bluuebunny/crossref_metadata_2025 huggingface dataset:
Ciguatera en el caribe colombiano: historia y comportamiento 2010–2014
Authors: Borbón Ramos Milena , Borbón Ramos Javier
Published: April 2023

Introducción: la ciguatera es una enfermedad que ocurre por el consumo de algunos peces que viven en regiones tropicales y subtropicales que contienen toxinas producidas por dinoflagelados; estas ingresan a la cadena alimentaria, siendo el ser humano la etapa final, originándose la enfermedad. Cada año se afectan entre 25 000 y 500 000 personas en el mundo causando un impacto a la salud y economía. Objetivo: realizar un análisis de la enfermedad en el caribe colombiano, describir casos, brotes (dos o más casos relacionados) y determinar la incidencia entre 2010 y 2014 en San Andrés y Providencia. Materiales y métodos: se realizó una revisión sistemática de literatura de casos de ciguatera identificados en el país y un estudio descriptivo de los casos y brotes notificados al Sistema de vigilancia de salud pública para San Andrés y Providencia durante 2010 a 2014. Resultados: según la literatura, entre 1968 y 2007 en el caribe colombiano se reportaron más de 80 casos de ciguatera, sin fallecimientos. Entre 2010 a 2014 se notificaron 101 casos y 22 brotes provenientes de San Andrés y Providencia, sin mortalidades asociadas y una incidencia de 17,4 por 100 000 habitantes. Las principales especies de peces asociadas fueron barracuda y jurel; se reportaron signos y síntomas principalmente gastrointestinales y neurológicos. Conclusiones: se identificaron casos de ciguatera notificados en el Sistema de vigilancia en salud pública. Para San Andrés y Providencia se estableció una incidencia similar a la de Islas Caimán y superando otros países del Caribe como Cuba, Jamaica, Belice y Bermudas, entre otros. Las especies de peces identificadas concuerdan con las principales implicadas en otros países. Se recomienda capacitar a entidades territoriales de salud sobre las intoxicaciones por toxinas de algas marinas para la zona Caribe con el fin de fortalecer la notificación del evento y la calidad de los datos.
ОСОБЛИВОСТІ ПРАВОВОГО СТАТУСУ ПОЛІЦЕЙСЬКОГО В УМОВАХ МІЖНАРОДНОГО ВОЄННОГО КОНФЛІКТУ
Authors: Кравченко І. М.
Published: April 2023

У контексті дослідження розглядається проблема визначення правового статусу співробітників Національної поліції України при залученні їх до участі в міжнародному воєнному конфлікті, і, як наслідок цього, виконання не властивих для них функцій щодо вирішення бойових завдань. В умовах правового режиму воєнного стану поліція може бути введена до складу збройних сил сторони, що перебуває у воєнному конфлікті. Водночас ця сторона зобов’язана попередити супротивника про таке рішення. У разі безпосередньої участі в бойових діях такий склад поліції стає законною військовою ціллю нападу для ворога. Тож проблема способу та/або форми оголошення всім іншим сторонам міжнародного збройного конфлікту (про введення органів Національної поліції до сил оборони) безпосередньо впливає на правовий статус поліцейського, перш за все, з огляду на те, як його сприймає/визначає інша сторона конфлікту. Поліцейські, які під час дії воєнного стану, відповідно до норм національного законодавства, беруть безпосередню участь у виконанні завдань територіальної оборони, забезпеченні та здійсненні заходів цього правового режиму, фактично діють у складі окремого роду сил Збройних Сил України, перебувають в оперативному підпорядкуванні військовому командуванню, а відтак, є воюючою стороною, бо залучені до особового складу збройних сил сторони міжнародного збройного конфлікту. У контексті проблеми щодо визначення способу та форми оголошення поліції та інших воєнізованих (напіввоєнних) організацій, що забезпечують охорону порядку, про прирівняння їх до збройних сил (сил оборони) держави всім іншим сторонам воєнного конфлікту (війни та збройного конфлікту), особливо гостро постає питання про законодавчу ініціативу прирівнювання поліцейських до військовослужбовців, а також щодо визнання їх законними комбатантами із введенням воєнного стану та під час їхньої участі у воєнному конфлікті, з детальним опрацюванням відповідних гарантій і компенсацій для співробітників поліції та членів сімей поліцейських.
ВИСНОВОК СПЕЦІАЛІСТА В ІНФОРМАЦІЙНОМУ ЗАБЕЗПЕЧЕННІ КРИМІНАЛЬНОГО ПРОВАДЖЕННЯ
Authors: Лук’янчиков Є. Д. , Лук’янчиков Б. Є. , Микитенко О. Б.
Published: April 2023

Статтю присвячено аналізу нормативного регулювання процесу використання спеціальних знань при формуванні судових доказів. Акцентовано, що запровадження у кримінальне провадження такого джерела доказів як висновок спеціаліста пов’язано з рядом невизначених питань, що стосуються вимог до особи, яка може залучатися як спеціаліст, форми і змісту процесуального документу, яким буде призначатися дослідження спеціалістом, форми і змісту висновку спеціаліста. Досліджено також еволюцію розвитку інституту спеціальних знань, звернено увагу на поступове розширення форм використання спеціальних знань у кримінальному провадженні та їх нормативне закріплення у відповідних статтях КПК. Проведено порівняльний аналіз таких джерел доказів, як висновок спеціаліста і висновок експерта. Це дозволило констатувати умови, за яких висновок спеціаліста може відповідати висновку експерта, що в кінцевому результаті дозволило поставити під сумнів необхідність та доцільність запровадження нового джерела доказів у чинному КПК України. Зазначено, що висновок спеціаліста не може відповідати висновку експерта, оскільки інші вимоги до одержання цих процесуальних документів, які становлять їх процесуальну форму, мають певні відмінності. Запропоновано дозволити проведення експертизи до внесення відомостей в ЄРДР якщо це необхідно для встановлення підстав до початку досудового розслідування.
ПРОБЛЕМИ ВСТАНОВЛЕННЯ ОСОБИ ПІД ЧАС КРИМІНАЛЬНОГО ПРОВАДЖЕННЯ
Authors: Бойко О. П.
Published: April 2023

У статті розглянуто проблеми встановлення особи під час кримінального провадження, анкетні дані якої не відомі; запропоновано шляхи їх вирішення. З огляду на аналіз кримінального процесуального законодавства України, автор акцентує увагу на тому, що однією з обов’язкових умов притягнення до кримінальної відповідальності є встановлення особи. Указано на необхідність доповнення переліку документів, які підтверджують особу, шляхом внесення змін до ч. 1 ст. 13 ЗУ «Про Єдиний державний демографічний реєстр та документи, що підтверджують громадянство України, посвідчують особу чи її спеціальний статус». Запропоновано у відомчих нормативно-правових актах закріпити способи встановлення особи підозрюваного під час кримінального провадження, до яких слід віднести таке: проведення перевірки інформації про особу, згідно з картотеками та базами даних розпорядника Єдиного державного демографічного реєстру, його територіальних органів чи підрозділів; перевірку інформації про особу за базами обліку Національної поліції та Міністерства внутрішніх справ України; дактилоскопіювання особи та перевірку наявності відомостей про неї в автоматизованій дактилоскопічній ідентифікаційній системі «ДАКТО»; проведення перевірки даних відомостей для встановлення особи за місцем проживання, місцем роботи (навчання), судимістю та ін.; використання можливостей інформаційної системи Міжнародної організації кримінальної поліції у випадках, якщо особа є іноземцем. Розглянуто зарубіжний досвід Федеративної республіки Німеччини щодо проблемних питань зі встановлення особи під час кримінального провадження Проаналізовано кримінально-процесуальне законодавство означеної держави для запозичення позитивного досвіду щодо порядку встановлення особи під час кримінального провадження. Запропоновано доповнити Кримінальний процесуальний кодекс України окремою главою з назвою: «Процедура встановлення особи, коли її анкетні дані невідомі», у якій передбачити наступні статті з процедурою встановлення особи в залежності від її статусу у кримінальному провадженні: 1. «Процедура встановлення особи свідка та потерпілого»; 2. «Процедура встановлення особи підозрюваного».
ОСОБЛИВОСТІ ПОЧАТКУ КРИМІНАЛЬНОГО ПРОВАДЖЕННЯ ТА ЕТАПІВ РОЗСЛІДУВАННЯ ЗАХОПЛЕННЯ ПРЕДСТАВНИКА ВЛАДИ АБО ПРАЦІВНИКА ПРАВООХОРОННОГО ОРГАНУ ЯК ЗАРУЧНИКА
Authors: Прокопенко О. Ю.
Published: April 2023

Стаття присвячена аналізу типових питань, що виникають під час розслідування кримінальних правопорушень за фактом захоплення представника влади або працівника правоохоронного органу як заручника. Наведено джерела, що характеризуються найбільшим обсягом первинної інформації про подію, яка відбулася, а також слугують приводами та підставами для порушення кримінального провадження. Наголошено, що на сьогодні, як серед науковців, так і серед практиків, найпопулярнішим підходом з питань організації досудового розслідування кримінальних правопорушень в Україні є ситуаційний підхід. Тобто, з метою ефективної побудови методики розслідування кримінальних правопорушень слід наводити приклади можливих слідчих ситуацій та відповідні їм алгоритми дій. На основі положень криміналістичної тактики, думок науковців та результатів узагальнення судово-слідчої практики досудового розслідування захоплення представника влади або працівника правоохоронного органу як заручника виокремлено найбільш типові слідчі ситуації початкового етапу розслідування: ситуація 1 – особа злочинця відома, він затриманий, заручника звільнено; ситуація 2 – особа злочинця встановлена, але він утік та переховується від правоохоронних органів, заручника звільнено; ситуація 3 – особа злочинця не встановлена, він утік, заручника звільнено; ситуація 4 – особа злочинця не встановлена, він переховується разом із заручником. У результаті аналізу наукових напрацювань і практичної діяльності вважаємо за доцільне на наступному етапі розслідування щодо захоплення представника влади або працівника правоохоронного органу як заручника виділити три слідчі ситуації: перша – особа злочинця затримана, останній провину визнає; друга – особа злочинця затримана, але свою причетність до злочину заперечує; третя – найбільш не сприятлива ситуація, коли особа злочинця встановлена, але не затримана (переховується від правоохоронних органів). Для кожної з наведених ситуацій визначено основні напрямки (завдання) розслідування та запропоновано типові алгоритми дій, необхідні для їх вирішення. Зроблено висновок про те, що врахування зазначених типових слідчих ситуацій надасть органам досудового розслідування можливість визначення напрямків розслідування та встановлення обставин захоплення представника влади або працівника правоохоронного органу як заручника. Звернено увагу на значення взаємодії під час розслідування захоплення представника влади або працівника правоохоронного органу як заручника та наведено перелік суб'єктів взаємодії.
Excessive addition split peak formed by the non-templated nucleotide addition property of Taq DNA polymerase after PCR amplification
Authors: Zhou Yongsong , Bo Fan , Tian Tian , Wu Buling , Zhu Bofeng
Published: April 2023

Because of its non-template addition feature, Taq DNA polymerase can catalyze one or more extra nucleotides onto the 3′ terminus of PCR products. An extra peak is observed at DYS391 locus after the PCR products stored for 4 days at 4°C. To explore the formation mechanism of this artifact, PCR primers and amplicon sequences of Y-STR loci are analyzed, furthermore, PCR products storage conditions and termination of PCR are discussed. The extra peak is a + 2 addition product, which we call excessive addition split peak (EASP). The most significant difference between EASP and the incomplete addition of adenine product is that the size of EASP is about one base larger than the true allele, and the EASP locates on the right side of the real allelic peak. The EASP cannot be eliminated by increasing loading mixture volume and conducting heat denaturation prior to electrophoresis injection. However, the EASP is not observed when the PCR is terminated with ethylenediaminetetraacetic acid or formamide. These findings suggest that formation of EASP is a result of 3′ end non-template extension by Taq DNA polymerase, rather than being the result of DNA fragment secondary structure produced under a suboptimal electrophoresis condition. In addition, the EASP formation is affected by the primer sequences and the storage conditions of PCR products.
Nanomaterials against intracellular bacterial infection: from drug delivery to intrinsic biofunction
Authors: Chen Yinglu , He Xiaoheng , Chen Qiuhong , He Yi , Chen Fangman , Yang Chao , Wang Liang
Published: April 2023

Fighting intracellular bacteria with strong antibiotics evading remains a long-standing challenge. Responding to and regulating the infectious microenvironment is crucial for treating intracellular infections. Sophisticated nanomaterials with unique physicochemical properties exhibit great potential for precise drug delivery towards infection sites, along with modulating infectious microenvironment via their instinct bioactivity. In this review, we first identify the key characters and therapeutic targets of intracellular infection microenvironment. Next, we illustrate how the nanomaterials physicochemical properties, such as size, charge, shape and functionalization affect the interaction between nanomaterials, cells and bacteria. We also introduce the recent progress of nanomaterial-based targeted delivery and controlled release of antibiotics in intracellular infection microenvironment. Notably, we highlight the nanomaterials with unique intrinsic properties, such as metal toxicity and enzyme-like activity for the treatment of intracellular bacteria. Finally, we discuss the opportunities and challenges of bioactive nanomaterials in addressing intracellular infections.
A comprehensive review of the relationship between autophagy and sorafenib-resistance in hepatocellular carcinoma: ferroptosis is noteworthy
Authors: Zhang Kangnan , Zhang Qinghui , Jia Rongrong , Xiang Shihao , Xu Ling
Published: April 2023

Patients with hepatocellular carcinoma (HCC) bear a heavy burden of disease and economic burden but have fewer treatment options. Sorafenib, a multi-kinase inhibitor, is the only approved drug that can be used to limit the progression of inoperable or distant metastatic HCC. However, enhanced autophagy and other molecular mechanisms after sorafenib exposure further induce drug resistance in HCC patients. Sorafenib-associated autophagy also generates a series of biomarkers, which may represent that autophagy is a critical section of sorafenib-resistance in HCC. Furthermore, many classic signaling pathways have been found to be involved in sorafenib-associated autophagy, including the HIF/mTOR signaling pathway, endoplasmic reticulum stress, and sphingolipid signaling, among others. In turn, autophagy also provokes autophagic activity in components of the tumor microenvironment, including tumor cells and stem cells, further impacting sorafenib-resistance in HCC through a special autophagic cell death process called ferroptosis. In this review, we summarized the latest research progress and molecular mechanisms of sorafenib-resistance-associated autophagy in detail, providing new insights and ideas for unraveling the dilemma of sorafenib-resistance in HCC.
Intratumoral microbiome impacts immune infiltrates in tumor microenvironment and predicts prognosis in esophageal squamous cell carcinoma patients
Authors: Zhang Shuyue , Zhang Shuishen , Ma Xiaofan , Zhan Jing , Pan Chuqing , Zhang Huizhong , Xie Xiuying , Wen Jing , Xie Xuan
Published: April 2023

Background

Different intratumoral microbiotaexist in different tumors and play a crucial function in carcinogenesis. However, whether they impact clinical outcomes in esophageal squamous cell carcinoma (ESCC) and their mechanism remain unclear.

Methods

16S rDNA amplicon sequencing was performed on surgically resected samples from 98 ESCC patients to analyze intratumoral microbiome abundance and composition. Multiplex fluorescent immunohistochemistry staining was used to profile the phenotypes of immune infiltrates in the tumor microenvironment (TME).

Results

Patients with higher intratumoral Shannon index had significantly worse surgical outcomes. When patients were divided into short-term survivors and long-term survivors based on the median survival time, both intratumoral alpha-diversity and beta-diversity were found to be significantly inconsistent, and the relative abundance of Lactobacillus and Leptotrichia emerged as the two microorganisms that probably influenced the survival of ESCC patients. Only Lactobacillus in ESCC was validated to significantly worsen patients’ prognoses and to be positively correlated with the Shannon index. Multivariate analysis revealed that the intratumoral Shannon index, the relative abundance of Lactobacillus, and the pathologic tumor–node–metastasis (pTNM) stage were independently associated with patients’ overall survival. Furthermore, the relative abundance of both Lactobacillus and Shannon index was positively correlated with the proportions of PD-L1+ epithelial cells (ECs) and tumor-associated macrophages (TAMs). The Shannon index was negatively correlated with the proportions of natural killer (NK) cells in the TME.

Conclusions

A high abundance of intratumoral Lactobacillus and bacterial alpha-diversity was associated with the formation of the immunosuppressive TME and predicted poor long-term survival in ESCC patients.
Tactile displays for auditory augmentation–A scoping review and reflections on music applications for hearing impaired users
Authors: Paisa Razvan , Nilsson Niels Christian , Serafin Stefania
Published: April 2023

The field of tactile augmentation has progressed greatly over the past 27 years and currently constitutes an emerging area of research, bridging topics ranging from neuroscience to robotics. One particular area of interest is studying the usage of tactile augmentation to provide inclusive musical experiences for deaf or hard-of-hearing individuals. This article details a scoping review that investigates and organizes tactile displays used for the augmentation of music from the field of hearing assistive devices, documented in 63 scientific publications. The focus is on the hardware, software, mapping, and evaluation of these displays, to identify established methods and techniques, as well as potential gaps in the literature. To achieve this purpose, a catalog of devices was created from the available literature indexed in the Scopus® database. We set up a list of 12 descriptors belonging to physical, auditory, perceptual, purpose and evaluation domains; each tactile display identified was categorized based on those. The frequency of use among these descriptors was analyzed and as well as the eventual relationship between them. Results indicate that the field is relatively new, with 80% of the literature indexed being published after 2009. Moreover, most of the research is conducted in laboratories, with limited industry reach. Most of the studies have low reliability due to small sample sizes, and sometimes low validity due to limited access to the targeted population (e.g., evaluating systems designed for cochlear implant users, on normal hearing individuals). When it comes to the tactile displays, the results show that the hand area is targeted by the majority of the systems, probably due to the higher sensitivity afforded by it, and that there are only a couple of popular mapping systems used by the majority of researchers. Additional aspects of the displays were investigated, including the historical distribution of various characteristics (e.g., number of actuators, or actuators type) as well as the sonic material used as input. Finally, a discussion of the current state of the tactile augmentation of music is presented, as well as suggestions for potential future research.
Integrated analysis of the lncRNA-miRNA-mRNA network based on competing endogenous RNA in atrial fibrillation
Authors: Wang Manman , An Guoying , Wang Benxuan , Chen Yuanyuan , Liu Genli , Wang Xin , Liu Shuai , Zhang Daozou , Sun Dandan , Zhang Yanyan , Shen Tong , Li Xiangting
Published: April 2023

Objective

Long non-coding RNAs (lncRNAs) play pivotal roles in the transcriptional regulation of atrial fibrillation (AF) by acting as competing endogenous RNAs (ceRNAs). In the present study, the expression levels of lncRNAs of sinus rhythm (SR) patients and AF patients were investigated with transcriptomics technology, and the lncRNA-miRNA-mRNA network based on the ceRNA theory in AF was elaborated.

Methods

Left atrial appendage (LAA) tissues were obtained from patients with valvular heart disease during cardiac surgery, and they were divided into SR and AF groups. The expression characterizations of differentially expressed (DE) lncRNAs in the two groups were revealed by high-throughput sequencing methods. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed, and the lncRNA-miRNA-mRNA-mediated ceRNA network was constructed.

Results

A total of differentially expressed 82 lncRNAs, 18 miRNAs, and 495 mRNAs in human atrial appendage tissues were targeted. Compared to SR patients, the following changes were found in AF patients: 32 upregulated and 50 downregulated lncRNAs; 7 upregulated and 11 downregulated miRNAs; and 408 upregulated and 87 downregulated mRNAs. A lncRNA-miRNA-mRNA network was constructed, which included 44 lncRNAs, 18 miRNAs, and 347 mRNAs. qRT-PCR was performed to verify these findings. GO and KEGG analyses suggested that inflammatory response, chemokine signaling pathway, and other biological processes play important roles in the pathogenesis of AF. Network analysis based on the ceRNA theory identified that lncRNA XR_001750763.2 and Toll-like receptor 2 (TLR2) compete for binding to miR-302b-3p. In AF patients, lncRNA XR_001750763.2 and TLR2 were upregulated, and miR-302b-3p was downregulated.

Conclusion

We identified a lncRNA XR_001750763.2/miR-302b-3p/TLR2 network based on the ceRNA theory in AF. The present study shed light on the physiological functions of lncRNAs and provided information for exploring potential treatments for AF.
Anti-apoptotic and anti-fibrotic efficacy of exercise training in hypertensive hearts: A systematic review
Authors: Akbar Adjar Yusrandi , Cui Zhen-Yang , Hsu Che-Jui , Li Yan-Zhang , Rahman Ferry Fadzlul , Xia Chunqiu , Yang Ai-Lun , Lee Shin-Da
Published: April 2023

Background

This review aims to summarize the antiapoptotic, pro-survival, and antifibrotic effects of exercise training in hypertensive hearts.

Methods

Keyword searches were conducted in PubMed, Web of Science, and Scopus in May 2021. Research published in English on the effects of exercise training on the apoptosis, survival, and fibrosis pathways in hypertension was included. The CAMARADES checklist was used to determine the quality of the studies. Two reviewers independently implemented predesigned protocols for the search and selection of studies, the assessment of study quality, and the evaluation of the strength of evidence.

Results

Eleven studies were included after selection. The duration of the exercise training ranged from 5 to 27 weeks. Nine studies showed that exercise training improved cardiac survival rates by increasing IGF-1, IGF-1 receptor, p-PI3K, Bcl-2, HSP 72, and p-Akt. Furthermore, 10 studies showed that exercise training reduced apoptotic pathways by downregulating Bid, t-Bid, Bad, Bak, Bax, TNF, and FADD. Finally, two studies reported the modification and subsequent improvement of physiological characteristics of fibrosis and decreased MAPK p38 and PTEN levels by exercise training in the left ventricle of the heart.

Conclusions

The findings of the review showed that exercise training could improve cardiac survival rates and attenuate cardiac apoptotic and fibrotic pathways in hypertension, suggesting that exercise training could act as a therapeutic approach to prevent hypertension-induced cardiac apoptosis and fibrosis.

Systematic Review Registration

https://www.crd.york.ac.uk, identifier: CRD42021254118.
A novel risk stratification model for STEMI after primary PCI: global longitudinal strain and deep neural network assisted myocardial contrast echocardiography quantitative analysis
Authors: Li Mingqi , Zeng Dewen , Zhou Yanxiang , Chen Jinling , Cao Sheng , Song Hongning , Hu Bo , Yuan Wenyue , Chen Jing , Yang Yuanting , Wang Hao , Fei Hongwen , Shi Yiyu , Zhou Qing
Published: April 2023

Background

In ST-segment elevation myocardial infarction (STEMI) with the restoration of TIMI 3 flow by percutaneous coronary intervention (PCI), visually defined microvascular obstruction (MVO) was shown to be the predictor of poor prognosis, but not an ideal risk stratification method. We intend to introduce deep neural network (DNN) assisted myocardial contrast echocardiography (MCE) quantitative analysis and propose a better risk stratification model.

Methods

194 STEMI patients with successful primary PCI with at least 6 months follow-up were included. MCE was performed within 48 h after PCI. The major adverse cardiovascular events (MACE) were defined as cardiac death, congestive heart failure, reinfarction, stroke, and recurrent angina. The perfusion parameters were derived from a DNN-based myocardial segmentation framework. Three patterns of visual microvascular perfusion (MVP) qualitative analysis: normal, delay, and MVO. Clinical markers and imaging features, including global longitudinal strain (GLS) were analyzed. A calculator for risk was constructed and validated with bootstrap resampling.

Results

The time-cost for processing 7,403 MCE frames is 773 s. The correlation coefficients of microvascular blood flow (MBF) were 0.99 to 0.97 for intra-observer and inter-observer variability. 38 patients met MACE in 6-month follow-up. We proposed A risk prediction model based on MBF [HR: 0.93 (0.91–0.95)] in culprit lesion areas and GLS [HR: 0.80 (0.73–0.88)]. At the best risk threshold of 40%, the AUC was 0.95 (sensitivity: 0.84, specificity: 0.94), better than visual MVP method (AUC: 0.70, Sensitivity: 0.89, Specificity: 0.40, IDI: −0.49). The Kaplan-Meier curves showed that the proposed risk prediction model allowed for better risk stratification.

Conclusion

The MBF + GLS model allowed more accurate risk stratification of STEMI after PCI than visual qualitative analysis. The DNN-assisted MCE quantitative analysis is an objective, efficient and reproducible method to evaluate microvascular perfusion.
Digital capital and belonging in universities: quantifying social inequalities in the Philippines
Authors: Clamor Wilfred Luis , Saloma Czarina
Published: April 2023

This study examines social inequalities in Philippine universities that were exacerbated during the COVID-19 pandemic. A quantitative approach using a national sample of 677 university students was utilized to measure the mediating role of digital capital on social inequalities associated with belonging to academic spaces. For the purpose of determining direct and indirect impacts, structural equation modeling (SEM) was employed. Sociodemographic (i.e., gender, age, type of residence, and family income) and educational (i.e., type of university, year in the university, and excellence criterion) characteristics were the direct predictors that were examined as exogenous variables for both digital capital and belonging. Results indicate that type of residence (β=0.200, p<0.05), family income (β=0.220, p <0.001), and excellence criterion (β=0.271, p <0.01) are major determinants of digital capital. The model also shows that belonging is significantly predicted by age (β=0.087, p <0.05), family income (β=-0.207, p <0.001), and digital capital (β=0.576, p <0.001). Lastly, the findings reveal that the impacts of type of residence (β=0.116, p <0.05), family income (β=0.127, p <0.001), and excellence criterion (β=0.156, p <0.001) on belonging are successfully mediated by digital capital. These results suggest that there are indeed differences in students’ abilities to accumulate digital capital and that digital capital enhances the sense of belonging to and together in academic spaces for certain groups.
Sequential biomolecular, macrofossil, and microfossil extraction from coprolites for reconstructing past behavior and environments
Authors: Blong John C. , Whelton Helen L. , van Asperen Eline N. , Bull Ian D. , Shillito Lisa-Marie
Published: April 2023

The study of macroscopic, microscopic, and biomolecular remains recovered from coprolites can provide a wide range of information on past human and animal behavior and environments. In earlier studies, research tended to focus on one or two proxies, but multiproxy approaches combining data from all remains within coprolites are becoming more common. Multiproxy analyses have demonstrated value for strengthening our understanding of the past and reducing equifinality. Here we present a sequential biomolecular, macrofossil, and microfossil extraction protocol that separates all different coprolite components and is intended as a best-practice guideline for coprolite analysis. We demonstrate the effectiveness of this method by applying it to an assemblage of coprolites from the Paisley Caves, Oregon, USA. By combining a wide range of proxies, this study provides important information on the taxonomy and behavior of organisms in the past as well as the paleoecological context of behavior.
Survive the north: transplantation for conservation of mangrove forests requires consideration of influences of low temperature, mating system and their joint effects on effective size of the reforested populations
Authors: Lu Wen-Xun , Zhang Bing-Huang , Yang Sheng-Chang
Published: April 2023

Mangrove forests, which occur in the intertidal regions of tropical and sub-tropical zones, have high ecological and economic values. They have rapidly reduced over the past decades due to various reasons. Reforestation is a common strategy for the conservation of mangroves, but information on the renewal capacity and viability of these artificial mangrove populations is still lacking. Here, we estimated the effective population size (NE) of an artificial population of Kandelia obovata (Rhizophoraceae) and explored the effects of intrinsic and extrinsic factors on changes in NE to evaluate population viability and develop appropriate management strategies for mangrove forests. This population consisted of three ecologically and genetically differentiated groups that had experienced a major low-temperature event during the winter of 2015–2016 and varied in cold resistance. We first detected population bottlenecks and estimated contemporary values of NE for different groups using microsatellite data. Next, we performed paternity analyses for seedlings and propagules to explore variations in the reproductive success of individuals within the three groups before and after the low-temperature event. Lastly, we simulated four scenarios to characterize the effects of low temperature, mating system, and variance in reproductive success on changes in NE in a hypothetical metapopulation based on empirical estimates. Our results show that groups with moderate or poor cold resistance experienced local bottlenecks, and shifts in effective breeders occurred following the low-temperature event, which indicates that low temperature has an effect on not only population size but also reproductive success. Furthermore, our simulations revealed that changes in NE are jointly affected by reproductive success, mating system, and environmental conditions. These findings enhance our understanding of the multiple factors that affect NE, and provide key information that will aid the reforestation and management of mangrove forests, especially when they are introduced to high-latitude areas.
Klf4 protects thymus integrity during late pregnancy
Authors: Depoërs Lucyle , Dumont-Lagacé Maude , Trinh Vincent Quoc-Huy , Houques Chloé , Côté Caroline , Larouche Jean-David , Brochu Sylvie , Perreault Claude
Published: April 2023

Pregnancy causes abrupt thymic atrophy. This atrophy is characterized by a severe decrease in the number of all thymocyte subsets and qualitative (but not quantitative) changes in thymic epithelial cells (TECs). Pregnancy-related thymic involution is triggered by progesterone-induced functional changes affecting mainly cortical TECs (cTECs). Remarkably, this severe involution is rapidly corrected following parturition. We postulated that understanding the mechanisms of pregnancy-related thymic changes could provide novel insights into signaling pathways regulating TEC function. When we analyzed genes whose expression in TECs was modified during late pregnancy, we found a strong enrichment in genes bearing KLF4 transcription factor binding motifs. We, therefore, engineered a Psmb11-iCre : Klf4lox/lox mouse model to study the impact of TEC-specific Klf4 deletion in steady-state conditions and during late pregnancy. Under steady-state conditions, Klf4 deletion had a minimal effect on TEC subsets and did not affect thymic architecture. However, pregnancy-induced thymic involution was much more pronounced in pregnant females lacking Klf4 expression in TECs. These mice displayed a substantial ablation of TECs with a more pronounced loss of thymocytes. Transcriptomic and phenotypic analyses of Klf4-/- TECs revealed that Klf4 maintains cTEC numbers by supporting cell survival and preventing epithelial-to-mesenchymal plasticity during late pregnancy. We conclude that Klf4 is essential for preserving TEC’s integrity and mitigating thymic involution during late pregnancy.
Highly reliable GIGA-sized synthetic human therapeutic antibody library construction
Authors: Huang Chao-Yang , Lok Ying-Yung , Lin Chia-Hui , Lai Szu-Liang , Wu Yen-Yu , Hu Chih-Yung , Liao Chu-Bin , Ho Chen-Hsuan , Chou Yu-Ping , Hsu Yi-Hsuan , Lo Yu-Hsun , Chern Edward
Published: April 2023

Background

Monoclonal antibodies (mAbs) and their derivatives are the fastest expanding category of pharmaceuticals. Efficient screening and generation of appropriate therapeutic human antibodies are important and urgent issues in the field of medicine. The successfulin vitrobiopanning method for antibody screening largely depends on the highly diverse, reliable and humanized CDR library. To rapidly obtain potent human antibodies, we designed and constructed a highly diverse synthetic human single-chain variable fragment (scFv) antibody library greater than a giga in size by phage display. Herein, the novel TIM-3-neutralizing antibodies with immunomodulatory functions derived from this library serve as an example to demonstrate the library’s potential for biomedical applications.

Methods

The library was designed with high stability scaffolds and six complementarity determining regions (CDRs) tailored to mimic human composition. The engineered antibody sequences were optimized for codon usage and subjected to synthesis. The six CDRs with variable length CDR-H3s were individually subjected to β-lactamase selection and then recombined for library construction. Five therapeutic target antigens were used for human antibody generationviaphage library biopanning. TIM-3 antibody activity was verified by immunoactivity assays.

Results

We have designed and constructed a highly diverse synthetic human scFv library named DSyn-1 (DCB Synthetic-1) containing 2.5 × 1010phage clones. Three selected TIM-3-recognizing antibodies DCBT3-4, DCBT3-19, and DCBT3-22 showed significant inhibition activity by TIM-3 reporter assays at nanomolar ranges and binding affinities in sub-nanomolar ranges. Furthermore, clone DCBT3-22 was exceptionally superior with good physicochemical property and a purity of more than 98% without aggregation.

Conclusion

The promising results illustrate not only the potential of the DSyn-1 library for biomedical research applications, but also the therapeutic potential of the three novel fully human TIM-3-neutralizing antibodies.
Serum cytokine and chemokine profiles and disease prognosis in hepatitis B virus-related acute-on-chronic liver failure
Authors: Zhu Bingbing , Gao Fangyuan , Li Yuxin , Shi Ke , Hou Yixin , Chen Jialiang , Zhang Qun , Wang Xianbo
Published: April 2023

Background

Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) has significant morbidity and mortality and is associated with the induction of cytokines/chemokines, which might contribute to the pathogenesis of liver injury. This study aimed to explore the cytokine/chemokine profiles of patients with HBV-ACLF and develop a composite clinical prognostic model.

Methods

We prospectively collected blood samples and the clinical data of 107 patients with HBV-ACLF admitted to the Beijing Ditan Hospital. The concentrations of 40-plex cytokines/chemokines were measured in 86 survivors and 21 non-survivors using the Luminex assay. Discrimination between the cytokine/chemokine profiles in different prognosis groups was analyzed using the multivariate statistical techniques of principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA). An immune-clinical prognostic model was obtained using multivariate logistic regression analysis.

Results

The PCA and PLS-DA indicated that cytokine/chemokine profiling could clearly distinguish patients with different prognoses. A total of 14 cytokines, namely, IL-1β, IL-6, IL-8, IL-10, TNF-α, IFN-γ, CXCL1, CXCL2, CXCL9, CXCL13, CX3CL1, GM-SCF, CCL21, and CCL23, were significantly correlated with disease prognosis. Multivariate analysis identified CXCL2, IL-8, total bilirubin, and age as independent risk factors that constituted the immune-clinical prognostic model, which showed the strongest predictive value of 0.938 compared with those of the Chronic Liver Failure Consortium (CLIF-C) ACLF (0.785), Model for End-Stage Liver Disease (MELD) (0.669), and MELD-Na (0.723) scores (p < 0.05 for all).

Conclusion

The serum cytokine/chemokine profiles correlated with the 90-day prognosis of patients with HBV-ACLF. The proposed composite immune-clinical prognostic model resulted in more accurate prognostic estimates than those of the CLIF-C ACLF, MELD, and MELD-Na scores.
Prediction of liver cancer prognosis based on immune cell marker genes
Authors: Liu Jianfei , Qu Junjie , Xu Lingling , Qiao Chen , Shao Guiwen , Liu Xin , He Hui , Zhang Jian
Published: April 2023

Introduction

Monitoring the response after treatment of liver cancer and timely adjusting the treatment strategy are crucial to improve the survival rate of liver cancer. At present, the clinical monitoring of liver cancer after treatment is mainly based on serum markers and imaging. Morphological evaluation has limitations, such as the inability to measure small tumors and the poor repeatability of measurement, which is not applicable to cancer evaluation after immunotherapy or targeted treatment. The determination of serum markers is greatly affected by the environment and cannot accurately evaluate the prognosis. With the development of single cell sequencing technology, a large number of immune cell-specific genes have been identified. Immune cells and microenvironment play an important role in the process of prognosis. We speculate that the expression changes of immune cell-specific genes can indicate the process of prognosis.

Method

Therefore, this paper first screened out the immune cell-specific genes related to liver cancer, and then built a deep learning model based on the expression of these genes to predict metastasis and the survival time of liver cancer patients. We verified and compared the model on the data set of 372 patients with liver cancer.

Result

The experiments found that our model is significantly superior to other methods, and can accurately identify whether liver cancer patients have metastasis and predict the survival time of liver cancer patients according to the expression of immune cell-specific genes.

Discussion

We found these immune cell-specific genes participant multiple cancer-related pathways. We fully explored the function of these genes, which would support the development of immunotherapy for liver cancer.
Sperm activate TLR2/TLR1 heterodimerization to induce a weak proinflammatory response in the bovine uterus
Authors: Mansouri Alireza , Yousef Mohamed Samy , Kowsar Rasoul , Usui Nonoka , Akthar Ihshan , Miyamoto Akio
Published: April 2023

Toll-like receptor 2 (TLR2) signaling pathway is involved in the sperm-triggered uterine inflammatory response at insemination, but its precise mechanism at molecular-level remains unknown. According to the ligand specificity, TLR2 forms a heterodimer with TLR1 or TLR6 as an initial step to mediate intracellular signaling, leading to a specific type of immune response. Hence, the present study aimed to identify the active TLR2 heterodimer (TLR2/1 or TLR2/6) that is involved in sperm-uterine immune crosstalk in bovine using various models. First, in-vitro (bovine endometrial epithelial cells, BEECs) and ex-vivo (bovine uterine explant) models were employed to test different TLR2 dimerization pathways in endometrial epithelia after exposure to sperm or TLR2 agonists; PAM3 (TLR2/1 agonist), and PAM2 (TLR2/6 agonist). Additionally, in-silico approaches were performed to confirm the dimer stability using de novo protein structure prediction model for bovine TLRs. The in-vitro approach revealed that sperm triggered the mRNA and protein expression of TLR1 and TLR2 but not TLR6 in BEECs. Moreover, this model disclosed that activation of TLR2/6 heterodimer, triggers a much stronger inflammatory response than TLR2/1 and sperm in bovine uterine epithelia. In the ex-vivo model that mimics the intact uterine tissue at insemination, sperm also induced the protein expression of both TLR1 and TLR2, but not TLR6, in bovine endometrium, particularly in uterine glands. Importantly, PAM3 and sperm induced similar and low mRNA expression of pro-inflammatory cytokines and TNFA protein to a lesser extent than PAM2 in endometrial epithelia. This implied that sperm might trigger a weak inflammatory response via TLR2/TLR1 activation which is similar to that of PAM3. Additionally, the in-silico analyses showed that the existence of bridging ligands is essential for heterodimer stability in bovine TLR2 with either TLR1 or TLR6. Altogether, the present findings revealed that sperm utilize TLR2/1, but not TLR2/6, heterodimerization to trigger a weak physiological inflammatory response in the bovine uterus. This might be the way to remove excess dead sperm remaining in the uterine lumen without tissue damage for providing an ideal uterine environment for early embryo reception and implantation.
Effects of obesity with reduced 25(OH)D levels on bone health in elderly Chinese people: a nationwide cross-sectional study
Authors: Yuan Chunchun , Wang Jing , Zhang Weiqiang , Yi Honggang , Shu Bing , Li Chenguang , Liang Qianqian , Liang De , Chen Bolai , Xie Xingwen , Lin Xinchao , Wei Xu , Wang Hui , Chen Peizhan , Huang Chen , Xu Hao , Sun Yueli , Zhao Yongjian , Shi Qi , Tang Dezhi , Wang Yongjun
Published: April 2023

Background

Obesity is often accompanied by lower 25(OH)D levels, whereas these two parameters exhibit opposite effects on bone health. It is uncertain what are the effects of lower 25(OH)D levels in obesity on bone health in elderly Chinese people.

Methods

A nationally representative cross-sectional analysis of China Community-based Cohort of Osteoporosis (CCCO) was performed from 2016 to 2021, which consisted of 22,081 participants. Demographic data, disease history, Body mass index (BMI), bone mineral density (BMD), the levels of the biomarkers of vitamin D status and those of bone metabolism markers were measured for all participants (N = 22,081). The genes (rs12785878, rs10741657, rs4588, rs7041, rs2282679 and rs6013897) related to 25(OH)D transportation and metabolism were performed in a selected subgroup (N = 6008).

Results

Obese subjects exhibited lower 25(OH)D levels (p < 0.05) and higher BMD (p < 0.001) compared with those of normal subjects following adjustment. The genotypes and allele frequency of rs12785878, rs10741657, rs6013897, rs2282679, rs4588 and rs7041 indicated no significant differences among three BMI groups following correction by the Bonferroni’s method (p > 0.05). The levels of total 25(OH)D (ToVD) were significantly different among the GC1F, GC1S and GC2 haplotype groups (p < 0.05). Correlation analysis indicated that ToVD levels were significantly correlated with parathyroid hormone levels, BMD, risk of osteoporosis (OP) and the concentration levels of other bone metabolism markers (p < 0.05). Generalized varying coefficient models demonstrated that the increasing BMI, ToVD levels and their interactions were positively associated with BMD outcomes (p < 0.001), whereas the reduced levels of ToVD and BMI increased the risk of OP, which was noted notably for the subjects with reduced ToVD levels (less than 20.69 ng/ml) combined with decreased BMI (less than 24.05 kg/m2).

Conclusion

There was a non-linear interaction of BMI and 25(OH)D. And higher BMI accompanied by decreased 25(OH)D levels is associated with increased BMD and decreased incidence of OP, optimal ranges exist for BMI and 25(OH)D levels. The cutoff value of BMI at approximately 24.05 kg/m2 combined with an approximate value of 25(OH)D at 20.69 ng/ml are beneficial for Chinese elderly subjects.
Mouse models of pemphigus: valuable tools to investigate pathomechanisms and novel therapeutic interventions
Authors: Emtenani Shirin , Hertl Michael , Schmidt Enno , Hudemann Christoph
Published: April 2023

Autoimmune blistering diseases (AIBD) are paradigms of autoantibody-mediated organ-specific autoimmune disorders that involve skin and/or mucous membranes. Compared to other autoimmune diseases, the pathogenicity of autoantibodies in AIBD is relatively well described. Pemphigus is a potentially lethal autoantibody driven autoimmune disorder with a strong HLA class II association. It is mainly characterized by IgG against the desmosomal adhesion molecules desmoglein 3 (Dsg3) and Dsg1. Several murine pemphigus models were developed subsequently, each allowing the analysis of a characteristic feature, such as pathogenic IgG or Dsg3-specific T or B cells. Thus, the models can be employed to preclinically evaluate potentially novel therapies. We here thoroughly summarize past and recent efforts in developing and utilizing pemphigus mouse models for pathomechanistic investigation and therapeutic interventions.
Integrative single-cell RNA sequencing and metabolomics decipher the imbalanced lipid-metabolism in maladaptive immune responses during sepsis
Authors: She Han , Tan Lei , Wang Yi , Du Yuanlin , Zhou Yuanqun , Zhang Jun , Du Yunxia , Guo Ningke , Wu Zhengbin , Li Qinghui , Bao Daiqin , Mao Qingxiang , Hu Yi , Liu Liangming , Li Tao
Published: April 2023

Background

To identify differentially expressed lipid metabolism-related genes (DE-LMRGs) responsible for immune dysfunction in sepsis.

Methods

The lipid metabolism-related hub genes were screened using machine learning algorithms, and the immune cell infiltration of these hub genes were assessed by CIBERSORT and Single-sample GSEA. Next, the immune function of these hub genes at the single-cell level were validated by comparing multiregional immune landscapes between septic patients (SP) and healthy control (HC). Then, the support vector machine-recursive feature elimination (SVM-RFE) algorithm was conducted to compare the significantly altered metabolites critical to hub genes between SP and HC. Furthermore, the role of the key hub gene was verified in sepsis rats and LPS-induced cardiomyocytes, respectively.

Results

A total of 508 DE-LMRGs were identified between SP and HC, and 5 hub genes relevant to lipid metabolism (MAPK14, EPHX2, BMX, FCER1A, and PAFAH2) were screened. Then, we found an immunosuppressive microenvironment in sepsis. The role of hub genes in immune cells was further confirmed by the single-cell RNA landscape. Moreover, significantly altered metabolites were mainly enriched in lipid metabolism-related signaling pathways and were associated with MAPK14. Finally, inhibiting MAPK14 decreased the levels of inflammatory cytokines and improved the survival and myocardial injury of sepsis.

Conclusion

The lipid metabolism-related hub genes may have great potential in prognosis prediction and precise treatment for sepsis patients.