHSCBs were designed with the main parameters of the span-to-height ratio of beams (L/H), the cubic strength of concrete (fcu), the eccentricity of H-shaped steel (eH), the volume stirrup ratio (pv), the longitudinal reinforcement ratio (p), and the tension control stress of tendons(σcon). Using the simplified bilinear constitutive model of steel and the nonlinear constitutive model of high-strength concrete, and introducing plastic damage of concrete, fine finite element models were established with ABAQUS software. 11 similar test specimens were conducted by above modeling method, by comparing existing test curves and numerical simulation curves, both of them match well, which verified the validity of the modeling method. Subsequently, parameter analysis for 13 PSRHSCB specimens was performed, and the influence regularity of different parameters on the seismic behavior of this kind of composite beams was obtained. The results show that hysteretic curves of this kind of composite beams are full, and the failure mode is manifested as bending failure. The ultimate load, the energy dissipation capacity and the ductility coefficient of specimens can be improved significantly by increasing pv, on the contrary, the energy dissipation capacity and the ductility coefficient decrease gradually by increasing fcu. The stiffness degradation of specimens significantly slows down with the increasing of L/H and σcon, and the decreasing of eH. Finally, the trilinear skeleton curve model and the restoring force model are established by statistical regression, and the corresponding seismic design suggestions are given, and these can provide theoretical support for the seismic design of such composite beams in actual engineering.
Bisphenol A exposure triggers endoplasmic reticulum stress pathway leading to ocular axial elongation in mice
Authors: Chen Junhan , Ikeda Shin-ichi , Kang Longdan , Negishi Kazuno , Tsubota Kazuo , Kurihara Toshihide
Published: September 2023

Background

Ocular axial elongation is one of the features of myopia progression. Endoplasmic reticulum (ER) stress-associated scleral remodeling plays an important role in ocular axial elongation. Bisphenol A (BPA) is one of the most common environmental pollutants and is known to affect various human organs through ER stress. However, whether BPA exerts an effect on scleral remodeling remains unknown. The purpose of this study was to determine the effect of BPA on the development of myopia and scleral ER stress.

Methods

BPA was administered by intraperitoneal injection. 4-PBA was administered as an endoplasmic reticulum stress inhibitor by eye drops. Refraction and axial length were measured by refractometer and SD-OCT system. Western blot was performed to detect the expression level of ER stress-related proteins.

Results

BPA-administered mice exhibit axial elongation and myopic refractive shift with endoplasmic reticulum stress in the sclera. BPA administration activated scleral PERK and ATF6 pathways, and 4-PBA eye drops attenuated ER stress response and suppressed myopia progression.

Conclusion

BPA controlled axial elongation during myopia development in a mouse model by inducing scleral ER stress and activation of the PERK/ATF6 pathway. 4-PBA eye drops as ER stress inhibitor suppressed BPA-induced myopia development.
Microbiota and its antibiotic resistance profile in avocado Guatemalan fruits (Persea nubigena var. guatemalensis) sold at retail markets of Ibarra city, northern Ecuador
Authors: Angamarca Evelyn , Castillejo Pablo , Tenea Gabriela N.
Published: September 2023

Introduction

Avocados are typically sold in unsanitary conditions at the retail markets in Ecuador, which can raise the risk of microbial contamination. These microorganisms could exhibit multi-antibiotic resistance (MAR), being a serious threat concern to human health. In this study, we aimed to evaluate the microbiota and its antibiotic resistance profile in avocado Guatemalan fruits (Persea nubigena var. guatemalensis), at ripe stage: immature, firm light green (ready to eat in 4 days), peel (AFPE) and pulp (AFPU), and mature intense green (ready to eat) peel (AMPE) and pulp (AMPU), to gain baseline information on the prevalence of MAR bacteria.

Methods

Culture-independent (16S rRNA metagenomics) and culture-dependent approach (to detect specific indicator microorganisms) were used. Moreover, antibiotic susceptibility of selected target indicator bacteria was assessed providing information about the antibiotic resistance (AR) among the groups.

Results

Based on 16S rRNA gene metagenomic analysis, over 99.78% of reads were classified as bacteria in all samples. Shannon diversity index varies from 1.22 to 2.22, with the highest bacterial population assigned to AFPE samples (1327 species). The highest microbial counts of indicator Staphylococcus spp. (STAPHY), Enterobacter spp. (ENT), and Listeria spp. (LIST), were detected in AMPE samples. Thirty percent of the selected STAPHYs, and 20.91% of Enterobacter (ENT) clones were resistant to various classes of antibiotics. The MAR index varies between 0.25 to 0.88 and was clone-, and fruit ripe stage-dependent.

Conclusions

The results indicated that ready to eat avocados contained detectable levels of MAR bacteria, including methicillin resistant (MR)-STAPHY, which may act as a potential vector for the spread of antibiotic resistance. To achieve the increase of the production and marketing of Fuerte cultivar in Ecuador, it is vitally important to consider valuable strategies to protect the fruits at the early ripe stage in future. Thus, it is crucial to set up efficient control measures and develop coordinated strategies to guarantee the microbiological quality of the food.
Regulation of biofilm formation in Klebsiella pneumoniae
Authors: Li Yin , Ni Ming
Published: September 2023

Klebsiella pneumoniae is an important Gram-negative opportunistic pathogen that is responsible for a variety of nosocomial and community-acquired infections. Klebsiella pneumoniae has become a major public health issue owing to the rapid global spread of extensively-drug resistant (XDR) and hypervirulent strains. Biofilm formation is an important virulence trait of K. pneumoniae. A biofilm is an aggregate of microorganisms attached to an inert or living surface by a self-produced exo-polymeric matrix that includes proteins, polysaccharides and extracellular DNA. Bacteria within the biofilm are shielded from antibiotics treatments and host immune responses, making it more difficult to eradicate K. pneumoniae-induced infection. However, the detailed mechanisms of biofilm formation in K. pneumoniae are still not clear. Here, we review the factors involved in the biofilm formation of K. pneumoniae, which might provide new clues to address this clinical challenge.
Epigenetic regulation of Parkinson’s disease risk variant GPNMB cg17274742 methylation by sex and exercise from Taiwan Biobank
Authors: Chen Yen-Chung , Liaw Yi-Chia , Nfor Oswald Ndi , Hsiao Chih-Hsuan , Zhong Ji-Han , Wu Shey-Lin , Liaw Yung-Po
Published: September 2023

Background

Parkinson’s disease (PD) is a complex neurodegenerative disease with an elusive etiology that involves the interaction between genetic, behavioral, and environmental factors. Recently, epigenetic modifications, particularly DNA methylation, have been recognized to play an important role in the onset of PD. Glycoprotein non-metastatic melanoma protein B (GPNMB), a type I transmembrane protein crucial for immune cell activation and maturation, has emerged as a potential biomarker for the risk of PD. This research aims to investigate the influence of exercise and gender on the regulation of methylation levels of GPNMB cg17274742 in individuals.

Methods

We analyze data from 2,474 participants in the Taiwan Biobank, collected from 2008 and 2016. Methylation levels at the GPNMB cg17274742 CpG site were measured using Illumina Infinium MethylationEPIC beads. After excluding individuals with incomplete data or missing information on possible risk factors, our final analysis included 1,442 participants. We used multiple linear regression models to assess the association between sex and exercise with adjusted levels of GPNMB cg17274742 for age, BMI, smoking, drinking, coffee consumption, serum uric acid levels, and hypertension.

Results

Our results demonstrated that exercise significantly influenced the methylation levels of GPNMB cg17274742 in males (β = −0.00242; p = 0.0026), but not in females (β = −0.00002362; p = 0.9785). Furthermore, male participants who exercised showed significantly lower levels of methylation compared to the reference groups of the female and non-exercising reference groups (β = −0.00357; p = 0.0079). The effect of the interaction between gender and exercise on the methylation of GPNMB cg17274742 was statistically significant (p = 0.0078).

Conclusion

This study suggests that gender and exercise can modulate GPNMB cg17274742, with hypomethylation observed in exercise men. More research is needed to understand the underlying mechanisms and implications of these epigenetic changes in the context of risk and prevention strategies.
Mechanistic insights into the role of herpes simplex virus 1 in Alzheimer’s disease
Authors: Feng Shu , Liu Yongzhen , Zhou Yu , Shu Zhenfeng , Cheng Zhuxi , Brenner Charles , Feng Pinghui
Published: September 2023

Alzheimer’s Disease (AD) is an aging-associated neurodegenerative disorder, threatening millions of people worldwide. The onset and progression of AD can be accelerated by environmental risk factors, such as bacterial and viral infections. Human herpesviruses are ubiquitous infectious agents that underpin numerous inflammatory disorders including neurodegenerative diseases. Published studies concerning human herpesviruses in AD imply an active role HSV-1 in the pathogenesis of AD. This review will summarize the current understanding of HSV-1 infection in AD and highlight some barriers to advance this emerging field.
Virtual reality in managing Complex Regional Pain Syndrome (CRPS): a scoping review
Authors: Arcos-Holzinger Mauricio , Biebl Johanna Theresia , Storz Claudia , Gutmann Marcus , Azad Shahnaz Christina , Holzapfel Boris Michael , Kraft Eduard
Published: September 2023

Background

Complex Regional Pain Syndrome (CRPS) is a severe pain disorder that does not yet have a specific treatment. Patients with CRPS not only suffer from a wide range of symptoms that affect their quality of life but also present psychological affections to the way they see their body and specifically their affected limb. Virtual Reality (VR) modalities have become a targeted treatment for chronic pain and in the case of CRPS, may be a valuable approach to the mechanisms that affect these patients.

Objectives

Using the PRISMA Scoping Review guidelines, we intend to uncover the key information from the studies available about VR modalities in the treatment of CRPS. We focus on the improvement of pain levels, body perception disturbances (BPD), and limb movement/daily function.

Results

Our search strategy resulted in 217 articles from PubMed. Twenty were assessed for eligibility and seven were included in the final qualitative synthesis. Of these seven articles, we included a clinical trial, three pilot studies, a blinded randomized controlled trial, a crossover double-blind trial, and a randomized controlled trial. These studies provide important subjective patient findings, along with some statistically significant results in the experiences of VR therapies modulating pain, BPD, and improving limb movement/daily function. However, not all the studies included statistical analysis, and there are contradicting data found from some patients that did not perceive any improvement from VR therapies.

Conclusions

We describe the results found in 7 articles that focus on the treatment of CRPS with VR modalities. Overall, the articles have various limitations, but the strategies related to immersive virtual reality, cardiac signaling, body switching and limb modulation have shown the most promising results for pain reduction and BPD improvement. These strategies reflect on pathophysiological mechanisms that are hypothesized to be affected in CRPS patients leading to the chronic pain and BPD that they experience. Not much evidence was found for improvement in limb movement and daily function. This review is a pathway for future studies on this topic and a more extensive data synthesis when more information is available.
Electroencephalography characteristics related to risk of sudden unexpected death in epilepsy in patients with Dravet syndrome
Authors: Kim Jeong-Youn , Shin Jeongyoon , Kim Laehyun , Kim Se Hee
Published: September 2023

Objective

To investigate the quantitative electroencephalography (EEG) features associated with a high risk of sudden unexpected death in epilepsy (SUDEP) in patients with Dravet syndrome (DS).

Methods

Patients with DS and healthy controls (HCs) who underwent EEG were included in the study. EEG signals were recorded using a 21 channel digital EEG system, and pre-processed data were analyzed to identify quantitative EEG features associated with a high SUDEP risk. To assess the risk of SUDEP, SUDEP-7 scores were used.

Results

A total of 64 patients with DS [38 males and 26 females, aged: 128.51 ± 75.50 months (range: 23–380 months)], and 13 HCs [7 males and 6 females, aged: 95.46 ± 86.48 months (range: 13–263 months)] were included. For the absolute band power, the theta power was significantly higher in the high-SUDEP group than in the low-SUDEP group in the central brain region. For the relative band power, the theta power was also significantly higher in the high-SUDEP group than in the low-SUDEP group in the central and occipital brain regions. The alpha power was significantly lower in the high-SUDEP group than in the low-SUDEP group in the central and parietal brain regions.

Conclusion

Patients with high SUDEP-7 scores have different EEG features from those with low SUDEP-7 scores, suggesting that EEG may be used as a biomarker of SUDEP in DS.

Significance

Early intervention in patients with DS at a high risk of SUDEP can reduce mortality and morbidity. Patients with high theta band powers warrant high-level supervision.
Predictive value of whole-brain CT perfusion combined with ABCD3 score for short-term secondary cerebral infarction after TIA
Authors: Liu Shushu , Chen Ting , Wu Wei
Published: September 2023

Objective

To investigate the predictive value of Whole Brain CT Perfusion (WB-CTP) combined with the ABCD3 score in patients with transient ischemic attack (TIA).

Methods

A total of 336 TIA patients with TIA underwent WB-CTP and ABCD3 score assessment within 48 h of admission. Spearman correlation test was performed to analyze the relationship between the degree of vascular stenosis, relative perfusion values, and ABCD3 score. Logistic regression analysis was used to identify independent risk factors for secondary cerebral infarction. Receiver operating characteristic (ROC) curves were generated to evaluate the predictive value of relative cerebral blood flow (rCBF), degree of vascular stenosis, ABCD3 score, and the WB-CTP-ABCD3 combined model for secondary cerebral infarction after TIA. Calibration curves and H-L tests were used to evaluate the predictive efficacy of the model.

Results

Among the 336 TIA patients, 143 showed abnormal perfusion areas and 146 had responsible vessel stenosis. The degree of vascular stenosis, relative time-to-maximum (rTmax), and relative mean transit time (rMTT) were positively correlated with the ABCD3 score, while rCBF and relative cerebral blood volume (rCBV) were negatively correlated with the ABCD3 score. ROC curve analysis identified a cutoff value of 0.8205 for rCBF, with a sensitivity of 84.10% and specificity of 58.10% for distinguishing the cerebral infarction group from the non-cerebral infarction group. Furthermore, rCBF ≤ 0.8205, degree of vascular stenosis, and ABCD3 score > 6 were identified as independent risk factors for secondary cerebral infarction in TIA patients within 90 days in TIA patients. The AUC of the WB-CTP-ABCD3 combined model for predicting secondary cerebral infarction within 90 days was 0.836. The model risk was assessed by plotting calibration curves. The value of p for the H-L goodness of fit test was 0.366 (p > 0.05), which indicated that the difference between the obtained model and the perfect model were statistically insignificant.

Conclusion

The combined model of WB-CTP-ABCD3 shows promise as a valuable method for predicting secondary cerebral infarction within 90 days following TIA.
Circuit-level theories for sensory dysfunction in autism: convergence across mouse models
Authors: Monday Hannah R. , Wang Han Chin , Feldman Daniel E.
Published: September 2023

Individuals with autism spectrum disorder (ASD) exhibit a diverse range of behavioral features and genetic backgrounds, but whether different genetic forms of autism involve convergent pathophysiology of brain function is unknown. Here, we analyze evidence for convergent deficits in neural circuit function across multiple transgenic mouse models of ASD. We focus on sensory areas of neocortex, where circuit differences may underlie atypical sensory processing, a central feature of autism. Many distinct circuit-level theories for ASD have been proposed, including increased excitation–inhibition (E–I) ratio and hyperexcitability, hypofunction of parvalbumin (PV) interneuron circuits, impaired homeostatic plasticity, degraded sensory coding, and others. We review these theories and assess the degree of convergence across ASD mouse models for each. Behaviorally, our analysis reveals that innate sensory detection behavior is heightened and sensory discrimination behavior is impaired across many ASD models. Neurophysiologically, PV hypofunction and increased E–I ratio are prevalent but only rarely generate hyperexcitability and excess spiking. Instead, sensory tuning and other aspects of neural coding are commonly degraded and may explain impaired discrimination behavior. Two distinct phenotypic clusters with opposing neural circuit signatures are evident across mouse models. Such clustering could suggest physiological subtypes of autism, which may facilitate the development of tailored therapeutic approaches.
Motor imagery has a priming effect on motor execution in people with multiple sclerosis
Authors: Tacchino Andrea , Pedullà Ludovico , Podda Jessica , Monti Bragadin Margherita , Battaglia Mario Alberto , Bisio Ambra , Bove Marco , Brichetto Giampaolo
Published: September 2023

Priming is a learning process that refers to behavioral changes caused by previous exposure to a similar stimulus. Motor imagery (MI), which involves the mental rehearsal of action representations in working memory without engaging in actual execution, could be a strategy for priming the motor system. This study investigates whether MI primes action execution in Multiple Sclerosis (MS). Here, 17 people with MS (PwMS) and 19 healthy subjects (HS), all right-handed and good imaginers, performed as accurately and quickly as possible, with a pencil, actual or mental pointing movements between targets of small (1.0 × 1.0 cm) or large (1.5 × 1.5 cm) size. In actual trials, they completed five pointing cycles between the left and right targets, whereas in mental trials, the first 4 cycles were imagined while the fifth was actually executed. The fifth cycle was introduced to assess the MI priming effect on actual execution. All conditions, presented randomly, were performed with both dominant (i.e., right) and non-dominant arms. Analysis of the duration of the first 4 cycles in both actual and mental trials confirmed previous findings, showing isochrony in HS with both arms and significantly faster mental than actual movements (anisochrony) in PwMS (p < 0.01) [time (s); HS right: actual: 4.23 ± 0.15, mental: 4.36 ± 0.16; left: actual: 4.32 ± 0.15, mental: 4.43 ± 0.18; PwMS right: actual: 5.85 ± 0.16, mental: 5.99 ± 0.21; left: actual: 6.68 ± 0.20, mental: 5.94 ± 0.23]; anisochrony in PwMS was present when the task was performed with the non-dominant arm. Of note, temporal analysis of the fifth actual cycle showed no differences between actual and mental trials for HS with both arms, whereas in PwMS the fifth actual cycle was significantly faster after the four actual cycles for the non-dominant arm (p < 0.05) [time (s); HS right: actual: 1.03 ± 0.04, mental: 1.03 ± 0.03; left: actual: 1.08 ± 0.04, mental: 1.05 ± 0.03; PwMS right: actual: 1.48 ± 0.04, mental: 1.48 ± 0.06; left: actual: 1.66 ± 0.05, mental: 1.48 ± 0.06]. These results seem to suggest that a few mental repetitions of an action might be sufficient to exert a priming effect on the actual execution of the same action in PwMS. This would indicate further investigation of the potential use of MI as a new motor-cognitive tool for MS neurorehabilitation.
Transcutaneous auricular Vagus Nerve Stimulation and Median Nerve Stimulation reduce acute stress in young healthy adults: a single-blind sham-controlled crossover study
Authors: Sanchez-Perez Jesus Antonio , Gazi Asim H. , Rahman Farhan N. , Seith Alexis , Saks Georgia , Sundararaj Srirakshaa , Erbrick Rachel , Harrison Anna B. , Nichols Christopher J. , Modak Mihir , Chalumuri Yekanth R. , Snow Teresa K. , Hahn Jin-Oh , Inan Omer T.
Published: September 2023

Stress is a major determinant of health and wellbeing. Conventional stress management approaches do not account for the daily-living acute changes in stress that affect quality of life. The combination of physiological monitoring and non-invasive Peripheral Nerve Stimulation (PNS) represents a promising technological approach to quantify stress-induced physiological manifestations and reduce stress during everyday life. This study aimed to evaluate the effectiveness of three well-established transcutaneous PNS modalities in reducing physiological manifestations of stress compared to a sham: auricular and cervical Vagus Nerve Stimulation (taVNS and tcVNS), and Median Nerve Stimulation (tMNS). Using a single-blind sham-controlled crossover study with four visits, we compared the stress mitigation effectiveness of taVNS, tcVNS, and tMNS, quantified through physiological markers derived from five physiological signals peripherally measured on 19 young healthy volunteers. Participants underwent three acute mental and physiological stressors while receiving stimulation. Blinding effectiveness was assessed via subjective survey. taVNS and tMNS relative to sham resulted in significant changes that suggest a reduction in sympathetic outflow following the acute stressors: Left Ventricular Ejection Time Index (LVETI) shortening (tMNS: p = 0.007, taVNS: p = 0.015) and Pre-Ejection Period (PEP)-to-LVET ratio (PEP/LVET) increase (tMNS: p = 0.044, taVNS: p = 0.029). tMNS relative to sham also reduced Pulse Pressure (PP; p = 0.032) and tonic EDA activity (tonicMean; p = 0.025). The nonsignificant blinding survey results suggest these effects were not influenced by placebo. taVNS and tMNS effectively reduced stress-induced sympathetic arousal in wearable-compatible physiological signals, motivating their future use in novel personalized stress therapies to improve quality of life.