bluuebunny/crossref_metadata_2025 huggingface dataset:
Tumour‐derived exosomal miR‐3473b promotes lung tumour cell intrapulmonary colonization by activating the nuclear factor‐κB of local fibroblasts
Authors: Du Cancan , Duan Xixi , Yao Xiaohan , Wan Jiajia , Cheng Yanru , Wang Yuan , Yan Yan , Zhang Lijing , Zhu Linyu , Ni Chen , Wang Ming , Qin Zhihai
Published: May 2020

Tumour‐derived exosomes have been shown to induce pre‐metastatic niche formation, favoring metastatic colonization of tumour cells, but the underlying molecular mechanism is still not fully understood. In this study, we showed that exosomes derived from the LLC cells could indeed significantly enhance their intrapulmonary colonization. Circulating LLC‐derived exosomes were mainly engulfed by lung fibroblasts and led to the NF‐κB signalling activation. Further studies indicated that the exosomal miR‐3473b was responsible for that by hindering the NFKB inhibitor delta's (NFKBID) function. Blocking miR‐3473b could reverse the exosome‐mediated NF‐κB activation of fibroblasts and decrease intrapulmonary colonization of lung tumour cells. Together, this study demonstrated that the miR‐3473b in exosomes could mediate the interaction of lung tumour cells and local fibroblasts in metastatic sites and, therefore, enhance the metastasis of lung tumour cells.
FOXO1 contributes to diabetic cardiomyopathy via inducing imbalanced oxidative metabolism in type 1 diabetes
Authors: Yan Dan , Cai Yin , Luo Jierong , Liu Jingjin , Li Xia , Ying Fan , Xie Xiang , Xu Aimin , Ma Xiaosong , Xia Zhengyuan
Published: May 2020

Forkhead box protein O1 (FOXO1), a nuclear transcription factor, is preferably activated in the myocardium of diabetic mice. However, its role and mechanism in the development of diabetic cardiomyopathy in non‐obese insulin‐deficient diabetes are unclear. We hypothesized that cardiac FOXO1 over‐activation was attributable to the imbalanced myocardial oxidative metabolism and mitochondrial and cardiac dysfunction in type 1 diabetes. FOXO1‐selective inhibitor AS1842856 was administered to streptozotocin‐induced diabetic (D) rats, and cardiac functions, mitochondrial enzymes PDK4 and CPT1 and mitochondrial function were assessed. Primary cardiomyocytes isolated from non‐diabetic control (C) and D rats were treated with or without 1 µM AS1842856 and underwent Seahorse experiment to determine the effects of glucose, palmitate and pyruvate on cardiomyocyte bioenergetics. The results showed diabetic hearts displayed elevated FOXO1 nuclear translocation, concomitant with cardiac and mitochondrial dysfunction (manifested as elevated mtROS level and reduced mitochondrial membrane potential) and increased cell apoptosis (all P < .05, D vs C). Diabetic myocardium showed impaired glycolysis, glucose oxidation and elevated fatty acid oxidation and enhanced PDK4 and CPT1 expression. AS1842856 attenuated or prevented all these changes except for glycolysis. We concluded that FOXO1 activation, through stimulating PDK4 and CPT1, shifts substrate selection from glucose to fatty acid and causes mitochondrial and cardiac dysfunction.
Characterization of the monoclonal antibody specific to the ORF72 protein of koi herpesvirus and cellular distribution analysis of the viral protein
Authors: Wu Ching‐Wei , Wu Ting‐Yun , Kuo Chih‐Jung , Lu Yi‐Ping , Chien Maw‐Sheng , Huang Chienjin
Published: May 2020

Koi herpesvirus (KHV) is an emerging pathogen of koi and common carp that causes a severe disease and mass mortality of infected fish. The KHV ORF72 protein is an important capsid protein that has been suggested to be a candidate for the development of diagnostic reagents and KHV vaccines. The purpose of this study was to clone and express the KHV ORF72 gene for further preparation of a specific monoclonal antibody (mAb) and to analyse cellular distribution of the viral protein. The mAb 3E1 could specifically recognize the expressed ORF72 protein of transfected cells by indirect immunofluorescence, and the antigenic site recognized by the mAb 3E1 was mapped to the region of N‐terminal 124 residues of KHV ORF72. This mAb was further demonstrated to specifically detect the KHV‐infected fish tissue by immunohistochemistry, thereby suggesting its high diagnostic potential. In addition, the cellular distribution analysis of the KHV ORF72 protein revealed that the region of amino acid residues 125–247 was related to mitochondrial localization and proliferation. Furthermore, a putative nuclear export signal (NES) of ORF72 at the residues 201–212 was confirmed on the basis of its function associated with NES activity.
The carbon footprint of foreign multinationals within the European Union
Authors: Ortiz Mateo , Cadarso María‐Ángeles , López Luis‐Antonio
Published: May 2020

Although European countries have made great efforts to reduce their territorial carbon emissions, global emissions are still growing. Multinational enterprises (MNEs) operating within Europe, as transnational institutions, can make significant contributions in translating European efforts into global emissions reduction. Here, we estimate the carbon footprint of the foreign multinationals’ affiliates (FMNEs) operating within the European Union (EU) in 2015 as a first assessment of the MNEs’ potential regarding European and global carbon emissions reduction targets. Our findings show that FMNEs generate 17% of the total carbon footprint of the EU but only 12% of the total value added. Thus, the net impacts of FMNE are considered to be in environmental deficit because their adverse environmental impacts are relatively higher than their positive economic ones. Calculations are made under the assumption that FMNEs produce using the same technology as their domestic peers; therefore, the carbon/economic imbalance found is attributed to the FMNEs’ distribution across sectors. The participation of FMNEs in carbon‐intensive industrial sectors are remarkably high in low‐income EU members; therefore, the effective reduction of the carbon footprint in those countries is largely conditioned by the decisions of foreign MNEs’ headquarters. Furthermore, those countries are more vulnerable to capital leakages in the case where a European carbon tax was to be imposed. We conclude by discussing the economic and policy implications of the country‐level inequality of MNEs’ environmental impacts within the EU.
Co‐regulation of indole glucosinolates and camalexin biosynthesis by CPK5/CPK6 and MPK3/MPK6 signaling pathways
Authors: Yang Liuyi , Zhang Yan , Guan Rongxia , Li Sen , Xu Xuwen , Zhang Shuqun , Xu Juan
Published: May 2020

Secondary plant metabolites, represented by indole glucosinolates (IGS) and camalexin, play important roles in Arabidopsis immunity. Previously, we demonstrated the importance of MPK3 and MPK6, two closely related MAPKs, in regulating Botrytis cinerea (Bc)‐induced IGS and camalexin biosynthesis. Here we report that CPK5 and CPK6, two redundant calcium‐dependent protein kinases (CPKs), are also involved in regulating the biosynthesis of these secondary metabolites. The loss‐of‐function of both CPK5 and CPK6 compromises plant resistance to Bc. Expression profiling of CPK5‐VK transgenic plants, in which a truncated constitutively active CPK5 is driven by a steroid‐inducible promoter, revealed that biosynthetic genes of both IGS and camalexin pathways are coordinately upregulated after the induction of CPK5‐VK, leading to high‐level accumulation of camalexin and 4‐methoxyindole‐3‐yl‐methylglucosinolate (4MI3G). Induction of camalexin and 4MI3G, as well as the genes in their biosynthesis pathways, is greatly compromised in cpk5 cpk6 mutant in response to Bc. In a conditional cpk5 cpk6 mpk3 mpk6 quadruple mutant, Bc resistance and induction of IGS and camalexin are further reduced in comparison to either cpk5 cpk6 or conditional mpk3 mpk6 double mutant, suggesting that both CPK5/CPK6 and MPK3/MPK6 signaling pathways contribute to promote the biosynthesis of 4MI3G and camalexin in defense against Bc.
Challenges, Extent of Involvement, and the Impact of Nurses’ Involvement in Politics and Policy Making in in Last Two Decades: An Integrative Review
Authors: Rasheed Subia Parveen , Younas Ahtisham , Mehdi Fahmida
Published: May 2020

Purpose

To determine nurses' challenges, extent of involvement, and the impact of involvement in politics and policy making.

Organizing Construct: Nurses in politics and health policy making.

Methods

Literature was searched in PubMed, Scopus, Google Scholar, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), OVID, and Open Grey using phrases comprising the following key words: “nurses”, “policy making”, “politics”, “health policy”, “nurses involvement in policy making/politics/health policy”, “nurses challenges in policy making/politics/policy”, and “impact of nursing policy making/politics/health policy”; 22 articles published from January 2000 to May 2019 were included.

Findings

The major challenges included intra‐ and interprofessional power dynamics, marginalization of nurses in policy making, and nursing profession–specific challenges. The extent of involvement was inadequate, and nurses mainly worked as policy implementers rather than as policy developers. Those nurses who participated in policy development focused on health promotion to build healthy communities and to empower nurses and the nursing profession.

Conclusions

Nurses' involvement in policy making has not improved over time. Nursing institutions and regulatory bodies should prepare and encourage nurses to work as policymakers rather than implementers and advocate for the rightful place of nurses at policy‐making forums.

Clinical Relevance

Preparation for health system policy making starts in the clinical settings. Educational institutions and nurse leaders should adequately prepare nurses for policy making, and nurses should participate in policy making at the organization, system, and national levels.
Cerebral Blood Flow Velocity is Not Associated with Serum Hemoglobin in Children with Malaria‐Associated Anemia
Authors: Taty Tshimanga M. , Mabiala Joseph B. , Lovett Marlina E. , Pongo Jean , Musungufu Davin A. , Uchama Mananu , O'Brien Nicole F.
Published: May 2020

BACKGROUND AND PURPOSE

Hemoglobin (Hbg) is often thought to impact cerebral blood flow velocity (CBFV). This study was performed to investigate the relationship between Hbg value and CBFV in African children with malaria.

METHODS

In this prospective, observational study, children aged 3 months to 18 years with malaria and a normal Blantyre coma score underwent a single transcranial Doppler ultrasound (TCD) examination with a concurrent Hbg check.

RESULTS

One hundred fifty‐six children with a mean age of 43 months were enrolled. Thirty‐three children (21%) had severe anemia (Hbg <5g/dL), 46 (29%) had moderate anemia (Hbg 5‐6.9 g/dL), 63 children (41%) had mild anemia (7‐9.9 g/dL), and 14 children (9%) had no anemia (Hbg >10 g/dL) at the time of TCD examination. Mean averaged CBFV in the middle cerebral artery (MCA) for the cohort was 99% of predicted based on normative values standardized for age. There was no significant correlation between Hbg levels and measured CBFV in the MCA (r = −.09; 95% CI, −.24‐.07; P = .29).

CONCLUSION

In a large sample of African children with malaria, Hbg did not correlate with CBFVs as measured by TCD. Future work that includes baseline TCD measurements and Hbg values as well as other physiological parameters known to influence CBFVs is necessary to confirm these findings.
Cigarette smoke modulates binding of the transcription factor MZF1 to the VEGF promoter and regulates VEGF expression in dependence of genetic variation SNP 405
Authors: Krüger Maximilian , Metzger Carmen , Al‐Nawas Bilal , Kämmerer Peer W. , Brieger Jürgen
Published: May 2020

Background

Vascular endothelial growth factor (VEGF) affects carcinogenesis of the upper aerodigestive tract. Cigarette smoke (CSE) influences VEGF‐gene regulation. The single nucleotide polymorphism +405 G/C (SNP +405 G/C) and the transcriptional factor (TF) myeloid zinc finger 1 (MZF1) are endogenic regulators of the VEGFpromoter as the polymorphism 405 potentially affects binding of the transcription factor MZF1. Therefore, this in vitro study analysed cancer cells of the upper aerodigestive tract after CSE incubation concerning MZF1‐binding specificity and VEGF expression in dependency of VEGF polymorphism +405 G/C compared to wild type (wt).

Methods

In human alveolar epithelial‐like type‐II cells (A549) and oral squamous cell cancer cells (HNSCCUM‐02T) SNP +405 G/C‐ and MZF1‐dependent VEGF promoter activity and VEGF expression were analysed by qRT‐PCR and Western blot after incubation with 10% CSE. Temporary knock‐down of MZF1 was performed using siRNA. MZF1 binding was analysed by Co‐Chromatin‐Immunoprecipitation (Co‐ChiP) (each test n = 3).

Results

We found a stronger MZF1 binding to VEGF polymorphism 405 in A549 cells (P < .05) compared to HNSCCUM‐02T cells (P = .02), where MZF1 binding was reduced. MZF1 knock out reduced VEGF promoter activity in HNSCCUM‐02T cells, showing the relevance of the factor for transcriptional activation of the VEGF promoter. Finally, we found that CSE increases promoter activity in both cell lines and no significant differences between the two analysed polymorphisms concerning their activating capacity.

Conclusion

In summary, both VEGF promoter polymorphisms are similar effective in terms of transcriptional activity, and MZF1 is a transcriptional activator of VEGF promoter. Moreover, cigarette smoke increases MZF1 binding of VEGF‐promoter and directly affects VEGF‐gene regulation.
The use of artificial intelligence, machine learning and deep learning in oncologic histopathology
Authors: Sultan Ahmed S. , Elgharib Mohamed A. , Tavares Tiffany , Jessri Maryam , Basile John R.
Published: May 2020

Background

Recently, there has been a momentous drive to apply advanced artificial intelligence (AI) technologies to diagnostic medicine. The introduction of AI has provided vast new opportunities to improve health care and has introduced a new wave of heightened precision in oncologic pathology. The impact of AI on oncologic pathology has now become apparent, and its use with respect to oral oncology is still in the nascent stage.

Discussion

A foundational overview of AI classification systems used in medicine and a review of common terminology used in machine learning and computational pathology will be presented. This paper provides a focused review on the recent advances in AI and deep learning in oncologic histopathology and oral oncology. In addition, specific emphasis on recent studies that have applied these technologies to oral cancer prognostication will also be discussed.

Conclusion

Machine and deep learning methods designed to enhance prognostication of oral cancer have been proposed with much of the work focused on prediction models on patient survival and locoregional recurrences in patients with oral squamous cell carcinomas (OSCC). Few studies have explored machine learning methods on OSCC digital histopathologic images. It is evident that further research at the whole slide image level is needed and future collaborations with computer scientists may progress the field of oral oncology.
Bayesian disease mapping and the ‘High‐Risk’ oral cancer population in Hong Kong
Authors: Adeoye John , Choi Siu‐Wai , Thomson Peter
Published: May 2020

Background

Preventive and early diagnostic methods such as health promotion and disease screening are increasingly advocated to improve detection and survival rates for oral cancer. These strategies are most effective when targeted at "high‐risk" individuals and populations. Bayesian disease‐mapping modelling is a statistical method to quantify and explain spatial and temporal patterns for risk and covariate factor influence, thereby identifying "high‐risk" sub‐regions or "case clustering" for targeted intervention. Rarely applied to oral cancer epidemiology, this paper highlights the efficacy of disease mapping for the Hong Kong population.

Methods

Following ethical approval, anonymized individual‐level data for oral cancer diagnoses were obtained retrospectively from the Clinical Data Analysis and Reporting System (CDARS) of the Hong Kong Hospital Authority (HA) database for a 7‐year period (January 2013 to December 2019). Data facilitated disease mapping and estimation of relative risks of oral cancer incidence and mortality.

Results

A total of 3,341 new oral cancer cases and 1,506 oral cancer‐related deaths were recorded during the 7‐year study period. Five districts, located in Hong Kong Island and Kowloon, exhibited considerably higher relative incidence risks with 1 significant "case cluster" hotspot. Six districts displayed higher mortality risks than expected from territory‐wide values, with highest risk identified for two districts of Hong Kong Island.

Conclusion

Bayesian disease mapping is successful in identifying and characterizing "high‐risk" areas for oral cancer incidence and mortality within a community. This should facilitate targeted preventive and interventional strategies. Further work is encouraged to enhance global‐level data and comprehensive mapping of oral cancer incidence, mortality and survival.
Detection, stratification and treatment of hepatitis C–positive prisoners in the United Kingdom prison estate: Development of a pathway of care to facilitate the elimination of hepatitis C in a London prison
Authors: Connoley Declan , Francis‐Graham Seth , Storer Michelle , Ekeke Nnenna , Smith Claire , Macdonald Douglas , Rosenberg William
Published: May 2020

The United Kingdom is committed to eliminating hepatitis C virus (HCV) infection by 2025. The prison estate provides an opportunity to identify and treat HCV‐positive individuals in a high‐prevalence environment. We designed and implemented a pathway of care within a London prison to diagnose, stratify and link HCV‐positive prisoners into care. This study was a two‐phase case study of a HCV care pathway. New arrivals to the prison were offered blood‐borne virus screening with dried blood spot testing at their secondary health check. Those with active infection completed disease stratification tests and were reviewed at a weekly hospital‐based multidisciplinary team meeting to determine management. In Phase‐2, the pathway was redesigned to improve testing and the referral of HCV‐positive prisoners into treatment. Over the 30‐month evaluation period, 12,946 people were received in the prison. During Phase‐1, 19.6% of new arrivals completed blood‐borne virus testing, with 7.3% identified as HCV‐positive. Just 8.3% of HCV‐positive individuals were treated or referred for treatment in Phase‐1. During Phase‐2, 30% of new receptions completed BBV testing and 3.9% were identified as HCV‐positive. Linkage into care was improved, with 38.9% treated or referred during the second phase. Poor access to testing and referral to treatment limit the effectiveness of care provision for prisoners with HCV. Elimination of HCV in prisons requires local service configuration to ensure high uptake of testing, with all HCV‐positive cases then offered treatment during custody or referral on to treatment after release.
Global real‐world evidence of sofosbuvir/velpatasvir as simple, effective HCV treatment: Analysis of 5552 patients from 12 cohorts
Authors: Mangia Alessandra , Milligan Scott , Khalili Mandana , Fagiuoli Stefano , Shafran Stephen D. , Carrat Fabrice , Ouzan Denis , Papatheodoridis George , Ramji Alnoor , Borgia Sergio M. , Wedemeyer Heiner , Losappio Ruggero , Pérez‐Hernandez Francisco , Wick Nicole , Brown Robert S. , Lampertico Pietro , Doucette Karen , Ntalla Ioanna , Ramroth Heribert , Mertens Michael , Vanstraelen Kim , Turnes Juan
Published: May 2020

Background and aims

Achieving sustained virological response (SVR; cure) in hepatitis C patients using a simple regimen is key to making elimination by 2030 possible. In the largest real‐world analysis to date, the effectiveness of pangenotypic, panfibrotic, single‐tablet, sofosbuvir/velpatasvir (SOF/VEL) once‐daily for 12 weeks was assessed in 12 clinical real‐world cohorts from various geographical areas, settings and treatment practices. Factors affecting risk of not achieving SVR were assessed.

Methods

Adults treated with SOF/VEL 400/100 mg, without ribavirin, were included. All HCV patients reaching Week 12 or 24 post‐treatment were assessed for SVR12/24. Factors associated with not achieving SVR12/24 for virological reasons were evaluated using logistic regression analysis.

Results

Overall, 5552 patients were included: 13.3% treatment‐experienced; 20.7% compensated cirrhotic; 30.2% genotype 1; 29.5% genotype 2; 32.9% genotype 3; 4.7% genotype 4; 3.7% HIV coinfection; 13.4% current/former intravenous drug use. Of the 5196 patients evaluated for effectiveness, 98.9% achieved SVR12/24. High SVR12/24 rates occurred in all genotypes including genotype 3 (98.3%; 1649/1677) and in those with compensated cirrhosis (97.9; 1055/1078). Only 55 patients did not achieve SVR12/24 due to a virological reason; the only factor statistically significantly associated with an increased risk of not achieving SVR12/24 was compensated cirrhosis (P = .002). Overall, 6% (332/5552) of patients did not achieve SVR12/24 for non‐virological reasons (67% lost to follow‐up; 26.5% early treatment discontinuation).

Conclusions

In this large cohort, representative of clinical practice, a simple 12‐week regimen of SOF/VEL without ribavirin resulted in high SVR12/24 rates in diverse patient populations, even among those with compensated cirrhosis.
Classification of CM chondrite breccias—Implications for the evaluation of samples from the OSIRIS‐REx and Hayabusa 2 missions
Authors: Lentfort Sarah , Bischoff Addi , Ebert Samuel , Patzek Markus
Published: May 2020

CM chondrites are complex impact (mostly regolith) breccias, in which lithic clasts show various degrees of aqueous alteration. Here, we investigated the degree of alteration of individual clasts within 19 different CM chondrites and CM‐like clasts in three achondrites by chemical analysis of the tochilinite‐cronstedtite‐intergrowths (TCIs; formerly named “poorly characterized phases”). To identify TCIs in various chondritic lithologies, we used backscattered electron (BSE) overview images of polished thin sections, after which appropriate samples underwent electron microprobe measurements. Thus, 75 lithic clasts were classified. In general, the excellent work and specific criteria of Rubin et al. (2007) were used and considered to classify CM breccias in a similar way as ordinary chondrite breccias (e.g., CM2.2‐2.7). In BSE images, TCIs in strongly altered fragments in CM chondrites (CM2.0‐CM2.2) appear dark grayish and show a low contrast to the surrounding material (typically clastic matrix), and can be distinguished from TCIs in moderately (CM2.4‐CM2.6) or less altered fragments (CM2.7‐CM2.9); the latter are bright and have high contrast to the surroundings. We found that an accurate subclassification can be obtained by considering only the “FeO”/SiO2 ratio of the TCI chemistry. One could also consider the TCIs’ S/SiO2 ratio and the metal abundance, but these were not used for classification due to several disadvantages. Most of the CM chondrites are finds that have suffered terrestrial weathering in hot and cold deserts. Thus, the observed abundance of metal is susceptible to weathering and may not be a reliable indicator of subtype classification. This study proposes an extended classification scheme based on Rubin’s scale from subtypes CM2.0‐CM2.9 that takes the brecciation into account and includes the minimum to maximum degree of alteration of individual clasts. The range of aqueous alteration in CM chondrites and small spatial scale of mixing of clasts with different alteration histories will be important for interpreting returned samples from the OSIRIS‐REx and Hayabusa 2 missions in the future.
Effects of the vibrating capsule on colonic circadian rhythm and bowel symptoms in chronic idiopathic constipation
Authors: Rao Satish S. C. , Lembo Anthony , Chey William D. , Friedenberg Keith , Quigley Eamonn M. M.
Published: May 2020

Background

Constipated patients remain dissatisfied with current treatments suggesting a need for alternative therapies.

Aim

Evaluate the mechanistic effects of oral vibrating capsule in chronic idiopathic constipation (CIC) by examining the temporal relationships between the onset of vibrations, complete spontaneous bowel movements (CSBM), and circadian rhythm.

Methods

In post hoc analyses of two double‐blind studies, CIC patients (Rome III) were randomized to receive 5 active or sham capsules/week for 8 weeks. The capsules were programmed for single vibration (study 1) or two vibration sessions with two modes, 8 hours apart (study 2). Daily electronic diaries assessed stool habit and percentage of CSBMs associated with vibrations. Responders were patients with ≥ 1 CSBM per week over baseline.

Results

250 patients were enrolled (active = 133, sham = 117). During and within 3 hours of vibration, there were significantly more % CSBMs in the active vs. sham group (50% vs. 42%; P = .0018). In study 2, there were two CSBM peaks associated with vibration sessions. Significantly more % CSBMs occurred in active mode 1 (21.5%) vs. sham (11.5%); (P = .0357). Responder rates did not differ in study 1 (active vs. sham: 26.9% vs. 35.9%, P = .19) or study 2 (mode 1 vs. sham: 50% vs. 31.8%, P = .24; mode 2 vs. sham: 38.1% vs. 31.8%, P = .75). Device was well‐tolerated barring mild vibration sensation.

Conclusions

Vibrating capsule may increase CSBMs possibly by enhancing the physiologic effects of waking and meals, and augmenting circadian rhythm, although responder rate was not different from sham. Two vibration sessions were associated with more CSBMs.
Temporal flexibility in the structure of plant–pollinator interaction networks
Authors: CaraDonna Paul J. , Waser Nickolas M.
Published: May 2020

Ecological communities consist of species that are joined in complex networks of interspecific interaction. These interactions often form and dissolve rapidly, but this temporal variation is not well integrated into our understanding of the causes and consequences of network structure. If interspecific interactions exhibit temporal flexibility across time periods over which organisms co‐occur, then the emergent structure of the corresponding network may also be flexible, something that a temporally‐static perspective will miss. Here, we use an empirical plant–pollinator system to examine short‐term (week‐to‐week) flexibility in network structure (connectance, nestedness and specialization) and in the individual species interactions that contribute to that structure across three summer growing seasons in a subalpine ecosystem. We then compared the properties of weekly networks to the properties of cumulative networks that aggregate field observations over each full summer season. As a test of the potential robustness of networks to perturbation, we also simulated the random loss of species from weekly networks. A week‐to‐week view reveals considerable flexibility in the interactions of individual species and their contributions to network structure. For example, species that would be considered relatively generalized across their entire activity period may be much more specialized at certain times, and at no point as generalized as the cumulative network may suggest. Furthermore, a week‐to‐week view reveals corresponding flexibility in network structure and potential robustness throughout each summer growing season. We conclude that short‐term flexibility in species interactions leads to short‐term variation in network properties, and that a cumulative, season‐long perspective may miss important aspects of the way in which species interact, with implications for understanding their ecology, evolution and conservation.
Dynamic QT response to cold‐water face immersion in long‐QT syndrome type 3
Authors: Takahashi Kazuhiro , Shimizu Wataru , Makita Naomasa , Nakayashiro Mami
Published: May 2020

Background

Abnormal dynamics of QT intervals in response to sympathetic nervous system stimulation are used to diagnose long‐QT syndrome (LQTS). We hypothesized that parasympathetic stimulation with cold‐water face immersion following exercise would influence QT dynamics in patients with LQTS type 3 (LQT3).

Methods

Study participants (n = 42; mean age = 11.2 years) comprised 20 genotyped LQTS children and 22 healthy children. The LQTS group was divided into LQT3 (n = 12) and non‐LQT3 (n = 8) subgroups. Provocative testing for assessing QT dynamics comprised a treadmill exercise followed by cold‐water face immersion. The QT intervals were automatically measured at rest and during exercise, recovery, and cold‐water face immersion. The QT/heart rate (HR) relationship was visualized by plotting beat‐to‐beat confluence of the data.

Results

The QT/HR slopes, determined by linear regression analysis, were steeper in the LQTS group than in the control group during exercise and immersion tests: −2.16 ± 0.63 versus −1.21 ± 0.28, P < 0.0001, and −2.02 ± 0.76 vs −0.75 ± 0.24, P < 0.0001, respectively. The LQT3 patients had steeper slopes in the immersion test than did non‐LQT3 and control individuals: −2.42 ± 0.52 vs −1.40 ± 0.65, P < 0.0001, and vs −0.75 ± 0.24, P < 0.0001.

Conclusions

The QT dynamics of LQT3 patients differ from those of other LQTS subtypes during the post‐exercise cold‐water face immersion test in this study. Abnormal QT dynamics during the parasympathetic provocative test are concordant with the fact that cardiac events occur when HRs are lower or during sleep in LQT3 patients.
Shared leadership development and team performance: A new look at the dynamics of shared leadership
Authors: Lorinkova Natalia M. , Bartol Kathryn M.
Published: May 2020

The present study offers new theoretical insights into the dynamics of shared leadership. Integrating arguments from shared leadership and team development theory, we examine how shared leadership changes over the course of a project team's life cycle and how this pattern of change relates to team performance. Guided by shared leadership theory and project team literature, we also explore team‐level factors, which may alter the pattern of shared leadership development. In particular, we propose that in project teams shared leadership develops in a nonuniform way, approximating an inverted U‐shaped pattern, increasing early in the team's life cycle, peaking around the midpoint, and then decreasing in the later phase. In turn, this development pattern relates positively to team performance. We also extend theory by explaining how specific team characteristics influence the pattern of shared leadership development. Using a three‐study approach, we empirically examine the hypothesized relationships and conclude with a general discussion of the theoretical and practical implications of our findings.
Human herpesvirus 8‐positive multicentric Castleman disease with germinotropic plasmablastic aggregates: Overlapping spectrum of human herpesvirus 8‐associated lymphoproliferative disorder
Authors: Nakaya Yosuke , Ishii Naomi , Kasamatsu Yu , Shimizu Katsujun , Tatsumi Naoko , Tsutsumi Minako , Yoshida Masahiro , Yoshimura Takuro , Hayashi Yoshiki , Nakao Takafumi , Inoue Takeshi , Yamane Takahisa
Published: May 2020

The diagnosis of human herpesvirus 8 (HHV8)‐associated lymphoproliferative disorder (LPD) is challenging because of the rarity and extended spectrum of each entity. A 43‐year‐old, human immunodeficiency virus seropositive, Japanese man was referred to our department because of persistent fever, generalized lymphadenopathy, jaundice and anasarca. Biopsy of a left axially lymph node demonstrated relatively preserved nodal structure with multicentric Castleman disease (MCD) features. In the germinal center, there were aggregates of HHV8‐infected plasmablasts that were diffusely positive for CD38, MUM1/IRF4, LCA, IgM and λ; partially positive for CD30, c‐MYC, p53; and negative for CD138, CD20, PAX‐5, κ, CD2, CD3 and CD5. A small number of Epstein–Barr virus encoded small RNA (EBER)‐positive large cells infiltrated in the outer part of the germinal center and the mantle layer, but the cells copositive for EBER and HHV8 were not evident. We diagnosed the patient as HHV8‐positive MCD with germinotropic plasmablastic aggregates, which demonstrated intermediate pathologic features between HHV8‐positive MCD and germinotropic lymphoproliferative disorder. The pathogenesis of each HHV8‐associated LPD differs in cellular origin, host immune status, cytoplasmic immunoglobulin expression, clonality pattern and EBV infection; however, these factors sometimes overlap and induce extended clinical and pathologic presentations.
Phoma diseases: Epidemiology and control
Authors: Deb Debasish , Khan Ahamed , Dey Nrisingha
Published: May 2020

Phomais the most widely distributed and omnipresent genus of the order Pleosporales and the largest genus with some 3,000 taxa described so far. Of these, approximately 110 species are pathogenic and occupy varied ecological niches. The genusPhomais polyphyletic and is not really delimited, with unclear species boundaries that make it a taxonomically controversial genus. Fungi belonging toPhomacommonly occur on crop plants that are economically important, where they cause devastating plant diseases. Pathogenic members ofPhomasensu lato species attack crop plants with symptoms ranging from leaf blight to root rot, and even wilting of the plant. In infected crop residues and field stubbles, the pathogen produces abundant pycnidia and pseudothecia that serve as the source of primary inoculum, whilst repeated crops of conidia produced inside pycnidia are the main source of secondary infection during the same growing season. After successful infection, the pathogen produces various phytotoxins that alter photosynthetic efficiency and actin cytoskeleton‐based functions, and cause electrolyte leakage from cells. Controlling the diseases caused by members ofPhomasensu lato is challenging and efforts have been made to identify resistant varieties that can be used in various plant breeding programmes. Studies have also been conducted to devise cultural and biological control measures as well as to evaluate the efficacy of fungicides against members ofPhomasensu lato. In this review we aim to discuss the disease epidemiology and control measures that can be practised to protect crops fromPhomadiseases.
Flood Footprint Assessment: A Multiregional Case of 2009 Central European Floods
Authors: Mendoza‐Tinoco David , Hu Yixin , Zeng Zhao , Chalvatzis Konstantinos J. , Zhang Ning , Steenge Albert E. , Guan Dabo
Published: May 2020

Hydrometeorological phenomena have increased in intensity and frequency in last decades, with Europe as one of the most affected areas. This accounts for considerable economic losses in the region. Regional adaptation strategies for costs minimization require a comprehensive assessment of the disasters’ economic impacts at a multiple‐region scale. This article adapts the flood footprint method for multiple‐region assessment of total economic impact and applies it to the 2009 Central European Floods event. The flood footprint is an impact accounting framework based on the input–output methodology to economically assess the physical damage (direct) and production shortfalls (indirect) within a region and wider economic networks, caused by a climate disaster. Here, the model is extended through the capital matrix, to enable diverse recovery strategies. According to the results, indirect losses represent a considerable proportion of the total costs of a natural disaster, and most of them occur in nonhighly directly impacted industries. For the 2009 Central European Floods, the indirect losses represent 65% out of total, and 70% of it comes from four industries: business services, manufacture general, construction, and commerce. Additionally, results show that more industrialized economies would suffer more indirect losses than less‐industrialized ones, in spite of being less vulnerable to direct shocks. This may link to their specific economic structures of high capital‐intensity and strong interindustrial linkages.
A Study of Risk Relevance Reasoning Based on a Context Ontology of Railway Accidents
Authors: Cao Tiancheng , Mu Wenxin , Gou Juanqiong , Peng Liyu
Published: May 2020

With the application of risk management and accident response in the railway domain, risk detection and prevention have become key research topics. Many dangers and associated risk sources must be considered in collaborative scenarios of heavy‐haul railways. In these scenarios, (1) various risk sources are involved in different data sources, and context affects their occurrence, (2) the relationships between contexts and risk sources in the accident cause mechanism need to be explicitly defined, and (3) risk knowledge reasoning needs to integrate knowledge from multiple data sources to achieve comprehensive results. To express the association rules among core concepts, this article constructs two ontologies: The accident‐risk ontology and the context ontology. Concept analysis is based on railway domain knowledge and accident analysis reports. To sustainably integrate knowledge, an integrated evolutionary model called scenario‐risk‐accident chain ontology (SRAC) is constructed by introducing new data sources. The SRAC is integrated through expert rules between the two ontologies, and its evolution process involves new knowledge through a new risk source database. After three versions of the upgrade process, potential risk sources can be mined and evaluated in specific contexts. To evaluate the risk source level, a long short‐term memory (LSTM) neural network model is used to capture context and risk text features. A model comparison for different neural network structures is performed to find the optimal evaluation results. Finally, new concepts, such as risk source level, and new instances are updated in the context‐aware risk knowledge reasoning framework.
How did we rapidly implement a convalescent plasma program?
Authors: Budhai Alexandra , Wu Annie A. , Hall Lucette , Strauss Donna , Paradiso Sarai , Alberigo Jill , Hillyer Christopher D. , Jett Betsy , Tobian Aaron A. R. , Bloch Evan M. , Sachais Bruce S. , Shaz Beth H.
Published: May 2020

Since the beginning of the COVID‐19 pandemic, the use of convalescent plasma as a possible treatment has been explored. Here we describe our experience as the first U.S. organization creating a COVID‐19 convalescent plasma program to support its use through the single‐patient emergency investigational new drug, the National Expanded Access Program, and multiple randomized controlled trials. Within weeks, we were able to distribute more than 8000 products, scale up collections to more than 4000 units per week, meet hospital demand, and support randomized controlled trials to evaluate the efficacy of convalescent plasma treatment. This was through strategic planning; redeployment of staff; and active engagement of hospital, community, and public health partners. Our partners helped with donor recruitment, testing, patient advocacy, and patient availability. The program will continue to evolve as we learn more about optimizing the product. Remaining issues to be resolved are antibody titers, dose, and at what stage of disease to transfuse.
Lack of collagen XVIII leads to lipodystrophy and perturbs hepatic glucose and lipid homeostasis
Authors: Petäistö Tiina , Vicente David , Mäkelä Kari A. , Finnilä Mikko A. , Miinalainen Ilkka , Koivunen Jarkko , Izzi Valerio , Aikio Mari , Karppinen Sanna‐Maria , Devarajan Raman , Thevenot Jerome , Herzig Karl‐Heinz , Heljasvaara Ritva , Pihlajaniemi Taina
Published: May 2020

Key points

Extracellular matrix is highly remodelled in obesity and associates with the development of metabolic disorders, such as insulin resistance.

Previously, we have shown that the lack of specific collagen XVIII isoforms impairs adipocyte differentiation in mice.

Here, we show that mice lacking the medium and long isoforms of collagen XVIII develop insulin resistance and glucose intolerance and show elevated serum triglycerides and fat accumulation in the liver.

We report that collagen XVIII‐deficient mice have increased heat production at low temperatures.

These results reveal a new role for collagen XVIII in the regulation of glucose and lipid metabolism, and they expand the understanding of the development of metabolic disorders.

Liver and adipose tissues play important roles in the regulation of systemic glucose and lipid metabolism. Extracellular matrix synthesis and remodelling are significantly altered in these tissues in obesity and type 2 diabetes. Collagen XVIII is a ubiquitous extracellular matrix component, and it occurs in three isoforms which differ in terms of molecular size, domain structure and tissue distribution. We recently showed that, in mice, the lack of collagen XVIII, and especially its medium and long isoforms, leads to reduced adiposity and dyslipidaemia. To address the metabolic consequences of these intriguing observations, we assessed whole‐body glucose homeostasis in mice challenged with a high‐fat diet and in normal physiological conditions. We observed that, in the high caloric diet, the overall adiposity was decreased by 30%, serum triglyceride values were threefold higher and the steatotic area in liver was twofold larger in collagen XVIII knockout mice compared with controls. We demonstrated that mice lacking either all three collagen XVIII isoforms, or specifically, the medium and long isoforms develop insulin resistance and glucose intolerance. Furthermore, we found that ablation of collagen XVIII leads to increased heat production in low temperatures and to reduction of the high blood triglyceride levels of the knockout mice to the level of wild‐type mice. Our data indicate that collagen XVIII plays a role in the regulation of glucose tolerance, insulin sensitivity and lipid homeostasis, principally through its ability to regulate the expansion of the adipose tissue. These findings advance the understanding of metabolic disorders.
Rater Reliability of the Tuck Jump Assessment: A Critically Appraised Topic (CAT)
Authors: McAdie Michael D. , Lininger Monica R. , Warren Meghan
Published: May 2020

Focused Clinical Question: In an individual who is physically active in recreation or sport, can the tuck jump assessment be reliably scored? Clinical Bottom Line: Current evidence regarding the reliability of the original tuck jump assessment and modified tuck jump assessment are conflicting.
Novel Antiparasitic Activity of the Antifungal Lead Occidiofungin
Authors: Ma Jingbo , Guo Fengguang , Jin Zi , Geng Mengxin , Ju Min , Ravichandran Akshaya , Orugunty Ravi , Smith Leif , Zhu Guan , Zhang Haili
Published: May 2020

Novel antiparasitic activity was observed for the antifungal occidiofungin. It efficaciously and irreversibly inhibited the zoonotic enteric parasite
Cryptosporidium parvum
in vitro
with limited cytotoxicity (50% effective concentration [EC
50
] = 120 nM versus 50% cytotoxic concentration [TC
50
] = 988 nM), and its application disrupted the parasite morphology. This study expands the spectrum of activity of a glycolipopeptide named occidiofungin.
Porcine Deltacoronavirus nsp5 Cleaves DCP1A To Decrease Its Antiviral Activity
Authors: Zhu Xinyu , Chen Jiyao , Tian Liyuan , Zhou Yanrong , Xu Shangen , Long Siwen , Wang Dang , Fang Liurong , Xiao Shaobo
Published: May 2020

Interferon (IFN)-stimulated gene (ISG) induction through IFN signaling is important to create an antiviral state and usually directly inhibits virus infection. The present study first demonstrated that PDCoV nsp5 can cleave mRNA-decapping enzyme 1a (DCP1A) to attenuate its antiviral activity. Furthermore, cleaving DCP1A is a common characteristic of nsp5 proteins from different coronaviruses (CoVs), which represents a common immune evasion mechanism of CoVs. Previous evidence showed that CoV nsp5 cleaves the NF-κB essential modulator and signal transducer and activator of transcription 2. Taken together, CoV nsp5 is a potent IFN antagonist because it can simultaneously target different aspects of the host IFN system, including IFN production and signaling and effector molecules.
The HIV-1 Env gp120 Inner Domain Shapes the Phe43 Cavity and the CD4 Binding Site
Authors: Prévost Jérémie , Tolbert William D. , Medjahed Halima , Sherburn Rebekah T. , Madani Navid , Zoubchenok Daria , Gendron-Lepage Gabrielle , Gaffney Althea E. , Grenier Melissa C. , Kirk Sharon , Vergara Natasha , Han Changze , Mann Brendan T. , Chénine Agnès L. , Ahmed Adel , Chaiken Irwin , Kirchhoff Frank , Hahn Beatrice H. , Haim Hillel , Abrams Cameron F. , Smith Amos B. , Sodroski Joseph , Pazgier Marzena , Finzi Andrés
Published: May 2020

The Phe43 cavity of HIV-1 envelope glycoproteins (Env) is an attractive druggable target. New promising compounds, including small CD4 mimetics (CD4mc), were shown to insert deeply into this cavity. Here, we identify a new network of residues that helps to shape this highly conserved CD4 binding pocket and characterize the structural determinants responsible for Env sensitivity to small CD4 mimetics.
Immune Profiling To Predict Outcome of Clostridioides difficile Infection
Authors: Abhyankar Mayuresh M. , Ma Jennie Z. , Scully Kenneth W. , Nafziger Andrew J. , Frisbee Alyse L. , Saleh Mahmoud M. , Madden Gregory R. , Hays Ann R. , Poulter Mendy , Petri William A.
Published: May 2020

Clostridioides difficileinfection is the most common health care-associated infection in the United States with more than 20% patients experiencing symptomatic recurrence. The complex nature of host-bacterium interactions makes it difficult to predict the course of the disease based solely on clinical parameters. In the present study, we built a robust prediction model using representative plasma biomarkers and clinical parameters for 90-day all-cause mortality. Risk prediction based on immune biomarkers and clinical variables may contribute to treatment selection for patients as well as provide insight into the role of immune system inC. difficilepathogenesis.
Antiviral Efficacies of FDA-Approved Drugs against SARS-CoV-2 Infection in Ferrets
Authors: Park Su-Jin , Yu Kwang-Min , Kim Young-Il , Kim Se-Mi , Kim Eun-Ha , Kim Seong-Gyu , Kim Eun Ji , Casel Mark Anthony B. , Rollon Rare , Jang Seung-Gyu , Lee Min-Hyeok , Chang Jae-Hyung , Song Min-Suk , Jeong Hye Won , Choi Younho , Chen Weiqiang , Shin Woo-Jin , Jung Jae U. , Choi Young Ki
Published: May 2020

The SARS-CoV-2 pandemic continues to spread worldwide, with rapidly increasing numbers of mortalities, placing increasing strain on health care systems. Despite serious public health concerns, no effective vaccines or therapeutics have been approved by regulatory agencies. In this study, we tested the FDA-approved drugs lopinavir-ritonavir, hydroxychloroquine sulfate, and emtricitabine-tenofovir against SARS-CoV-2 infection in a highly susceptible ferret infection model. While most of the drug treatments marginally reduced clinical symptoms, they did not reduce virus titers, with the exception of emtricitabine-tenofovir treatment, which led to diminished virus titers in nasal washes at 8 dpi. Further, the azathioprine-treated immunosuppressed ferrets showed delayed virus clearance and low SN titers, resulting in a prolonged infection. As several FDA-approved or repurposed drugs are being tested as antiviral candidates at clinics without sufficient information, rapid preclinical animal studies should proceed to identify therapeutic drug candidates with strong antiviral potential and high safety prior to a human efficacy trial.