bluuebunny/crossref_metadata_2025 huggingface dataset:
Variasi Massa Roller dan Ukuran V-belt CVT Terhadap Daya dan Torsi Motor Matic 125 cc
Authors: Abrar Sinatrya Cahyacerananda Abrar Sinatrya Cahyacerananda
Published: December 2023

Tujuan penelitian ini untuk menganalisis hasil daya dan torsi yang dihasilkan oleh kendaraan motor 125 cc tahun 2014 dalam penggunaan variasi massa roller dan ukuran v-belt. Metode penelitian yang digunakan metode penelitian eksperimental. Hasil penelitian menggunakan v-belt variasi 1 diperoleh daya dan torsi tertinggi oleh roller 8 gram sebesar 9,93 HP, untuk roller 10 gram sebesar 9,16 HP, sedangkan roller 12 gram sebesar 8,36 HP pada 3500 rpm. Torsi tertinggi oleh roller 8 gram mencapai 24,05 N.m. Untuk roller 10 gram mencapai 27,67 N.m, sedangkan roller 12 gram mencapai 26,19 N.m pada putaran 1500 rpm. Daya dan torsi tertinggi menggunakan v-belt variasi 2 dihasilkan oleh roller 8 gram sebesar 9,7 HP, untuk roller 10 gram sebesar 9,23 HP, sedangkan roller 12 gram sebesar 9 HP, pada 5500 rpm. Torsi tertinggi roller 8 gram mencapai 25,9 N.m. Untuk roller 10 gram mencapai 23,41 N.m, sedangkan roller 12 gram mencapai 24,31 N.m.
JENIS PLASTIK DAN MINYAK PLASTIK PYROLYSIS-RON 90 TERHADAP DAYA DAN EMISI MOTOR 150 CC
Authors: Fath Agung Brigytta Fath Agung Brigytta
Published: December 2023

Energi merupakan salah satu kebutuhan dalam kehidupan sehari-hari dimana kebutuhan utama energi masih tergantung pada bahan bakar fosil minyak bumi dan gas, Bahan bakar merupakan salah satu kebutuhan kedua yang terpenting setelah kebutuhan manusia akan pangan, sandang dan papan.

Tujuan dari penelitian ini untuk mengetahui daya dan emisi gas buang menggunakan minyak plastik jenis PP dan PE serta variasi campuran bahan bakar minyak hasil pirolisis limbah plastik dengan pertalite. Adapun variasi campuran bahan bakar yang digunakan terdiri dari 0% atau pertalite murni, 10% minyak hasil pirolisis limbah plastik 90% pertalite, 20% hasil pirolisis limbah plastik 80% pertalite, 30% hasil pirolisis limbah plastik 70% pertalite.

Metode yang digunakan adalah eksperimental dengan tujuan penelitan untuk mencari campuran terbaik antara pertalite dengan bahan bakar hasil pirolisis limbah plastik.

Hasil pengujian ini menunjukkan bahwa untuk daya tertinggi dan emisi terendah menggunakan bahan bakar hasil pirolisis limbah plastik jenis PP pada campuran 10% minyak plastik dan 90% ron 90  menghasilkan  9,49 hp dan emisi CO 0,48 % dan HC 68 ppm
Alcohol induced behavioral and immune perturbations are attenuated by activation of CB2 cannabinoid receptors
Authors: Roberts Aaliyah , Christian Mahli , Dilone Lizbeth Nivar , Nelson Natania , Endrino Mark Joseph , Kneebone Adam , Embaby Shymaa , Fernandez Justin , Liu Qing-Rong , Onaivi Emmanuel S. , Kibret Berhanu Geresu
Published: December 2023

The endocannabinoidome (eCBome) is the expanded endocannabinoid system (ECS) and studies show that there is a link between this system and how it modulates alcohol induced neuroinflammation. Using conditional knockout (cKO) mice with selective deletion of cannabinoid type 2 receptors (CB2Rs) in dopamine neurons (DAT-Cnr2) and in microglia (Cx3Cr1-Cnr2), we investigated how CB2Rs modulate behavioral and neuroinflammation induced by alcohol. Behavioral tests including locomotor and wheel running activity, rotarod performance test, and alcohol preference tests were used to evaluate behavioral changes induced by alcohol. Using ELISA assay, we investigated the level of pro-inflammatory cytokines, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1α (IL-1α), and interleukin-1β (IL-1β) in the hippocampus of mice. The findings demonstrated that locomotor activity, wheel running, and rotarod performance activities were significantly affected by cell-type specific deletion of CB2Rs in dopamine neurons and microglia. The non-selective CB2R agonist, WIN 55,212-2, reduced alcohol preference in the wild type and cell-type specific CB2R cKO mice. In addition, the result showed that cell-type specific deletion of CB2Rs per se and administration of alcohol to CB2R cKO mice increased the expression of proinflammatory cytokines in the hippocampus. These findings suggest the involvement of CB2Rs in modulating behavioral and immune alterations induced by alcohol.
Enhancing photoelectrochemical CO2 reduction with silicon photonic crystals
Authors: Zhou Chu , Zhang Gaotian , Guo Peiyuan , Ye Chenxi , Chen Zhenjun , Ma Ziyi , Zhang Menglong , Li Jingbo
Published: December 2023

The effectiveness of silicon (Si) and silicon-based materials in catalyzing photoelectrochemistry (PEC) CO2 reduction is limited by poor visible light absorption. In this study, we prepared two-dimensional (2D) silicon-based photonic crystals (SiPCs) with circular dielectric pillars arranged in a square array to amplify the absorption of light within the wavelength of approximately 450 nm. By investigating five sets of n + p SiPCs with varying dielectric pillar sizes and periodicity while maintaining consistent filling ratios, our findings showed improved photocurrent densities and a notable shift in product selectivity towards CH4 (around 25% Faradaic Efficiency). Additionally, we integrated platinum nanoparticles, which further enhanced the photocurrent without impacting the enhanced light absorption effect of SiPCs. These results not only validate the crucial role of SiPCs in enhancing light absorption and improving PEC performance but also suggest a promising approach towards efficient and selective PEC CO2 reduction.
Social media users' online behavior with regard to the circulation of hate speech
Authors: Megersa Tadesse , Minaye Abebaw
Published: December 2023

Online hate speech is ripping Ethiopian society apart and threatening the values of democracy, human dignity, and peaceful coexistence. The current study argues that understanding people's responses to hateful posts helps combat hate speech online. Therefore, this study aims to comprehend the roles social media users play in responding to online hate speech. To this end, 14 ethnic-based hate speech posts each with more than 1,000 comments were collected from the public space of four purposefully selected YouTube news channels and four Facebook accounts, which are considered as hot spots for the circulation of hate speech during data collection period. Then, 100 random comments were collected from each hate speech post using “exportcomment.com” which automatically extract comments from social media posts in excel format. After extracting a total of 1,400 random comments, 460 of them were removed because they were found irrelevant and unclear to be coded and analyzed. Then, inductive coding was employed to identify, refine, and name codes and themes that describe the main roles played by social media users in reacting to the hate speeches. The findings showed five major roles social media users play in responding to hatful contents: trolling, pace-making, peace-making, informing, and guarding. The paper discusses the findings and provides recommendations deemed necessary to counter online hate speeches.
Anthracycline-induced cardiotoxicity: mechanisms, monitoring, and prevention
Authors: Qiu Yun , Jiang Piao , Huang Yingmei
Published: December 2023

Anthracyclines are the most fundamental and important treatment of several cancers especially for lymphoma and breast cancer. However, their use is limited by a dose-dependent cardiotoxicity which may emerge early at the initiation of anthracycline administration or several years after termination of the therapy. A full comprehending of the mechanisms of anthracycline-induced cardiotoxicity, which has not been achieved and is currently under the efforts, is critical to the advance of developing effective methods to protect against the cardiotoxicity, as well as to early detect and treat it. Therefore, we review the recent progress of the mechanism underlying anthracycline-induced cardiotoxicity, as well as approaches to monitor and prevent this issue.
The global burden of cardiovascular diseases and type 2 diabetes attributable to low physical activity, 1990–2019: an analysis from the global burden of disease study
Authors: Zhang Junhan , Yuan Zongxiang , Mo Chuye , Kang Yiwen , Wang Fengyi , Wei Xueqin , Huang Shihui , Qin Fang , Jiang Junjun , Liang Hao , Ye Li
Published: December 2023

Background

Cardiovascular diseases (CVD) and type 2 diabetes (T2D) account for the majority of the burden of noncommunicable disease caused by low physical activity (LPA). In order to inform future interventions, this study aims to assess the burden and trends in mortality and disability-adjusted life years (DALYs) of CVD and T2D attributable to LPA by year, location, sex, and age from 1990 to 2019.

Methods

Mortality, DALYs, and their age-standardised rates (ASMR, ASDR) for CVD and T2D attributable to LPA were retrieved from Global Burden of Disease (GBD) 2019. The estimated annual percentage changes (EAPCs) were calculated using linear regression model to describe the trend over time.

Results

From 1990 to 2019, the number of deaths caused by both CVD and T2D due to LPA increased significantly globally. However, the overall ASMR and ASDR for CVD declined over this same period [EAPC for ASMR (CVD) = −1.44 (95% CI: −1.50–1.38), EAPC for ASDR (CVD) = −1.30 (95% CI: −1.35 to −1.25)]. In terms of disparities, ASMR (CVD) and ASDR (CVD) in North Africa and the Middle East were consistently higher than the global average; also, the sex difference in ASMR was greatest in Central Asia. ASMR among people aged 25–44 in high Socio-Demographic Index (SDI) region has increased significantly over the past three decades. ASMR (T2D) due to LPA showed an increasing trend year by year, with EAPC = 0.26 (95% CI: 0.13–0.39), and this rate increased faster in males than in females. Consistent with cardiovascular diseases, ASMR of type 2 diabetes attributable to LPA increased among people aged 25–44, while decreased in other age groups in high SDI region.

Conclusion

Interventions targeting LPA are warranted in controlling the burden of cardiovascular diseases and type 2 diabetes. Countries should adapt strategies to their local contexts, considering the sex and age differences among their populations. The 25–44 age group should be given special attention to prevent the disease burden from worsening among younger people.
Circulating microRNAs as biomarkers of Chagas cardiomyopathy
Authors: Antonietti Laura , Mariani Javier , Martínez María Jose , Santalla Manuela , Vensentini Natalia , Kyle Diego Alfredo , de Abreu Maximiliano , Tajer Carlos , Lacunza Ezequiel , Ferrero Paola
Published: December 2023

Background

Chagas cardiomyopathy (CHCM) is the most important clinical manifestation of Chagas disease. The analysis of cardiac miRNAs may contribute to predicting the progression to CHCM in Chagas indeterminate phase and/or to the differential diagnosis for cardiomyopathy.

Methods

We carried out a case-control study to identify circulating miRNAs associated with CHCM. We assigned 104 participants to four groups: healthy controls (HC), Chagas non-cardiomyopathy controls, CHCM cases, and ischemic cardiomyopathy controls. We performed a clinical, echocardiographic, and laboratory evaluation and profiled circulating miRNA in the serum samples.

Results

Differences between groups were observed in clinical variables and in the analysis of miRNAs. Compared to HC, CHCM participants had 4 over-expressed and 6 under-expressed miRNAs; miR-95-3p and miR-130b-3p were upregulated in CHCM compared with controls, Chagas non-cardiomyopathy and ischemic cardiomyopathy participants, suggesting that might be a hallmark of CHCM. Analysis of gene targets associated with cardiac injury yielded results of genes involved in arrhythmia generation, cardiomegaly, and hypertrophy.

Conclusions

Our data suggest that the expression of circulating miRNAs identified by deep sequencing in CHCM could be associated with different cardiac phenotypes in CHCM subjects, compared with Chagas non-CHCM, ischemic cardiomyopathy controls, and healthy controls.
Pedagogical interventions and their influences on university-level students learning pharmacology-a realist review
Authors: Khurshid Faraz , O’Connor Elizabeth , Thompson Rachel , Hegazi Iman
Published: December 2023

Introduction

The knowledge complexity and varied delivery formats in pharmacology education can leave students unprepared in essential pharmacotherapy skills. This significantly influences their ways of thinking and working in clinical environments, resulting in a challenging clinical transition. This need demands pedagogical innovations to strengthen pharmacology education and improve learners’ skills and competencies in pharmacotherapy. This evidence-based realist review aimed to examine the contextual factors and program theories or causal mechanisms crucial for effective pedagogical interventions in pharmacology, seeking to answer the question of ‘what works for whom, under what circumstances, how, and why’.

Method

The realist synthesis was initiated after retrieving data from Medline (OVID), Cochrane, EBSCO hosted ERIC, SCOPUS, and Embase (OVID) including other sources for additional records. The preliminary analysis enabled the establishment of context, mechanism, and outcome configurations (CMOC) and formulation and refinement of the initial program theory regarding the pedagogical interventions in pharmacology. Data synthesis iteration helped to identify the relevant context and unravel its relationships with underlying causal mechanisms through which said interventions generate outcomes of interest.

Results

A realist review analyzed 1,217 records and identified 75 articles examining a range of educational interventions from individual efforts to faculty-wide curriculum changes in pharmacology education. The key contexts for pharmacology education were troublesome content, traditional delivery methods, inadequate and limited opportunities for knowledge integration, and application. Active participation in interactive learning, along with enjoyment and motivation, was proposed as a causal mechanism for optimizing cognitive load and achieving positive outcomes. The outcomes of the review include subjective perceptions of improved confidence and satisfaction, objective measurements of high post-test scores.

Discussion

Pedagogical scaffolding in constructivist learning environments helps students overcome challenges in learning troublesome pharmacology knowledge. Considering the human cognitive system’s processing capacity, these interventions improve learning by effectively using cognitive resources. Innovations that focus on enhancing cognitive load through task construction can also promote positive emotional experiences in students, such as engagement and enjoyment, as explained by flow theory. A constructive learning environment, where the cognitive load is optimized and high flow is achieved, can maximize the impact of pedagogical interventions in pharmacology.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=160441, PROSPERO (CRD42020160441).
Writing experiences of neurodiverse students in graduate STEM programs
Authors: Syharat Connie Mosher , Hain Alexandra , Zaghi Arash E. , Deans Thomas
Published: December 2023

Background

Despite efforts to increase the participation of marginalized students, neurodivergent students remain underrepresented in graduate STEM programs. Prior research shows that these students often experience challenges related to key aspects of writing. The objective of this qualitative study is to deepen understanding of the writing experiences, strengths, and challenges of neurodivergent students pursuing graduate degrees in STEM fields. In this analysis, we consider the factors that influence the writing-specific challenges faced by neurodivergent students in graduate STEM programs. This work also explores how neurodivergent students leverage strengths and strategies for success in graduate-level writing tasks.

Results

This qualitative study draws on Social Cognitive Theory (SCT) to consider the ways cognitive, behavioral, and environmental factors impact writing experiences. We used thematic analysis of the transcripts from 13 focus groups and 1 interview to examine the writing experiences of 31 students who identify as neurodivergent in graduate STEM programs. The findings suggest that many writing challenges faced by neurodivergent graduate students are behaviors and beliefs that emerge in response to environmental factors such as the culture of STEM fields, prior experiences with writing assignments, anxiety driven by intensive feedback cycles, and perceived and experienced stigma. Study participants employed a range of collaborative and situational strategies to support and enhance their writing productivity.

Conclusion

These findings may provide insight for current and future neurodivergent graduate students as they adjust to the intense writing demands of graduate degree programs and for graduate program administrators and faculty advisors as they consider new ways to support the academic success of neurodivergent graduate students.
Exploring the spatial distribution of social impacts in protected areas
Authors: Jones Nikoleta , Begley Alfie , Malesios Chrysovalantis , Svajda Juraj , McGinlay James , Dimitrakopoulos Panayiotis G.
Published: December 2023

Protected Areas (PAs) are the most widely applied tool for biodiversity conservation. The primary role of these areas is to protect and restore ecosystems, but it has become increasingly evident that in order to designate effective PAs it is also crucial to take into consideration how they contribute to sustainable local socio-economic targets. In the past decade studies focusing on social impacts of PAs have increasingly studied a number of impacts such as on people’s quality of life, income and connectedness to nature. Although the literature on social impacts of PAs has increased there is limited evidence regarding the distribution of these impacts across different locations inside and near PAs. Addressing this gap is useful for practitioners considering that it is now widely accepted that social impacts are a significant predictor for the level of public support for PA. In the current study we explore this topic and analyse the spatial distribution of perceived social impacts in 4 European Protected Areas using primary data from 1,251 households. We apply a new modeling framework using Bayesian statistics revealing that social impacts are often unevenly distributed between local communities and extend outside the boundaries of a PA. Our analysis also shows that spatial proximity with other people (what are the perceptions of people who live nearby) is more important for predicting most perceived social impacts of PAs compared to how close respondents are to a PA. Our results highlight that social impacts may be geographically unevenly distributed in PAs and we present a new way of measuring the spatial distribution of these impacts which can be useful for national park authorities and in general managers of PAs.
Functional and structural analysis of a novel splice site HMBS variant in a Chinese AIP patient
Authors: Wang Xiaoqing , Zhang Huifen , Huang Huanhuan , Wang Wenli , Wen Yuping , Dai Zhuojin , Huang Shuling , Zhou Jingyi , Zhou Yuqing
Published: December 2023

Background: Acute intermittent porphyria (AIP) is a rare metabolic disorder that results from mutations in the gene encoding hydroxymethylbilane synthase (HMBS), an enzyme involved in heme biosynthesis. AIP follows an autosomal dominant inheritance pattern, but most carriers are asymptomatic. The clinical manifestations of AIP include acute attacks of abdominal pain and neuropsychiatric disturbances. The pathogenicity of novel HMBS variants identified in Chinese patients has not been well established.

Objective: The article aims to identify the pathogenic mutation in an AIP patient and prove its pathogenicity through in vitro experiments.

Methods: A 22-year-old female diagnosed with AIP participated in the study. Variant screening of her HMBS gene was carried out through Sanger sequencing. To ascertain the consequences of the newly discovered variant, we conducted in vitro experimentation targeting HMBS gene expression and enzymatic function. Additionally, protein structure analysis was performed. Cycloheximide treatment and UPF1-specific siRNA knockdown were employed to assess the impact of the mutation on the mechanism of non-sense-mediated mRNA decay (NMD).

Results: A novel splice site variant in the HMBS gene (c.648_651+1delCCAGG) was detected in the patient, which caused aberrant mRNA splicing. In vitro experiments demonstrated that this variant significantly decreased the expression of HMBS. Further investigation confirmed that this decrease was due to NMD. Additionally, structural analysis indicated that this variant would destabilize the HMBS protein and impair its catalytic activity. To gain a comprehensive understanding of HMBS mutations in the context of AIP, we conducted a literature search on PubMed using the keywords ‘HMBS’ and ‘Acute intermittent porphyria’ from 2013 to 2023. This search yielded 19 clinical case reports written in English, which collectively described 220 HMBS gene mutations worldwide.

Conclusion: The study identified and proved the pathogenicity of a novel splice site HMBS variant for the first time. Our results elucidated the pathological mechanism by which this mutation causes AIP through reducing HMBS expression and activity. These findings provide theoretical guidance for the diagnosis, treatment and genetic counseling of AIP patients.
Food allergy spectrum in the tropic: clinical and epidemiological profiles in a colombian hospital. A cross-sectional study
Authors: Olaya-Hernandez Manuela , Vasquez Laura Del Mar , Silva Diana Lucia , Martinez-Betancur Sofia , Guerra Maria , Arias Oriana , Ramirez Luis Fernando , Serrano Carlos Daniel
Published: December 2023

Introduction

Food allergy affects 2-10% of the general population; it is more frequent among children than among adults, and it is one of the leading causes of anaphylaxis. Diagnosis of food allergy requires a detailed medical history, skin tests, specific immunoglobulin E (IgE) tests for the food involved, and an oral challenge as final confirmation.

Objectives

This study aimed to describe the clinical and epidemiological characteristics of patients who underwent oral food challenges for suspected food allergies in a reference center in Colombia.

Methodology

An observational, descriptive, cross-sectional and retrospective study was conducted. Data were retrospectively collected from patients who were evaluated in the allergology service and suspected of food allergy from 2011 to 2018. Quantitative variables are presented as means or medians depending on the normality of the distribution (assessed by the Shapiro-Wilk test), and categorical variables are presented as frequencies and percentages.

Results

A total of 215 controlled open challenges were performed on 176 patients, most of whom were children (69%). Thirty-one patients (17%) required another oral challenge with a second food, and 11 (6.25%) required another oral challenge with three foods. Twelve oral challenges (5.58%) were positive. Of these, five challenges were positive for cow’s milk, 5 were positive for shrimp, and 2 were positive for legumes (peanuts and lentils).

Conclusion

The frequency of confirmed food allergies and the profile of food allergies in our population differs from that reported in other parts of the world.
Exosomes as a potential therapeutic approach in osteoimmunology
Authors: Zhivodernikov Ivan V. , Markina Yuliya V. , Kirichenko Tatiana V. , Popov Mikhail A. , Markin Alexander M.
Published: December 2023

Exosomes are natural extracellular vesicles that play a key role in inter- and intracellular communication. Currently they are considered as a promising therapeutic strategy for the treatment of various diseases. In osteoimmunology, exosomes can serve as biomarkers of bone homeostasis disorders and, at the same time, promising therapeutic agents with high stability in the biological environment, low immunogenicity and good bioavailability. In this review, we attempted to examine exosomes as natural mediators of intercellular communication, playing an essential role in the interaction of the immune system and bone tissue, based on an analysis of the PubMed database up to October 2023.
Unlocking the potential of dimethyl fumarate: enhancing oncolytic HSV-1 efficacy for wider cancer applications
Authors: Alwithenani Akram , Taha Zaid , Thomson Max , Chen Andrew , Wong Boaz , Arulanandam Rozanne , Diallo Jean-Simon
Published: December 2023

Immunotherapy and specifically oncolytic virotherapy has emerged as a promising option for cancer patients, with oncolytic herpes simplex virus-1 (oHSV-1) expressing granulocyte macrophage colony stimulating factor being the first OV to be approved by the FDA for treatment of melanoma. However, not all cancers are sensitive and responsive to oncolytic viruses (OVs). Our group has demonstrated that fumaric and maleic acid esters (FMAEs) are very effective in sensitizing cancer cells to OV infection. Of note, these FMAEs include dimethyl fumarate (DMF, also known as Tecfidera®), an approved treatment for multiple sclerosis and psoriasis. This study aimed to assess the efficacy of DMF in combination with oncolytic HSV-1 in preclinical cancer models. We demonstrate herewith that pre-treatment with DMF or other FMAEs leads to a significant increase in viral growth of oHSV-1 in several cancer cell lines, including melanoma, while decreasing cell viability. Additionally, DMF was able to enhance ex vivo oHSV-1 infection of mouse-derived tumor cores as well as human patient tumor samples but not normal tissue. We further reveal that the increased viral spread and oncolysis of the combination therapy occurs via inhibition of type I IFN production and response. Finally, we demonstrate that DMF in combination with oHSV-1 can improve therapeutic outcomes in aggressive syngeneic murine cancer models. In sum, this study demonstrates the synergistic potential of two approved therapies for clinical evaluation in cancer patients.
Mechanism-guided fine-tuned microbiome potentiates anti-tumor immunity in HCC
Authors: Liu Tao , Guo Ya , Liao Yanxia , Liu Jinping
Published: December 2023

Microbiome, including bacteria, fungi, and viruses, plays a crucial role in shaping distal and proximal anti-tumor immunity. Mounting evidence showed that commensal microbiome critically modulates immunophenotyping of hepatocellular carcinoma (HCC), a leading cause of cancer-related death. However, their role in anti-tumor surveillance of HCC is still poorly understood. Herein, we spotlighted growing interests in how the microbiome influences the progression and immunotherapeutic responses of HCC via changing local tumor microenvironment (TME) upon translocating to the sites of HCC through different “cell-type niches”. Moreover, we summarized not only the associations but also the deep insight into the mechanisms of how the extrinsic microbiomes interplay with hosts to shape immune surveillance and regulate TME and immunotherapeutic responses. Collectively, we provided a rationale for a mechanism-guided fine-tuned microbiome to be neoadjuvant immunotherapy in the near future.
The most common founder pathogenic variant c.868G > A (p.Val290Met) in the NPHS2 gene in a representative adult Czech cohort with focal segmental glomerulosclerosis is associated with a milder disease and its underdiagnosis in childhood
Authors: Thomasová Dana , Zelinová Michaela , Libik Malgorzata , Geryk Jan , Votýpka Pavel , Rajnochová Bloudíčková Silvie , Krejčí Karel , Reiterová Jana , Jančová Eva , Machová Jana , Kollárová Martina , Rychík Ivan , Havrda Martin , Horáčková Miroslava , Putzová Martina , Šafránek Roman , Kollár Marek , Macek Milan
Published: December 2023

Background

Genetic focal segmental glomerulosclerosis (FSGS) is caused by pathogenic variants in a broad spectrum of genes that have a variable representation based on subjects' ethnicity and/or age. The most frequently mutated autosomal recessive gene in FSGS is NPHS2. In this study, we analyzed the spectrum of NPHS2 variants and their associated phenotype in Czech adult FSGS patients.

Methods

A representative cohort of 234 adult patients with FSGS, derived from 225 families originating from all regions of Czechia, was analyzed by massively parallel sequencing. In this study, we focused on the comprehensive analysis of the NPHS2 gene. The histological classification of FSGS followed the Columbia classification.

Results

We detected seven (3%) cases bearing homozygous or compound heterozygous pathogenic NPHS2 variants. A single pathogenic variant c.868G > A (p.Val290Met) was found in the majority of NPHS2-positive cases (86%; 6 out of 7) in histologically confirmed instances of FSGS. Its allele frequency among unrelated NPHS2-associated FSGS patients was 50% (6/12), and Haplotype analysis predicted its origin to be a result of a founder effect. There is an identical V290M-related haplotype on all V290M alleles spanning a 0,7 Mb region flanking NPHS2 in Central European FSGS populations. The phenotype of the p.Val290Met NPHS2-associated FSGS demonstrated a later onset and a much milder course of the disease compared to other NPHS2 pathogenic variants associated with FSGS. The mean age of the FSGS diagnosis based on kidney biopsy evaluation was 31.2 ± 7.46 years. In 50% of all cases, the initial disease manifestation of proteinuria occurred only in adulthood, with 83% of these cases not presenting with edemas. One-third (33%) of the studied subjects progressed to ESRD (2 out of 6) at the mean age of 35.0 ± 2.82 years.

Conclusions

We identified the most prevalent pathogenic variant, p.Val290Met, in the NPHS2 gene among Czech adult FSGS patients, which has arisen due to a founder effect in Central Europe. The documented milder course of the disease associated with this variant leads to the underdiagnosis in childhood. We established the histopathological features of the NPHS2-associated adult FSGS cases based on the Columbia classification. This might improve patient stratification and optimize their treatment.
Molecular modeling and phylogenetic analyses highlight the role of amino acid 347 of the N1 subtype neuraminidase in influenza virus host range and interspecies adaptation
Authors: Elli Stefano , Raffaini Giuseppina , Guerrini Marco , Kosakovsky Pond Sergei , Matrosovich Mikhail
Published: December 2023

The N1 neuraminidases (NAs) of avian and pandemic human influenza viruses contain tyrosine and asparagine, respectively, at position 347 on the rim of the catalytic site; the biological significance of this difference is not clear. Here, we used molecular dynamics simulation to model the effects of amino acid 347 on N1 NA interactions with sialyllacto-N-tetraoses 6’SLN-LC and 3’SLN-LC, which represent NA substrates in humans and birds, respectively. Our analysis predicted that Y347 plays an important role in the NA preference for the avian-type substrates. The Y347N substitution facilitates hydrolysis of human-type substrates by resolving steric conflicts of the Neu5Ac2–6Gal moiety with the bulky side chain of Y347, decreasing the free energy of substrate binding, and increasing the solvation of the Neu5Ac2–6Gal bond. Y347 was conserved in all N1 NA sequences of avian influenza viruses in the GISAID EpiFlu database with two exceptions. First, the Y347F substitution was present in the NA of a specific H6N1 poultry virus lineage and was associated with the substitutions G228S and/or E190V/L in the receptor-binding site (RBS) of the hemagglutinin (HA). Second, the highly pathogenic avian H5N1 viruses of the Gs/Gd lineage contained sporadic variants with the NA substitutions Y347H/D, which were frequently associated with substitutions in the HA RBS. The Y347N substitution occurred following the introductions of avian precursors into humans and pigs with N/D347 conserved during virus circulation in these hosts. Comparative evolutionary analysis of site 347 revealed episodic positive selection across the entire tree and negative selection within most host-specific groups of viruses, suggesting that substitutions at NA position 347 occurred during host switches and remained under pervasive purifying selection thereafter. Our results elucidate the role of amino acid 347 in NA recognition of sialoglycan substrates and emphasize the significance of substitutions at position 347 as a marker of host range and adaptive evolution of influenza viruses.
Characterization of community-acquired Clostridioides difficile strains in Israel, 2020–2022
Authors: Schwartz Orna , Rohana Hanan , Azrad Maya , Shor Anna , Rainy Nir , Maor Yasmin , Nesher Lior , Sagi Orli , Ken-Dror Shifra , Kechker Peter , Peretz Avi
Published: December 2023

Background

The prevalence of community-acquired Clostridioides difficile infection (CA-CDI) has been rising, due to changes in antibiotics prescribing practices, emergence of hypervirulent strains and improved diagnostics. This study explored CA-CDI epidemiology by examining strain diversity and virulence factors of CA-CDI isolates collected across several geographical regions in Israel.

Methods

Stool samples of 126 CA-CDI patients were subjected to PCR and an immunoassay to identify toxin genes and proteins, respectively. Toxin loci PaLoc and PaCdt were detected by whole-genome sequencing (WGS). Biofilm production was assessed by crystal violet-based assay. Minimum inhibitory concentration was determined using the Etest technique or agar dilution. WGS and multi-locus sequence typing (MLST) were used to classify strains and investigate genetic diversity.

Results

Sequence types (ST) 2 (17, 13.5%), ST42 (13, 10.3%), ST104 (10, 8%) and ST11 (9, 7.1%) were the most common. All (117, 92.8%) but ST11 belonged to Clade 1. No associations were found between ST and gender, geographic area or antibiotic susceptibility. Although all strains harbored toxins genes, 34 (27%) produced toxin A only, and 54 (42.9%) strains produced toxin B only; 38 (30.2%) produced both toxins. Most isolates were biofilm-producers (118, 93.6%), primarily weak producers (83/118, 70.3%). ST was significantly associated with both biofilm and toxin production.

Conclusion

C. difficile isolates in Israel community exhibit high ST diversity, with no dominant strain. Other factors may influence the clinical outcomes of CDI such as toxin production, antibiotic resistance and biofilm production. Further studies are needed to better understand the dynamics and influence of these factors on CA-CDI.
EEG-controlled tele-grasping for undefined objects
Authors: Kim Minki , Choi Myoung-Su , Jang Ga-Ram , Bae Ji-Hun , Park Hyung-Soon
Published: December 2023

This paper presents a teleoperation system of robot grasping for undefined objects based on a real-time EEG (Electroencephalography) measurement and shared autonomy. When grasping an undefined object in an unstructured environment, real-time human decision is necessary since fully autonomous grasping may not handle uncertain situations. The proposed system allows involvement of a wide range of human decisions throughout the entire grasping procedure, including 3D movement of the gripper, selecting proper grasping posture, and adjusting the amount of grip force. These multiple decision-making procedures of the human operator have been implemented with six flickering blocks for steady-state visually evoked potentials (SSVEP) by dividing the grasping task into predefined substeps. Each substep consists of approaching the object, selecting posture and grip force, grasping, transporting to the desired position, and releasing. The graphical user interface (GUI) displays the current substep and simple symbols beside each flickering block for quick understanding. The tele-grasping of various objects by using real-time human decisions of selecting among four possible postures and three levels of grip force has been demonstrated. This system can be adapted to other sequential EEG-controlled teleoperation tasks that require complex human decisions.
Weighted residual network for SAR automatic target recognition with data augmentation
Authors: Li Junyu , Peng Cheng
Published: December 2023

Introduction

Decades of research have been dedicated to overcoming the obstacles inherent in synthetic aperture radar (SAR) automatic target recognition (ATR). The rise of deep learning technologies has brought a wave of new possibilities, demonstrating significant progress in the field. However, challenges like the susceptibility of SAR images to noise, the requirement for large-scale training datasets, and the often protracted duration of model training still persist.

Methods

This paper introduces a novel data augmentation strategy to address these issues. Our method involves the intentional addition and subsequent removal of speckle noise to artificially enlarge the scope of training data through noise perturbation. Furthermore, we propose a modified network architecture named weighted ResNet, which incorporates residual strain controls for enhanced performance. This network is designed to be computationally efficient and to minimize the amount of training data required.

Results

Through rigorous experimental analysis, our research confirms that the proposed data augmentation method, when used in conjunction with the weighted ResNet model, significantly reduces the time needed for training. It also improves the SAR ATR capabilities.

Discussion

Compared to existing models and methods tested, the combination of our data augmentation scheme and the weighted ResNet framework achieves higher computational efficiency and better recognition accuracy in SAR ATR applications. This suggests that our approach could be a valuable advancement in the field of SAR image analysis.
Enhanced simulations of whole-brain dynamics using hybrid resting-state structural connectomes
Authors: Manos Thanos , Diaz-Pier Sandra , Fortel Igor , Driscoll Ira , Zhan Liang , Leow Alex
Published: December 2023

The human brain, composed of billions of neurons and synaptic connections, is an intricate network coordinating a sophisticated balance of excitatory and inhibitory activities between brain regions. The dynamical balance between excitation and inhibition is vital for adjusting neural input/output relationships in cortical networks and regulating the dynamic range of their responses to stimuli. To infer this balance using connectomics, we recently introduced a computational framework based on the Ising model, which was first developed to explain phase transitions in ferromagnets, and proposed a novel hybrid resting-state structural connectome (rsSC). Here, we show that a generative model based on the Kuramoto phase oscillator can be used to simulate static and dynamic functional connectomes (FC) with rsSC as the coupling weight coefficients, such that the simulated FC aligns well with the observed FC when compared with that simulated traditional structural connectome.
Effectiveness of early glucocorticoids in myasthenia gravis: a retrospective cohort study
Authors: Zhen Lulu , Zhao Xue , Li Wenbo , Wu Jinru , Shang Haodong , Chen Shufan , Zhu Xiaoyan , Wang Yiren , Yu Xiaoxiao , Hu Guanlian , Sun Zhan , Zhang Yingna , Zhang Jing , Fang Hua , Zhang Yunke , Zhang Qingyong , Cui Xinzheng , Lv Jie , Yang Junhong , Gao Feng
Published: December 2023

Purpose

This study aimed to clarify the effect of early glucocorticoid (GC) application on achieving minimal manifestation (MM) status or better in the treatment of myasthenia gravis (MG) in the early clinical phase.

Methods

A retrospective analysis was performed using data from 336 patients with MG who received GC therapy from January 2015 to September 2022 in the Zhengzhou University Henan Institute of Medical and Pharmaceutical Sciences Myasthenia Gravis Biobank (ZMB). Patients were divided into two groups: the early mono-GC group (treated with GC within 6 months of MG onset) and the delayed mono-GC group.

Results

Kaplan–Meier analysis showed that the early mono-GC group achieved MM status earlier and more frequently than the delayed mono-GC group (log-rank test, p = 0.0082; hazard ratio [HR], 1.66; p = 0.011). The early mono-GC group had a lower maintenance oral GC dose than the delayed mono-GC group. In multivariate Cox regression analysis, early mono-GC (HR, 1.50; p = 0.043), early-onset MG (EOMG) (HR, 1.74; p = 0.034), and ocular MG (OMG) (HR, 1.90; p = 0.007) were associated with MM status or better. In conclusion, early mono-GC, EOMG, and OMG were positive predictors of treatment goals. In EOMG, OMG, and acetylcholine receptor antibody-positive MG (AChR-MG) subgroups, the maintenance oral GC doses in the early mono-GC group were significantly lower than the doses in the delayed mono-GC group (p < 0.05).

Conclusion

Early intervention with GC led to better long-term outcomes and reduced the necessary maintenance dose of oral GC for patients with MG. EOMG and OMG were positive predictors of MM status or better with mono-GC.
Evaluation of Parkinson’s disease early diagnosis using single-channel EEG features and auditory cognitive assessment
Authors: Molcho Lior , Maimon Neta B. , Hezi Neomi , Zeimer Talya , Intrator Nathan , Gurevich Tanya
Published: December 2023

Background

Parkinson’s disease (PD) often presents with subtle early signs, making diagnosis difficult. F-DOPA PET imaging provides a reliable measure of dopaminergic function and is a primary tool for early PD diagnosis. This study aims to evaluate the ability of machine-learning (ML) extracted EEG features to predict F-DOPA results and distinguish between PD and non-PD patients. These features, extracted using a single-channel EEG during an auditory cognitive assessment, include EEG feature A0 associated with cognitive load in healthy subjects, and EEG feature L1 associated with cognitive task differentiation.

Methods

Participants in this study are comprised of cognitively healthy patients who had undergone an F-DOPA PET scan as a part of their standard care (n = 32), and cognitively healthy controls (n = 20). EEG data collected using the Neurosteer system during an auditory cognitive task, was decomposed using wavelet-packet analysis and machine learning methods for feature extraction. These features were used in a connectivity analysis that was applied in a similar manner to fMRI connectivity. A preliminary model that relies on the features and their connectivity was used to predict initially unrevealed F-DOPA test results. Then, generalized linear mixed models (LMM) were used to discern between PD and non-PD subjects based on EEG variables.

Results

The prediction model correctly classified patients with unrevealed scores as positive F-DOPA. EEG feature A0 and the Delta band revealed distinct activity patterns separating between study groups, with controls displaying higher activity than PD patients. In controls, EEG feature L1 showed variations between resting state and high-cognitive load, an effect lacking in PD patients.

Conclusion

Our findings exhibit the potential of single-channel EEG technology in combination with an auditory cognitive assessment to distinguish positive from negative F-DOPA PET scores. This approach shows promise for early PD diagnosis. Additional studies are needed to further verify the utility of this tool as a potential biomarker for PD.
Using dual-task gait to recognize Alzheimer’s disease and mild cognitive impairment: a cross-sectional study
Authors: Li Zhaoying , Zhu Jingyi , Liu Junyan , Shi Min , Liu Pan , Guo Junjie , Hu Zhenzhu , Liu Shanyu , Yang Dongdong
Published: December 2023

Background

Gait is a potential diagnostic tool for detecting mild cognitive impairment (MCI) and Alzheimer’s disease (AD). Nevertheless, little attention has been paid to arm movements during walking, and there is currently no consensus on gait asymmetry. Therefore, in this study, we aimed to determine whether arm motion and gait asymmetry could be utilized for identifying MCI and AD.

Methods

In total, 102 middle-aged and elderly individuals were included in the final analysis and were assigned to the following three groups: AD (n = 27), MCI (n = 35), and a normal control group (n = 40). Gait and cognitive assessments were conducted for all participants. Gait detection included a single-task gait with free-speed walking and a dual-task gait with adding a cognitive task of successive minus seven to walking. Original gait parameters were collected using a wearable device featuring the MATRIX system 2.0. Gait parameters were shortened to several main gait domains through factor analysis using principal component extraction with varimax rotation. Subsequently, the extracted gait domains were used to differentiate the three groups, and the area under the receiver operating characteristic curve was calculated.

Results

Factor analysis of single-task gait identified five independent gait domains: rhythm symmetry, rhythm, pace asymmetry, arm motion, and variability. Factor analysis of the dual-task gait identified four gait domains: rhythm, variability, symmetry, and arm motion. During single-task walking, pace asymmetry was negatively correlated with MoCA scores and could distinguish between the AD group and the other two groups. Arm motion was not associated with MoCA scores, and did not exhibit adequate discrimination in either task.

Conclusion

Currently, there is no reliable evidence suggesting that arm motion can be used to recognize AD or MCI. Gait asymmetry can serve as a potential gait marker for the auxiliary diagnosis of AD but not for MCI.
Liquid biopsy in ovarian cancer in China and the world: current status and future perspectives
Authors: Zhang Hui , Wang Lingxia , Wu Huanwen
Published: December 2023

Ovarian cancer (OC) is the eighth most common cancer in women, but the mild, non-specific clinical presentation in early stages often prevents diagnosis until progression to advanced-stage disease, contributing to the high mortality associated with OC. While serum cancer antigen 125 (CA-125) has been successfully used as a blood-borne marker and is routinely monitored in patients with OC, CA-125 testing has limitations in sensitivity and specificity and does not provide direct information on important molecular characteristics that can guide treatment decisions, such as homologous recombination repair deficiency. We comprehensively review the literature surrounding methods based on liquid biopsies, which may provide improvements in sensitivity, specificity, and provide valuable additional information to enable early diagnosis, monitoring of recurrence/progression/therapeutic response, and accurate prognostication for patients with OC, highlighting applications of this research in China.