bluuebunny/crossref_metadata_2025 huggingface dataset:
The Acidic Fraction of Isatidis Radix Regulates Inflammatory Response in LPS-Stimulated RAW264.7 Macrophages through MAPKs and NF-κB Pathway
Authors: Fan Zhenyu , Cai Liangliang , Wang Yage , Zhu Qiuyan , Wang Shengnan , Chen Bohua
Published: March 2021

Isatidis Radix, the dried root of Isatidis indigotica Fort, is a traditional heat-clearing and detoxicating herb, which has the antiviral and anti-inflammatory activity and immune regulation. It has been widely used to treat cold, fever, sore throat, mumps, and tonsillitis in clinics. A previous study demonstrated that the acidic fraction of Isatidis Radix (RIAF) had strong anti-inflammatory activity, but the mechanism of action was not well elucidated. Lipopolysaccharide- (LPS-) induced RAW264.7 cells were employed to observe the anti-inflammatory activity of RIAF. The level of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), nitric oxide (NO), prostaglandin E2 (PGE2), and interleukin-6 (IL-6) was determined by enzyme-linked immunosorbent assay kits. Western blot was performed to quantify the expression of extracellular signal-regulated kinase (ERK) 1/2, c-jun NH2-termianl kinase (JNK), p38, inducible NO synthetase (iNOS), cyclooxygenase (COX)-2, andnuclear factor-κB (NF-κB). Immunofluorescence assay and electrophoretic mobility shift assay (EMSA) were used to quantify the translocation and the binding-DNA activity of NF-κB. RIAF could inhibit the secretion of inflammatory cytokines (PGE2, IL-6, IL-1β, and NO, other than TNF-α) in a dose-dependent manner. Further investigation showed that the expression of iNOS and COX-2 induced by LPS were downregulated by treatment with RIAF. Meanwhile, data from the signal pathway exhibited that RIAF significantly suppressed the phosphorylation of ERK1/2, JNK, and p38 and reduced the translocation of NF-κB from the cytoplasm to nucleus, as well as the binding-DNA activity. The anti-inflammatory mechanism of action of RIAF was to reduce inflammation-associated gene expression (iNOS, COX-2, IL-1β, IL-6) by regulating the phosphorylation of the mitogen-activated protein kinases (MAPK) pathway and interventing the activation of the NF-κB pathway, which partly illustrated the basis of treatment of Isatidis Radix on cold, fever, sore throat, mumps, and tonsillitis in clinics.
Dynamic Characteristics Analysis of the Hub Direct Drive‐Air Suspension System from Vertical and Longitudinal Directions
Authors: Li Zhongxing , Song Xinyan , Chen Xin , Xue Hongtao
Published: March 2021

Hub direct‐drive electric vehicles are driving with hub motors, which cause negative vibration directly on wheels and suspensions. To better analyze the problems of dynamic deterioration resulted by coupling excitations from random road and unbalanced magnetic pull (UMP), a cooperative hub direct drive‐air suspension (HDD‐AS) system is developed, and evaluation indices based on vertical and longitudinal dynamic coupling mechanism are proposed. The vertical and longitudinal characteristics in the time domain under different damping coefficients and motor speeds are demonstrated, and comparison between traditional electric wheel and suspension‐integrating models and HDD‐AS system model is conducted. Then, the responses of random road excitation and UMP are analyzed, and explanations of vertical and longitudinal characteristics in the frequency domain under different damping coefficients are given. These results provide important insights into the influence of coupling excitations and damping coefficient on the HDD‐AS system model. Finally, the effectiveness of the proposed model is verified by the experiment on the test bench.
Islet Transplantation Reverses Podocyte Injury in Diabetic Nephropathy or Induced by High Glucose via Inhibiting RhoA/ROCK/NF-κB Signaling Pathway
Authors: Huang Chongchu , Zhou Yi , Huang Hongjian , Zheng Yushu , Kong Lijun , Zhang Hewei , Zhang Yan , Wang Hongwei , Yang Mei , Xu Xiaona , Chen Bicheng
Published: March 2021

Objective. Abnormal signaling pathways play a crucial role in the mechanisms of podocyte injury in diabetic nephropathy. They also affect the recovery of podocytes after islet transplantation (IT). However, the specific signaling abnormalities that affect the therapeutic effect of IT on podocytes remains unclear. The purpose of this study was to assess whether the RhoA/ROCK/NF-κB signaling pathway is related to podocyte restoration after IT. Methods. A mouse model of diabetic nephropathy was established in vivo using streptozotocin. The mice were then subsequently reared for 4 weeks after islet transplantation to determine the effect of IT. Islet cells, CCG-1423 (RhoA Inhibitor), and fasudil (ROCK inhibitor) were then cocultured with podocytes in vitro to assess their protective effects on podocyte injury induced by high glucose (HG). Protein expression levels of RhoA, ROCK1, synaptopodin, IL-6, and MCP-1 in kidney tissues were then measured using immunohistochemistry and Western blotting techniques. Results. Islet transplantation reduced the expression levels of RhoA/ROCK1 and that of related inflammatory factors such as IL-6 and MCP-1 in the kidney podocytes of diabetic nephropathy. In the same line, islet cells reduced the expression of RhoA, ROCK1, and pp65 in immortalized podocytes under high glucose (35.0 mmol/L glucose) conditions. Conclusions. Islet transplantation can reverse podocyte injury in diabetes nephropathy by inhibiting the RhoA/ROCK1 signaling pathway. Islet cells have a strong protective effect on podocytes treated with high glucose (35.0 mmol/L glucose). Discovery of signaling pathways affecting podocyte recovery is helpful for individualized efficacy evaluation and targeted therapy of islet transplantation patients.
Dynamic Changes of Post-Radiotherapy Plasma Epstein–Barr Virus DNA in a Randomized Trial of Adjuvant Chemotherapy Versus Observation in Nasopharyngeal Cancer
Authors: Hui Edwin Pun , Ma Brigette B.Y. , Lam W.K. Jacky , Chan K.C. Allen , Mo Frankie , Ai Qi-yong Hemis , King Ann D. , Wong Chi Hang , Wong Kenneth C.W. , Lam Daisy C.M. , Tong Macy , Poon Darren M.C. , Li Leung , Lau Thomas K.H. , Wong Kwan Hung , Lo Y.M. Dennis , Chan Anthony T.C.
Published: March 2021

Purpose:

To study the dynamic changes in plasma Epstein–Barr virus (pEBV) DNA after radiotherapy in nasopharyngeal cancer (NPC).

Experimental Design:

We conducted a randomized controlled trial of adjuvant chemotherapy versus observation in patients with NPC who had detectable pEBV DNA at 6 weeks post-radiotherapy. Randomized patients had a second pEBV DNA checked at 6 months post-randomization. The primary endpoint was progression-free survival (PFS).

Results:

We prospectively enrolled 789 patients. Baseline post-radiotherapy pEBV DNA was undetectable in 573 (72.6%) patients, and detectable in 216 (27.4%) patients, of whom 104 (13.2%) patients were eligible for randomization to adjuvant chemotherapy (n = 52) versus observation (n = 52). The first post-radiotherapy pEBV DNA had a sensitivity of 0.48, specificity of 0.81, area under receiver-operator characteristics curve (AUC) of 0.65, false positive (FP) rate of 13.8%, and false negative (FN) rate of 14.4% for disease progression. The second post-radiotherapy pEBV DNA had improved sensitivity of 0.81, specificity of 0.75, AUC of 0.78, FP rate of 14.3%, and FN rate of 8.1%. Patients with complete clearance of post-radiotherapy pEBV DNA (51%) had survival superior to that of patients without post-radiotherapy pEBV DNA clearance (5-year PFS, 85.5% vs. 23.3%; HR, 9.6; P < 0.0001), comparable with patients with initially undetectable post-radiotherapy pEBV DNA (5-year PFS, 77.1%), irrespective of adjuvant chemotherapy or observation.

Conclusions:

Patients with NPC with detectable post-radiotherapy pEBV DNA who experienced subsequent pEBV DNA clearance had superior survival comparable with patients with initially undetectable post-radiotherapy pEBV DNA. Post-radiotherapy pEBV DNA clearance may serve as an early surrogate endpoint for long-term survival in NPC.
Antidrug Antibodies and Drug Development: Challenges in the Immunotherapy Era
Authors: de Spéville Bernard Doger , Moreno Victor
Published: March 2021

Novel antibody formats such as bispecifics have increased risk of immunogenicity, impacting safety and efficacy. LY3415244, a novel T-cell immunoglobulin and mucin-domain-containing molecule-3 (TIM3)-PDL1 (programmed death (ligand) 1) bispecific caused neutralizing antibody–drug antibodies (ADA) in 12 of 12 patients and required study termination. Novel approaches are needed to ameliorate and manage this undesirable effect of therapeutic antibodies.

See related article by Hellmann et al., p. 2773
НЕОНАТАЛЬНИЙ СКРИНІНГ НА ТЯЖКІ КОМБІНОВАНІ ІМУНОДЕФІЦИТИ: РЕТРОСПЕКТИВА І СУЧАСНІСТЬ
Authors: Yarema Н. M. , Boyarchuk O. R. , Mochulska O. M.
Published: March 2021

Мета роботи – аналіз даних наукових публікацій, які висвітлюють зарубіжний досвід імплементації тяжких комбінованих імунодефіцитів у неонатальний скринінг.

Матеріали та методи. Проаналізовані публікації з баз даних Web of Science, Scopus і PubMed, що описують клінічну й економічну ефективність скринінгу на тяжкі комбіновані імунодефіцити.

Тяжкі комбіновані імунодефіцити відносять до найтяжчих станів серед первинних імунодефіцитів. Немовлята із тяжким комбінованим імунодефіцитом схильні до небезпечних для життя інфекцій. Без ранньої діагностики й ефективного лікування їх смертність значно зростає, що зумовлює медико-соціальну значущість цих захворювань. У багатьох країнах впроваджено обстеження новонароджених на тяжкі комбіновані імунодефіцити методом ПЛР для аналізу TREC/KREC.

Результати дослідження та їх обговорення. За даними літератури, практичний досвід впровадження у практику неонатального скринінгу на тяжкі комбіновані імунодефіцити у зарубіжних країнах показує, що таке тестування є чутливе і специфічне, має відносно низьку вартість, легко виявляє дітей із безсимптомним перебігом. Зазначені можливості дозволяють швидко виявити порушення клітинного імунітету, ідентифікувати тяжкі комбіновані імунодефіцити, розпочати адекватне лікування пацієнтів, проводити заходи для попередження розвитку інфекцій та рятувати життя.

Висновки. Тяжкі комбіновані імунодефіцити відповідають критеріям включення нозології в систему широкомасштабного неонатального скринінгу, а зарубіжний досвід впровадження в практику неонатального скринінгу може бути корисним для України. Cкринінг на тяжкі комбіновані імунодефіцити новонароджених можна імплементувати у клінічну практику в Україні.
ВПЛИВ ХІРУРГІЧНОЇ СТИМУЛЯЦІЇ ОВУЛЯЦІЇ ШЛЯХОМ ФЕРТИЛОСКОПІЧНОГО ОВАРІАЛЬНОГО ДРИЛІНГУ НА ГОРМОНАЛЬНИЙ СТАТУС ПАЦІЄНТОК ІЗ КЛОМІФЕН-РЕЗИСТЕНТНОЮ ФОРМОЮ СИНДРОМУ ПОЛІКІСТОЗНИХ ЯЄЧНИКІВ ТА ОЖИРІННЯМ
Authors: Chaika V. V.
Published: March 2021

Мета дослідження – вивчити вплив хірургічної стимуляції овуляції шляхом фертилоскопічного оваріального дрилінгу на гормональний статус пацієнток із кломіфен-резистентною формою синдрому полікістозних яєчників (СПКЯ) та ожирінням.

Матеріали та методи. Під спостереженням перебувала 61 жінка репродуктивного віку. В основну групу ввійшла 31 жінка із кломіфен-резистентним СПКЯ і з індексом маси тіла >30 кг/м2, яким хірургічну стимуляцію овуляції виконано з використанням ТВГЛ у Київському міському центрі репродуктивної та перинатальної медицини за період 2017–2019 рр. У контрольну групу увійшли 30 умовно соматично і гінекологічно здорових жінок. Пацієнтки пройшли комплексне обстеження. Концентрації гонадотропінів, статевих стероїдів та антимюллерового гормону в сироватці периферичної крові досліджували імунохімічним методом на 2–3-й день менструального циклу перед операцією, через 1, 3 і 6 місяців після операції.

Результати дослідження та їх обговорення. Після проведення хірургічної стимуляції відмічали поліпшення гормонального профілю сироватки периферичної крові зі зниженням лютеїнізуючого гормону, статевих стероїдів та підвищенням фолікулостимулюючого гормону, але через 3 місяці спостерігали тенденцію до поступового повернення вмісту гонадотропінів та статевих стероїдів до вихідного передопераційного рівня. Через 6 місяців після хірургічної стимуляції овуляції найбільш стійкими залишалися зниження порівняно з контрольними значеннями сироваткової концентрації антимюллерового гормону в 1,24 (р<0,01), вільного тестостерону – в 1,61 (р<0,01) і дегідроепіандростерону – в 1,69 раза (р<0,01). Поліпшення гормонального статусу безпосередньо після хірургічної стимуляції овуляції привело до настання у прооперованих пацієнток вагітності впродовж 3 місяців у 26,81 % випадків, впродовж 6 місяців – у 35,48 %.

Висновок. Отримані дані вказують на те, що перші 6 місяців після хірургічної стимуляції овуляції є найбільш перспективними для планування і настання вагітності у кломіфен-резистентних пацієнток із СПКЯ і ожирінням.
EXPRESSION OF MARKERS OF HYPOXIA, ANGIOGENESIS, AS MICROCIRCULATORY-TISSUE FACTORS IN PROLIFERATIVE PROCESSES OF THE ENDOMETRIUM
Authors: Chumak Z. V. , Shapoval M. V. , Nadvorna О. М. , Zhovtenko O. V.
Published: March 2021

The aim of the study – to learn the expression of VEGF and HIF-1α in physiological, hyperplastic, atypical endometrium at different ages of women.

Materials and Methods. Evaluation of VEGF expression and HIF-1α performed in endometrial tissue samples in 458 women of late reproductive, perimenopausal and postmenopausal age. Expression of VEGF and HIF-1α was performed at the mRNA level by polymerase chain reaction of cDNA obtained by reverse transcription. The results were processed by the method of variation statistics with the assessment of reliability according to the Student's criterion using standard computer systems.

Results and Discussion. Analyzing the data of the presented work, higher VEGF expression rates were found in atypical hyperplasia in all age categories, but probably higher rates were found in the postmenopausal period, in atypical endometrial hyperplasia, which indicates the need for vigilance in detecting this process in the appropriate age category. Studies have shown that HIF-1α can potentiate the activation of vasomotor genes that are required for the vascular response to hypoxia. These studies demonstrate the informativeness of the method of determining HIF-1α in the examination of patients with endometrial hyperplastic processes (EHP). The introduction of this method in practical medicine will not only understand the details of the changes occurring in the body (pathological, physiological), but also develop strategic maneuvers for possible therapeutic or surgical treatments.

Conclusions. Expression of VEGF and HIF-1α levels in endometrial tissue cells as a marker can be a promising method for diagnosing the risk of proliferative conditions and their prognosis, especially in combination with other markers that characterize immunohistochemical and molecular genetic cellular parameters. Hypoxia and its relationship with indicators of angiogenesis may have some promising significance. Because the development of pathological conditions develops at a certain stage of hypoxic conditions. Under certain conditions, as a result of disruption of tissue processes, possibly metabolic, changes in angiogenesis are reduced with increasing hypoxia, which may in the long run provoke atypical disorders.
Порушення регуляторних механізмів серцевої діяльності при етаноловому пошкодженні печінки у щурів із різною емоційністю
Authors: Kostyuk O. A. , Denefil O. V. , Pelykh V. E.
Published: March 2021

Мета роботи: встановити особливості регуляції серцево-судинної системи автономною нервовою системою при етаноловому пошкодженні печінки у високо- і низькоемоційних щурів-самців.

Матеріали і методи. Досліди виконано на 192 білих безпородних високо- і низькоемоційних щурах-самцях (ВЕ і НЕ). Емоційність щурів визначали за методом “відкрите поле”. Усіх щурів поділили на групи: контроль, глюкоза 7 днів, етаноловий гепатит (ЕГ); глюкоза 67 днів, етаноловий гепатоз (Гз), етаноловий фіброз (ЕФ), етаноловий цироз (ЕЦ). Оцінювали стан центральної гемодинаміки, автономної регуляції серцевим ритмом, морфологічні зміни у серці.

Результати досліджень та їх обговорення. Етанолове пошкодження призвело до порушення автономної регуляції серцевого ритму, гемодинаміки та морфологічних змін, що залежало від модельованої патології та емоційності щурів. ЕГ спричинив збільшення варіаційного розмаху, змін кровонаповнення, периферійного опору судин, що більше виражено у ВЕ. У ВЕ при ЕГз зросла мода, зменшилася амплітуда моди, при ЕФ та ЕЦ зменшилася мода, вираженіші морфологічні зміни. У НЕ при ЕГз зросла мода, при ЕФ зменшився варіаційний розмах, були більше виражені компенсаторні гемодинамічні зміни.

Етанолове пошкодження організму щурів призводить до порушення автономної регуляції серцевого ритму та гемодинаміки. Гострий етаноловий гепатит призводить до активації вагусних впливів на серцеву діяльність, порушення кровонаповнення, підвищується периферійний опір судин. Дисфункціональні зміни центральної гемодинаміки та морфологічні зміни вираженіші у ВЕ тварин. При етаноловому гепатозі зменшуються симпатичні регуляторні впливи на серце. При етаноловому фіброзі та цирозі печінки у ВЕ щурів зростають симпатичні впливи, при фіброзі у НЕ зменшуються вагусні впливи. При цьому компенсаторні гемодинамічні зміни більше виражені у НЕ, а морфологічні – у ВЕ.
Абдомінальна травма
Authors: Zaporozhan S. Y. , Khomenko V. S.
Published: March 2021

Абдомінальна травма, без сумніву, є однією з найбільш складних розділів хірургії. Постійне зростання показників травматизму призводить до інвалідизації та смертності постраждалих, що підкреслює соціальну значущість проблеми. Тяжкість клінічного перебігу травматичної хвороби, яка   характеризується пошкодженням кісткової системи та травматичних ушкоджень органів черевної порожнини, характеризують дану проблему як один з найскладніших розділів невідкладної хірургії. Cмертність від ізольованої тупої травми живота становить близько 5 %. Своєчасна та рання діагностика ушкоджень можуть реально зменшити показники смертності при абдомінальній травмі. Стандартизація діагностики має на меті раціональне та “таргентне” використання певного конкретного та необхідного в тій чи іншій клінічній ситуації методу. Показання до операційного лікування досі є предметом дискусій, особливе значення лапароскопії в діагностично-лікувальному алгоритмі. В статті представлено огляд літератури з аналізом основних причин травми черевної порожнини, її поширення, класифікації, можливостей інструментальної діагностики, використання прогностичних шкал, ролі лапароскопії та традиційної хірургії у даної категорії хворих, значення стратегії “demage control” у світлі сучасних концепцій надання допомоги постраждалими з тяжкою абдомінальною травмою.
Experiências em ensino remoto de publicidade e propaganda na pandemia da Covid-19
Authors: Rabaiolli Janderle , Hansen Fábio
Published: March 2021

Este artigo relata a experiência da pesquisa “Ensino remoto de Publicidade e Propaganda em tempos de pandemia”, realizada com o objetivo de mapear práticas docentes em cursos do campo publicitário na pandemia da covid-19. A coleta de dados ocorreu em maio de 2020 por meio de questionário on-line de autopreenchimento junto a 283 docentes de cursos de Publicidade e Propaganda. O estudo apresenta, entre os principais resultados, o desgaste e o engajamento docente, o despreparo das Instituições de Ensino (IES) e prejuízos à aprendizagem e à qualidade do ensino. Discute-se ainda outros aspectos relevantes do ensino remoto na pandemia, a saber: relação com as IES; condições do trabalho docente; desafios da atuação docente; recursos didáticos empregados; metodologias de ensino; experiências com aulas remotas.
Da Pedagogia da Educomunicação à Pedagogia na Educomunicação
Authors: Reginaldo Thiago , Sartori Ademilde Silveira
Published: March 2021

A Educomunicação é uma área que tem tido gradativamente mais visibilidade em instituições educacionais e suscita, portanto, articulação com a Pedagogia em pesquisas no intuito de compreender e contribuir para o paradigma educomunicativo. Nesse sentido, este estudo apresenta uma análise linguística das palavras e dos conceitos que a Educomunicação tem em seu âmbito pedagógico. A partir da reflexão teórica os autores deste artigo redefiniram terminologias e chegaram a área de interlocução denominada “Pedagogia na Educomunicação” como proposta que incorpora a Pedagogia da Comunicação, as Práticas Pedagógicas Educomunicativas (PPE) e os Ecossistemas Educomunicativos.
Programas de metas municipais sob olhar do Tribunal de Justiça de São Paulo
Authors: De Oliveira Souza Rebeca , Vilella Mariana
Published: March 2021

A pesquisa se debruçou sobre o entendimento do Tribunal de Justiça do Estado de São Paulo (TJSP) acerca da constitucionalidade de leis municipais instituidoras dos programas (ou “planos) de metas. Para isso, tomou como referência os primeiros estudos sobre a implementação do programa de metas no estado de São Paulo e a análise empírica das decisões judiciais sobre o tema no TJSP entre 2009-2019. A hipótese inicial era a de que as decisões pela inconstitucionalidade representavam uma interferência indevida do TJSP na elaboração de políticas públicas e inviabilizariam a utilização do instrumento a nível municipal. Notou-se, no entanto, que os casos foram trazidos ao Judiciário pelo próprio Executivo, que questionava a legitimidade do Poder Legislativo em editar normas referentes ao exercício de sua atividade administrativa. E que não é claro o impacto das decisões judiciais nos municípios, em que a referência a instrumentos similares se manteve. No âmbito do TJSP, careceu um olhar mais atento às particularidades de cada caso e até mesmo o enfrentamento de previsões similares a do programa de metas presentes no ordenamento jurídico brasileiro.
S-Nitrosylation of Histone Deacetylase 2 by Neuronal Nitric Oxide Synthase as a Mechanism of Diastolic Dysfunction
Authors: Yoon Somy , Kim Mira , Lee Hangyeol , Kang Gaeun , Bedi Kenneth , Margulies Kenneth B. , Jain Rajan , Nam Kwang-Il , Kook Hyun , Eom Gwang Hyeon
Published: March 2021

Background:

Although the clinical importance of heart failure with preserved ejection fraction has been extensively explored, most therapeutic regimens, including nitric oxide (NO) donors, lack therapeutic benefit. Although the clinical characteristics of heart failure with preserved ejection fraction are somewhat heterogeneous, diastolic dysfunction (DD) is one of the most important features. Here we report that neuronal NO synthase (nNOS) induces DD by S-nitrosylation of HDAC2 (histone deacetylase 2).

Methods:

Two animal models of DD—SAUNA (SAlty drinking water/Unilateral Nephrectomy/Aldosterone) and mild transverse aortic constriction mice—as well as human heart samples from patients with left ventricular hypertrophy were used. Genetically modified mice that were either nNOS-ablated or HDAC2 S-nitrosylation–resistant were also challenged. N(ω)-propyl-
L
-arginine, an nNOS selective inhibitor, and dimethyl fumarate, an NRF2 (nuclear factor erythroid 2–related factor 2) inducer, were used. Molecular events were further checked in human left ventricle specimens.

Results:

SAUNA or mild transverse aortic constriction stress impaired diastolic function and exercise tolerance without overt systolic failure. Among the posttranslational modifications tested, S-nitrosylation was most dramatically increased in both models. Utilizing heart samples from both mice and humans, we observed increases in nNOS expression and NO production. N(ω)-propyl-
L
-arginine alleviated the development of DD in vivo. Similarly, nNOS knockout mice were resistant to SAUNA stress. nNOS-induced S-nitrosylation of HDAC2 was relayed by transnitrosylation of GAPDH. HDAC2 S-nitrosylation was confirmed in both DD mouse and human left ventricular hypertrophy. S-nitrosylation of HDAC2 took place at C262 and C274. When DD was induced, HDAC2 S-nitrosylation was detected in wild-type mouse, but not in HDAC2 knock-in mouse heart that expressed HDAC2 C262A/C274A. In addition, HDAC2 C262A/C274A mice maintained normal diastolic function under DD stimuli. Gene delivery with adenovirus-associated virus 9 (AAV9)–NRF2, a putative denitrosylase of HDAC2, or pharmacological intervention by dimethyl fumarate successfully induced HDAC2 denitrosylation and mitigated DD in vivo.

Conclusions:

Our observations are the first to demonstrate a new mechanism underlying DD pathophysiology. Our results provide theoretical and experimental evidence to explain the ineffectiveness of conventional NO enhancement trials for improving DD with heart failure symptoms. More important, our results suggest that reduction of NO or denitrosylation of HDAC2 may provide a new therapeutic platform for the treatment of refractory heart failure with preserved ejection fraction.
Endothelial-Specific Deletion of CD146 Protects Against Experimental Glomerulonephritis in Mice
Authors: Abed Ahmed , Leroyer Aurélie S. , Kavvadas Panagiotis , Authier Florence , Bachelier Richard , Foucault-Bertaud Alexandrine , Bardin Nathalie , Cohen Clemens D. , Lindenmeyer Maja T. , Genest Magali , Joshkon Ahmad , Jourde-Chiche Noémie , Burtey Stéphane , Blot-Chabaud Marcel , Dignat-George Françoise , Chadjichristos Christos E.
Published: March 2021

CD146 is an endothelial junctional adhesion molecule, which expression is increased in human glomerular diseases. However, the pathological significance of this overexpression remains unknown. Induction of glomerulonephritis in mice, by using nephrotoxic serum, showed that CD146 expression was highly induced within damaged glomeruli and was associated with renal inflammation and fibrosis. Interestingly, 2 weeks after glomerulonephritis induction, CD146 knockout mice showed preserved renal function as proteinuria and blood urea nitrogen levels were significantly lower compared with wild-type littermates. Furthermore, renal structure was considerably conserved, since crescents formation, tubular dilation, monocyte and lymphocyte infiltration, and interstitial renal fibrosis were highly reduced. Colocalization with markers for different types of glomerular cells showed that CD146 expression was mainly increased within the injured endothelium of the glomerular tuft. Consequently, we generated a new transgenic strain in which CD146 was specifically deleted in the vascular endothelium. Similarly to CD146 knockout, these mice showed preservation of renal structure and function after the induction of glomerulonephritis compared with wild-type animals. These data show that endothelial CD146 plays a major role in glomerulonephritis and may represent a novel therapeutic target to reduce glomerular damage and the progression of renal disease.
Taxonomy and nomenclature of the southern Malagasy Kalanchoe peltigera, with reference to K. rosei var. seyrigii (Crassulaceae subfam. Kalanchooideae)
Authors: SHTEIN RONEN , SMITH GIDEON F.
Published: March 2021

The taxonomy and nomenclature of Kalanchoe peltigera (Crassulaceae subfam. Kalanchooideae) and K. rosei var. seyrigii, a long-overlooked name published in the 1940s, are evaluated with an aim to resolve the taxonomic status and affinities of K. peltigera, which was described in the mid-2000s. In particular, the taxonomic status of K. peltigera as an accepted species is examined in detail and verified based on a comparison with other known phyllo-bulbiliferous species of Kalanchoe i.e., those species that produce bulbils on the margins of their leaf blades typically between crenations, as opposed to flori-bulbiliferous, or stoloniferous species. We show that both K. peltigera and the original description of K. rosei var. seyrigii are based on collections made of a single species from locations in close proximity in southern Madagascar. Based on an examination of living material and type specimens, as well as other herbarium accessions, of which only a limited number exist, we conclude that K. peltigera and one of the two specimens cited when K. rosei var. seyrigii was described apply to the same species. However, despite its original description, the type of the name K. rosei var. seyrigii is that of the synonym it replaced, i.e., K. rosei subsp. serratifolia, a taxon less closely related to K. peltigera, and therefore the two names are not synonymous. A morphological evaluation suggests that K. rosei is likely to be sister to K. peltigera. The name K. peltigera is neotypified as its holotype is no longer extant.
A new species and genus of Alienopteridae (Blattodea) from mid-Cretaceous amber of northern Myanmar
Authors: CHEN XIN-YU , ZHANG HUA-CHUAN , SHI XIAOXIAO
Published: March 2021

Eminespina burma gen. et sp. nov., is described and illustrated based on a female embedded in Cretaceous Burmese amber of Cenomanian age. Autapomorphic are three unique spines distributed anterior quarter of pronotum from longer posterior part. The new evidence of Batesian mimicry in the insect fossil record is briefly discussed.
Analysis of the Atmospheric Water Cycle for the Laurentian Great Lakes Region Using CMIP6 Models
Authors: Minallah Samar , Steiner Allison L.
Published: March 2021

This study evaluates the historical climatology and future changes of the atmospheric water cycle for the Laurentian Great Lakes region using 15 models from phase 6 of the Coupled Model Intercomparison Project (CMIP6). While the models have unique seasonal characteristics in the historical (1981–2010) simulations, common patterns emerge in the midcentury SSP2–4.5 scenario (2041–70), including a prevalent shift in the precipitation seasonal cycle with summer drying and wetter winter and spring months, and a ubiquitous increase in the magnitudes of convective precipitation, evapotranspiration, and moisture inflow into the region. The seasonal cycle of moisture flux convergence is amplified (i.e., the magnitude of winter convergence and summer divergence increases), which is the primary driver of future total precipitation changes. The precipitation recycling ratio is also projected to decline in summer and increase in winter by midcentury, signifying a larger contribution of the regional moisture (via evapotranspiration) to total precipitation in the colder months. Most models (10/15) either do not represent the Great Lakes or have major inconsistencies in how the lakes are simulated both in terms of spatial representation and treatment of lake processes. In models with some lake presence, the contribution of lake grid cells to the regional evapotranspiration magnitude can be more than 50% in winter. In the future, winter months have a larger increase in evaporation over water surfaces than the surrounding land, which corroborates past findings of sensitivity of deep lakes to climate warming and highlights the importance of lake representation in these models for reliable regional hydroclimatic assessments.
The use of whole blood capillary samples to measure 15 analytes for a home-collect biochemistry service during the SARS-CoV-2 pandemic: A proposed model from North West London Pathology
Authors: Ansari Saleem , Abdel-Malek Mariana , Kenkre Julia , Choudhury Sirazum M , Barnes Sophie , Misra Shivani , Tan Tricia , Cegla Jaimini
Published: March 2021

Background

The COVID-19 pandemic has drastically changed the delivery of secondary care services. Self-collection of capillary blood at home can facilitate the monitoring of patients with chronic disease to support virtual clinics while mitigating the risk of SARS-CoV-2 infection and transmission.

Objective

To investigate the comparability of whole blood capillary and plasma venous samples for 15 routinely used biochemical analytes and to develop and pilot a user-friendly home-collection kit to support virtual outpatient clinical services.

Methods

To investigate the comparability of whole blood capillary and plasma venous samples for 15 routinely requested biochemical analytes, simultaneous samples of venous and capillary blood were collected in EDTA and lithium-heparin plasma separation tubes that were of 4–6 mL and 400–600 µL draw volume, respectively. Venous samples were analysed within 4 h of collection while capillary samples were kept at ambient temperature for three days until centrifugation and analysis. Analyte results that were comparable between the matrices were then piloted in a feasibility study in three outpatient clinical services.

Results

HbA1c, lipid profile and liver function tests were considered comparable and piloted in the patient feasibility study. The home-collect kit demonstrated good patient usability.

Conclusion

Home collection of capillary blood could be a clinically-useful tool to deliver virtual care to patients with chronic disease.
Emotional dysregulation mediates the impact of childhood trauma on psychological distress: First Italian data during the early phase of COVID-19 outbreak
Authors: Janiri Delfina , Moccia Lorenzo , Dattoli Luigi , Pepe Maria , Molinaro Marzia , De Martin Valentina , Chieffo Daniela , Di Nicola Marco , Fiorillo Andrea , Janiri Luigi , Sani Gabriele
Published: March 2021

Background:

The coronavirus disease 2019 pandemic represents an unprecedented traumatic stressor to mental health. Psychological distress is considered a reliable proxy for psychopathology and can be negatively influenced by childhood trauma through sensitization effects. Emotion dysregulation has been proposed as a potential mediator of this mechanism. We aimed to test this hypothesis in a national Italian sample assessed in the early phase of the coronavirus disease 2019 outbreak.

Methods:

We investigated the relationship between psychological distress and childhood trauma in 500 healthy participants assessed through a survey-based study, after the coronavirus disease 2019 pandemic lockdown in Italy. Levels of psychological distress and history of childhood trauma were obtained using the Kessler-10 (K10) and the Childhood Trauma Questionnaire, respectively. We used bootstrapped mediation analysis to test the mediator role of emotional dysregulation, measured through the Difficulties in Emotion Regulation Scale, on the effect of childhood trauma on psychological distress.

Results:

In total, 190 (38%) reported psychological distress related to the coronavirus disease 2019 outbreak. Individuals with psychological distress experienced more childhood trauma, specifically emotional abuse ( F = 23.51, df = 1, p < 0.001) and neglect ( F = 10.98, df = 1, p = 0.001). After modelling the effect of emotional dysregulation, the impact of childhood trauma on coronavirus disease 2019-related psychological distress resulted in indirect effects and mediated by deficits in emotion regulation mechanisms (bootstrapped lower level of confidence interval = 0.345, upper level of confidence interval = 0.598).

Conclusion:

Childhood trauma is associated with increased vulnerability to the stressful effect of the coronavirus disease 2019 outbreak. Our data suggest that emotional dysregulation may represent a dimension mediating the impact of childhood trauma on coronavirus disease 2019-related psychological distress and may be considered as specific target for interventions aiming at empowering resilience.
Looking Back to Move Forward: Canadian Occupational Therapy In Public Health, 1914–2019
Authors: Lewis Kathryn E. , Lehman Michelle J. , Cockburn Lynn
Published: March 2021

Background.

Decades of literature demonstrate that occupational therapy is well-suited to collaborate with public health due to overlapping views of health. However, there has been little collaboration between these professions with few examinations of why they remain distinct.

Purpose.

This study examines historical events that have led to the present-day separation of occupational therapy and public health.

Method.

This narrative review and thematic analysis of the scholarly, archival, and grey literature was conducted to examine the development of both fields.

Findings.

Fifty texts were analyzed revealing four themes: the influence of structural and social forces; professional, societal, and institutional hindrances; potential for a shared vision; and next steps for integration. These themes highlight historical barriers to collaboration and provide evidence that occupational therapy could benefit public health.

Implications.

Collaboration between occupational therapy and public health has many potential benefits, however new approaches to bridge the divide are needed to advance collaboration.
Drinking Alone: Local Socio-Cultural Degradation and Radical Right Support—The Case of British Pub Closures
Authors: Bolet Diane
Published: March 2021

Little is known about how local context influences radical right voting. This paper advances the theory that the degradation of local socio-cultural hubs is linked to radical right support by contributing to loss of community and cultural identity. I examine this thesis by exploiting an original dataset on British community pub closures. I argue that the disappearance of community pubs triggers social isolation and signals the decline of the British working class condition, which is associated with UKIP support. Combining district-level data with UK panel data (2013–2016), I show that individuals living in districts that experience one additional community pub closure (relative to the total number of pubs per district) are more likely to support UKIP than any other party by 4.3 percentage points. The effect is magnified under conditions of material deprivation. This paper highlights the significance of local socio-cultural degradation as a mechanism to explain radical right support.
Identifying Constraints on Everyday Clinical Practice: Applying Work Domain Analysis to Emergency Department Care
Authors: Austin Elizabeth , Blakely Brette , Salmon Paul , Braithwaite Jeffrey , Clay-Williams Robyn
Published: March 2021

Background

Emergency departments (EDs) are complex socio-technical work systems that require staff to manage patients in an environment of fluctuating resources and demands. To better understand the purpose, and pressures and constraints for designing new ED facilities, we developed an abstraction hierarchy model as part of a work domain analysis (WDA) from the cognitive work analysis (CWA) framework. The abstraction hierarchy provides a model of the structure of the ED, encompassing the core objects, processes, and functions relating to key values and the ED’s overall purpose.

Methods

Reviews of relevant national and state policy, guidelines, and protocol documents applicable to care delivery in the ED were used to construct a WDA. The model was validated through focus groups with ED clinicians and subsequently validated using a series of WDA prompts.

Results

The model shows that the ED system exhibits extremely interconnected and complex features. Heavily connected functions introduce vulnerability into the system with function performance determined by resource availability and prioritization, leading to a trade-off between time and safety priorities.

Conclusions

While system processes (e.g., triage, fast-track) support care delivery in ED, this delivery manifests in complex ways due to the personal and disease characteristics of patients and the dynamic state of the ED system. The model identifies system constraints that create tension in care delivery processes (e.g., electronic data entry, computer availability) potentially compromising patient safety.

Application

The model identified aspects of the ED system that could be leveraged to improve ED performance through innovative ED system design.
Comparing traditional and constrained disturbance-observer based positional control
Authors: Bélai Igor , Huba Mikulas , Vrancic Damir
Published: March 2021

This paper compares three different position controllers of electrical drives equipped by binomial [Formula: see text] th order filters, which are offering filtering properties important in a quantization noise attenuation. To demonstrate their impact, a non-filtered P-PI control is considered, as a reference. The comparative framework includes a filtered P-PI control, a filtered linear pole assignment PD controllers with a disturbance observer (DO) based integral action and its constrained modification. In terms of a total variation, depending on noise and process properties, all filtered controllers are capable to bring down the undue controller activity at the plant input from 10 to more than 100 times. Furthermore, thanks to the applied disturbance observer, the constrained control derived for a double integrator is shown to fully exploit the closed loop capabilities without any trajectory generation, taking into account the control constraints. Thus, the simplified controller design may focus on other important aspects.
Postcolonial disjuncture: Kashmir as the other in Basharat Peer’s Curfewed Night
Authors: Pal Payel
Published: March 2021

Basharat Peer’s Curfewed Night (2008) is a perspicacious commentary on the violence, exile and dispossession that have wrecked the lives of ordinary Kashmiris since 1947. Peer compellingly ruminates on the gradual loss of the Kashmiris’ belongingness in the last few decades that eventually curtailed their sense of individual and collective selfhood. The present article aims to analyse how Peer’s memoir emerges as a crucial intervention in focusing on the othering of Kashmiris in postcolonial India. This article will examine how Peer’s personal story shapes his creative expression of homeland and uncovers the gradual stymieing of Kashmiri Muslim citizenship and identity under Indian statehood, perhaps most alarmingly manifested in the abrogation of Article 370 in 2019. This article will look at how Peer’s narrative interrogates the predominating imaginations of Kashmir as the other in the pan-Indian psyche and engages with the inherent "ambivalence" of the nationalist discourse of India. Accordingly, the article will also study how Peer positions Kashmir as a "heterotopic space" that transcends any form of monolithic comprehension. In so doing, Peer’s memoir emerges as an alternative and autoethnographic chronicling of the Kashmir story undercutting the dominant assumptions, reinforced by the Indian nationalist project. Pertinently, the concepts of "ambivalence" and "heterotopia" are drawn from the theoretical perspectives of Homi Bhabha and Michael Foucault, respectively.
The Lockerbie Aircraft Bombing Case and the Final Appeal
Authors: Shiels Robert
Published: March 2021

The only person against whom a charge of murder was proved in regard to the Lockerbie bombing case in 1988 had an appeal against conviction refused. A subsequent referral of the case back for further consideration by appellate judges was abandoned by the appellant. He was released on the statutory ground of compassion due to his imminent death. The appeal was revived after further investigation and fresh evidence and referred to the criminal appeal court for Scotland.
Redefining a Secondary Education Program Through the Use of Service-Learning Field Experiences
Authors: Tinkler Alan , Tinkler Barri , Prue Jennifer , Cravedi Lia
Published: March 2021

To expand the field component of our secondary education program, we added service-learning field experiences to three courses. This qualitative study ( n = 99) was designed to determine what our students learned from participating in these experiences and to examine whether the experiences supported our programmatic goals. The findings demonstrate that students developed an increased awareness of diversity in the local schools and community, they acquired knowledge of strategies for engaging and communicating with parents, they developed a more nuanced understanding of learners, and they improved their foundation of effective pedagogy for English language learners.
Family Interaction and Depressive Symptoms in Chinese Emerging Adults: A Mediation Model of Gratitude
Authors: Lam Kelly Ka Lai , Chen Wei-Wen
Published: March 2021

In this study, we investigated the relations between family interaction, gratitude, and depressive symptoms among Chinese emerging adults. It also investigated gratitude as a mediator in the relation between family interaction and depression. Data were obtained from 321 college students who completed the online questionnaire about the Family Assessment Instrument, Gratitude Questionnaire, Patient Health Questionnaire, and demographic information. Structural equation modeling (SEM) was used to test hypotheses and bootstrapping with 5,000 resamplings (95% confidence interval) was used to confirm the mediation model. Results showed that gratitude partially mediated the relation between family interaction and depression. In other words, students with healthy family interaction, as indicated by perceived better family communication, mutuality, and harmony with family members, tended to report higher general gratitude, and subsequently diminished depressive symptoms. The practical implications were discussed.
Distance Between Home and the Admitting Hospital and Its Effect on Survival of Low Socioeconomic Status Population With Staphylococcus aureus Bacteremia
Authors: Minejima Emi , Wang Joshua , Boettcher Stormmy , Liu Lihua , Lou Mimi , She Rosemary C. , Wenzel Suzanne L. , Spellberg Brad , Wong-Beringer Annie
Published: March 2021

Objective:

Bacteremia is the presence of bacteria in the bloodstream. The objective of this study was to determine the relationship between low socioeconomic status (SES) and the epidemiology, process of care, and outcomes of patients with Staphylococcus aureus bacteremia (SAB).

Methods:

We conducted a multicenter, retrospective, cohort study that evaluated adult patients with SAB in 3 Los Angeles County hospitals from July 15, 2012, through May 31, 2018. We determined SES (low SES, intermediate SES, and high SES) for each patient and compared sociodemographic and epidemiologic characteristics, management of care received by patients with SAB (ie, process of care), and outcomes. We used a Cox proportional hazards model to determine predictors of 30-day mortality for each SES group.

Results:

Of 915 patients included in the sample, 369 (40%) were in the low-SES group, 294 (32%) in the intermediate-SES group, and 252 (28%) in the high-SES group. Most significant predictors of 30-day mortality in the Cox proportional hazards model were admission to an intensive care unit (hazard ratio [HR] = 9.04; 95% CI, 4.26-19.14), Pitt bacteremia score ≥4 indicating critical illness (HR = 4.30; 95% CI, 2.49-7.44), having ≥3 comorbidities (HR = 2.05; 95% CI, 1.09-3.85), and advanced age (HR = 1.03; 95% CI, 1.01-1.05). Distance between home and admitting hospital affected mortality only in the low-SES group (HR = 1.02; 95% CI, 1.00-1.02).

Conclusions:

SES did not independently affect the outcome of SAB; however, the farther the patient’s residence from the hospital, the greater the negative effect on survival in a low-SES population. Our findings underscore the need to develop multipronged, targeted public health efforts for populations that have transportation barriers to health care.
Investigation of fiber slippage in the chopping process of carbon fiber tows under rigid support
Authors: Lu Longsheng , Gao Fei , Chen Yang , Xie Yingxi
Published: March 2021

As an important application form of carbon fiber (CF), short CFs and their production process have self-evident research value. In this work, the chopping process of CF tows under rigid support and the essential cause of high cutting forces were explored. Large-tow CFs containing 1–3000 single filaments were chopped, and the fracture processes were observed and described. It was found that obvious fiber slippage phenomena and intermediate fracture behaviors occurred during the chopping process. These factors not only increased the cutting force but also caused an uneven distribution of the cutting force along the width. A mechanical model was established to explain the fiber slippage and intermediate fracture. Based on material mechanics and analytical mechanics, the real process of fiber slippage and intermediate fracture was described by Hamilton’s principle. Moreover, a width constraint experiment was designed to indirectly verify fiber slippage phenomena and intermediate fracture behaviors. Through the analysis of the stress curve, it was proven that a reasonable width constraint could effectively limit fiber slippage and improve the uniformity of the distribution of the cutting force along the width of the tool, thus reducing the cutting force. This work can be used as an excellent guide for the chopping process in CF production.