bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rodent models of hypertension
Authors: Jama Hamdi A. , Muralitharan Rikeish R. , Xu Chudan , O'Donnell Joanne A. , Bertagnolli Mariane , Broughton Bradley R. S. , Head Geoffrey A. , Marques Francine Z. 
Published: August 2021

Elevated blood pressure (BP), or hypertension, is the main risk factor for cardiovascular disease. As a multifactorial and systemic disease that involves multiple organs and systems, hypertension remains a challenging disease to study. Models of hypertension are invaluable to support the discovery of the specific genetic, cellular and molecular mechanisms underlying essential hypertension, as well as to test new possible treatments to lower BP. Rodent models have proven to be an invaluable tool for advancing the field. In this review, we discuss the strengths and weaknesses of rodent models of hypertension through a systems approach. We highlight the ways how target organs and systems including the kidneys, vasculature, the sympathetic nervous system (SNS), immune system and the gut microbiota influence BP in each rodent model. We also discuss often overlooked hypertensive conditions such as pulmonary hypertension and hypertensive‐pregnancy disorders, providing an important resource for researchers.LINKED ARTICLESThis article is part of a themed issue on Preclinical Models for Cardiovascular disease research (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.5/issuetoc
Loss of Krüppel‐like factor 9 facilitates stemness in ovarian cancer ascites‐derived multicellular spheroids via Notch1/slug signaling
Authors: Wang Kun , Liu Shujie , Dou Zhiyuan , Zhang Shuo , Yang Xingsheng 
Published: August 2021

AbstractThe ascites that develops in advanced OC, both at diagnosis and upon recurrence, is a rich source of multicellular spheroids/aggregates (MCSs/MCAs), which are the major seeds of tumor cell dissemination within the abdominal cavity. However, the molecular mechanism by which specific ascites‐derived tumor cells survive and metastasize remains largely unknown. In this study, we elucidated cancer stem cell (CSC) properties of ascites‐derived MCSs, concomitant with enhanced malignancy, induced EMT, and low KLF9 (Krüppel‐like factor 9) expression, compared with PTCs. KLF9 was also downregulated in OC cell line‐derived spheroids and the CD117+CD44+ subpopulation in MCSs. Functional experiments demonstrated that KLF9 negatively modulated stem‐like properties in OC cells. Mechanistic studies revealed that KLF9 reduced the transcriptional expression of Notch1 by directly binding to the Notch1 promoter, thereby inhibiting the function of slug in a CSL‐dependent manner. Clinically, expression of KLF9 was associated with histological grade and loss of KLF9 predicts poor prognosis in OC.
Evidence for causal associations between prenatal and postnatal antibiotic exposure and asthma in children, England
Authors: Souza da Cunha Sergio , Santorelli Gillian , Pearce Neil , Wright John , Oddie Sam , Petherick Emily , Pembrey Lucy 
Published: August 2021

AbstractBackgroundHigher risks of asthma have been observed in children with prenatal exposure to antibiotics and during early life compared with those who have not. However, the causality of such associations is unclear.ObjectiveTo assess whether exposure to antibiotics in early life had a causal effect in increasing the risk of asthma in children diagnosed at 5–8 years of life, and the impact in the target population.MethodsData were from electronic health records and questionnaires for children and their mothers in the Born in Bradford birth cohort. Exposure variables were prescriptions of systemic antibiotics to the mother during pregnancy (prenatal) and to the children at 0–24 months of life (postnatal). We assessed the association in 12,476 children with several approaches to deal with different sources of bias (triangulation): the interactions with mother's ethnicity, mode of delivery, and between prenatal and postnatal exposures; dose‐response; and estimated the population attributable risk.ResultsThere was an association between prenatal exposure at 7–27 days before the child's birth and asthma (adjusted OR = 1.40; 1.05, 1.87), but no association with the negative control exposure (before pregnancy) (adjusted OR = 0.99 (0.88, 1.12)). For postnatal exposure, the adjusted OR was 2.00 (1.71, 2.34), and for sibling analysis, it was 1.99 (1.00, 3.93). For postnatal exposure, the risk of asthma increased with the number of prescriptions. The observed effect of both exposures was lower among children with mothers of Pakistani ethnicity, but inconclusive (p > .25). The interaction between prenatal and postnatal exposures was also inconclusive (p = .287). The population attributable risk of postnatal exposure for asthma was 4.6% (0.1% for prenatal).ConclusionsWe conclude that the associations between both late‐pregnancy prenatal exposure to antibiotics and postnatal exposure to antibiotics and an increased risk of asthma are plausible and consistent with a causal effect.
Safety and efficacy of mycophenolate mofetil in myelin oligodendrocyte glycoprotein‐immunoglobulin G‐associated disorder among adults: A meta‐analysis
Authors: Kharel Sanjeev , Ojha Rajeev , Ghimire Rakesh , Guragain Neha , Mudvari Anish 
Published: August 2021

AbstractObjectiveMyelin oligodendrocyte glycoprotein immunoglobulin G‐associated disorder (MOGAD) is an autoimmune demyelinating disorder of the central nervous system having distinct clinical phenotypes and epidemiological distribution than multiple sclerosis and neuromyelitis optica spectrum disorder. Mycophenolate mofetil has shown good safety and efficacy in multiple sclerosis and neuromyelitis optica spectrum disorder patients, but the published case series and observational studies of MOGAD showed contrasting results. Thus, we felt the need to carry out a meta‐analysis.MethodsWe searched PubMed, Embase, Cochrane Library, Google Scholar and additional sources for suitable studies. Meta‐analysis through representative forest plot was carried out for the proportion of relapse‐free patients, change in annualized relapse ratio and Expanded Disability Status Scale before and after treatment, and reduction of relapse risk.ResultsA total of nine studies were included in our meta‐analysis. Mycophenolate mofetil treatment showed approximately half the proportion (49%; 95% CI 0.26–0.73, P < .001) of relapse‐free patients at follow up. It also significantly reduced the mean annualized relapse (mean difference 0.76, 95% CI 0.49–1.03, P < .001) and relapse risk (hazard ratio 1.25, 95% CI −2.48 to −0.01, P < 0.05), but did not show a significant difference in change in Expanded Disability Status Scale score (mean difference 0.34, 95% CI −0.79 to 1.47, P = 0.56). On subgroup analysis, administration of a high dose (>2000 mg/day) showed a greater proportion of relapse‐free patients. Infections, leukopenia, fatigue, alopecia and diarrhea were common side‐effects. A total of 10.32% of patients discontinued treatment, mainly due to treatment failure.ConclusionsThe present meta‐analysis shows mycophenolate mofetil therapy as cost‐effective, well tolerated and effective for the treatment of relapses in MOGAD among adult patients.
Patient perspectives on surveillance after head and neck cancer treatment: A systematic review
Authors: McLaren Oliver , Perkins Clare , Zhu Yinan , Smith Mary , Williams Richard 
Published: August 2021

AbstractObjectivesCurrent guidelines advise post‐treatment surveillance of head and neck cancer (HNC) patients should involve scheduled appointments with a variety of practitioners. Increasing numbers of HNC survivors raise the burden to provide efficient and effective care. With resource limitation, there is growing importance to identify how surveillance can be justified and optimised for survivors. This systematic review presents current evidence on patient perspectives of post‐treatment HNC surveillance, aiming to inform future work putting patient priorities at the forefront of surveillance planning.DesignMEDLINE, Embase, the Cochrane Library, NIHR Dissemination Centre, The Kings Fund Library, Clinical Evidence, NHS Evidence and NICE Clinical Evidence were searched to identify publications regarding patient perspectives of HNC post‐treatment surveillance. Studies not reporting on both surveillance and patient perspectives were excluded.ResultsThree thousand five hundred fifty‐eight citations were screened and 49 full‐text articles reviewed. Sixteen studies were included in the final review. Three authors reviewed all articles prior to final analysis to ensure all met inclusion criteria. Most evidence was low quality. Study models returned included cross‐sectional surveys, structured interviews and one systematic review. Overall, positive perceptions of HNC surveillance were mostly related to increased reassurance. Negative perceptions predominantly focused on anxiety and fear of recurrence, but a lack of psychological support and inadequate access to certain aspects of care were also reported.ConclusionsThis systematic review demonstrates that patients’ perceptions of surveillance after HNC are mostly positive, feeling it provides reassurance. However, several studies report unmet needs, particularly regarding managing anxiety.
Poor‐quality monitoring data underestimate the impact of Australia's megafires on a critically endangered songbird
Authors: Crates Ross , Rayner Laura , Stojanovic Dejan , Scheele Ben C. , Roff Adam , MacKenzie Jason , Heinsohn Robert 
Published: August 2021

AbstractAimCatastrophic events such as south‐eastern Australia's 2019/20 megafires are predicted to increase in frequency and severity under climate change. Rapid, well‐informed conservation prioritization will become increasingly crucial for minimizing biodiversity losses resulting from megafires. However, such assessments are susceptible to bias, because the quality of monitoring data underpinning knowledge of species' distributions is highly variable and they fail to account for differences in life history traits such as aggregative breeding. We aimed to assess how impact estimates of the 2019/20 megafires on the critically endangered regent honeyeater Anthochaera phrygia varied according to the quality of available input data and assessment methodology.InnovationUsing Google Earth Engine Burnt Area Mapping, we estimated the impact of the megafires on the regent honeyeater using six monitoring datasets that differ in quality and temporal span. These datasets are representative of the variable quality of monitoring data available for assessing fire impact on 326 other threatened species; most are poorly monitored, and few have standardized, species‐specific monitoring programmes. We found that assessments based on area of occupancy (AOO), extent of occurrence (EOO) and public sightings underestimated the fire impact relative to recent, targeted monitoring datasets: a MaxEnt model, sightings from a national monitoring programme and nest locations since 2015. Using an impact threshold of 30% of habitat burned, regent honeyeaters would not meet these criteria using estimates derived from EOO, AOO or public sightings, but would exceed the cut‐off based on estimates derived from the targeted monitoring data that account for population density.Main conclusionsTo ensure that conservation prioritization has the greatest capacity to minimize biodiversity losses, we highlight the need to improve targeted, threatened species monitoring. We demonstrate the importance of using recent, standardized monitoring data to estimate accurately the impact of major ecological disturbances, particularly for declining, nomadic species undergoing range contractions.
Trade openness and income inequality: New empirical evidence
Authors: Dorn Florian , Fuest Clemens , Potrafke Niklas 
Published: August 2021

AbstractWe examine how trade openness influences income inequality within countries. The sample includes 139 countries over the period 1970–2014. We employ predicted openness as instrument to deal with the endogeneity of trade openness. The effect of trade openness on income inequality differs across countries. Trade openness tends to disproportionately benefit the relative income shares of the very poor, but not necessarily all poor, in emerging and developing economies. In most advanced economies, trade openness increased income inequality, an effect that is driven by outliers. Our results suggest a strong effect of trade openness on inequality in China and transition countries.
Field evaluation of resistance to tea green leafhopper, Empoasca onukii, in tea plant
Authors: Yorozuya Hiroshi , Sudo Masaaki , Sato Yasushi 
Published: August 2021

AbstractThe tea green leafhopper, Empoasca onukii Matsuda (Hemiptera: Cicadellidae, Typhlocybinae), is a serious pest of tea plants in East Asia. In the laboratory, tea genotypes CA278, Cd19, and Cd289 [Camellia sinensis (L.) O. Kuntze (Theaceae)] sustain fewer feeding damage symptoms known as hopperburn than the susceptible cultivar ‘Yabukita,’ and E. onukii excretes less honeydew on them than on Yabukita. Here, we evaluated whether these genotypes have practical and sufficient resistance under field conditions. The densities of E. onukii eggs, larvae, and adults on tea shoots and the degree of feeding damage were compared as indicators of resistance. Genotypes Cd19 and Cd289 showed strong resistance and CA278 showed moderate resistance under field conditions. Therefore, Cd19 and Cd289 are favorable materials for breeding tea cultivars with resistance to tea green leafhopper. We propose selection methods for breeding new resistant tea cultivars.
Drosophila melanogaster mutant for the dopamine recycling pathway shows altered biological parameters and increased lifespan
Authors: Pérez Martín M. , Rossi Fabiana A. , Sabio Germán A. , Bochicchio Pablo A. , Leal María C. , Quesada‐Allué Luis A. , Rabossi Alejandro 
Published: August 2021

AbstractThe ebony and tan genes in Drosophila melanogaster Meigen (Diptera: Drosophilidae) participate in a very peculiar (and exclusive to insects) recycling pathway of neurotransmitters, mainly dopamine (DA) and histamine, in the nervous system and regulate the intensity of tanning in the cuticle. The ebony and tan mutants show altered levels of neurotransmitters, which give rise to developmental and behavioral impairments. The mutant tan lacks N‐β‐alanyldopamine hydrolase (NBAD‐hydrolase) activity; therefore it is unable to liberate DA from NBAD. Here, we studied developmental traits in tan1 mutant and previously unknown biological parameters in adult males, such as oxygen consumption, antioxidant capacity, lifespan, and the expression of detoxifying enzymes in the central nervous system. We compared them with those of wt Canton S and the mutant ebony1. Our results show that although tan1 mutant had high mortality during the immature stages, adult males had a significantly longer lifespan than wt and ebony1 mutant; the latter had the shortest lifespan. The longer lifespan of tan1 was not due to caloric restriction. We found that the nervous system of tan1 males had a higher antioxidant capacity. After provoking mild oxidative stress by the ingestion of hematoporphyrin, tan1 males still had a significantly longer lifespan than wt, whereas the ebony1 mutant had a shorter one. Under these conditions, tan1 showed an increased expression of catalase mRNA. Our results suggest that lower levels of free DA in the nervous system together with higher antioxidant activities seem to favor an extended lifespan in D. melanogaster tan1 males.
Secondary cluster headache due to a contralateral demyelinating periaqueductal gray matter lesion
Authors: Fiore Alessia , Tsantes Elena , Curti Erica , Bazzurri Veronica , Granella Franco 
Published: August 2021

AbstractObjectives/BackgroundTension‐type headache and migraine without aura are the most common primary headaches occurring in people with demyelinating diseases, whereas cluster headache (CH) can be considered exceptional. The location of demyelinating lesions could be strategic in these cases, involving areas interacting with the trigeminovascular system.Methods and ResultsWe report a case of a 54‐year‐old woman with right‐sided CH as the initial manifestation of multiple sclerosis and showing a left dorsal brainstem lesion on magnetic resonance imaging, in the region of the dorsal longitudinal fasciculus (DLF).ConclusionOur case seems to suggest a possible role of the DLF in the process that leads to CH attacks. Because neuroimaging clearly showed a lesion contralateral to CH pain, we hypothesize that some fibers from periaqueductal gray matter project to the contralateral side, besides the known ipsilateral connections.
Cutaneous myiasis in skin cancer and malignant wounds: a systematic review
Authors: Cuestas Daniel , Pedraza John , Herrera Hugo , Motta Adriana , Cuestas Andrés , Forero Yency , Porras Ricardo , Urrea Fernando , Galvis Dany , Galvis Ingrid , Bernal Maria‐Alejandra , Alvarado Maria‐Victoria , Bula Rosa , Velasquez Oscar , Villalba Dennys , Lamus Sergio , Ariza Gabriel , Bayona Natalia , Gutierrez Ana , Segura Alexandra , Patiño Monica , Perafan Alejandra , Ramirez‐Rodriguez Santiago , Rolon Mariam 
Published: August 2021

AbstractBackgroundCutaneous myiasis in patients with malignant wounds or skin cancer is a rare and undesirable event with limited epidemiological data. A subregister of reports, lack of education in the population, inadequate empirical treatments, and medical underestimation are components of a public health problem that threatens patients' lives.MethodsWe conducted a systematic review of the literature of cutaneous myiasis associated with malignant wounds and skin cancer, characterizing sociodemographic variables, risk factors, clinical and histological features, and treatment. Additionally, we present a demonstrative case with the adequate taxonomic evaluation.DiscussionCutaneous myiasis is an underestimated and poorly managed infestation, which can generate severe complications in oncological patients. This is the first systematic review in the literature about this clinical scenario, which provides information to the physician and clinical researcher about the epidemiological gaps and what has been published so far.ConclusionsFindings from the current review have helped to display the sociodemographic, epidemiological, and clinical behavior of myiasis in skin cancer and malignant wounds. Its contribution to the greater tumor tissue destruction is clear; however, more studies are required. The therapeutic management in these patients is equally clarified.
Regulation of mitochondrial dynamics in skin: role in pathophysiology
Authors: Gupta Divya , Abdullah Tasduq S. 
Published: August 2021

AbstractSkin is a dynamic interface between the external environment and internal organs. It has high turnover that allows the renewal of dead skin cells, thus maintaining a healthy skin homeostasis. Mitochondria fulfills all the energy needs for these cells. In addition, mitochondria are an active source of free radicals that have been determined as crucially important in skin health and disease. The common notion of limited role of mitochondria as merely the cellular powerhouse has drastically changed. Several extracellular stressors have proved to induce impairment in the dynamic properties of mitochondria such as fusion and fission, which further leads to an activation of selective autophagic response known as mitophagy. Altered mitochondrial dynamics have been lately associated with skin photodamage and cutaneous manifestations of several diseased states, thereby suggesting it to be an effective therapeutic target. This review summarizes the molecular mechanisms involved with impaired mitochondrial dynamics and its potential role in skin health and disease.
LINC00472 suppressed by ZEB1 regulates the miR‐23a‐3p/FOXO3/BID axis to inhibit the progression of pancreatic cancer
Authors: Bi Cong , Wang Gang 
Published: August 2021

AbstractThe tumour‐suppressive role of LINC00472 has been extensively reported in various human cancers such as lung, colon and ovarian cancers, yet its function in pancreatic cancer remains unidentified. Here, the current research aimed to explore the role and regulatory axis mediated by LINC00472 in the progression of pancreatic cancer. RT‐qPCR was adopted to determine LINC00472 expression in the harvested pancreatic cancer tissues and adjacent normal tissues. Loss‐of‐function and gain‐of‐function experiments were performed to examine the effects of LINC00472 on proliferation and apoptosis in vitro and tumorigenesis in vivo. Immunoblotting was performed to detect the expression of several proliferation and apoptosis‐related proteins. Bioinformatic analysis, dual‐luciferase reporter assay and RNA pull‐down were conducted to profile the relationships between LINC00472 and miR‐23a‐3p, between miR‐23a‐3p and FOXO3 and between FOXO3 and BID. The LINC00472 expression was down‐regulated by ZEB1 in the pancreatic cancer cells and tissues. LINC00472 could competitively bind to miR‐23a‐3p to enhance the expression of FOXO3, which consequently could promote the BID expression, thereby suppressing proliferation and promoting the apoptosis of pancreatic cancer cells. Meanwhile, the inhibitory role of LINC00472 in tumorigenesis was validated in vivo, and the LINC00472‐mediated miR‐23a‐3p/FOXO3/BID axis was also demonstrated in the nude mouse tumour formation model. The study substantiated the antitumour activity of LINC00472 in pancreatic cancer and proposed a regulatory axis in which LINC00472 competitively binds to miR‐23a‐3p to enhance the FOXO3 expression and promote BID expression. Consequently, these findings provide theoretical basis for developing potential targets for the treatment of pancreatic cancer.
The stressosome, a caspase‐8‐activating signalling complex assembled in response to cell stress in an ATG5‐mediated manner
Authors: Mnich Katarzyna , Koryga Izabela , Pakos‐Zebrucka Karolina , Thomas Melissa , Logue Susan E. , Eriksson Leif A. , Gorman Adrienne M. , Samali Afshin 
Published: August 2021

AbstractStress‐induced apoptosis is mediated primarily through the intrinsic pathway that involves caspase‐9. We previously reported that in caspase‐9‐deficient cells, a protein complex containing ATG5 and Fas‐associated death domain (FADD) facilitated caspase‐8 activation and cell death in response to endoplasmic reticulum (ER) stress. Here, we investigated whether this complex could be activated by other forms of cell stress. We show that diverse stress stimuli, including etoposide, brefeldin A and paclitaxel, as well as heat stress and gamma‐irradiation, caused formation of a complex containing ATG5‐ATG12, FADD and caspase‐8 leading to activation of downstream caspases in caspase‐9‐deficient cells. We termed this complex the ‘stressosome’. However, in these cells, only ER stress and heat shock led to stressosome‐dependent cell death. Using in silico molecular modelling, we propose the structure of the stressosome complex, with FADD acting as an adaptor protein, interacting with pro‐caspase‐8 through their respective death effector domains (DEDs) and interacting with ATG5‐ATG12 through its death domain (DD). This suggests that the complex could be regulated by cellular FADD‐like interleukin‐1β‐converting enzyme–inhibitory protein (cFLIPL), which was confirmed experimentally. This study provides strong evidence for an alternative mechanism of caspase‐8 activation involving the stressosome complex.