bluuebunny/crossref_metadata_2025 huggingface dataset:
Comorbidities in the Cardiorenal Syndrome
Authors:   , Nguyen Tuyet Nhi
Published: January 2024

A growing number of patients with kidney failure, mainly female, are dealing with a chronic variant of heart failure characterized by a gradual stiffening and impaired relaxation of the heart. Comorbidities, such as obesity, diabetes, and high blood pressure, are often present in these patients and these conditions further affect the progression of concurrent kidney and heart failure. In this thesis, we aimed to gain more insight in how these risk factors affect the development of renal and cardiovascular disease. The importance of recognizing the underlying comorbidities is highlighted as these determine cardiac remodeling, fibrotic and inflammatory dynamics. Interestingly, obesity and hypertension show opposing effects on energy metabolism in the cardiomyocytes. This shows that the existing comorbidities associated with heart failure with impaired relaxation forces the heart to adapt in different ways. In addition, we assess the therapeutic potential of sodium thiosulfate (STS), a hydrogen sulfide metabolite, as a monotherapy or in combination with a blood pressure lowering agent in the experimental setting of hypertensive kidney and heart failure. Promising effects of oral treatment with STS were observed on hypertension, renal and cardiac function and damage but requires further validation in comorbidity-associated kidney and heart failure.
Kemampuan penalaran matematis siswa dalam menyelesaikan masalah (studi kasus pada siswa SMA materi barisan dan deret)
Authors: Taqiya Farah Ayyun , Hasanah Aan , Yulianti Kartika
Published: January 2024

Studi ini bertujuan untuk mendapatkan gambaran tentang kemampuan penalaran matematis siswa sekolah menengah atas dalam menyelesaikan masalah yang berkaitan dengan barisan dan deret yang ada di kelas X. Penelitian ini adalah jenis penelitian kualitatif dan dirancang sebagai studi kasus. Penelitian ini mengumpulkan data dengan menggunakan alat tes soal uraian yang terdiri dari lima soal. Subjek dalam penelitian ini adalah peserta didik kelas XJ di salah satu SMA Negeri Kota Bandung. Hasil penelitian menunjukkan bahwa kemampuan penalaran matematis siswa dikategorikan rendah dengan persentase total 54,6%. Adapun rincian per indikatornya meliputi: 1) kemampuan menyajikan pernyataan matematika dengan gambar diperoleh 37,7% dalam kategori rendah, 2) kemampuan mengajukan dugaan diperoleh 57% dalam kategori sedang, 3) kemampuan memeriksa kesahihan diperoleh 50% dalam kategori rendah, 4) kemampuan memberikan alasan diperoleh 74% dalam kategori tinggi, dan 5) kemampuan membuat generalisasi diperoleh 66,5% dengan kategori sedang. Disimpulkan bahwa siswa sekolah menengah atas (SMA) memiliki kemampuan penalaran matematis yang cukup rendah pada materi deret dan barisan, terutama pada indikator kemampuan memeriksa kesahihan suatu argumen dan menyajikan pernyataan matematika melalui gambar.
Rapid Evidence Analysis of Diversity in UK Public Service Television: What Do We Know and What Should We Find Out?
Authors: Edwards Lee , Moss Giles
Published: January 2024

This article reports the results of a rapid evidence analysis (REA) of academic research focused on diversity in UK public service television broadcasting, published between 2016 and 2021. The aim of the REA was to establish the scale and quality of academic research on diversity in the context of public service television production, representation and reception, as well as to understand trends in research and gaps in knowledge that need to be addressed. The findings show that research is both sparse and fragmented. It is dominated by studies of on-screen diversity, rather than production or reception, and BBC content receives most attention, while other public service broadcasters are analysed much less frequently. In light of the findings, we propose a number of new directions for research, including a broader range of topics and methods and a more inclusive approach to the broadcast landscape. Analyses should facilitate an understanding of the impact of diversity across production, on-screen and among audiences, and adopt a longitudinal design, so that progress towards diversity over time can be evaluated.
Pediatric Psychiatrists’ Experiences and Perceptions Concerning Individuals with Autism Spectrum Disorder and Savant Syndrome
Authors:   Korean Association For Persons With Autism, Park Hyun Ok , Kang Hae Kyung
Published: January 2024

The purpose of this study was to explore pediatric psychiatrists’ experiences of working with individuals with ASD and savant syndrome. It identifies ways to support such individuals based on these experiences. For this purpose, in-depth interviews were conducted with seven pediatric psychiatrists with more than ten years of clinical experience in treating students with ASD. The interviews were analyzed using continuous comparative analysis. Seven core themes, 24 subthemes, and 54 thematic units were derived. The key themes that emerged were: 1) referrals; 2) ASD and savant syndrome encountered in the clinic being a spectrum; 3) savant syndrome being a concept that requires the understanding of all; 4) the notion of being savant as indicating that one possess abilities as a strength and a blessing; 5) talent that grows through immersion, or special challenges caused by immersion; 6) the time before special talents become special abilities; and 7) how to support students with ASD or savant syndrome. Based on the results, we discuss possible ways to cooperate with professionals of various fields to support students with ASD and savant syndrome, and ways to support students with savant syndrome in the future.
Effects of Picture Exchange Communication System on Spontaneous Requesting Behaviors of Verbal and Non-verbal Elementary School Students with Developmental Disabilities
Authors:   Korean Association For Persons With Autism, Lim Jae I , Kim EunKyung
Published: January 2024

The purpose of this study was to investigate the impact of the Picture Exchange Communication System (PECS) on the spontaneous requesting behaviors of verbal and non‑verbal elementary school students with developmental disabilities. The participants were four first‑grade students with developmental disabilities from Y special school in City I. The PECS intervention, serving as the independent variable, was applied to two verbal and two non‑verbal students. The dependent variables were spontaneous requesting behaviors. The multiple probe design across participants was utilized in the research. The PECS intervention was implemented up to Phase IV. The maintenance and generalization effects across people and settings were investigated. The result of this study was as follows. The PECS intervention was effective for increasing the spontaneous requesting behaviors of verbal and non‑verbal elementary school students with developmental disabilities. The effect of the intervention was maintained in the follow‑up phase and generalized to other settings and people. Non‑verbal students demonstrated spontaneous requesting behaviors by presenting picture cards, and verbal students used both picture cards and spoken language. The PECS can be an effective intervention that positively affects the spontaneous requesting behaviors of verbal and non‑verbal elementary school students with developmental disabilities.
PETUNJUK DAN LANDASAN DALAM PENETAPAN GARIS NASAB PESPEKTIF HUKUM ISLAM
Authors: Ahmad Muhammad Sa'dul Kholqi
Published: January 2024

In Islamic jurisprudence, Nasab holds a crucial position, being one of the five elements categorized under "kulliyatul khoms" that demand safeguarding, thus subjecting it to the application of Islamic laws. The preservation of Nasab stands as a primary objective in the implementation of Islamic law, and its significance has escalated in the contemporary era. The prevalence of various deviations in the process of childbirth underscores the urgency of upholding this aspect. Furthermore, the Republic of Indonesia's legal framework recognizes numerous rights for children, emphasizing the necessity of a legitimate lineage for the entitlement to these rights. As Muslims residing in a nation governed by laws and regulations, it becomes imperative for us to comprehend the foundational aspects that contribute to the determination of our lineage. An awareness of these factors becomes pivotal, as it directly impacts our ability to establish lineage connections and, consequently, secure the associated legal rights within the societal and legal framework of Indonesia.
Sex differences in mortality and hospitalization in heart failure with preserved and mid-range ejection fraction: a systematic review and meta-analysis of cohort studies
Authors: Deng You , Zhang Jun , Ling Jitao , Hu Qingwen , Song Tianggang , Xu Yi , Liu Menglu , Wu Yuting , Mei Kaibo , Chen Jiawei , Zhao Huilei , Liu Xiao
Published: January 2024

Introduction

The influence of sex on the prognosis of heart failure with preserved or intermediate ejection fraction (HFpEF and HFmrEF) remains uncertain. This study aimed to investigate whether sex differences impact the prognosis of patients diagnosed with HFpEF and HFmrEF.

Methods

A comprehensive search across three databases (PubMed, the Cochrane Library, and Embase) was conducted to identify sex-related prognostic cohort studies focusing on HFpEF and HFmrEF. Risk estimates were synthesized using the random effects model. The analysis included 14 cohorts comprising 41,508 HFpEF patients (44.65% males) and 10,692 HFmrEF patients (61.79% males).

Results

Among HFpEF patients, men exhibited significantly higher rates of all-cause mortality (13 studies; hazard ratio (HR): 1.24, 95% confidence interval (CI): 1.15 to 1.33)) and cardiovascular disease mortality (5 studies; HR: 1.22, 95% CI: 1.14 to 1.31) compared to women. However, no significant difference was observed in HF admissions. For HFmrEF patients, men displayed notably higher all-cause mortality (HR: 1.21, 95% CI: 1.12 to 1.31) but no significant differences in cardiovascular mortality or HF admissions.

Discussion

These findings suggest that male patients diagnosed with HFpEF and HFmrEF may face a more unfavorable prognosis in terms of all-cause mortality. Variations were noted in cardiovascular mortality and HF admissions, indicating potential complexities in sex-related prognostic factors within these heart failure categories. In summary, male patients with HFpEF and HFmrEF may have a more unfavorable prognosis.
Digital patient twins for personalized therapeutics and pharmaceutical manufacturing
Authors: Fischer Rene-Pascal , Volpert Annika , Antonino Pablo , Ahrens Theresa D.
Published: January 2024

Digital twins are virtual models of physical artefacts that may or may not be synchronously connected, and that can be used to simulate their behavior. They are widely used in several domains such as manufacturing and automotive to enable achieving specific quality goals. In the health domain, so-called digital patient twins have been understood as virtual models of patients generated from population data and/or patient data, including, for example, real-time feedback from wearables. Along with the growing impact of data science technologies like artificial intelligence, novel health data ecosystems centered around digital patient twins could be developed. This paves the way for improved health monitoring and facilitation of personalized therapeutics based on management, analysis, and interpretation of medical data via digital patient twins. The utility and feasibility of digital patient twins in routine medical processes are still limited, despite practical endeavors to create digital twins of physiological functions, single organs, or holistic models. Moreover, reliable simulations for the prediction of individual drug responses are still missing. However, these simulations would be one important milestone for truly personalized therapeutics. Another prerequisite for this would be individualized pharmaceutical manufacturing with subsequent obstacles, such as low automation, scalability, and therefore high costs. Additionally, regulatory challenges must be met thus calling for more digitalization in this area. Therefore, this narrative mini-review provides a discussion on the potentials and limitations of digital patient twins, focusing on their potential bridging function for personalized therapeutics and an individualized pharmaceutical manufacturing while also looking at the regulatory impacts.
Engaging stakeholders to inform policy developments in early childhood education and outside school hours care
Authors: Hadley Fay , Harrison Linda J. , Lavina Leanne , Barblett Lennie , Irvine Susan , Bobongie-Harris Francis , Cartmel Jennifer
Published: January 2024

The application of engagement strategies to ensure democracy of decisions is increasingly valued and adopted by governments to ensure trust in the process and ownership of the outcome. This paper describes the approach and methods used to engage early childhood education and care (ECEC) and outside school hours care (OSHC) stakeholders in the contemporizing and updating of Australia’s national Approved Learning Frameworks (ALFs): Belonging, Being and Becoming: The Early Years Learning Framework for Australia (EYLF) and My Time Our Place: Framework for School Age Care (MTOP). Theoretical underpinnings of a robust stakeholder engagement strategy ensured a range of methods were developed to communicate with and encourage participation by the diversity of stakeholders who are invested in ECEC and OSHC in Australia – broadly defined as approved providers, teachers, educators, families, children and young people, regulatory authorities and other professionals who provide support and advice. A mixed-method, sequential 3-Stage design was developed to gather the insights, responses, and perspectives of stakeholders who provided, worked in, used, attended, or supported ECEC and/or OSHC settings. Stakeholder feedback included survey ratings and written comments, focus group and panel discussions, educator documentation and video-diaries, and the writings, talking, and drawings of children and young people. Evaluation methods focus on the number, diversity, and depth of stakeholder responses. In conclusion, we reflect on the usefulness, benefits, limitations, and effectiveness of our approach to participatory engagement to inform government policy development and decision making.
Scientific workshops with a dialogical approach: an effective tool for introducing science into vulnerable educational contexts
Authors: Guardiola-Fígols Miquel , González Aitor Gómez , Natividad-Sancho Laura , Gairal-Casadó Regina
Published: January 2024

The literature shows not only that science communication excludes the most vulnerable groups in society but also that it is of the utmost importance to make it more inclusive and available to all citizens. However, the inclusive communication experiences that are having some impact on society by including vulnerable groups have yet to cover all aspects of the issue. This article shows the positive results of scientific workshops that take a dialogical approach from researchers from the Institute of Human Palaeoecology and Social Evolution (IPHES). The workshops on the “IPHES in the Local Area” program are designed to communicate science looking for scientific excellence in urban centers that are of special complexity. The data were collected using pre-and post-test questionnaires given to 117 pupils from three primary schools where the science workshops were held. The data analysis shows that, after the workshops, participants had a greater interest in and appreciation of science.
Design and implementation of virtual laboratories for higher education sustainability: a case study of Nankai University
Authors: Zhang Nan , Liu Yin
Published: January 2024

Laboratory learning has a vital role in science education. With the application of information technologies in educational domain, virtual experiment has become an effective supplement to traditional experimental teaching. Moreover, virtual experimentation can expand experimental field, enrich teaching content and reduce experimental risk, which provides strong support for the sustainable development of higher education. Using cutting-edge technologies such as virtual reality (VR), augmented reality (AR), computer simulation and interaction, we developed two public virtual laboratories and 41 virtual-simulation-experiment projects. They are integrated into an interactive learning environment, that is, virtual experiment learning management platform. The method is based on ADDIE (Analysis, Design, Development, Implementation, and Evaluation). In this paper, one virtual-simulation-experiment project is taken as a case study. The project includes 4 virtual practical activities mapped to the medical courses; and they were implemented in the third year of the bachelor’s degree. The proposed virtual learning environment has been evaluated by learners for 2 years. The results achieved and similar findings from other studies, show that the use of virtual learning environment has a positive impact on the learning process and outcomes.
Demands, resources and institutional factors in the work of academic staff in Central and Eastern Europe: results of a qualitative research among university teachers in five countries
Authors: Kovács Klára , Dobay Beáta , Halasi Szabolcs , Pinczés Tamás , Tódor Imre
Published: January 2024

Introduction

The increased stress, pressure, and organizational change draw attention to the importance of doing research on workplace stress and resources, as well as other sources of stress among university teachers. Based on the job demands-resources theory (JD-R theory) this paper investigates the workplace factors affecting the health and wellbeing of Central and Eastern European (CEE) academics. A further question is, what are the institutional factors that (could) improve or worsen their wellbeing, as well as how they are able to cope with the stress on an individual level.

Methods

For the analyses, seven focus group interviews were conducted with academics from nine higher education institutions in Hungary, Slovakia, Ukraine, Romania, and Serbia (N = 41).

Results

According to our results of the focus group interviews the most important workplace difficulties, challenges, and resources are related to teaching roles, interpersonal relationships, support by the management, and infrastructural conditions.

Discussion

Institutions can contribute to the wellbeing and health of the academics primarily by offering free or at least discounted participation in sports, cultural and leisure events, as well as mental health counseling, but it is important for these not to be self-serving (the colleagues from the university should not participate in the programs to make up for the missing audiences of the otherwise overfunded organizations of the institution) and haphazard: without a targeted health strategy, these are not sufficiently effective.
Advancements in greenhouse gas emission reduction methodology for fluorinated compounds and N2O in the semiconductor industry via abatement systems
Authors: Zhou Yue , Li Yuanzhe , Ong Emily
Published: January 2024

Greenhouse gases (GHGs), particularly fluorinated compounds (FCs), nitrous oxide (N2O), and nitrogen trifluoride (NF3), contribute significantly to climate change, and the semiconductor industry is a notable emitter of these gases. This report introduces an innovative methodology for GHG emission reduction in the semiconductor industry by utilizing advanced abatement systems, referencing Clean Development Mechanism (CDM) published methods AM0078 and AM0111. The proposed methodology shows promising potential, with substantial reductions in FCs, N2O, and NF3 emissions, positioning the semiconductor industry as a key player in climate change mitigation efforts. The main results indicate that by applying the latest abatement systems, a significant reduction in the targeted GHGs can be achieved. The methodology’s verification process confirms the effectiveness of GHG reduction, ensuring that semiconductor manufacturing’s environmental impact is minimized. Our findings suggest that the implementation of this methodology could lead to industry-wide adoption, resulting in a substantial contribution towards stabilizing atmospheric GHG concentrations.
Impact of environmental regulation on government subsides of public-private partnership waste-to-energy incineration projects: evidence from 66 cities in China
Authors: Shen Ye , Xu Min , Cui Caiyun , Xia Bo , Skitmore Martin , Moorhead Matthew , Liu Yong
Published: January 2024

Introduction: Environmental regulation, as a vital component of public regulation in China, plays a crucial role in coordinating regional eco-efficiency, while the traditional hypothesis, Porter hypothesis, and uncertainty hypothesis offer three different perspectives for understanding the relationship between industry performance and environmental regulations.

Methods: Based on the assumption of industry heterogeneity, 81 public-private partnership (PPP) waste-to-energy (WTE) incineration projects are analyzed using panel data from 66 cities within China during the period from 2013 to 2017 with the aims to reveal the underlying mechanism behind environmental regulation and the government subsides of public-private partnership waste-to-energy incineration projects by using multiple regression modeling.

Results: The results show that the impact of environmental regulation on government subsides of PPP WTE projects has demonstrated an “Inverted-U”-shaped relationship with an inflection point, of which an increase in environmental regulation is positively correlated with an increase in subsidies at first then a negative correlation developing later.

Discussion: The findings are significant in setting flexible environmental regulations according to the needs of regional economic and social development. In addition, they also supply a theoretical reference for promoting the WTE incineration industry’s sustainable and healthy development.
Stay or return? The role of city environment and digital economy in migrants in China
Authors: Chen Qiang , Qi Ping , Deng Lanfang
Published: January 2024

With the rapid development of digital economy, green environment and digital economy are constantly and deeply integrated. This paper examines the effect of city environment and digital economy on return intentions based on the logit model proposed by McFadden (1974). The results of this study show that both urban environment and digital economy have a significant impact on laborers’ decisions about return migration. Moreover, the study reveals that the older individuals are more responsive to the environmental quality, while the decision-making process regrading return migration is more evidently influenced by the digital economy for individuals with higher abilities and those within province. Furthermore, the wages of the migrants who intend to return also increase with the growth of the city’s digital economy, which may be attributed to the enhanced work efficiency. In addition, the increased impact of the green environment and digital economy on wages for the migrants intending to return is primarily observed in the middle-skilled and middle-income laborers.
High emissions or carbon neutral? Inclusion of “anthropogenic” forest sinks leads to underreporting of forestry emissions
Authors: Bysouth David , Boan Julee J. , Malcolm Jay R. , Taylor Anthony R.
Published: January 2024

Recent research has shown forest-related emissions reported in national greenhouse gas inventories are much lower than global estimates from models summarized in Intergovernmental Panel on Climate Change reports. A substantial part of this discrepancy could be explained by conceptual differences in what is counted as part of the anthropogenic forest carbon sink and the way countries report on their forest harvesting sectors. With Canada as a case study, we used published National Inventory Report and Common Reporting Format tables to isolate emissions and removals directly associated with forestry from those associated with forests more broadly. Forestry-related factors that affect CO2 emissions and removals include tree harvesting, post-harvest forest regeneration and growth, and carbon storage in long-lived harvested wood products. We found that between 2005 and 2021, forestry in Canada represented a net source of carbon (annual mean = 90.8 Mt. CO2e), and that total area logged was a significant predictor of net forestry emissions. In contrast, Canada’s NIR reported a small net carbon sink during the same time period (annual mean = −4.7 Mt. CO2e). We show this discrepancy can be explained by Canada’s GHG reporting approach that claims GHG emissions from wildfires are natural, but GHG removals from forests at the age of commercial maturity, despite being primarily natural disturbance origin, are anthropogenic. This reporting approach may lead to climate mitigation policies that are ineffectual or detrimental to reducing net carbon in the global atmosphere.
Comparative transcriptomic analysis of Illumina and MGI next-generation sequencing platforms using RUNX3- and ZBTB46-instructed embryonic stem cells
Authors: Póliska Szilárd , Fareh Chahra , Lengyel Adél , Göczi Loránd , Tőzsér József , Szatmari Istvan
Published: January 2024

Introduction: We have previously observed phenotypic and developmental changes upon the ectopic expression of the RUNX3 or the ZBTB46 transcription factors in mouse embryonic stem cell (ESC) derived progenitors. In this study, we evaluated the gene expression profiles of the RUNX3- and the ZBTB46-instructed murine ESCs with RNA-seq testing two next-generation sequencing technologies.

Methods: We compared the DNA nanoball-based DNBSEQ G400 sequencer (MGI) with the bridge-PCR-based NextSeq 500 instrument (Illumina) for RNA sequencing. Moreover, we also compared two types of MGI sequencing reagents (Standard versus Hot-massive parallel sequencing (MPS)) with the DNBSEQ G400.

Results: We observed that both sequencing platforms showed comparable levels of quality, sequencing uniformity, and gene expression profiles. For example, highly overlapping RUNX3- and ZBTB46-regulated gene lists were obtained from both sequencing datasets. Moreover, we observed that the Standard and the Hot-MPS-derived RUNX3- and ZBTB46-regulated gene lists were also considerably overlapped. This transcriptome analysis also helped us to identify differently expressed genes in the presence of the transgenic RUNX3 or ZBTB46. For example, we found that Gzmb, Gzmd, Gzme, Gdf6, and Ccr7 genes were robustly upregulated upon the forced expression of Runx3; on the other hand, Gpx2, Tdpoz4, and Arg2 were induced alongside the ectopic expression of Zbtb46.

Discussion: Similar gene expression profile and greatly overlapping RUNX3- and ZBTB46-regulated gene sets were detected with both DNA sequencing platforms. Our analyses demonstrate that both sequencing technologies are suitable for transcriptome profiling and target gene selection. These findings suggest that DNBSEQ G400 represents a cost-effective alternative sequencing platform for gene expression monitoring. Moreover, this analysis provides a resource for exploration of the RUNX3- and ZBTB46-dependent gene regulatory networks.
Next-generation sequencing testing in children with epilepsy reveals novel clinical, diagnostic and therapeutic implications
Authors: Krygier Magdalena , Pietruszka Marta , Zawadzka Marta , Sawicka Agnieszka , Lemska Anna , Limanówka Monika , Żurek Jan , Talaśka-Liczbik Weronika , Mazurkiewicz-Bełdzińska Maria
Published: January 2024

Introduction: Epilepsy is one of the commonest diseases in children, characterized by extensive phenotypic and genetic heterogeneity. This study was conducted to determine the diagnostic utility and to identify novel clinical and therapeutic implications of genetic testing in pediatric patients with epilepsy.

Methods: Large multigene panel and/or exome sequencing was performed in 127 unrelated Polish and Ukrainian patients with suspected monogenic epilepsy. Diagnostic yields were presented for five phenotypic subgroups, distinguished by seizure type, electroencephalographic abnormalities, anti-seizure treatment response, and neurodevelopmental deficits.

Results: A definite molecular diagnosis was established in 46 out of 127 cases (36%). Alterations in six genes were detected in more than one patient: SCN1A, MECP2, KCNT1, KCNA2, PCDH19, SLC6A1, STXBP1, and TPP1, accounting for 48% of positive cases. 4/46 cases (8.7%) were mosaic for the variant. Although the highest rates of positive diagnoses were identified in children with developmental delay and generalized seizures (17/41, 41%) and in developmental end epileptic encephalopathies (16/40, 40%), a monogenic etiology was also frequently detected in patients with solely focal seizures (10/28, 36%). Molecular diagnosis directly influenced anti-seizure management in 15/46 cases.

Conclusion: This study demonstrates the high diagnostic and therapeutic utility of large panel testing in childhood epilepsies irrespective of seizure types. Copy number variations and somatic mosaic variants are important disease-causing factors, pointing the need for comprehensive genetic testing in all unexplained cases. Pleiotropy is a common phenomenon contributing to the growing phenotypic complexity of single-gene epilepsies.
Variable clinical presentation of split hand/foot malformation syndrome in a family with microduplication of 10q24.32: a case report
Authors: Akimova Daria , Markova Tatiana , Ampleeva Maria , Skoblov Mikhail
Published: January 2024

SHFM (Split Hand/Foot Malformation) is a heterogeneous group of disorders characterized by the presence of clefts in the hands and feet, along with syndactyly of the digits. In this article, we describe a family in which two members exhibit characteristic developmental abnormalities associated with SHFM, presenting with variable clinical features. Using whole-genome sequencing, we identified a microduplication of a chromosomal segment on locus 10q24.32, specifically spanning positions 102934495 to 103496555, encompassing genes BTRC, POLL, FBXW4 and LBX1 in the proband. Genomic duplications, including these genes, were previously described in patients diagnosed with the third type of SHFM. We validated the presence of this structural rearrangement in 7 family members, including the proband and the proband’s father. Remarkably, further investigation demonstrated that the detected duplication exhibits a mosaic state in the phenotypically normal paternal grandmother of the proband, thereby providing a plausible explanation for the absence of a pathological phenotype in her.
IL4I1 in M2-like macrophage promotes glioma progression and is a promising target for immunotherapy
Authors: Ye Feng , Wang Lichong , Li Yuanyou , Dong Chengyuan , Zhou Liangxue , Xu Jianguo
Published: January 2024

Background

Glioma is the prevailing malignant intracranial tumor, characterized by an abundance of macrophages. Specifically, the infiltrating macrophages often display the M2 subtype and are known as tumor-associated macrophages (TAMs). They have a critical role in promoting the oncogenic properties of tumor cells. Interleukin-4-induced-1 (IL4I1) functions as an L-phenylalanine oxidase, playing a key part in regulating immune responses and the progression of various tumors. However, there is limited understanding of the IL4I1-mediated cross-talk function between TAMs and glioma cell in the glioma microenvironment.

Methods

TCGA, GTEx, and HPA databases were applied to assess the IL4I1 expression, clinical characteristics, and prognostic value of pan-cancer. The link between IL4I1 levels and the prognosis, methylation, and immune checkpoints (ICs) in gliomas were explored through Kaplan–Meier curve, Cox regression, and Spearman correlation analyses. The IL4I1 levels and their distribution were investigated by single-cell analysis and the TIMER 2 database. Additionally, validation of IL4I1 expression was performed by WB, RT-qPCR, IHC, and IF. Co-culture models between glioma cells and M2-like macrophages were used to explore the IL4I1-mediated effects on tumor growth, invasion, and migration of glioma cells. Moreover, the function of IL4I1 on macrophage polarization was evaluated by ELISA, RT-qPCR, WB, and siRNA transfection.

Results

Both transcriptome and protein levels of IL4I1 were increased obviously in various tumor types, and correlated with a dismal prognosis. Specifically, IL4I1 was implicated in aggressive progression and a dismal prognosis for patients with glioma. A negative association was noticed between the glioma grade and DNA promoter methylation of IL4I1. Enrichment analyses in glioma patients suggested that IL4I1 was linked to cytokine and immune responses, and was positively correlated with ICs. Single-cell analysis, molecular experiments, and in vitro assays showed that IL4I1 was significantly expressed in TAMs. Importantly, co-culture models proved that IL4I1 significantly promoted the invasion and migration of glioma cells, and induced the polarization of M2-like macrophages.

Conclusion

IL4I1 could be a promising immunotherapy target for selective modulation of TAMs and stands as a novel macrophage-related prognostic biomarker in glioma.
The pyrin inflammasome, a leading actor in pediatric autoinflammatory diseases
Authors: La Bella Saverio , Di Ludovico Armando , Di Donato Giulia , Basaran Ozge , Ozen Seza , Gattorno Marco , Chiarelli Francesco , Breda Luciana
Published: January 2024

The activation of the pyrin inflammasome represents a highly intriguing mechanism employed by the innate immune system to effectively counteract pathogenic agents. Despite its key role in innate immunity, pyrin has also garnered significant attention due to its association with a range of autoinflammatory diseases (AIDs) including familial Mediterranean fever caused by disruption of the MEFV gene, or in other genes involved in its complex regulation mechanisms. Pyrin activation is strictly dependent on homeostasis-altering molecular processes, mostly consisting of the disruption of the small Ras Homolog Family Member A (RhoA) GTPases by pathogen toxins. The downstream pathways are regulated by the phosphorylation of specific pyrin residues by the kinases PKN1/2 and the binding of the chaperone 14-3-3. Furthermore, a key role in pyrin activation is played by the cytoskeleton and gasdermin D, which is responsible for membrane pores in the context of pyroptosis. In addition, recent evidence has highlighted the role of steroid hormone catabolites and alarmins S100A8/A9 and S100A12 in pyrin-dependent inflammation. The aim of this article is to offer a comprehensive overview of the most recent evidence on the pyrin inflammasome and its molecular pathways to better understand the pathogenesis behind the significant group of pyrin-related AIDs.
Visceral adipose tissue and osteoarthritis, a two-sample Mendelian randomized study
Authors: Zhang Yinzhen , Wang Yanpeng , Xu Ji , Wang Zhengyan , Zhao Wenhai , Zhao Changwei
Published: January 2024

Background

The relationship between visceral adipose tissue and osteoarthritis is not clear. The purpose of our study was to explore the relationship between visceral adipose tissue and osteoarthritis.

Methods

We used a two-sample Mendelian randomization method to select single-nucleotide polymorphisms (SNPs) significantly associated with visceral adipose tissue as instrumental variables to explore the relationship between visceral adipose tissue and all osteoarthritis, hand osteoarthritis, hip osteoarthritis, knee osteoarthritis, and spine osteoarthritis. The reliability of the results was tested using sensitivity analysis.

Results

Our findings indicated that visceral adipose tissue was associated with all osteoarthritis, hip osteoarthritis, knee osteoarthritis, and spine osteoarthritis (all osteoarthritis: OR = 1.399, 95% CI: 1.335–1.467, p = 7.95e-44; hip osteoarthritis: OR = 1.399, 95% CI: 1.284–1.524, p = 1.41e-14; knee osteoarthritis: OR = 1.794, 95% CI: 1.662–1.937, p = 1.33e-50; and spine osteoarthritis: OR = 1.445, 95% CI: 1.314–1.589, p = 2.89e-14). Sensitivity analysis demonstrated the reliability of these results.

Conclusion

Our study suggests that genetically predicted visceral adipose tissue is associated with osteoarthritis. Reducing the accumulation of visceral adipose tissue could potentially have an impact on the incidence of osteoarthritis.
Strengthening the genomic surveillance of Francisella tularensis by using culture-free whole-genome sequencing from biological samples
Authors: Isidro Joana , Escudero Raquel , Luque-Larena Juan José , Pinto Miguel , Borges Vítor , González-Martín-Niño Rosa , Duarte Sílvia , Vieira Luís , Mougeot François , Vidal Dolors , Herrera-Rodríguez Daniel , Rodríguez-Pastor Ruth , Herrero-Cófreces Silvia , Jubete-Tazo Fernando , Gomes João Paulo , Lopes de Carvalho Isabel
Published: January 2024

Introduction

Francisella tularensis is a highly infectious bacterium that causes the zoonotic disease tularemia. The development of genotyping methods, especially those based on whole-genome sequencing (WGS), has recently increased the knowledge on the epidemiology of this disease. However, due to the difficulties associated with the growth and isolation of this fastidious pathogen in culture, the availability of strains and subsequently WGS data is still limited.

Methods

To surpass these constraints, we aimed to implement a culture-free approach to capture and sequence F. tularensis genomes directly from complex samples. Biological samples obtained from 50 common voles and 13 Iberian hares collected in Spain were confirmed as positive for F. tularensis subsp. holarctica and subjected to a WGS target capture and enrichment protocol, using RNA oligonucleotide baits designed to cover F. tularensis genomic diversity.

Results

We obtained full genome sequences of F. tularensis from 13 animals (20.6%), two of which had mixed infections with distinct genotypes, and achieved a higher success rate when compared with culture-dependent WGS (only successful for two animals). The new genomes belonged to different clades commonly identified in Europe (B.49, B.51 and B.262) and subclades. Despite being phylogenetically closely related to other genomes from Spain, the detected clusters were often found in other countries. A comprehensive phylogenetic analysis, integrating 599 F. tularensis subsp. holarctica genomes, showed that most (sub)clades are found in both humans and animals and that closely related strains are found in different, and often geographically distant, countries.

Discussion

Overall, we show that the implemented culture-free WGS methodology yields timely, complete and high-quality genomic data of F. tularensis, being a highly valuable approach to promote and potentiate the genomic surveillance of F. tularensis and ultimately increase the knowledge on the genomics, ecology and epidemiology of this highly infectious pathogen.
Thespesialampas mediated green synthesis of silver and gold nanoparticles for enhanced biological applications
Authors: Nath Sunayana , Shyanti Ritis Kumar , Singh Rana Pratap , Mishra Manoj , Pathak Bhawana
Published: January 2024

The present study investigated the synthesis and biological applications of green, economical, and multifunctional silver and gold nanoparticles (TSAgNPs and TSAuNPs) using the ethnomedical important medicinal plant Thespesia lampas for biological activities. Relatively higher levels of antioxidant components were measured in T. lampas compared to the well-known Adhatoda vasica, and Diplocyclos palmatus suggested the potential of T. lampas for the study. Synthesized TSAgNPs and TSAuNPs were characterized through UV–Vis, XRD, SEM-EDS, HR-TEM, SAED, and FTIR techniques. SEM revealed that TSAgNPs and TSAuNPs were predominantly spherical in shape with 19 ± 7.3 and 43 ± 6.3 nm crystal sizes. The sizes of TSAgNPs and TSAuNPs were found to be12 ± 4.8 and 45 ± 2.9 nm, respectively, according to TEM measurements. The FTIR and phytochemical analyses revealed that the polyphenols and proteins present in T. lampas may act as bio-reducing and stabilizing agents for the synthesis. Synthesized NPs exhibited enhanced scavenging properties for ABTS and DPPH radicals. TSAgNPs and TSAuNPs were able to protect DNA nicking up to 13.48% and 15.38%, respectively, from oxidative stress. TSAgNPs possessed efficient antibacterial activities in a concentration-dependent manner against human pathogenic bacteria, such as E. coli, B. subtilis, P. vulgaris, and S. typhi. Furthermore, TSAgNPs and TSAuNPs showed significant cytotoxicity against FaDu HNSCC grown in 2D at 50 and 100 μg mL−1. Tumor inhibitory effects on FaDu-derived spheroid were significant for TSAgNPs > TSAuNPs at 100 μg mL−1 in 3D conditions. Dead cells were highest largely for TSAgNPs (76.65% ± 1.76%), while TSAuNPs were non-significant, and Saq was ineffectively compared with the control. However, the diameter of the spheroid drastically reduced for TSAgNPs (3.94 folds) followed by TSAuNPs (2.58 folds), Saq (1.94 folds), and cisplatin (1.83 folds) at 100 μg mL−1. The findings of the study suggested the bio-competence of TSAgNPs and TSAuNPs as multi-responsive agents for antioxidants, DNA protection, antibacterial, and anti-tumor activities to provide a better comprehension of the role of phytogenic nanoparticles in healthcare systems.
A multiplex real-time fluorescence-based quantitative PCR assay for calf diarrhea viruses
Authors: Meng Wenxin , Chen Zihan , Jiang Qifeng , Chen Jinping , Guo Xiaoying , Ma Zihang , Jia Kun , Li Shoujun
Published: January 2024

Introduction

Calf diarrhea is a significant condition that has a strong effect on the cattle industry, resulting in huge economic losses annually. Bovine torovirus (BToV), bovine enterovirus (BEV), bovine norovirus (BNoV), bovine coronavirus (BCoV), bovine rotavirus (BRV), and bovine viral diarrhea virus (BVDV) are key pathogens that have been implicated in calf diarrhea. Among these viruses, there remains limited research on BToV, BEV, and BNoV, with no available vaccines or drugs for their prevention and control. Although commercial vaccines exist for BCoV, BRV, and BVDV, the prevalence of these diseases remains high.

Methods

To address this issue, we developed a multiplex real-time fluorescence quantitative PCR method for detecting BToV, BEV, BNoV, BCoV, BRV, and BVDV. This method can be used to effectively monitor the prevalence of these six viruses and serve as a reference for future prevention and control strategies. In this study, we specifically designed primers and probes for the BNoV Rdrp, BEV 5′UTR, BToV M, BCoV N, BRV NSP5, and BVDV 5′UTR genes.

Results

This method was determined to be efficient, stable, and sensitive. The lowest detectable levels of plasmids for BNoV, BEV, BToV, BRV, BCoV, and BVDV were 1.91 copies/μL, 96.0 copies/μL, 12.8 copies/μL, 16.4 copies/μL, 18.2 copies/μL, and 65.3 copies/μL, respectively. Moreover, the coefficients of variation for all six detection methods were < 3%; they also exhibited a strong linear relationship (R2 ≥ 0.98), and an amplification efficiency of 90%−110%. A total of 295 fecal and anal swabs were collected from calves with diarrhea in Guangdong, China. The positive rates for BToV, BEV, BNoV, BCoV, BR, and BVDV were determined to be 0.34% (1/295), 6.10% (18/295), 0.68% (2/295), 1.36% (4/295), 10.85% (32/295), and 2.03% (6/295), respectively. Notably, BEV and BRV exhibited the highest prevalence.

Discussion

Additionally, this study identified the occurrence of BToV and BNoV in Guangdong for the first time. In summary, this study successfully established an effective method for detecting several important bovine viruses; ultimately, this holds strong implications for the future development of the cattle industry.
Toward an understanding of the DNA replication initiation in bacteria
Authors: Wegrzyn Katarzyna , Konieczny Igor
Published: January 2024

Although the mechanism of DNA replication initiation has been investigated for over 50 years, many important discoveries have been made related to this process in recent years. In this mini-review, we discuss the current state of knowledge concerning the structure of the origin region in bacterial chromosomes and plasmids, recently discovered motifs recognized by replication initiator proteins, and proposed in the literature models describing initial origin opening. We review structures of nucleoprotein complexes formed by replication initiators at chromosomal and plasmid replication origins and discuss their functional implications. We also discuss future research challenges in this field.
Evaluation of the antibacterial effect of Epigallocatechin gallate on the major pathogens of canine periodontal disease and therapeutic effects on periodontal disease mice
Authors: Song Peijia , Hao Yibing , Lin Degui , Jin Yipeng , Lin Jiahao
Published: January 2024

Background

Periodontal disease (PD) is a prevalent oral affliction in canines, with limited therapeutic options available. The potential transmission of oral bacteria from canines to humans through inter-species contact poses a risk of zoonotic infection. Epigallocatechin gallate (EGCG), the principal catechin in green tea polyphenols, exhibits antibacterial properties effective against human PD. Given the clinical parallels between canine and human PD, this study explores the feasibility of employing EGCG as a therapeutic agent for canine PD.

Methods and results

Initially, a survey and statistical analysis of bacterial infection data related to canine PD in China were conducted. Subsequently, the primary pathogenic bacteria of canine PD were isolated and cultivated, and the in vitro antibacterial efficacy of EGCG was assessed. Furthermore, verify the therapeutic effect of EGCG on a mouse PD model in vivo. The high-throughput 16S rRNA gene sequencing identified Porphyromonas, Fusobacterium, Treponema, Moraxella, and Capnocytophaga as the genera that distinguishing PD from healthy canines’ gingival crevicular fluid (GCF) samples in China. The anaerobic culture and drug susceptibility testing isolated a total of 92 clinical strains, representing 22 species, from 72 canine GCF samples, including Porphyromonas gulae, Prevotella intermedia, Porphyromonas macacae, etc. The minimum inhibitory concentration (MIC) ranging of EGCG was from 0.019 to 1.25 mg/mL. Following a 7 days oral mucosal administration of medium-dose EGCG (0.625 mg/mL), the abundance of periodontal microorganisms in PD mice significantly decreased. This intervention ameliorated alveolar bone loss, reducing the average cementoenamel junction to the alveolar bone crest (CEJ-ABC) distance from 0.306 mm ± 0.050 mm to 0.161 mm ± 0.026 mm. Additionally, EGCG (0.3125 mg/mL) markedly down-regulated the expression of inflammatory factor IL-6 in the serum of PD mice.

Conclusion

Our research demonstrates the significant antibacterial effects of EGCG against the prevalent bacterium P. gulae in canine PD. Moreover, EGCG exhibits anti-inflammatory properties and proves effective in addressing bone loss in a PD mouse model. These findings collectively suggest the therapeutic potential of EGCG in the treatment of canine PD. The outcomes of this study contribute valuable data, laying the foundation for further exploration and screening of alternative antibiotic drugs to advance the management of canine PD.