bluuebunny/crossref_metadata_2025 huggingface dataset:
Case study: design of a vacuum gripper
Authors: Kiss Dániel , Szilágyi Attila
Published: January 2022

In this paper we present the design process of a vacuum gripper based on an existing design, which have to be modified. During the design process each step was analysed by finite element methods, to see that the change in the model was made into the right direction. During these steps an appropriate solution was selected to be used later. In the paper we present the base design and the results of its analysis. Later we discuss the modifications made on the model and the final result of simulations of the modified geometries.
Designing a filament recycling extruder
Authors: Kmetz Barbara , Takács Ágnes
Published: January 2022

In this paper we can read about designing and building a filament recycling machine especially designed for 3D printers. 3D printing is quite popular nowadays, but unfortunately the base material of this technique is polymer, which is not an environmentally friendly material, but it can be recycled in most of the cases. The filament pieces are shredded beforehand with a shredding machine to get the appropriate size. After being chopped up and heated up to the given temperature, according to the materials specific parameters the filament can be melted down and extruded again. The study deals with designing a recycling machine as mentioned.
Steps of generative design in integrated CAD systems
Authors: Szabó Kristóf
Published: January 2022

Due to the continuous development of various areas of the industry, such as modern production equipment, material technology, computer and software development, it is possible to expand the range of conventional production technologies. These include additive manufacturing technology, which provides a new opportunity to produce everyday products, thereby satisfying market needs. Integrated CAD systems have occupied a place in the product design and development process for decades, which has partially reformed classical design methods and its steps.
Application of topological methods
Authors: Szabó Kristóf
Published: January 2022

The following article briefly summarizes the design aids currently in use, such as topology optimization and generative design, which are common in integrated CAD systems. The results provided by these methods are presented and compared based on a case study.
Teachers and students opinion regarding updated MBBS curriculum 2012 in a teaching hospital.
Authors: Badhon NM , Nahar N , Jahan I , Zaman F , Hossain MI
Published: January 2022

The modern concept of a curriculum originally derived from the Latin word for a race course. Undergraduate medical education is part of a continuum of education and training.The new curriculum is structured to provide a balance among learning opportunities through integrated teaching system.  This study was carried out to explore the views of teachers and students regarding the current undergraduate medical curriculum.  This cross-sectional descriptive study was conducted between October 2019 to October 2020 among the teachers and students of a private medical college and hospital (MH Samorita medical collegesandhospital) in Dhaka Bangladesh. The sample size were 100 in total.  Most of the participants suggested for changes in overall existing MBBS curriculum. Highest satisfaction was seen in content related to learning objectives that were 90% and highest dissatisfaction was seen in Phase distribution of subjects that were 89%.However, they were satisfied with present pattern of course content, objectives, evaluation system and carry on system. Teachers and students evaluation may prove useful if analyzed further to overcome the shortcomings of existing MBBS curriculum.
Bangladesh Journal of Medical Education Vol.13(1) January 2022: 27-32
Current Status of Quality Assurance Scheme in Selected Undergraduate Medical Colleges of Bangladesh
Authors: Rahman Shamima , Sultana Mossammat Nigar , Biswas Pratima Rani , Manjari Mamata , Khatun Rokhshana
Published: January 2022

This descriptive cross sectional study was carried out to determine the current status of Quality Assurance Scheme in undergraduate medical colleges of Bangladesh. This study was carried out in eight (four Government and four Non- Government) medical colleges in Bangladesh over a period from July 2015 to June 2016. The present study had an interview schedule with open question for college authority and another interview schedule with open question for head of department of medical college. Study revealed that 87.5% of college had Quality Assurance Scheme (QAS) in their college, 75% of college authority had regular meeting of academic coordination committee in their college, 50% of college had active Medical Education Unit in their college, 87.5% of college authority said positively on publication of journal in their college. In the present study researchers interviewed 53 heads of department with open question about distribution, collection of personal review form, submission with recommendation to the academic co-coordinator, and annual review meeting of faculty development. The researchers revealed from the interviews that there is total absence of this practice which is directed in national guidelines and tools for Quality Assurance Scheme (QAS) for medical colleges of Bangladesh.
Bangladesh Journal of Medical Education Vol.13(1) January 2022: 33-39
Editorial Vol.13(1)
Authors: Talukder Md Humayun Kabir
Published: January 2022

Abstract not available

Bangladesh Journal of Medical Education Vol.13(1) January 2022: 1-2
È possibile una gestione “ideale” della pandemia da malattia renale cronica?
Authors: Michelassi Stefano
Published: January 2022

Chronic Kidney Disease (CKD) is recognized as one of the major categories of noncommunicable epidemic diseases and in the last decades it has been largely growing in incidence and prevalence all over the world. Ideal management of CKD pandemic should be comprehensive of measures of tertiary, secondary, primary and primordial prevention. So, it should include prompt diagnosis and treatment of traditional and non-traditional risk factors for CKD, optimal conservative treatment for non-dialysis dependent CKD patients and appropriated dialysis therapy or renal transplantation for patients with end-stage renal disease. However, these goals are not easy to obtain on a global scale. It would be possible only by a broad and holistic approach, ranging from good governance to achievement of the sustainable development goals (SDGs).
Narrativa de campaña en Instagram: espectáculo y autorrepresentación de candidatos. El caso de las elecciones generales 2019
Authors: Ferré-Pavia Carme , Codina Mariona
Published: January 2022

Este artículo tiene como objetivo analizar las estrategias que usaron los partidos políticos en Instagram durante la campaña de las elecciones del 10 de noviembre de 2019, en términos de su contenido y recursos mediáticos en un entorno de política-espectáculo. Se han analizado 655 publicaciones en total, procedentes de los partidos estatales y autonómicos catalanes, a través del análisis de contenido con mirada cuantitativa y cualitativa. Desde un punto de vista comparativo, se localiza una brecha entre los partidos de nueva y vieja política en el uso de Instagram y se evidencia que el recurso a la personalización varía entre formaciones. En el caso de los partidos catalanes, la campaña se mezcla con los efectos de la situación de sus exdirigentes. Con alguna excepción, las propuestas programáticas durante la campaña se difuminan en prácticamente todos los casos. Se concluye que, en Instagram, la narrativa electoral se construye como un relato de acciones autorreferenciales escenificadas, con el contexto de los sucesos políticos en el caso catalán.
A Novel Cleavage Pattern of Complement C5 Induced by Chlamydia trachomatis Infection via the Chlamydial Protease CPAF
Authors: Peng Liang , Gao Jingping , Hu Zihao , Zhang Hongbo , Tang Lingli , Wang Fuyan , Cui Lei , Liu Shanshan , Zhao Yujie , Xu Hong , Su Xin , Feng Xiaojing , Fang Yiyuan , Chen Jianlin
Published: January 2022

Urogenital Chlamydia trachomatis infection is one of the most common bacterial sexually transmitted diseases globally. Untreated C. trachomatis infections can ascend to the upper genital tract and establish a series of severe complications. Previous studies using C3−/− and C5−/− mice models demonstrated that C3-independent activation of C5 occurred during C. trachomatis infection. However, the mechanism of how chlamydial infection activates C5 in the absence of C3 has yet to be elucidated. To delineate interactions between C5 and chlamydial infection, cleavage products in a co-incubation system containing purified human C5 and C. trachomatis-HeLa229 cell lysates were analyzed, and a novel cleavage pattern of C5 activation induced by C. trachomatis infection was identified. C5 was cleaved efficiently at the previously unidentified site K970, but was cleaved poorly at site R751. C5b was modified to C5bCt, which later formed C5bCt-9, which had enhanced lytic ability compared with C5b-9. The chlamydial serine protease CPAF contributed to C3-independent C5 activation during C. trachomatis infection. Nafamostat mesylate, a serine protease inhibitor with a good safety profile, had a strong inhibitory effect on C5 activation induced by chlamydial infection. These discoveries reveal the mechanism of C3-independent C5 activation induced by chlamydial infection, and furthermore provide a potential therapeutic target and drug for preventing tubal fibrosis caused by chlamydial infection.
Role of F-box Protein Cdc4 in Fungal Virulence and Sexual Reproduction of Cryptococcus neoformans
Authors: Wu Ting , Fan Cheng-Li , Han Lian-Tao , Guo Yuan-Bing , Liu Tong-Bao
Published: January 2022

Cryptococcus neoformans is an opportunistic yeast-like pathogen that mainly infects immunocompromised individuals and causes fatal meningitis. Sexual reproduction can promote the exchange of genetic material between different strains of C. neoformans, which is one of the reasons leading to the emergence of highly pathogenic and drug-resistant strains of C. neoformans. Although much research has been done on the regulation mechanism of Cryptococcus sexual reproduction, there are few studies on the sexual reproduction regulation of Cryptococcus by the ubiquitin-proteasome system. This study identified an F-box protein, Cdc4, which contains a putative F-box domain and eight WD40 domains. The expression pattern analysis showed that the CDC4 gene was expressed in various developmental stages of C. neoformans, and the Cdc4 protein was localized in the nucleus of cryptococcal cells. In vitro stress responses assays showed that the CDC4 overexpression strains are sensitive to SDS and MMS but not Congo red, implying that Cdc4 may regulate the cell membrane integrity and repair of DNA damage of C. neoformans. Fungal virulence assay showed that although the cdc4Δ mutant grows normally and can produce typical virulence factors such as capsule and melanin, the cdc4Δ mutant completely loses its pathogenicity in a mouse systemic-infection model. Fungal mating assays showed that Cdc4 is also essential for fungal sexual reproduction in C. neoformans. Although normal mating hyphae were observed during mating, the basidiospores’ production was blocked in bilateral mating between cdc4Δ mutants. Fungal nuclei development assay showed that the nuclei failed to undergo meiosis after fusion inside the basidia during the bilateral mating of cdc4Δ mutants, indicating that Cdc4 is critical to regulating meiosis during cryptococcal mating. In summary, our study revealed that the F-box protein Cdc4 is critical for fungal virulence and sexual reproduction in C. neoformans.
A Submodular Receding Horizon Control Strategy to Distributed Persistent Monitoring
Authors: Zhao Xiaohu , Zou Yuanyuan , Li Shaoyuan
Published: January 2022

This paper investigates the multi-agent persistent monitoring problem via a novel distributed submodular receding horizon control approach. In order to approximate global monitoring performance, with the definition of sub-modularity, the original persistent monitoring objective is divided into several local objectives in a receding horizon framework, and the optimal trajectories of each agent are obtained by taking into account the neighborhood information. Specifically, the optimization horizon of each local objective is derived from the local target states and the information received from their neighboring agents. Based on the sub-modularity of each local objective, the distributed greedy algorithm is proposed. As a result, each agent coordinates with neighboring agents asynchronously and optimizes its trajectory independently, which reduces the computational complexity while achieving the global performance as much as possible. The conditions are established to ensure the estimation error converges to a bounded global performance. Finally, simulation results show the effectiveness of the proposed method.
The Association Between Long-Term Exposure to Particulate Matter and Incidence of Hypertension Among Chinese Elderly: A Retrospective Cohort Study
Authors: Wensu Zhou , Wen Chen , Fenfen Zhou , Wenjuan Wang , Li Ling
Published: January 2022

Background and Objectives: Studies that investigate the links between particulate matter ≤2. 5 μm (PM2.5) and hypertension among the elderly population, especially those including aged over 80 years, are limited. Therefore, we aimed to examine the association between PM2.5 exposure and the risk of hypertension incidence among Chinese elderly.

Methods: This prospective cohort study used 2008, 2011, 2014, and 2018 wave data from a public database, the Chinese Longitudinal Healthy Longevity Survey, a national survey investigating the health of those aged over 65 years in China. We enrolled cohort participants who were free of hypertension at baseline (2008) from 706 counties (districts) and followed up in the 2011, 2014, and 2018 survey waves. The annual PM2.5 concentration of 706 counties (districts) units was derived from the Atmospheric Composition Analysis Group database as the exposure variable, and exposure to PM2.5 was defined as 1-year average of PM2.5 concentration before hypertension event occurrence or last interview (only for censoring). A Cox proportional hazards model with penalized spline was used to examine the non-linear association between PM2.5 concentration and hypertension risk. A random-effects Cox proportional hazards model was built to explore the relationship between each 1 μg/m3, 10 μg/m3 and quartile increment in PM2.5 concentration and hypertension incidence after adjusting for confounding variables. The modification effects of the different characteristics of the respondents were also explored.

Results: A total of 7,432 participants aged 65–116 years were enrolled at baseline. The median of PM2.5 exposure concentration of all the participants was 52.7 (inter-quartile range, IQR = 29.1) μg/m3. Overall, the non-linear association between PM2.5 and hypertension incidence risk indicated that there was no safe threshold for PM2.5 exposure. The higher PM2.5 exposure, the greater risk for hypertension incidence. Each 1 μg/m3 [adjusted hazard ratio (AHR): 1.01; 95% CI: 1.01–1.02] and 10 μg/m3 (AHR: 1.12; 95% CI: 1.09–1.16) increments in PM2.5, were associated with the incidence of hypertension after adjusting for potential confounding variables. Compared to first quartile (Q1) exposure, the adjusted HRs of hypertension incidence for the Q2, Q3 and Q4 exposure of PM2.5 were 1.31 (95% CI: 1.13–1.51), 1.35 (95% CI: 1.15–1.60), and 1.83 (95% CI: 1.53–2.17), respectively. The effects appear to be stronger among those without a pension, living in a rural setting, and located in central/western regions.

Conclusion: We found no safe threshold for PM2.5 exposure related to hypertension risk, and more rigorous approaches for PM2.5 control were needed. The elderly without a pension, living in rural and setting in the central/western regions may be more vulnerable to the effects of PM2.5 exposure.
Geo-Temporal Signatures of Physicochemical and Heavy Metals Pollution in Groundwater of Khulais Region—Makkah Province, Saudi Arabia
Authors: Khan Mohd Yawar Ali , El Kashouty Mohamed , Gusti Waleed , Kumar Amit , Subyani Ali Mohammad , Alshehri Ahmed
Published: January 2022

Seawater has intruded into many of Saudi Arabia’s Red Sea coastal aquifers, with varying degrees of extension depending on location, hydrogeology, and population density. This study aimed to evaluate and comprehend the processes that influence the hydrogeochemical characteristics of the coastal aquifer in Saudi Arabia’s Khulais region. Groundwater samples were taken from nineteen locations during the winter and summer of 2021, and data from major ions and trace elements were examined and interpreted using ArcGIS software. The total dissolved solids (TDS) concentrations ranged between 480 and 15,236 mg/L and 887–18,620 mg/L in winter and summer, respectively. Groundwater TDS concentration was observed to be influenced by groundwater flow, lithogenic, anthropogenic, and seawater intrusion in this study (2021) when compared to 2016. The concentration of nitrate (NO3−) and strontium (Sr) in most samples exceeds the drinking guidelines. The occurrence of high concentrations of bromide (Br), Fluoride (F), Iron (Fe) (winter and summer) and Aluminum (Al), Boron (B), Chromium (Cr), Nickel (Ni), lead (Pb), cadmium (Cd), cobalt (Co), copper (Cu) and manganese (Mn) (winter) was also exhibited and observed up to more than drinking and irrigation limits. The central part of the study area was affected by seawater intrusion. The hydraulic conductivity of the topsoil was measured, and it ranged from 0.24 to 29.3 m/day. Based on electrical conductivity (EC) and sodium absorption ratio, most aquifer samples were unsuitable for irrigation (SAR).
Natural Killer Cells in the Malignant Niche of Multiple Myeloma
Authors: Venglar Ondrej , Bago Julio Rodriguez , Motais Benjamin , Hajek Roman , Jelinek Tomas
Published: January 2022

Natural killer (NK) cells represent a subset of CD3- CD7+ CD56+/dim lymphocytes with cytotoxic and suppressor activity against virus-infected cells and cancer cells. The overall potential of NK cells has brought them to the spotlight of targeted immunotherapy in solid and hematological malignancies, including multiple myeloma (MM). Nonetheless, NK cells are subjected to a variety of cancer defense mechanisms, leading to impaired maturation, chemotaxis, target recognition, and killing. This review aims to summarize the available and most current knowledge about cancer-related impairment of NK cell function occurring in MM.
Effects of Dietary Phospholipids on Growth Performance, Digestive Enzymes Activity and Intestinal Health of Largemouth Bass (Micropterus salmoides) Larvae
Authors: Wang Shilin , Han Zhihao , Turchini Giovanni M. , Wang Xiaoyuan , Fang Zishuo , Chen Naisong , Xie Ruitao , Zhang Haitao , Li Songlin
Published: January 2022

While the beneficial roles of dietary phospholipids on health status and overall performances of fish larvae have been well demonstrated, the underlying mechanisms remain unclear. To address this gap, the present study was conducted to investigate the effects of dietary phospholipids on growth performance, intestinal development, immune response and microbiota of larval largemouth bass (Micropterus salmoides). Five isonitrogenous and isolipidic micro-diets were formulated to contain graded inclusion levels of phospholipids (1.69, 3.11, 5.23, 7.43 and 9.29%). Results showed that the supplementation of dietary phospholipids linearly improved the growth performance of largemouth bass larvae. The inclusion of dietary phospholipids increased the activity of digestive enzymes, such as lipase, trypsin and alkaline phosphatase, and promoted the expression of tight junction proteins including ZO-1, claudin-4 and claudin-5. Additionally, dietary phospholipids inclusion alleviated the accumulation of intestinal triacylglycerols, and further elevated the activity of lysozyme. Dietary phospholipids inhibited the transcription of some pro-inflammatory cytokines, including il-1β, and tnf-α, but promoted the expression of anti-inflammatory cytokines tgf-β, with these modifications being suggested to be mediated by the p38MAPK/Nf-κB pathway. The analysis of bacterial 16S rRNA V3-4 region indicated that the intestinal microbiota profile was significantly altered at the genus level with dietary phospholipids inclusion, including a decreased richness of pathogenic bacteria genera Klebsiella in larval intestine. In summary, it was showed that largemouth bass larvae have a specific requirement for dietary phospholipids, and this study provided novel insights on how dietary phospholipids supplementation contributes to improving the growth performance, digestive tract development and intestinal health.
Controlled Growth of Indium Selenides by High-Pressure and High-Temperature Method
Authors: Dai Yajie , Zhao Shouxin , Han Hui , Yan Yafei , Liu Wenhui , Zhu Hua , Li Liang , Tang Xi , Li Yang , Li Hui , Zhang Changjin
Published: January 2022

The controlled growth of indium selenides has attracted considerable research interests in condensed matter physics and materials science yet remains a challenge due to the complexity of the indium–selenium phase diagram. Here, we demonstrate the successful growth of indium selenides in a controllable manner using the high-pressure and high-temperature growth technique. The γ-InSe and α-In2Se3 crystals with completely different stoichiometries and stacking manner of atomic layers have been controlled grown by subtle tuning growth temperature, duration time, and growth pressure. The as-grown γ-InSe crystal features a semiconducting property with a prominent photoluminescence peak of ∼1.23 eV, while the α-In2Se3 crystal is ferroelectric. Our findings could lead to a surge of interest in the development of the controlled growth of high-quality van der Waal crystals using the high-pressure and high-temperature growth technique and will open perspectives for further investigation of fascinating properties and potential practical application of van der Waal crystals.
Genetic Predisposition to Low-Density Lipoprotein Cholesterol May Increase Risks of Both Individual and Familial Alzheimer's Disease
Authors: Tan Jiang-Shan , Hu Meng-Jin , Yang Yan-Min , Yang Yue-Jin
Published: January 2022

Background: Previous observational studies provided conflicting results on the association between low-density lipoprotein cholesterol (LDL-C) level and the risk of Alzheimer's disease (AD).

Objective: We used two-sample Mendelian randomization (MR) study to explore the causal associations between LDL-C level and the risks of individual, paternal, maternal, and family history of AD.

Methods: Summary-level genetic data for LDL-C were acquired from results of the UK Biobank GWAS. Corresponding data for paternal, maternal, and family history of AD were obtained from the NHGRI-EBI Catalog of human genome-wide association studies. Data for individual AD were obtained from the MR-Base platform. A two-sample MR study was performed to explore the causal association between LDL-C level and the risks of individual, paternal, maternal, and family history of AD.

Results: Genetically predicted LDL-C was positively associated with individual [Odds ratio (OR) = 1.509, 95% confidence interval (CI) = 1.140–1.999; P = 4.0 × 10−3], paternal [OR = 1.109, 95% CI = 1.053–1.168; P = 9.5 × 10−5], maternal [OR = 1.132, 95% CI = 1.070–1.199; P = 2.0 × 10−5], and family history of AD [OR = 1.124, 95% CI = 1.070–1.181; P = 3.7 × 10−6] in inverse variance weighted analysis. After performing weighted median and MR-Egger analysis, consistent results were observed. There was no horizontal pleiotropy in the two-sample MR analysis.

Conclusions: High level of LDL-C may increase the risks of both individual and familial AD. Decreasing the LDL-C to a reasonable level may help to reduce the related risk.
Rare Occurrence of Inhibitors in Von Willebrand Disease: A Case Report
Authors: Kulkarni Bipin P. , Ghargi Kirti , Shanmukhaiah Chandrakala , Shetty Shrimati D.
Published: January 2022

Introduction: Type 3 Von Willebrand Disease (VWD) is the least common but the most severe form of a disease, with a prevalence of about 0. 5 to 1 per million in Western countries. The prevalence of type 3 VWD in the developing countries, with a high degree of consanguinity, is about 6 per million. Moreover, due to underdiagnosis of the milder cases, the prevalence of type 3 VWD is about 50% of the cases. Rarely, some patients develop the Von Willebrand Factor (VWF) inhibitors, which may subsequently develop severe anaphylactic reactions on further exposure to the VWF containing factor replacement therapy. The prevalence of inhibitor development in patients with type 3 VWD has been shown to be in the range of 5.8 to 9.5%. In the absence of a gold standard assay for the quantitation of VWF inhibitors, a correct diagnosis and management of these patients are often challenging.

Objectives: The objective of this study is to standardize the Bethesda assay for the VWF inhibitors and to estimate the VWD inhibitor titer in two cases of congenital type 3 VWD, which developed the VWF inhibitors.

Results and Conclusions: We could successfully standardize the Bethesda assay for the quantitation of VWF inhibitors in two patients with congenital type 3 VWD with inhibitors.
Prevalence and Risk Factors of Subclinical Tuberculosis in a Low-Incidence Setting in China
Authors: Tang Peijun , Liang Ermin , Zhang Xuxia , Feng Yanjun , Song Huafeng , Xu Junchi , Wu Meiying , Pang Yu
Published: January 2022

Objectives: Subclinical tuberculosis (TB) represents a substantial proportion of individuals with TB disease, although limited evidence is available to understand the epidemiological characteristics of these cases. We aimed to explore the prevalence of subclinical patients with TB and identify the underlying association between the subclinical TB cases in the study setting and the Beijing genotype.

Methods: A retrospective study was conducted among patients with incident TB at the Fifth People’s Hospital of Suzhou between January and December 2018. A total of 380 patients with TB were included in our analysis.

Results: Of the 380 patients, 81.8% were active TB cases, whereas the other 18.2% were subclinical TB cases. Compared with patients aged 65 years and older, the risk of having subclinical TB is higher among younger patients. The use of smear, culture, and Xpert identified 3, 16, and 13 subclinical TB cases, respectively. When using a combination of positive culture and Xpert results, the sensitivity improved to 33.3%. In addition, the neutrophil-to-lymphocyte ratio was significantly elevated in the active TB group compared with that in the subclinical TB group. We also observed that the proportion of the Beijing genotype in the subclinical TB group was significantly lower than that in the active TB group.

Conclusion: To conclude, our data demonstrate that approximately one-fifth of patients with TB were subclinical in Suzhou. Mycobacterium tuberculosis could be detected by the existing microbiologic diagnostics in one-third of patients with subclinical TB. The patients with subclinical TB are more prone to having low neutrophil-to-lymphocyte ratio values than those with active TB. Additionally, non-Beijing genotype strains are associated with subclinical TB.
Experimental Evolution of Anticipatory Regulation in Escherichia coli
Authors: Mahilkar Anjali , Venkataraman Pavithra , Mall Akshat , Saini Supreet
Published: January 2022

Environmental cues in an ecological niche are often temporal in nature. For instance, in temperate climates, temperature is higher in daytime compared to during night. In response to these temporal cues, bacteria have been known to exhibit anticipatory regulation, whereby triggering response to a yet to appear cue. Such an anticipatory response in known to enhance Darwinian fitness, and hence, is likely an important feature of regulatory networks in microorganisms. However, the conditions under which an anticipatory response evolves as an adaptive response are not known. In this work, we develop a quantitative model to study response of a population to two temporal environmental cues, and predict variables which are likely important for evolution of anticipatory regulatory response. We follow this with experimental evolution of Escherichia coli in alternating environments of rhamnose and paraquat for ∼850 generations. We demonstrate that growth in this cyclical environment leads to evolution of anticipatory regulation. As a result, pre-exposure to rhamnose leads to a greater fitness in paraquat environment. Genome sequencing reveals that this anticipatory regulation is encoded via mutations in global regulators. Overall, our study contributes to understanding of how environment shapes the topology of regulatory networks in an organism.
Genomic Analysis and Antimicrobial Resistance of Campylobacter jejuni and Campylobacter coli in Peru
Authors: Quino Willi , Caro-Castro Junior , Hurtado Verónica , Flores-León Diana , Gonzalez-Escalona Narjol , Gavilan Ronnie G.
Published: January 2022

Campylobacter is the leading cause of human bacterial gastroenteritis worldwide and has a major impact on global public health. Whole Genome Sequencing (WGS) is a powerful tool applied in the study of foodborne pathogens. The objective of the present study was to apply WGS to determine the genetic diversity, virulence factors and determinants of antimicrobial resistance of the populations of C. jejuni and C. coli in Peru. A total of 129 Campylobacter strains (108 C. jejuni and 21 C. coli) were sequenced using Illumina Miseq platform. In silico MLST analysis identified a high genetic diversity among those strains with 30 sequence types (STs), several of them within 11 clonal complexes (CC) for C. jejuni, while the strains of C. coli belonged to a single CC with 8 different STs. Phylogeny analysis showed that Peruvian C. jejuni strains were divided into 2 clades with 5 populations, while C. coli formed a single clade with 4 populations. Furthermore, in silico analyses showed the presence of several genes associated with adherence, colonization and invasion among both species: cadF (83.7%), jlpA (81.4%), racR (100%), dnaJ (83.7%), pebA (83.7%), pldA (82.1%), porA (84.5%), ceuE (82.9%), ciaB (78.3%), iamB (86.8%), and flaC (100%). The majority (82.9%) of the Campylobacter strains carried the cdtABC operon which code for cytolethal distending toxin (CDT). Half of them (50.4%) carried genes associated with the presence of T6SS, while the frequency of genes associated with T4SS were relatively low (11.6%). Genetic markers associated with resistance to quinolones, tetracycline (tetO, tetW/N/W), beta-lactamases (blaoxa–61), macrolides (A2075G in 23S rRNA) were found in 94.5, 21.7, 66.7, 6.2, 69.8, and 18.6% of strains, respectively. The cmeABC multidrug efflux operon was present in 78.3% of strains. This study highlights the importance of using WGS in the surveillance of emerging pathogens associated with foodborne diseases, providing genomic information on genetic diversity, virulence mechanisms and determinants of antimicrobial resistance. The description of several Campylobacter genotypes having many virulence factors and resistance to quinolones and tetracyclines circulating in Peru provides important information which helps in the monitoring, control and prevention strategies of this emerging pathogen in our country.
Molecular Big Data in Sports Sciences: State-of-Art and Future Prospects of OMICS-Based Sports Sciences
Authors: Sellami Maha , Elrayess Mohamed A. , Puce Luca , Bragazzi Nicola Luigi
Published: January 2022

Together with environment and experience (that is to say, diet and training), the biological and genetic make-up of an athlete plays a major role in exercise physiology. Sports genomics has shown, indeed, that some DNA single nucleotide polymorphisms (SNPs) can be associated with athlete performance and level (such as elite/world-class athletic status), having an impact on physical activity behavior, endurance, strength, power, speed, flexibility, energetic expenditure, neuromuscular coordination, metabolic and cardio-respiratory fitness, among others, as well as with psychological traits. Athletic phenotype is complex and depends on the combination of different traits and characteristics: as such, it requires a “complex science,” like that of metadata and multi-OMICS profiles. Several projects and trials (like ELITE, GAMES, Gene SMART, GENESIS, and POWERGENE) are aimed at discovering genomics-based biomarkers with an adequate predictive power. Sports genomics could enable to optimize and maximize physical performance, as well as it could predict the risk of sports-related injuries. Exercise has a profound impact on proteome too. Proteomics can assess both from a qualitative and quantitative point of view the modifications induced by training. Recently, scholars have assessed the epigenetics changes in athletes. Summarizing, the different omics specialties seem to converge in a unique approach, termed sportomics or athlomics and defined as a “holistic and top-down,” “non-hypothesis-driven research on an individual’s metabolite changes during sports and exercise” (the Athlome Project Consortium and the Santorini Declaration) Not only sportomics includes metabonomics/metabolomics, but relying on the athlete’s biological passport or profile, it would enable the systematic study of sports-induced changes and effects at any level (genome, transcriptome, proteome, etc.). However, the wealth of data is so huge and massive and heterogenous that new computational algorithms and protocols are needed, more computational power is required as well as new strategies for properly and effectively combining and integrating data.
Parkinson's Disease With Visual Hallucinations Is Associated With Epileptiform Activity on EEG
Authors: Fry Adam , Singh Dharampreet , Manganas Louis , Gordon Marc L. , Christodoulou Christopher , Leung Hoi-Chung , Schwartz Guy J.
Published: January 2022

Background: Visual hallucinations (VHs) in Parkinson's disease (PD) are the cardinal symptoms which declare the onset of PD psychosis (PDP). The anthropomorphic and zoomorphic VHs of PD resemble those of Charles Bonnet syndrome and temporal lobe epilepsy. In both of these disorders electroencephalography (EEG) abnormalities have been described. We therefore sought to examine whether VHs in PD were associated with similar EEG abnormalities.

Methods: This retrospective observational study searched the medical records of 300 PD patients and filtered for those containing clinical 20-min scalp EEGs. Remaining records were separated into two groups: patients with reported VHs and those without. The prevalence of epileptiform discharges in the EEGs of both groups was identified.

Results: Epileptiform discharges were present in 5 of 13 (38.5%) PD patients with VHs; all localized to the temporal lobe. No epileptiform discharges were observed in the EEGs of the 31 PD patients without VHs.

Conclusion: The significantly high incidence of temporal lobe epileptiform discharges in PD patients with VHs as compared to those without VHs lends to the possibility of an association visual cortex epileptogenic focus. Accordingly, for treatment-refractory patients, antiepileptic drugs might be considered, as in the case of Charles Bonnet syndrome, temporal lobe epilepsy and migraine with visual aura. Future prospective studies involving larger samples and multi-center cohorts are required to validate these observational findings.
Levetiracetam Prophylaxis Therapy for Brain Tumor-Related Epilepsy (BTRE) Is Associated With a Higher Psychiatric Burden
Authors: Dono Fedele , Consoli Stefano , Evangelista Giacomo , Ricci Annalisa , Russo Mirella , Carrarini Claudia , Di Iorio Angelo , Bonanni Laura , Anzellotti Francesca , Onofrj Marco , Sensi Stefano L.
Published: January 2022

Purpose: Brain tumor-related epilepsy (BTRE) is a condition characterized by the development of seizures in the context of an undergoing oncological background. Levetiracetam (LEV) is a third-generation anti-seizure medication (ASM) widely used in BTRE prophylaxis. The study evaluated LEV neuropsychiatric side effects (SEs) in BTRE prophylaxis.

Method: Twenty-eight patients with brain tumors were retrospectively selected and divided into two groups. In one group, we evaluated patients with a BTRE diagnosis using LEV (BTRE-group). The other group included patients with brain tumors who never had epilepsy and used a prophylactic ASM regimen with LEV (PROPHYLAXIS-group). Neuropsychiatric SEs of LEV were monitored using the Neuropsychiatric Inventory Questionnaire (NPI-Q) at the baseline visit and the 6- and 12-month follow-up.

Results: Eighteen patients of the BTRE-group and 10 patients of the PROPHYLAXIS-group were included. Compared to the BTRE-group, the PROPHYLAXIS-group showed a higher severity of neuropsychiatric symptoms. According to Linear Mixed Models (LMM), a multiplicative effect was observed for the interaction between group treatment and time. For the caregiver distress score (CDS), only a time-effect was observed.

Conclusion: Prophylactic ASM with LEV is associated with an increased frequency of neuropsychiatric SE. Accurate epileptological evaluations in patients with brain tumors are mandatory to select who would benefit most from ASM.
Contact Heat Evoked Potentials in China: Normal Values and Reproducibility
Authors: Sun Bo , Wang Hongfen , Chen Zhaohui , Cui Fang , Yang Fei , Huang Xusheng
Published: January 2022

Background: Contact heat evoked potentials (CHEPs) is used to diagnose small fiber neuropathy (SFN). We established the normal values of CHEPs parameters in Chinese adults, optimized the test technique, and determined its reproducibility.

Methods: We recruited 151 healthy adults (80 men; mean age, 37 ± 14 years). CHEPs was performed on the right forearm to determine the optimal number of stimuli, and then conducted at different sites to establish normal values, determine the effects of demographic characteristics and baseline temperature, and assess the short- (30 min) and long-term (1 year) reproducibility. N2 latency/height varied with age and sex, while P2 latency/height and N2–P2 amplitude varied with age. The optimal number of stimuli was three.

Results: N2 latency/height (t = 5.45, P < 0.001) and P2 latency/height (χ2 = −4.06, P < 0.001) decreased and N2–P2 amplitude (t = −5.01, P < 0.001) and visual analog scale score (χ2 = −5.84, P < 0.001) increased with increased baseline temperature (35 vs. 32°C). CHEPs parameters did not differ with time (baseline vs. 30 min vs. 1 year).

Conclusion: We established normal CHEPs values in Chinese adults. We found that CHEPs parameters changed with baseline temperature and that the short- and long-term test reproducibility were satisfactory.
An Immune Feature-Based, Three-Gene Scoring System for Prognostic Prediction of Head-and-Neck Squamous Cell Carcinoma
Authors: Zhang Yamin , Luo Xiayan , Yu Jing , Qian Kejia , Zhu Huiyong
Published: January 2022

Head-and-neck squamous cell carcinoma (HNSCC) is characterized by a high frequency of neck lymph node metastasis (LNM), a key prognostic factor. Therefore, identifying the biological processes during LNM of HNSCC has significant clinical implications for risk stratification. This study performed Gene Ontology enrichment analysis of differentially expressed genes between tumors with LNM and those without LNM and identified the involvement of immune response in the lymphatic metastasis of HNSCC. We further identified greater infiltrations of CD8+ T cells in tumors than in adjacent normal tissues through immunochemistry in the patient cohort (n = 62), indicating the involvement of CD8+ T cells in the antitumor immunity. Hierarchical clustering analysis was conducted to initially identify the candidate genes relevant to lymphocyte-mediated antitumor response. The candidate genes were applied to construct a LASSO Cox regression analysis model. Three genes were eventually screened out as progression‐related differentially expressed candidates in HNSCC and a risk scoring system was established based on LASSO Cox regression model to predict the outcome in patients with HNSCC. The score was calculated using the formula: 0.0636 × CXCL11 − 0.4619 × CXCR3 + 0.2398 × CCR5. Patients with high scores had significantly worse overall survival than those with low scores (p < 0.001). The risk score showed good performance in characterizing tumor-infiltrating lymphocytes and provided a theoretical basis for stratifying patients receiving immune therapies. Additionally, a nomogram including the risk score, age, and TNM stage was constructed. The prediction model displayed marginally better discrimination ability and higher agreement in predicting the survival of patients with HNSCC compared with the TNM stage.
Impact of Epstein-Barr Virus on Peripheral T-Cell Lymphoma Not Otherwise Specified and Angioimmunoblastic T-Cell Lymphoma
Authors: Kim Tong-Yoon , Min Gi-June , Jeon Young-Woo , Park Sung-Soo , Park Silvia , Shin Seung-Hawn , Yahng Seung-Ah , Yoon Jae-Ho , Lee Sung-Eun , Cho Byung-Sik , Eom Ki-Seong , Kim Yoo-Jin , Lee Seok , Kim Hee-Je , Min Chang-Ki , Lee Jong-Wook , Cho Seok-Goo
Published: January 2022

Purpose

The significance of Epstein-Barr virus (EBV) infections for the prognosis of patients with peripheral T-cell lymphomas (PTCLs), specifically angioimmunoblastic T-cell lymphoma (AITL) and PTCL not otherwise specified (PTCL-NOS), remains unclear. The Epstein-Barr encoding region can be used to detect EBV in tissue sections by in situ hybridization (ISH) and by polymerase chain reaction (PCR) assays of peripheral blood samples from patients with PTCLs. This study compared the outcomes patients with AITL or PTCL-NOS for whom the presence of EBV infection was assessed by these two methods.

Patients and Methods

This was a retrospective study of patients newly diagnosed with AITL or PTCL-NOS. All patients were selected from a single transplantation center. EBV-positive lymphomas were detected at the time of diagnosis in tissue sections by ISH or in the blood by PCR.

Results

Out of a cohort of 140 patients with histologically confirmed AITL or PTCL-NOS, 105 were EBV-positive. The 3-year overall survival of patients with EBV-positive TCL was 43.3% compared to 68.6% in patients with EBV-negative TCL (p = .01). Patients who were treated with autologous or allogeneic hematopoietic stem cell transplantation (n = 28 and n = 11, respectively) or chemotherapy alone (n = 66) had 3-year survival rates of 67.0%, 62.3%, and 30.2%, respectively (p <.02). Patients with EBV-positive TCL had a better prognosis after treatment with hematopoietic stem cell transplantation compared to chemotherapy alone, but no difference was seen among patients with EBV-negative TCL.

Conclusions

EBV infection was shown to negatively affect the clinical outcomes of patients with TCL. Stem cell transplantation has been found to be an effective treatment for EBV-associated lymphomas. Further investigations are warranted to determine the optimal treatment for these patients.
ASF1B Serves as a Potential Therapeutic Target by Influencing Cell Cycle and Proliferation in Hepatocellular Carcinoma
Authors: Ouyang Xiaoxi , Lv Longxian , Zhao Yalei , Zhang Fen , Hu Qingqing , Li Zuhong , Zhu Danhua , Li Lanjuan
Published: January 2022

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors with high morbidity and mortality. Therefore, it is very important to find potential biomarkers that can effectively predict the prognosis and progression of HCC. Recent studies have shown that anti-silencing function 1B (ASF1B) may be a new proliferative marker for tumor diagnosis and prognosis. However, the expression and function of ASF1B in hepatocellular carcinoma remain to be determined. In this study, integrated analysis of the Cancer Genome Atlas (TCGA), genotypic tissue expression (GTEx), and Gene Expression Omnibus (GEO) databases revealed that ASF1B was highly expressed in HCC. Kaplan-Meier survival curve showed that elevated ASF1B expression was associated with poor survival in patients with liver cancer. Correlation analysis of immune infiltration suggested that ASF1B expression was significantly correlated with immune cell infiltration in HCC patients. Gene set enrichment analysis (GSEA) indicated that ASF1B regulated the cell cycle, DNA Replication and oocyte meiosis signaling. Our experiments confirmed that ASF1B was highly expressed in HCC tissues and HCC cell lines. Silence of ASF1B inhibited hepatocellular carcinoma cell growth in vitro. Furthermore, ASF1B deficiency induced apoptosis and cell cycle arrest. Mechanistically, ASF1B knockdown reduced the expression of proliferating cell nuclear antigen (PCNA), cyclinB1, cyclinE2 and CDK9.Moreover, ASF1B interacted with CDK9 in HCC cells. Taken together, these results suggest that the oncogenic gene ASF1B could be a target for inhibiting hepatocellular carcinoma cell growth.
Aurantio-Obtusin Attenuates Non-Alcoholic Fatty Liver Disease Through AMPK-Mediated Autophagy and Fatty Acid Oxidation Pathways
Authors: Zhou Fei , Ding Mingning , Gu Yiqing , Fan Guifang , Liu Chuanyang , Li Yijie , Sun Rong , Wu Jianzhi , Li Jianchao , Xue Xiaoyong , Li Hongjuan , Li Xiaojiaoyang
Published: January 2022

Nonalcoholic fatty liver disease (NAFLD), manifested as the aberrant accumulation of lipids in hepatocytes and inflammation, has become an important cause of advanced liver diseases and hepatic malignancies worldwide. However, no effective therapy has been approved yet. Aurantio-obtusin (AO) is a main bioactive compound isolated from Cassia semen that has been identified with multiple pharmacological activities, including improving adiposity and insulin resistance. However, the ameliorating effects of AO on diet-induced NAFLD and underlying mechanisms remained poorly elucidated. Our results demonstrated that AO significantly alleviated high-fat diet and glucose-fructose water (HFSW)-induced hepatic steatosis in mice and oleic acid and palmitic acid (OAPA)-induced lipid accumulation in hepatocytes. Remarkably, AO was found to distinctly promote autophagy flux and influence the degradation of lipid droplets by inducing AMPK phosphorylation. Additionally, the induction of AMPK triggered TFEB activation and promoted fatty acid oxidation (FAO) by activating PPARα and ACOX1 and decreasing the expression of genes involved in lipid biosynthesis. Meanwhile, the lipid-lowing effect of AO was significantly prevented by the pretreatment with inhibitors of autophagy, PPARα or ACOX1, respectively. Collectively, our study suggests that AO ameliorates hepatic steatosis via AMPK/autophagy- and AMPK/TFEB-mediated suppression of lipid accumulation, which opens new opportunities for pharmacological treatment of NAFLD and associated complications.