bluuebunny/crossref_metadata_2025 huggingface dataset:
A Covid-19-fertőzés neuropszichiátriai szövődményei
Authors: Frecska Ede , Balla Petra
Published: August 2021

A Covid-19-fertőzés vizsgálata kezdetben – amely leginkább az akut és viszonylag behatárolható időtartamú szomatikus tüneteket jelentette – a pandémia terjedése folyamán kiterjedt az elhúzódó, szövődményként értelmezhető tünetekre is. Gyűlnek az adatok a keringést, légzést, véralvadást érintő, valamint a reumatológiai, a bőrgyógyászati, a szemészeti következményekre vonatkoztatva csakúgy, mint a központi idegrendszeri elváltozások okozta akut és elhúzódó tünetekkel kapcsolatban. Eleinte szórványos esetközlések, majd populációs vizsgálatok, állatmodellek eredményei voltak olvashatók, a közlemény írásakor pedig már rendszerezést ígérő, áttekintő írások is megjelentek. A központi idegrendszerben okozott elváltozások megnyilvánulhatnak neurológiai tünetekben, megbetegedésekben, és pszichiátriai panaszokban, szindrómákban egyaránt. A tüneti skála széles, a patomechanizmust még nem térképezték fel tökéletesen; ebből fakadóan a terápiás próbálkozások még gyerekcipőben járnak. A neu­ropszichiátriai szövődmények epidemiológiai adatai egyelőre hiányosak, de gyors ütemben pontosodnak. Mértéktartó becslések szerint is több tízmillió személy érintettségét feltételezik világszerte. Az elhúzódó tünetek gyógyulásának vagy perzisztálásának megítéléséhez még nem telt el elég idő. Mindezek miatt jelenleg a legfontosabb feladat a vírusterjedés minél hatékonyabb megakadályozásán túl a vírus okozta központi idegrendszeri kórfolyamatok mind pontosabb megismerése és hatékony terápiájuk kidolgozása. Jelenlegi ismereteink szerint a neuropszichiátriai szö­vődmények patomechanizmusa multifaktoriális. A vírus közvetlen neuron- és gliaműködést károsító hatásán túlmenően sokkal inkább számolnunk kell az agyi keringészavar, a hiányos oxigenizáció ká­ros következményeivel, valamint kiterjedt szisztémás, elhúzódó immunfolyamatokkal, amelyek kimutatható módon károsítják az agyszövetet, beleértve a neuronokat, axonokat, szinapszisokat és a gliasejteket is. Az említett mechanizmusokat részletezi a cikk nem szisztematikus irodalmi áttekintés formájában, ugyanakkor kitér a terápiás lehetőségekre is.
A GLP-receptor-agonisták alkalmazásának potenciális előnyei Covid-19-járvány idején
Authors: Kis János Tibor , Grósz Andrea , Schandl László
Published: August 2021

Cukorbetegségben fokozott a SARS-CoV-2-fertőződés esélye, és a betegség lefolyása is súlyosabb. Az alapbetegséghez társuló el­hízás és cardiovascularis betegség szintén súlyosbítja a fertőzés kimenetelének prognózisát. A 2-es típusú cukorbetegség ke­ze­lésére használt glükagonszerű peptid-1-receptor-agonisták (GLP1-RA) erőteljesen, a hypoglykaemia kockázatának jelentős növelése nélkül csökkentik a vércukorszintet, hozzásegítik a betegeket a fogyáshoz, és csökkentik a cardiovascularis betegségek kialakulásának, rosszabbo­dá­sá­nak va­ló­színűségét. Számos hatásuk révén mint­egy felkészítik a cukorbetegeket arra, hogy SARS-CoV-2-fertőzés esetén kevesebb szövődménnyel vészeljék át a betegséget, és kedvező immunológiai hatásuk miatt a citokinvihar kifejlődését is mérsé­ke­lik. A szer­zők összefoglalják a GLP1-RA-k potenciális kedvező hatását a SARS-CoV-2-fertőzésre.
ПРАВОВІ ЗАСАДИ ОРГАНІЗАЦІЇ ТА ЗДІЙСНЕННЯ ГОСПОДАРСЬКОЇ ДІЯЛЬНОСТІ В УМОВАХ ПАНДЕМІЇ COVID-19
Authors: Попова Л.М. , Нестеренко О.В.
Published: August 2021

У статті вказано, які саме загрози зараження коронавірусною хворобою існують для населення, та обґрунтовано необхідність забезпечення державою заходів щодо організації та здійснення господарської діяльності в умовах пандемії COVID-19. Проаналізовано чинне законодавство щодо наявності дієвих програм, покликаних допомогти населенню на кожному етапі коригування протиепідемічних заходів з урахуванням особливостей поточної ситуації в країні. Проведено аналіз профілактичних заходів, що проводяться в Україні суб’єктами господарювання під час здійснення господарської діяльності задля уникнення зараження коронавірусною хворобою. Обґрунтовано необхідність запровадження комплексної системи захисту вітчизняної економіки від наслідків пандемії, розробки та втілення ефективної безпекової стратегії України в умовах нових глобальних біологічних викликів.
КРИМІНАЛІСТИЧНА КЛАСИФІКАЦІЯ КРИМІНАЛЬНИХ ПРАВОПОРУШЕНЬ ПРОТИ ДОВКІЛЛЯ
Authors: Снітко Д.І.
Published: August 2021

Стаття присвячена проблемі криміналістичної класифікації кримінальних правопорушень проти довкілля. Проведено аналіз особливостей зазначених кримінальних правопорушень, з огляду на кримінально-правові та криміналістичні складові.Викладені аргументи щодо необхідності об’єднання кримінально-правових та криміналістичних критеріїв класифікації. Як нововведення, представлений варіант криміналістичної класифікації вищезгаданих злочинних діянь, відповідно до якого основним класифікаційним критерієм виступають типові судові експертизи, що можуть призначатися в процесі досудового розслідування.
СПІВВІДНОШЕННЯ СУДОВОГО ТА ВІДОМЧОГО КОНТРОЛІВ ЗА ДІЯЛЬНІСТЮ ПРИВАТНИХ ВИКОНАВЦІВ У МЕХАНІЗМІ ЗАБЕЗПЕЧЕННЯ ПРАВ ОСОБИ
Authors: Верба-Сидор О. Б.
Published: August 2021

У статті автором розглянуто і досліджено правову природу та предмет, відповідно до судового та відомчого контролів, за діяннями приватних виконавців. Доведено, що процесуальні діяння приватного виконавця, вчинені в ході примусового виконання рішення як завершальної стадії юридичного процесу, відповідно до Закону України «Про виконавче провадження», є предметом виключно судового контролю. Автором акцентовано увагу, що предметом відомчого контролю Міністерства юстиції України є сфера організації діяльності приватних виконавців – обов’язки, передбачені Законом України «Про органи та осіб, які здійснюють примусове виконання судових рішень і рішень інших органів», а не їхні процесуальні діяння в ході виконавчого провадження. Зроблено висновок, що виключно суд наділений повноваженнями щодо перевірки законності процесуальних діянь ПВ лише за умови надходження від сторін (учасників) виконавчого провадження скарг.
ЗАВДАННЯ ТА ФУНКЦІЇ IP-СУДУ ЯК СУБ’ЄКТА РЕАЛІЗАЦІЇ ДЕРЖАВНОЇ ПОЛІТИКИ У СФЕРІ ІНТЕЛЕКТУАЛЬНОЇ ВЛАСНОСТІ В УКРАЇНІ
Authors: Воловик С. В.
Published: August 2021

У статті досліджено завдання та функції IP-суду як суб’єкта реалізації державної політики у сфері інтелектуальної власності в Україні. Запропоновано авторське розуміння таких понять: «завдання IP-суду як суб’єкта реалізації державної політики у сфері інтелектуальної власності» та «функції IP-суду як суб’єкта реалізації державної політики у сфері інтелектуальної власності». Наголошено на перспективах закріплення авторського переліку завдань та функцій IP-суду як суб’єкта реалізації державної політики у сфері інтелектуальної власності.
Особливості соціально-економічного становища Волинської губернії під час Першої світової війни
Authors: Kovshun Nataliia , Mazur Nataliia , Tsetsyk Jaroslav
Published: August 2021

У розвідці досліджено особливості соціально-економічного становища Волинської губернії під час Першої світової війни. Проаналізовано ключові фактори, які вплинули на погіршення рівня життя населення регіону, насамперед незаможних верств. Встановлено, що в результаті відступу російських військ у 1915 р. на Волині було проведено не лише евакуацію державних установ, підприємств, середніх навчальних закладів, а й примусово виселялося місцеве населення з прифронтових повітів. Така діяльність імперської влади призвела до зубожіння величезної кількості жителів регіону. Окрема увага приділена ролі органів міського самоуправління та земств у регулюванні цін на товари першої необхідності та наданні допомоги біженцям.
Епідеміологічна ситуація в Одесі у добу Гетьманату (по матеріалам одеських газет 1918 р.)
Authors: Kiazymova Halyna
Published: August 2021

На основі аналізу одеської періодичної преси 1918 року розкрита санітарно-епідеміологічна ситуація в місті доби Гетьманату та спалах епідемії холери й «іспанки» у 1918 р. В умовах ще слабкої державної влади, війни та німецько-австрійської окупації центральний уряд не залишається осторонь, мобілізуючи організаційні та матеріальні можливості. Одеська міська влада та медичний персонал стають головною силою опору небезпеці, активно використовуючи усі доступні медичні, профілактичні та санітарні заходи.
Роль закарпатської політичної та духовної еліти у проголошенні «Карпатської України»
Authors: Sinitskyi Andrii
Published: August 2021

У статті досліджено участь закарпатської політичної та духовної еліти у процесі проголошення, розбудови й захисту Карпатської України. Спираючись на принципи історизму, а також комплексності та наукової об’єктивності, автор статті здійснив осмислення конкретно-історичних передумов формування закарпатської політичної та духовної еліти у геополітичних процесах початку ХХ ст. Окреслено детермінуючі фактори, що спричинили особливості політичної диференціації та суспільної сегментації політичної еліти Закарпаття досліджуваного періоду, на основі чого здійснено характеристику сегментного складу та функціональних особливостей політичної й духовної еліти Закарпаття у період між двома світовими війнами.
Міністри-мусульмани у французьких урядах (2012-2017)
Authors: Sypko Bohdana
Published: August 2021

У статті, на основі офіційного державного друкованого органу «Journal officiel de la République Française», звітів Сенату та Національної Асамблеї, матеріалів виступів, інтерв’ю та мемуарів проаналізовано склади французьких урядів періоду президентства Ф. Олланда та простежено, яку роль у них відігравали мусульмани. З’ясовано, що концептуальною для Ф. Олланда була злагодженість уряду, тому більшість міністрів-мусульман були членами Соціалістичної партії. Троє з чотирьох політиків народилися не у Франції, половина зберегла подвійне громадянство. Тому у риториці апелювали до культурного, релігійного й етнічного різноманіття Республіки, а питання історії, політики пам’яті, світськості, боротьби проти усіх форм дискримінації були ключовими.
Каталонські референдуми 2014 р. та 2017 р.: позиції центральної та регіональної влади
Authors: Hutsalo Liudmyla , Mishchuk Galyna
Published: August 2021

У статті вивчено сучасну політичну ситуацію в Іспанії, динаміку каталонського конфлікту, увагу акцентовано на незаконних, з точки зору іспанської влади, референдумах про незалежність Каталонії 2014 і 2017 років, здійснено їхню порівняльну характеристику. У ході аналізу зроблено спробу пояснення, чому каталонські референдуми були по-різному осмислені регіональними політичними лідерами. Увагу зосереджено на дослідженні засобів і методів протидії центральної влади у Мадриді сецесійним проявам в автономному співтоваристві Каталонія.
«Епоха вікінгів»: сутність та основні підходи до вивчення
Authors: Zhyriakov Kostiantyn
Published: August 2021

У статті розглянуто сутність дефініції «Епоха вікінгів» в історичній науці. Проаналізовано способи генезису та інтерпретації дефініції в історіографії.

Виявлено взаємозв’язок між методом інтерпретації дефініції та науковим підходом до проблематики «Епохи вікінгів». На основі аналізу історіографічних джерел встановлена хронологія вивчення «Епохи вікінгів». Виявлено характерні та загальні риси підходів у межах проблематики «Епохи вікінгів».
Писанкарство Поділля у рукописній спадщині 20-х років ХХ ст.
Authors: Tkachenko Viktor
Published: August 2021

У статті розглянуто й оприлюднено архівні матеріали Інституту археології та Інституту мистецтвознавства, фольклористики та етнології імені М.Т. Рильського НАН України пов’язані з писанками. Зокрема, це листування Г.Т. Танцюри з Н.А. Коцюбинською, його записи, що стосуються великодньої обрядовості на Поділлі, а також рукописні матеріали фонду «Етнографічна комісія» ВУАН.

Невідомі широкому загалу, розглянуті джерела засвідчують існування писанок та їх використання під час великодніх звичаєво-обрядових традицій, у віруваннях українців 1920-х рр., збирання колекцій тощо.

Водночас епістолярна спадщина є цікавим і малодослідженим історичним джерелом.
Bir Okuma Etkinliği: Clarissa Pinkola Estes ve Kurtlarla Koşan Kadınlar
Authors: Gürlek Nazlı
Published: August 2021

Şubat 2016'dan beri İstanbul'da Amerikalı şair ve psikanalist Dr. Clarissa Pinkola Estes'in Kurtlarla Koşan Kadınlar: Vahşi Kadın Arketipine Dair Mit ve Öyküler kitabından okumalar düzenliyorum. Yazarın yazmaya 1971 yılında başlayıp yirmi yılı aşan bir sürede bitirdiği bu kitap, onsekiz dile çevrilmiş. 2017 yılında itibarıyla Türkçe’de de 21 baskı yapmış bulunuyor. New York Times'ın en iyi satanlar listesinde 145 hafta boyunca yer alan Kurtlarla Koşan Kadınlar, kadınların içsel yaşamı konusunda bir klasik olarak değerlendiriliyor. Doğayla bağını koparmamış bir kadınlık tahayyülü barındıran kitap, kendi bedensel, döngüsel ve cinsel gerçekliği ile barışık, bu gerçekliğin içinden yaşama katılan, söz alan ve eyleme geçen bir kadına geri dönüşü öneriyor.
Woman Existence in the Rural Population of Turkey
Authors: Şahin Güven
Published: August 2021

The level of development throughout the world is explained on the basis of various criteria population are some of these development indicators. For many countries, the rural population and the characteristics of this population are accepted as an important indicator of development.  Also, in Turkey, focusing the rural population particularly on the issue of rehabilitation since the founding of the Republic remained on the agenda. Indeed, the rural population in Turkey since the first years of the Republic showed a great change and transformation in terms of both quantitative and qualitative. The continuous contraction of the share of the rural population in the face of the urban population, the change in the rural labor force and finally some changes in the administrative sense, led to the situation of addressing the rural population and especially the female population from a significantly different perspective. Finally, in 2012, in accordance with Law No. 6360, Metropolitan Municipality 30 Metropolitan Municipalities organized in Turkey, rural population in these cities was adopted as 0 (zero). In addition to the many disadvantages of this situation, there are drawbacks to criticism in terms of ignoring the presence of women, which constitutes the largest part of the informal labor force in rural areas. It is debatable that rural women, who are deprived of their social rights and have a low level of awareness and quality of life, are inaccessible with the relevant law in comparison with the relatively urban women. In this study, the state of the overall presence of women in rural areas as a result of administrative arrangements with the relevant distribution in Turkey explained the outlines of the female population in the metropolitan municipalities in rural areas was discussed.
Analyzing the Relationship between Spatial Representations and Gender in Charlotte Gilman’s Novel, HERLAND
Authors: Al Sahli Layal , Tuna Ultav Zeynep , Sever Müge
Published: August 2021

The aim of this paper is to explore the connections between architecture, interior spaces, urban environment, and social issues through the medium of literary fiction. In particular, it is to analyze the spatial representations through cues and interpretations as well as their impact on social inequalities, specifically gender discrimination, which is the governing theme that shapes the plot, within Charlotte P. Gilman’s utopian fiction Herland. Space within literature can be seen as an essential part of storytelling because it allows the reader to fully comprehend the surroundings that the author hopes to portray throughout the literature. In relevance to the novel, the portrayed environment emphasizes the gender inequalities that were evident through Gilman’s lifetime. In addition, gender governs the overall space within Herland, therefore, the space holds the same characteristics as women; the country existed as it is for the sole purpose of benefitting the user profile – the inhabitants of Herland. Gilman also criticizes architecture and interior spatial norms of her time throughout the novel by suggesting a completely different layout and function. To address the questions and issues mentioned, an in-depth study of the novel, the author, the authors’ time, and related publications were employed to further understand the relationship between space, gender and literature. The conducted analysis revealed this relationship by the elimination of gender roles and the alteration of conventional spaces; thus depicting a more utopian country, as a form of literary criticism to her dystopian era.
Etin Cinsel Politikası
Authors: Karabulut Müzeyyen
Published: August 2021

Etin Cinsel Politikası, et yeme pratiği ile erkek egemenliği arasındaki ilişkiyi ve bu ilişkinin kadın ile insan olmayan diğer canlılar arasında kurduğu bağını zengin örneklerle sunan bir kitap. İddiası,  et yeme pratiğinin beslediği erkek egemen kültürde tüm ezme biçimlerinin kayıp göndergelerle biribirini desteklediği yönünde. Kadınların kadın olmaları ile ilgili sömürülmelerinin ve hayvanların da dişi olduklarından dolayı çifte bir sömürüye, önce dişileştirilmiş protein, sonra ise hayvanlaştırılmış protein olarak iki kademeli bir zulme maruz bırakılmalarının göz ardı edilmesine yol açan ataerkil et yeme kültürü, savaşları da başlatan bir sebep olarak görülür. Etin Cinsel Politikası'nın tespitleri ve kavramsallaştırmalarının ele alınacağı bu yazıda, et yiyici egemen kültürlerin kadına ve hayvana yönelik baskısını çözümleyecek örnekler incelenecektir.
Deep Reinforcement Learning for Constrained Field Development Optimization in Subsurface Two-phase Flow
Authors: Nasir Yusuf , He Jincong , Hu Chaoshun , Tanaka Shusei , Wang Kainan , Wen XianHuan
Published: August 2021

Oil and gas field development optimization, which involves the determination of the optimal number of wells, their drilling sequence and locations while satisfying operational and economic constraints, represents a challenging computational problem. In this work, we present a deep-reinforcement-learning-based artificial intelligence agent that could provide optimized development plans given a basic description of the reservoir and rock/fluid properties with minimal computational cost. This artificial intelligence agent, comprising of a convolutional neural network, provides a mapping from a given state of the reservoir model, constraints, and economic condition to the optimal decision (drill/do not drill and well location) to be taken in the next stage of the defined sequential field development planning process. The state of the reservoir model is defined using parameters that appear in the governing equations of the two-phase flow (such as well index, transmissibility, fluid mobility, and accumulation, etc.,). A feedback loop training process referred to as deep reinforcement learning is used to train an artificial intelligence agent with such a capability. The training entails millions of flow simulations with varying reservoir model descriptions (structural, rock and fluid properties), operational constraints (maximum liquid production, drilling duration, and water-cut limit), and economic conditions. The parameters that define the reservoir model, operational constraints, and economic conditions are randomly sampled from a defined range of applicability. Several algorithmic treatments are introduced to enhance the training of the artificial intelligence agent. After appropriate training, the artificial intelligence agent provides an optimized field development plan instantly for new scenarios within the defined range of applicability. This approach has advantages over traditional optimization algorithms (e.g., particle swarm optimization, genetic algorithm) that are generally used to find a solution for a specific field development scenario and typically not generalizable to different scenarios. The performance of the artificial intelligence agents for two- and three-dimensional subsurface flow are compared to well-pattern agents. Optimization results using the new procedure are shown to significantly outperform those from the well pattern agents.
Vind: A Blockchain-Enabled Supply Chain Provenance Framework for Energy Delivery Systems
Authors: Bandara Eranga , Shetty Sachin , Tosh Deepak , Liang Xueping
Published: August 2021

Enterprise-level energy delivery systems (EDSs) depend on different software or hardware vendors to achieve operational efficiency. Critical components of these systems are typically manufactured and integrated by overseas suppliers, which expands the attack surface to adversaries with additional opportunities to infiltrate into EDSs. Due to this reason, the risk management of the EDS supply chain is crucial to ensure that we are knowledgeable about the vulnerabilities in software and hardware components that comprise any critical part, quantifiable risk metrics to assess the severity and exploitability of the attack, and provide remediation solutions that can influence a prioritized mitigation plan. There is a need to realize cyber supply chain risk management for industrial control systems’ hardware, software, and computing and networking services associated with bulk electric system (BES) operations. This article proposes a blockchain-based cyber supply chain provenance platform (“Vind”) for EDSs to realize data provenance in a cyber supply chain ecosystem.
EZH2/EHMT2 Histone Methyltransferases Inhibit the Transcription of DLX5 and Promote the Transformation of Myelodysplastic Syndrome to Acute Myeloid Leukemia
Authors: Zheng Zhuanzhen , Li Ling , Li Guoxia , Zhang Yaofang , Dong Chunxia , Ren Fanggang , Chen Wenliang , Ma Yanping
Published: August 2021

Myelodysplastic syndrome (MDS) is characterized by clonal hematopoiesis and impaired differentiation, and may develop to acute myeloid leukemia (AML). We explored the mechanism of histone methyltransferase EZH2/EHMT2 during the transformation of MDS into AML. Expression of EZH2/EHMT2 in patients and NHD13 mice was detected. EZH2 and EHMT2 were silenced or overexpressed in SKM-1 cells. The cell proliferation and cycle were evaluated. Levels of DLX5, H3K27me3, and H3K9me2 in SKM-1 cells were detected. Binding of DLX5 promoter region to H3K27me3 and H3K9me2 was examined. Levels of H3K27me3/H3K9me2 were decreased by EZH2/EHMT2 inhibitor (EPZ-6438/BIX-01294), and changes of DLX5 expression and cell proliferation were observed. EZH2 was poorly expressed in MDS patients but highly expressed in MDS-AML patients. EHMT2 was promoted in both MDS and MDS-AML patients. EZH2 expression was reduced and EHMT2 expression was promoted in NHD13 mice. NHD13 mice with overexpressing EZH2 or EHMT2 transformed into AML more quickly. Intervention of EZH2 or EHMT2 inhibited SKM-1 cell proliferation and promoted DLX5 expression. When silencing EZH1 and EZH2 in SKM-1 cells, the H3K27me3 level was decreased. EZH2 silencing repressed the proliferation of SKM-1 cells. Transcription level of DLX5 in SKM-1 cells was inhibited by H3K27me3 and H3K9me2. Enhanced DLX5 repressed SKM-1 cell proliferation. In conclusion, EZH2/EHMT2 catalyzed H3K27me3/H3K9me2 to inhibit the transcription of DLX5, thus promoting the transformation from MDS to AML.
MCM5 Aggravates the HDAC1-Mediated Malignant Progression of Lung Cancer
Authors: Zhang Lin-lin , Li Qi , Zhong Dian-sheng , Zhang Wei-jian , Sun Xiao-jie , Zhu Yu
Published: August 2021

Background

Histone deacetylase 1 (HDAC1) is essential in the malignant progression of tumors. However, there is no obvious relationship between the expression of HDAC1 and the survival of lung cancer patients. Herein, we explored the involvement of minichromosome maintenance complex component 5 (MCM5) and HDAC1 interaction in the epithelial-to-mesenchymal transition (EMT)-dependent malignant progression of lung cancer.

Methods

We analyzed the expression of MCM5 and HDAC1 in The Cancer Genome Atlas database and clinical samples, as well as their impact on patient survival. Cell and animal experiments were performed to verify the promotion of EMT in lung cancer cells mediated by MCM5 and HDAC1.

Results

We found that lung adenocarcinoma patients with high expression of MCM5 and HDAC1 had poor survival time. Overexpression of MCM5 and HDAC1 in A549 and H1975 cells can promote proliferation and invasion in vitro and tumor growth and metastasis in vivo. Moreover, astragaloside IV can block the interaction between HDAC1 and MCM5, which can then inhibit the malignant progression of lung cancer in vivo and in vitro.

Conclusion

The interaction between MCM5 and HDAC1 aggravated the EMT-dependent malignant progression of lung cancer. Astragaloside IV can block the interaction between MCM5 and HDAC1 to inhibit the progression of lung cancer.
Insights Into the Mechanisms of Brain Endothelial Erythrophagocytosis
Authors: Sun Jiahong , Vyas Prema , Mann Samar , Paganini-Hill Annlia , Nunes Ane C. F. , Lau Wei Ling , Cribbs David H. , Fisher Mark J. , Sumbria Rachita K.
Published: August 2021

The endothelial cells which form the inner cellular lining of the vasculature can act as non-professional phagocytes to ingest and remove emboli and aged/injured red blood cells (RBCs) from circulation. We previously demonstrated an erythrophagocytic phenotype of the brain endothelium for oxidatively stressed RBCs with subsequent migration of iron-rich RBCs and RBC degradation products across the brain endothelium in vivo and in vitro, in the absence of brain endothelium disruption. However, the mechanisms contributing to brain endothelial erythrophagocytosis are not well defined, and herein we elucidate the cellular mechanisms underlying brain endothelial erythrophagocytosis. Murine brain microvascular endothelial cells (bEnd.3 cells) were incubated with tert-butyl hydroperoxide (tBHP, oxidative stressor to induce RBC aging in vitro)- or PBS (control)-treated mouse RBCs. tBHP increased the reactive oxygen species (ROS) formation and phosphatidylserine exposure in RBCs, which were associated with robust brain endothelial erythrophagocytosis. TNFα treatment potentiated the brain endothelial erythrophagocytosis of tBHP-RBCs in vitro. Brain endothelial erythrophagocytosis was significantly reduced by RBC phosphatidylserine cloaking with annexin-V and with RBC-ROS and phosphatidylserine reduction with vitamin C. Brain endothelial erythrophagocytosis did not alter the bEnd.3 viability, and tBHP-RBCs were localized with early and late endosomes. Brain endothelial erythrophagocytosis increased the bEnd.3 total iron pool, abluminal iron levels without causing brain endothelial monolayer disruption, and ferroportin levels. In vivo, intravenous tBHP-RBC injection in aged (17–18 months old) male C57BL/6 mice significantly increased the Prussian blue-positive iron-rich lesion load compared with PBS-RBC-injected mice. In conclusion, RBC phosphatidylserine exposure and ROS are key mediators of brain endothelial erythrophagocytosis, a process which is associated with increased abluminal iron in vitro. tBHP-RBCs result in Prussian blue-positive iron-rich lesions in vivo. Brain endothelial erythrophagocytosis may provide a new route for RBC/RBC degradation product entry into the brain to produce iron-rich cerebral microhemorrhage-like lesions.
Application of Ovarian Cancer Organoids in Precision Medicine: Key Challenges and Current Opportunities
Authors: Yang Jiani , Huang Shan , Cheng Shanshan , Jin Yue , Zhang Nan , Wang Yu
Published: August 2021

Ovarian cancer (OC) is the leading cause of death among gynecologic malignances. Over the past decades, human-derived models have advanced from monolayer cell cultures to three-dimensional (3D) organoids that could faithfully recapitulate biological characteristics and tumor heterogeneity of primary tissues. As a complement of previous studies based on cell lines or xenografts, organoids provide a 3D platform for mutation–carcinogenesis modeling, high-throughput drug screening, genetic engineering, and biobanking, which might fulfill the gap between basic research and clinical practice. Stepwise, cutting-edge bioengineering techniques of organoid-on-a-chip and 3D bioprinting might converge current challenges and contribute to personalized therapy. We comprehensively reviewed the advantages, challenges, and translational potential of OC organoids. Undeniably, organoids represent an excellent near-physiological platform for OC, paving the way for precision medicine implementation. Future efforts will doubtlessly bring this innovative technique from bench to bedside.
Role of the Forkhead Transcription Factors Fd4 and Fd5 During Drosophila Leg Development
Authors: Ruiz-Losada Mireya , Pérez-Reyes Cristian , Estella Carlos
Published: August 2021

Appendage development requires the coordinated function of signaling pathways and transcription factors to pattern the leg along the three main axes: the antero-posterior (AP), proximo-distal (PD), and dorso-ventral (DV). The Drosophila leg DV axis is organized by two morphogens, Decapentaplegic (Dpp), and Wingless (Wg), which direct dorsal and ventral cell fates, respectively. However, how these signals regulate the differential expression of its target genes is mostly unknown. In this work, we found that two members of the Drosophila forkhead family of transcription factors, Fd4 and Fd5 (also known as fd96Ca and fd96Cb), are identically expressed in the ventro-lateral domain of the leg imaginal disc in response to Dpp signaling. Here, we analyze the expression regulation and function of these genes during leg development. We have generated specific mutant alleles for each gene and a double fd4/fd5 mutant chromosome to study their function during development. We highlight the redundant role of the fd4/fd5 genes during the formation of the sex comb, a male specific structure that appears in the ventro-lateral domain of the prothoracic leg.
Iron(II) Spin Crossover Coordination Polymers Derived From a Redox Active Equatorial Tetrathiafulvalene Schiff-Base Ligand
Authors: Qiu Ya-Ru , Cui Long , Ge Jing-Yuan , Kurmoo Mohamedally , Ma Guijun , Su Jian
Published: August 2021

Two polymorphic FeII coordination polymers [FeIIL (TPPE)0.5] 1) and [(FeII3L3 (TPPE)1.5)] 2), were obtained from a redox-active tetrathiafulvalene (TTF) functionalized ligand [H2L = 2,2’-(((2-(4,5-bis-(methylthio)-1,3-dithiol-2-ylidene)benzo(d) (1,3) dithiole-5,6-diyl)bis-(azanediyl))bis-(meth anylylidene)) (2E,2E')-bis(3-oxobutanoate)] and a highly luminescent connector {TPPE = 1,1,2,2-tetrakis[4-(pyridine-4-yl)phenyl]-ethene}. Complex 1 has a layered structure where the TPPE uses its four diverging pyridines from the TPPE ligand are coordinated by the trans positions to the flat TTF Schiff-base ligand, and complex 2 has an unprecedented catenation of layers within two interpenetrated frameworks. These coordination polymers reserved the redox activity of the TTF unit. Complex 1 shows gradual spin transition behavior without hysteresis. And the fluorescence intensity of TPPE in 1 changes in tandem with the spin crossover (SCO) transition indicating a possible interplay between fluorescence and SCO behavior.
A Luminescent 1D Silver Polymer Containing [2.2]Paracyclophane Ligands
Authors: Mackenzie Campbell F. R. , Delforce Lucie , Rota Martir D. , Cordes David B. , Slawin Alexandra M. Z. , Zysman-Colman Eli
Published: August 2021

[2.2]Paracyclophane scaffolds have seen limited use as building blocks in supramolecular chemistry. Here, we report the synthesis and characterization of a 1D coordination polymer consisting of silver(I) ions bound to a [2.2]paracyclophane scaffold functionalized with two 4-pyridyl units. The structure of the polymer has been determined from single crystal X-ray diffraction analysis and reveals two different silver coordination motifs that alternate along the 1D coordination polymer. The coordination polymer exhibits strong blue and sky-blue fluorescence in solution and in the crystalline solid state, respectively.
Cytospora and Diaporthe Species Associated With Hazelnut Canker and Dieback in Beijing, China
Authors: Gao Hong , Pan Meng , Tian Chengming , Fan Xinlei
Published: August 2021

Hazelnut (Corylus heterophylla Fisch.) is an important nut crop in China but has been declining owing to the destructive effects of fungal branch canker and dieback. The identification and management of these pathogens are difficult because of the lack of attention to branch canker, insufficient understanding of phylogenetic, and overlapping morphological characteristics of the pathogens. In total, 51 strains were isolated from Chinese wild hazelnut in this study, and three species of Cytospora and two of Diaporthe were identified through morphological observation and multi-locus phylogenetic analyses (ITS, act, rpb2, tef1-α, and tub2 for Cytospora; ITS, cal, his3, tef1-α, and tub2 for Diaporthe). Three new species, Cytospora corylina, C. curvispora, and Diaporthe corylicola, and two known species, Cytospora leucostoma and Diaporthe eres, grew at 5–30°C and a pH of 3.0–11.0, with optimum growth at approximately 25°C and pH 4.0–7.0. Additionally, the effects of six carbon sources on mycelial growth were investigated. This study explored the main pathogenic fungi species of Corylus heterophylla, completed the corresponding database of pathogenic fungi information, and clarified their biological characteristics. Moreover, the results of this study provided a theoretical basis for Corylus heterophylla disease management and prevention in China.
The Anti-Biofilm Efficacy of Caffeic Acid Phenethyl Ester (CAPE) In Vitro and a Murine Model of Oral Candidiasis
Authors: de Barros Patrícia Pimentel , Rossoni Rodnei Dennis , Garcia Maíra Terra , Kaminski Valéria de Lima , Loures Flávio Vieira , Fuchs Beth Burgwyn , Mylonakis Eleftherios , Junqueira Juliana Campos
Published: August 2021

Candida albicans is the main fungal species associated with the development of oral candidiasis. Currently, therapeutic options for these infections are limited by the adverse effects of antifungal drugs and by the emergence of drug resistant strains. Thus, the development of new antifungal agents is needed for the prevention and treatment of oral Candida infections. Caffeic acid phenethyl ester (CAPE) is a natural compound from propolis polyphenolic groups that exhibits many pharmacological properties. In this study, we investigated whether CAPE can have antifungal and immunomodulatory effects on oral candidiasis. Preliminary tests to assess the antifungal activity of CAPE were performed using the Minimum Inhibitory Concentration (MIC) assay that demonstrated inhibition in a range from 16 to 32 μg/mL, confirming its antifungal activity on several C. albicans strains isolated from the oral cavity. Subsequently, we analyzed Candida spp biofilms formed in vitro, in which CAPE treatment at 5 x MIC caused a reduction of 68.5% in the total biomass and ~2.60 Log in the viable cell count (CFU/mL) in relation to the untreated biofilm (p<0.0001). Next, RNA was extracted from untreated and CAPE-treated biofilms and analyzed by real-time qPCR. A series of genes analyzed (ALS1, ECE1, EPA1, HWP1, YWP1, BCR1, BGR1, CPH1, EFG1, NDT80, ROB1, TEC1, UME6, SAP2, SAP5, PBL2, and LIP9) were downregulated by CAPE compared to the untreated control group (p<0.0001). In in vivo studies using Galleria mellonella, the treatment with CAPE prolonged survival of larvae infected by C. albicans by 44.5% (p < 0.05) and accompanied by a 2.07-fold increase in the number of hemocytes. Flow cytometry revealed the most prominent increases were in types P2 and P3 hemocytes, granular cells, which phagocytize pathogens. In addition, CAPE treatment decreased the fungal load in the hemolymph and stimulated the expression of antifungal peptide genes such as galiomicin and gallerimycin. The antifungal and immunomodulatory activities observed in G. mellonella were extended to a murine model of oral candidiasis, in which CAPE decreased the levels of C. albicans colonization (~2 log CFU/mL) in relation to the untreated control group. In addition, CAPE treatment significantly reduced pseudomembranous lesions, invasion of hyphae on epithelium surfaces, tissue damage and inflammatory infiltrate (p < 0.05). CAPE was also able to increase the expression of β-defensin 3 compared to the infected and untreated group by 3.91-fold (p < 0.0001). Taken together, these results show that CAPE has both antifungal and immunomodulatory effects, making it a promising natural antifungal agent for the treatment and prevention of candidiasis and shows impact to oral candidiasis.
Assessing the Quality and Reliability of COVID-19 Information on Patient Organization Websites
Authors: Brown Erin E.
Published: August 2021

This article employed a content analysis method utilizing the Centers for Disease Control and Prevention’s Clear Communication Index to evaluate the quality and reliability of 15 patient organization websites designed for patients to access information about COVID-19. The objective of this content analysis was to assess the clarity of online communication of information on COVID-19 by patient organizations by determining how well the websites score for clarity and identify ways to improve the websites. This study suggests that the patient organization websites that were analyzed are not adequately designed to communicate relevant information about COVID-19 in meaningful and effective ways. The findings from this study will help reveal major deficits in the communication of COVID-19 health information on patient organization websites, identify best practices and improvements that can be made to enhance communication, and build on existing literature regarding e-health literacy and clear communication on public health websites.
Cannabis Use and the Risk of Cardiovascular Diseases: A Mendelian Randomization Study
Authors: Zhao Jianqiang , Chen Heng , Zhuo Chengui , Xia Shudong
Published: August 2021

Several observational studies have shown that cannabis use has negative effects on the cardiovascular system, but the causality of this relationship has not been confirmed. The aim of the current study was to estimate the effects of genetically determined cannabis use on risk of cardiovascular diseases. Ten single-nucleotide polymorphisms related to cannabis use were employed as instruments to estimate the association between genetically determined cannabis use and risk of cardiovascular diseases using a two-sample Mendelian randomization (MR) method. Summary statistics data on exposure and outcomes were obtained from different genome-wide association meta-analysis studies. The results of this MR analysis showed no causal effects of cannabis use on the risk of several common cardiovascular diseases, including coronary artery disease, myocardial infarction, stroke and ischemic stroke subtypes, atrial fibrillation (AF), and heart failure. Various sensitivity analyses yielded similar results, and no heterogeneity and directional pleiotropy were observed. After adjusting for tobacco use and body mass index, multivariable MR analysis suggested a causal effect of cannabis use on small vessel stroke (SVS) [odds ratio (OR) 1.17; 95% CI 1.02–1.35; p = 0.03] and AF (OR 1.06; 95% CI 1.01–1.10; p = 0.01), respectively. This two-sample MR study did not demonstrate a causal effect of genetic predisposition to cannabis use on several common cardiovascular outcomes. After adjusting for tobacco use and body mass index, the multivariable MR analysis suggested a detrimental effect of cannabis use on the risk of SVS and AF, respectively.
Efficacy and Safety of High-Density Lipoprotein/Apolipoprotein A1 Replacement Therapy in Humans and Mice With Atherosclerosis: A Systematic Review and Meta-Analysis
Authors: Abudukeremu Ayiguli , Huang Canxia , Li Hongwei , Sun Runlu , Liu Xiao , Wu Xiaoying , Xie Xiangkun , Huang Jingjing , Zhang Jie , Bao Jinlan , Zhang Yuling
Published: August 2021

Background: Although elevation of HDL-C levels by pharmaceutical drugs have no benefit of cardiovascular endpoint, the effect of high-density lipoprotein/apolipoprotein A1 (HDL/apoA-1) replacement therapy on atherosclerosis is controversial. The current meta-analysis analyzed the effects of HDL/apoA-1 replacement therapies on atherosclerotic lesions both in humans and mice.

Methods: The PubMed, Cochrane Library, Web of Science, and EMBASE databases were searched through June 6, 2020. The methodological quality of the human studies was assessed using Review Manager (RevMan, version 5.3.). The methodological quality of the mouse studies was assessed using a stair list. STATA (version 14.0) was used to perform all statistical analyses.

Results: Fifteen randomized controlled human trials and 17 animal studies were included. The pooled results showed that HDL/apoA-1 replacement therapy use did not significantly decrease the percent atheroma volume (p = 0.766) or total atheroma volume (p = 0.510) in acute coronary syndrome (ACS) patients (N = 754). However, HDL/apoA-1 replacement therapies were significantly associated with the final percent lesion area, final lesion area, and changes in lesion area (SMD, −1.75; 95% CI: −2.21~-1.29, p = 0.000; SMD, −0.78; 95% CI: −1.18~-0.38, p = 0.000; SMD: −2.06; 95% CI, −3.92~-0.2, p = 0.03, respectively) in mice.

Conclusions: HDL/apoA-1 replacement therapies are safe but do not significantly improve arterial atheroma volume in humans. The results in animals suggest that HDL/apoA-1 replacement therapies decrease the lesion area. Additional studies are needed to investigate and explain the differences in HDL/apoA-1 replacement therapy efficacies between humans and animals.

Trial registration number: Human pooled analysis: PROSPERO, CRD42020210772. prospectively registered.
Variations in Forearc Stress and Changes in Principle Stress Orientations Caused by the 2004–2005 Megathrust Earthquakes in Sumatra, Indonesia
Authors: Rafie Muhammad Taufiq , Cummins Phil R. , Sahara David P. , Widiyantoro Sri , Triyoso Wahyu , Nugraha Andri Dian
Published: August 2021

Coseismic changes in principal stress orientation in the northern Sumatra subduction zone due to two giant megathrust earthquakes there in 2004 and 2005 are estimated to investigate the in-situ stress. The two megathrust earthquakes, the 2004 Sumatra-Andaman and the 2005 Nias-Simeulue events, are both among the 11 largest earthquakes ever recorded. Previous studies have shown that these giant earthquakes perturbed the stress field in the Sumatra subduction zone enough to alter the principal stress directions there, and here we investigate whether these changes can be used to better understand spatial variations in stress along the subduction zone. We used 330 previously published focal mechanisms to estimate pre- and post-mainshock principal stress orientations in 3 outer forearc segments and assessed whether orientation differences were resolved and what they imply about the pre- and post-mainshock stress fields. Our results agree with previous studies in establishing that coseismic changes in stress orientation in the forearc are resolvable, and consistent with a low level of stress in the outer Sumatran forearc before the earthquake, with almost all the shear stress on the megathrust relieved in the 2004 and 2005 earthquakes. In this study, we reveal that both the stress orientations and coseismic changes in them exhibit along-strike variations, with a decrease in both the pre-mainshock stress and stress drop found in the rupture area of 2005 relative to that of the 2004 earthquake. The forearc segment between the 2004 and 2005 rupture areas, which coincides with a well-known megathrust rupture barrier beneath the island of Simeulue is observed to have a characteristic signature, with lower shear stress relative to the pre-mainshock stress field and higher shear stress relative to the post-mainshock stress field in the adjacent segments.
Diminishing Opportunities for Sustainability of Coastal Cities in the Anthropocene: A Review
Authors: Day John W. , Gunn Joel D. , Burger Joseph Robert
Published: August 2021

The world is urbanizing most rapidly in tropical to sub-temperate areas and in coastal zones. Climate change along with other global change forcings will diminish the opportunities for sustainability of cities, especially in coastal areas in low-income countries. Climate forcings include global temperature and heatwave increases that are expanding the equatorial tropical belt, sea-level rise, an increase in the frequency of the most intense tropical cyclones, both increases and decreases in freshwater inputs to coastal zones, and increasingly severe extreme precipitation events, droughts, freshwater shortages, heat waves, and wildfires. Current climate impacts are already strongly influencing natural and human systems. Because of proximity to several key warming variables such as sea-level rise and increasing frequency and intensity of heatwaves, coastal cities are a leading indicator of what may occur worldwide. Climate change alone will diminish the sustainability and resilience of coastal cities, especially in the tropical-subtropical belt, but combined with other global changes, this suite of forcings represents an existential threat, especially for coastal cities. Urbanization has coincided with orders of magnitude increases in per capita GDP, energy use and greenhouse gas emissions, which in turn has led to unprecedented demand for natural resources and degradation of natural systems and more expensive infrastructure to sustain the flows of these resources. Most resources to fuel cities are extracted from ex-urban areas far away from their point of final use. The urban transition over the last 200 years is a hallmark of the Anthropocene coinciding with large surges in use of energy, principally fossil fuels, population, consumption and economic growth, and environmental impacts such as natural system degradation and climate change. Fossil energy enabled and underwrote Anthropocene origins and fueled the dramatic expansion of modern urban systems. It will be difficult for renewable energy and other non-fossil energy sources to ramp up fast enough to fuel further urban growth and maintenance and reverse climate change all the while minimizing further environmental degradation. Given these trajectories, the future sustainability of cities and urbanization trends, especially in threatened areas like coastal zones in low-income countries in the tropical to sub-tropical belt, will likely diminish. Adaptation to climate change may be limited and challenging to implement, especially for low-income countries.
Phosphorylation of Shrimp Tcf by a Viral Protein Kinase WSV083 Suppresses Its Antiviral Effect
Authors: Wang Chuanqi , Ruan Lingwei , Shi Hong , Lin Wenyang , Liu Linmin , Li Sujie
Published: August 2021

Nuclear DNA-binding TCF proteins, which act as the main downstream effectors of Wnt signaling, are essential for the regulation of cell fate and innate immunity. However, their role during viral infection in shrimp remains unknown. Herein, we demonstrated that Litopenaeus vannamei TCF (LvTcf) acts independently of Lvβ-catenin to promote interferon-like protein LvVago1 production, thus mounting the response to WSSV infection. Further, we observed that WSV083, a WSSV serine/threonine protein kinase, bound to LvTcf and phosphorylated it. Phosphorylated LvTcf was then recognized and degraded via the ubiquitin-proteasome pathway. Moreover, mass spectrometry analyses indicated that the T39 and T104 residues of LvTcf were target sites phosphorylated by WSV083. Point mutation analyses suggested that additional sites of LvTcf may undergo phosphorylation via WSV083. Taken together, the current work provides valuable insights into host immunity and viral pathogenesis. LvTcf is not only a modulator of shrimp innate immunity but is also an important target for WSSV immune evasion. Thus, the current findings will help improve disease control in shrimps.