bluuebunny/crossref_metadata_2025 huggingface dataset:
Metabolic flexibility of SUP05 under low DO growth conditions
Authors: Mattes Timothy E. , Ingalls Anitra E. , Burke Susan , Morris Robert M.
Published: September 2020

Chemoautotrophic bacteria from the SUP05 clade often dominate anoxic waters within marine oxygen minimum zones (OMZs) where they use energy gained from the oxidation of reduced sulfur to fuel carbon fixation. Some of these SUP05 bacteria are facultative aerobes that can use either nitrate or oxygen as a terminal electron acceptor making them ideally suited to thrive at the boundaries of OMZs where they experience fluctuations in dissolved oxygen (DO). SUP05 metabolism in these regions, and therefore the biogeochemical function of SUP05, depends largely on their sensitivity to oxygen. We evaluated growth and quantified differences in gene expression in Ca. T. autotrophicus strain EF1 from the SUP05 clade under high DO (22 μM), anoxic, and low DO (3.8 μM) concentrations. We show that strain EF1 cells respire oxygen and nitrate and that cells have higher growth rates, express more genes, and fix more carbon when oxygen becomes available for aerobic respiration. Evidence that facultatively aerobic SUP05 are more active and respire nitrate when oxygen becomes available at low concentrations suggests that they are an important source of nitrite across marine OMZ boundary layers.
The impact of the endophytic bacterial community on mulberry tree growth in the Three Gorges Reservoir ecosystem, China
Authors: Xie Jie , Xu Weifang , Zhang Meng , Qiu Changyu , Liu Jia , Wisniewski Michael , Ou Ting , Zhou Zeyang , Xiang Zhonghuai
Published: September 2020

Plant‐associated microbes influence plant performance and may also impact biotic and abiotic stress tolerance. The microbiome of mulberry trees planted for ecological restoration in the hydro‐fluctuation belt of the Three Gorges Reservoir Region, China, exhibited distinct patterns of localization. The endosphere exhibited lower α‐diversity relative to the rhizosphere, but was more closely related to host growth status, especially in stem tissues. Pantoea was the predominant bacterial genus inhabiting the stems of two well‐growing plants, while sequences identified as Pseudomonas and Pantoea were abundant in poorly growing plants. The complexity of the endophytic community was more connected to growth status in well‐growing plants than it was in poorly growing plants. Among 151 endophytes cultured from collected samples of mulberry, 64 exhibited plant growth‐promoting (PGP) potential in vitro and the majority of beneficial taxa were harvested from well‐growing plants. Collectively, the present study indicates that the recruitment of beneficial endophytes may contribute to mulberry fitness under abiotic stress, and it provides a foundation for the development of a new strategy in vegetation restoration.
Digital systemic practices in Europe: a survey before the Covid‐19 pandemic
Authors: Borcsa Maria , Pomini Valeria , Saint‐Mont Uwe
Published: September 2020

Knowledge regarding digital practices in the field of systemic therapy is poor. A few surveys have been conducted in non‐European countries investigating the provision of digitally based therapy, counselling, training, and supervision by systemic family and couple therapists (SCFTs). Thus, a survey aiming to investigate the use of information and communication technology (ICT) among European SCFTs was launched in 2017. A sample of 220 SCFTs was included in the survey. The majority were residents in Greece, France and Italy. Descriptive analysis compared SCFTs’ digital practices and concerns from the above three countries with those from the rest of Europe. Results showed that 81.4 per cent of European SCFTs used ICT for clinical purposes and 47.7 per cent in training and supervision. Main concerns among European SCFTs related to the quality of therapeutic relationship, ethical and legal issues, and a lack of national and transnational regulation.

Practitioner points

ICT use and e‐therapy increase access to mental health services and maintain therapeutic contact

Systemic individual therapy, supervision and training are workable online settings

Legislation regulating ICT use in therapy, supervision and training (e.g. General Data Protection Regulation) has to be respected

Training and continuous education in online practices enhance therapists’ and clients’ options, and ensure digital safeness and effective treatment
External validation of models to predict the outcome of pregnancies of unknown location: a multicentre cohort study
Authors: Christodoulou E , Bobdiwala S , Kyriacou C , Farren J , Mitchell‐Jones N , Ayim F , Chohan B , Abughazza O , Guruwadahyarhalli B , Al‐Memar M , Guha S , Vathanan V , Gould D , Stalder C , Wynants L , Timmerman D , Bourne T , Van Calster B
Published: September 2020

Objective

To validate externally five approaches to predict ectopic pregnancy (EP) in pregnancies of unknown location (PUL): the M6P and M6NP risk models, the two‐step triage strategy (2ST, which incorporates M6P), the M4 risk model, and beta human chorionic gonadotropin ratio cut‐offs (BhCG‐RC).

Design

Secondary analysis of a prospective cohort study.

Setting

Eight UK early pregnancy assessment units.

Population

Women presenting with a PUL and BhCG >25 IU/l.

Methods

Women were managed using the 2ST protocol: PUL were classified as low risk of EP if presenting progesterone ≤2 nmol/l; the remaining cases returned 2 days later for triage based on M6P. EP risk ≥5% was used to classify PUL as high risk. Missing values were imputed, and predictions for the five approaches were calculated post hoc. We meta‐analysed centre‐specific results.

Main outcome measures

Discrimination, calibration and clinical utility (decision curve analysis) for predicting EP.

Results

Of 2899 eligible women, the primary analysis excluded 297 (10%) women who were lost to follow up. The area under the ROC curve for EP was 0.89 (95% CI 0.86–0.91) for M6P, 0.88 (0.86–0.90) for 2ST, 0.86 (0.83–0.88) for M6NP and 0.82 (0.78–0.85) for M4. Sensitivities for EP were 96% (M6P), 94% (2ST), 92% (N6NP), 80% (M4) and 58% (BhCG‐RC); false‐positive rates were 35%, 33%, 39%, 24% and 13%. M6P and 2ST had the best clinical utility and good overall calibration, with modest variability between centres.

Conclusions

2ST and M6P performed best for prediction and triage in PUL.

Tweetable abstract

The M6 model, as part of a two‐step triage strategy, is the best approach to characterise and triage PULs.
Second‐trimester transvaginal ultrasound measurement of cervical length for prediction of preterm birth: a blinded prospective multicentre diagnostic accuracy study
Authors: Kuusela P , Jacobsson B , Hagberg H , Fadl H , Lindgren P , Wesström J , Wennerholm U‐B , Valentin L
Published: September 2020

Objective

To estimate the diagnostic performance of sonographic cervical length for the prediction of preterm birth (PTB).

Design

Prospective observational multicentre study.

Setting

Seven Swedish ultrasound centres.

Sample

A cohort of 11 456 asymptomatic women with a singleton pregnancy.

Methods

Cervical length was measured with transvaginal ultrasound at 18–20 weeks of gestation (C×1) and at 21–23 weeks of gestation (C×2, optional). Staff and participants were blinded to results.

Main outcome measures

Area under receiver operating characteristic curve (AUC), sensitivity, specificity, positive and negative predictive values (PPV and NPV), positive and negative likelihood ratios (LR+ and LR−), number of false‐positive results per true‐positive result (FP/TP), number needed to screen to detect one PTB (NNS) and prevalence of ‘short’ cervix.

Results

Spontaneous PTB (sPTB) at <33 weeks of gestation occurred in 56/11 072 (0.5%) women in the C×1 population (89% white) and in 26/6288 (0.4%) in the C×2 population (92% white). The discriminative ability of shortest endocervical length was better the earlier the sPTB occurred and was better at C×2 than at C×1 (AUC to predict sPTB at <33 weeks of gestation 0.76 versus 0.65, difference in AUC 0.11, 95% CI 0.01–0.23). At C×2, the shortest endocervical length of ≤25 mm (prevalence 4.4%) predicted sPTB at <33 weeks of gestation with sensitivity 38.5% (10/26), specificity 95.8% (5998/6262), PPV 3.6% (10/274), NPV 99.7% (5988/6014), LR+ 9.1, LR− 0.64, FP/TP 26 and NNS 629.

Conclusions

Second‐trimester sonographic cervical length can identify women at high risk of sPTB. In a population of mainly white women with a low prevalence of sPTB its diagnostic performance is at best moderate.

Tweetable abstract

Cervical length screening to predict preterm birth in a white low‐risk population has moderate performance.
Ethylene‐removing packaging: Basis for development and latest advances
Authors: Awalgaonkar Gauri , Beaudry Randolph , Almenar Eva
Published: September 2020

Produce is rapidly gaining market share worldwide. Ethylene is a gas molecule that causes detrimental changes in produce. Thus, it is crucial to reduce surrounding ethylene besides inhibiting ethylene biosynthesis to extend produce shelf life and reduce food waste. Ethylene‐removing packaging (ERP) can reduce ethylene concentration surrounding produce during transportation and commercialization. The information found in the literature on the topic is minimal and incomplete compared to other types of active packaging. It focuses on compounds with an ethylene‐removing capacity rather than on the packaging technology per se. The goal of this literature review is to compile and discuss information from peer‐reviewed scientific papers and industry websites on the basics on ERP and on recent developments that can be used to build on and to advance this type of active packaging. This review first focuses on factors needed to design effective ERP including produce characteristics, in‐package composition, material properties and their changes after compounding, remover properties, integration techniques, and environment. Next, this review presents a classification for ERP and provides a detailed analysis of various ethylene‐removing compounds including their mechanisms of action, integration techniques, impacts on produce shelf life, advantages and drawbacks including safety, commercial applications, and combinations with other shelf‐life extending technologies. Some ERP designs are more promising to extend produce shelf life than others, but there is still room for further research to advance this packaging strategy. Specific needs include investigation of ethylene removal for fresh‐cut produce and exploring different integration techniques and materials for such integration.
Microscopical discrimination of human head hairs sharing a mitochondrial haplogroup
Authors: Koch Sandra L. , Liebowitz Corey , Shriver Mark D. , Jablonski Nina G.
Published: September 2020

In forensic analyses, determining the level of consensus among examiners for hair comparison conclusions and ancestry identifications is important for assessing the scientific validity of microscopical hair examinations. Here, we present data from an interlaboratory study on the accuracy of microscopical hair comparisons among a subset of experienced hair examiners currently analyzing hair in forensic laboratories across the United States. We examined how well microscopical analysis of hair can reliably be used to differentiate hair samples, many of which were macroscopically similar. Using cut hair samples, many sharing similar macroscopic and microscopic features, collected from individuals who share the same mitochondrial haplogroup as an indication of genetic relatedness, we tested multiple aspects that could impact hair comparisons. This research tested the extent to which morphological features related to ancestry and hair length influence conclusions. Microscopical hair examinations yielded accurate assessments of inclusion/exclusion relative to the reference samples among 85% of the pairwise comparisons. We found shorter hairs had reduced levels of accuracy and hairs from populations examiners were not familiar with may have impacted their ability to resolve features. The reliability of ancestry determinations is not yet clear, but we found indications that the existing categories are only somewhat related to current ethnic and genetic variation. Our results provide support for the continued utility of microscopical comparison of hairs within forensic laboratories and to advocate for a combined analytical approach using both microscopical analysis and mtDNA data on all forensic analyses of hair.
A novel chitosan/tripolyphosphate/L‐lysine conjugates for latent fingerprints detection and enhancement
Authors: Vučković Nemanja , Glođović Nikola , Radovanović Željko , Janaćković Đorđe , Milašinović Nikola
Published: September 2020

Most chemical and physical methods employed in visualizing latent marks have shown detrimental effects on human health and, therefore, some research groups have directed their attention to the utilization of various (bio)polymers with the aforementioned purpose. Although chitosan is widely used in medicine, pharmacy, food, and drug delivery systems, there are very few studies that address this biopolymer utilization in forensic applications, such as the detection of latent fingerprints. We used chitosan crosslinked with sodium tripolyphosphate and conjugated with L‐lysine to enhance the visualization of latent fingerprints, due to its ability to interact with fingerprint sweat residues. These conjugates were prepared using different (w/w) amounts of chitosan and tripolyphosphate (6/1; 4/1; 1/1; 1/4; and 1/6), and those with the most promising results (i.e., 6/1 formulation) were investigated in detail. Fourier transform infrared (FT‐IR) spectroscopy confirmed interactions between components of the systems. Optical microscopy and scanning electron microscope (SEM) analysis showed that prepared powder formulations were uniform in size and confirmed that chitosan/tripolyphosphate/lysine conjugates bind easily to the sweat and lipid residues present in the latent fingerprints. The testing of prepared conjugates demonstrated the potential of these systems as bio‐based powder substitution for commercially available powders.
Quantitative structure‐activity relationships (QSAR) of aroma compounds in different aged Huangjiu
Authors: Feng Tao , Hu Zhongshan , Chen Ling , Chen Da , Wang Xu , Yao Lingyun , Sun Min , Song Shiqing , Wang Huatian
Published: September 2020

Huangjiu is a traditional wine in China with special taste and flavor. However, changes of aroma compounds during storage of Huangjiu remain unclear. In this study, aroma compounds in Jinse Nianhua Huangjiu of three different storage ages were qualitatively and quantitatively analyzed via headspace solid phase microextraction (HS‐SPME) combined with gas chromatography‐mass spectrometry (GC‐MS). Based on odor activity value (OAV), the most important aroma compounds were found to be esters, aldehydes, alcohols, acids, ketones, phenols, and lactones. Even though the types of the aroma compounds were similar in different‐aged Huangjiu, the concentrations of some compounds varied. Some aroma compounds’ thresholds and OAV in Huangjiu were obtained by AC'Scent Intl. Olfactometer. It showed the key aroma compounds in Huangjiu had a positive correlation with their OAV instead of concentration. Quantitative structure‐activity relationship (QSAR) models were developed to predict the flavor thresholds for alcohols, acids, and esters in Huangjiu, with higher accuracy for alcohols (R2 = 0.978) and acids (R2 = 0.987). This study will provide valuable information to unveil the regulation of Huangjiu flavor from molecular basis.

Practical Application

The built mathematical model enables to predict changes of aroma compounds in Huangjiu during storage, based on the relationship between the quantum structure parameters of those aroma compounds and the odor activity value of flavor chemicals. This research will contribute to simplifying the wine flavor analysis for wine industry and also help to identify the age of the Huangjiu for customers.
Impacts of post‐radiotherapy lymphocyte count on progression‐free and overall survival in patients with stage III lung cancer
Authors: Matiello Juliana , Dal Pra Alan , Zardo Laise , Silva Ricardo , Berton Danilo C
Published: September 2020

Background

We evaluated the impact of thoracic radiation in patients with non‐small cell lung cancer (NSCLC), considering the depletion of total lymphocytes, use or not of chemotherapy, and radiation doses in healthy lung tissue.

Methods

Patients with stage III NSCLC, ECOG 0 to 2, receiving radiotherapy with or without chemotherapy were prospectively evaluated. All patients should be treated with three‐dimensional radiotherapy and received biologically effective doses (BED10α/β 10) of 48 to 80 Gy. Peripheral blood lymphocyte total counts were measured at the start of radiotherapy and at 2, 6 and 12 months after radiotherapy. Along with lymphocytes, PTV and doses of 5 Gy and 20 Gy in healthy lung tissue were also evaluated as potential factors influencing overall survival (OS) and progression‐free survival (PFS).

Results

A total of 46 patients were prospectively evaluated from April 2016 to August 2019, with a median follow‐up of 13 months (interquartile range, 1–39 months). The median of OS of all cohort was 22,8 months (IC 95% 17,6–28,1) and the median PFS was 19,5 months (IC 95%: 14,7–24,2). Most patients received concurrent or neoadjuvant chemotherapy (43; 93.4%). No patient received adjuvant immunotherapy. The lower the lymphocyte loss at 6 months after radiotherapy (every 100 lymphocytes/mcL), the greater the chance of PFS (HR, 0.44; 95%CI, 0.25–0.77; P = 0.004) and OS (HR, 0.83; 95%CI, 0.70–0.98; P = 0.025; P = 0.025). BED was a protective factor for both PFS (HR, 0.52; 95%CI 0.33–0.83; P = 0.0006) and OS (HR, 0.73; 95%CI 0.54–0.97; P = 0.029).

Conclusions

Our results suggest that lymphocyte depletion after radiotherapy reduces tumor control and survival in patients with stage III lung cancer. Radiation doses equal or higher than 60 Gy (BED1072 Gy) improve PFS and OS, but they negatively affect lymphocyte counts for months, which reduces survival and the potential of immunotherapy.

Key points

Significant findings of the study

Thoracic irradiation for locally advanced lung cancer depletes T lymphocytes for months. Patients whose lymphocyte loss is lower have better overall survival and progression‐free survival.

What this study adds

It is necessary to protect the lymphocyte population, as well as other organs at risk. New forms of irradiation for large fields are needed. Furthermore, could immunotherapy before chemo‐radiotherapy, with a greater number of lymphocytes, bring an even better result?
M2 macrophages reduce the effect of gefitinib by activating AKT/mTOR in gefitinib‐resistant cell lines HCC827/GR
Authors: Xiao Fengqi , Liu Ni , Ma Xinchun , Qin Jing , Liu Yanguo , Wang Xiuwen
Published: September 2020

Background

The biological behavior of cells change after they develop drug resistance, and the degree of resistance will be affected by the tumor microenvironment. Here, we aimed to explore the changes in the biological behavior of tumors and to observe the differences in the release of cytokines and chemokines which can influence the tumor microenvironment. We also aimed to study how TKIs‐resistant cell lines recruit macrophages to reduce the sensitivity of the cells following gefitinib administration.

Methods

We generated and maintained gefitinib‐resistant cell lines to study the differences between gefitinib‐sensitive cell lines according to clone formation, cell growth curve analysis, whole‐exome sequencing, and qPCR ARRAY technology. We used the WNT/β‐catenin inhibitor, WNT/β‐catenin activator and overexpression β‐catenin lentivirus to observe the changes in CCL2. M2 macrophages and gefitinib‐resistant cell lines HCC827/GR were cocultured to detect the viability gefitinib for inducing cell death.

Results

The proliferation and migratory activities were much more pronounced in HCC827/GR cells. CCL2 expression was also enhanced and regulated by β‐catenin in HCC827/GR. CCL2 promoted the chemotactic ability of M2 macrophages. M2 macrophages reduced the antitumor effect of gefitinib treatment by activating AKT/mTOR.

Conclusions

Gefitinib‐resistant cell lines have stronger proliferation and migration capabilities, and attract macrophages by releasing more CCL2 to reduce the sensitivity of cells to gefitinib.
The Competitive Intelligence Unit at Deloitte
Authors: Dunn Paul
Published: September 2020

The goal of competitive intelligence is to acquire information that can be used to make strategic decisions that further the objectives of the firm. Using publicly available information, this case describes the Competitive Intelligence Unit at the Big 4 accounting firm Deloitte and the techniques that the unit used to obtain strategic information about the plight of the consulting firm BearingPoint, a firm that Deloitte subsequently purchased in March 2009. This case can be used in an advanced undergraduate accounting theory, assurance, or capstone accounting course. It raises several interesting questions: What are acceptable and unacceptable competitive intelligence gathering techniques? Does competitive intelligence gathering by accounting firms serve the public interest?
Underlying features of epigenetic aging clocks in vivo and in vitro
Authors: Liu Zuyun , Leung Diana , Thrush Kyra , Zhao Wei , Ratliff Scott , Tanaka Toshiko , Schmitz Lauren L. , Smith Jennifer A. , Ferrucci Luigi , Levine Morgan E.
Published: September 2020

Epigenetic clocks, developed using DNA methylation data, have been widely used to quantify biological aging in multiple tissues/cells. However, many existing epigenetic clocks are weakly correlated with each other, suggesting they may capture different biological processes. We utilize multi‐omics data from diverse human tissue/cells to identify shared features across eleven existing epigenetic clocks. Despite the striking lack of overlap in CpGs, multi‐omics analysis suggested five clocks (Horvath1, Horvath2, Levine, Hannum, and Lin) share transcriptional associations conserved across purified CD14+ monocytes and dorsolateral prefrontal cortex. The pathways enriched in the shared transcriptional association suggested links between epigenetic aging and metabolism, immunity, and autophagy. Results from in vitro experiments showed that two clocks (Levine and Lin) were accelerated in accordance with two hallmarks of aging—cellular senescence and mitochondrial dysfunction. Finally, using multi‐tissue data to deconstruct the epigenetic clock signals, we developed a meta‐clock that demonstrated improved prediction for mortality and robustly related to hallmarks of aging in vitro than single clocks.
Multiomic features associated with mucosal healing and inflammation in paediatric Crohn’s disease
Authors: Taylor Henry , Serrano‐Contreras Jose Ivan , McDonald Julie A. K. , Epstein Jenny , Fell JM , Seoane Rocio C. , Li Jia V. , Marchesi Julian R. , Hart Ailsa L.
Published: September 2020

Background

The gastrointestinal microbiota has an important role in mucosal immune homoeostasis and may contribute to maintaining mucosal healing in Crohn's disease (CD).

Aim

To identify changes in the microbiota, metabolome and protease activity associated with mucosal healing in established paediatric CD

Methods

Twenty‐five participants aged 3‐18 years with CD, disease duration of over 6 months, and maintenance treatment with biological therapy were recruited. They were divided into a low calprotectin group (faecal calprotectin <100 μg/g, “mucosal healing,” n = 11), and a high calprotectin group (faecal calprotectin >100 μg/g, “mucosal inflammation,” n = 11). 16S gene‐based metataxonomics, 1H‐NMR spectroscopy‐based metabolic profiling and protease activity assays were performed on stool samples.

Results

Relative abundance of Dialister species was six‐times greater in the low calprotectin group (q = 0.00999). Alpha and beta diversity, total protease activity and inferred metagenomic profiles did not differ between groups. Pentanoate (valerate) and lysine were principal discriminators in a machine‐learning model which differentiated high and low calprotectin samples using NMR spectra (R2 0.87, Q2 0.41). Mean relative concentration of pentanoate was 1.35‐times greater in the low calprotectin group (95% CI 1.03‐1.68, P = 0.036) and was positively correlated with Dialister. Mean relative concentration of lysine was 1.54‐times greater in the high calprotectin group (95% CI 1.05‐2.03, P = 0.028).

Conclusions

This multiomic study identified an increase in Dialister species and pentanoate, and a decrease in lysine, in patients with “mucosal healing.” It supports further investigation of these as potential novel therapeutic targets in CD.
Icariin‐induced inhibition of SIRT6/NF‐κB triggers redox mediated apoptosis and enhances anti‐tumor immunity in triple‐negative breast cancer
Authors: Song Linjiang , Chen Xian , Mi Ling , Liu Chi , Zhu Shaomi , Yang Tianlin , Luo Xiaohong , Zhang Qinxiu , Lu Hua , Liang Xin
Published: September 2020

Abnormal activation of the nuclear factor‐kappa B (NF‐κB) signaling pathway is closely implicated in triple‐negative breast cancer growth, metastasis, and tumor immune escape. In this study, the anti‐cancer effects of icariin, a natural flavonol glycoside, toward breast cancer cells and the underlying mechanisms were investigated. This investigation showed that icariin selectively inhibited proliferation and triggered apoptosis in breast cancer cells in a concentration‐ and time‐dependent manner, but exhibited little cytotoxicity in normal breast cells. Moreover, icariin induced cell apoptosis via a mitochondria‐mediated pathway, as indicated by the upregulated ratio of Bax/Bcl‐2 and reactive oxygen species induction. Importantly, icariin impaired the activation of the NF‐κB/EMT pathway, as evidenced by upregulation of SIRT6, resulting in inhibition of migration and invasion of breast cancer cells. Additionally, oss‐128167, an inhibitor of SIRT6, dramatically attenuated anti‐migration and anti‐invasion effects of icariin. Transcriptomic analysis verified that impairment of NF‐κB led to the selective function of icariin in breast cancer cells. Notably, icariin exhibited a significant tumor growth inhibition and anti‐pulmonary metastasis effect in a tumor mouse model of MDA‐MB‐231 and 4T1 cells by regulating the tumor immunosuppressive microenvironment. Together, these results showed that icariin could effectively trigger apoptosis and inhibit the migration of breast cancer cells via the SIRT6/NF‐κB signaling pathway, suggesting that icariin might serve as a potential candidate drug for the treatment of breast cancer.
The Weight of Evidence From Electrophysiology, Observational, and Cardiovascular End Point Studies Demonstrates the Safety of Azithromycin
Authors: Cook Jack , Pressler Milton L. , Damle Bharat , Alemayehu Demissie , Knirsch Charles A.
Published: September 2020

Increased use of azithromycin (AZ) in treating infections associated with coronavirus disease 2019 (COVID‐19) and reports of increased incidence of prolonged corrected QT (QTc) interval associated with AZ used with hydroxychloroquine prompted us to review the latest evidence in the literature, present additional analyses of human cardiovascular (CV) electrophysiology studies, and to describe sequential steps in research and development that were undertaken to characterize the benefit‐risk profile of AZ. Combined QTc findings from electrocardiograms taken during oral and i.v. pharmacokinetic‐pharmacodynamic studies of AZ suggest that clinically meaningful QTc prolongation is unlikely. Findings from several observational studies were heterogeneous and not as consistent as results from at least two large randomized controlled trials (RCTs). The QTc findings presented and observational data from studies with large numbers of events are not consistent with either a proarrhythmic action of AZ or an increase in frequency of CV deaths. Well‐powered RCTs do not suggest a presence of increased risk of CV or sudden cardiac death after short‐term or protracted periods of AZ usage, even in patients at higher risk from pre‐existing coronary disease.
Sodium‐glucose co‐transporter‐2 inhibition and ocular outcomes in patients with type 2 diabetes: A systematic review and meta‐analysis
Authors: Li Chao , Zhou Zien , Neuen Brendon L. , Yu Jie , Huang Yuli , Young Tamara , Li Jingwei , Li Lin , Perkovic Vlado , Jardine Meg J. , Keay Lisa , Markoulli Maria , Rosenthal Norm , Capuano George , Yavin Yshai , Neal Bruce , Arnott Clare
Published: September 2020

Sodium‐glucose co‐transporter‐2 (SGLT2) inhibitors are effective for the treatment of macrovascular complications and nephropathy in type 2 diabetes, but effects on microvascular eye outcomes are unclear. We conducted a systematic review and meta‐analysis of randomized placebo‐controlled trials to evaluate the effect of SGLT2 inhibition on total ocular events and retinopathy in patients with type 2 diabetes. We searched MEDLINE and Embase for the period from database inception date to October 11, 2019. Two reviewers working independently extracted relevant data. Random‐effects models with inverse variance weighting were selected to estimate summary risk ratios (RRs) and 95% confidence intervals (CIs). We included nine studies, involving 39 982 patients with a mean follow‐up of 2.8 years. There were 1414 total ocular events, of which 624 were retinopathy events. SGLT2 inhibition was not associated with a change in the risk of total ocular events (RR 0.97, 95% CI 0.85, 1.11) or retinopathy (RR 0.98, 95% CI 0.84, 1.16), with consistent effects across studies (P for heterogeneity = 0.35 and 0.45, respectively). The effects of SGLT2 inhibition on eye disease in individuals with type 2 diabetes are probably null, although the available data cannot exclude small to moderate benefits or harms.
SPORTING EVENTS, EMOTIONAL CUES, AND CRIME: SPATIAL AND TEMPORAL EVIDENCE FROM BRAZILIAN SOCCER GAMES
Authors: Ge Qi , Sarmiento Barbieri Ignacio , Schneider Rodrigo
Published: September 2020

Utilizing a novel data set of police reports that provides granular street‐ and vehicle‐level information on vehicle thefts and robberies in the city of São Paulo, Brazil, we explore the impact of soccer games and their outcomes on crime and study its spatial heterogeneity. Estimates from a regression discontinuity design suggest that crime increases immediately after home games in streets that are within a tight radius from the stadiums. The effect is driven by vehicle thefts with popular car models being more likely to be targeted and is particularly salient after upset losses and derby games.(JEL D91, R12, Z2)
Construction of a 3D brain extracellular matrix model to study the interaction between microglia and T cells in co‐culture
Authors: Frühauf Marie , Zeitschel Ulrike , Höfling Corinna , Ullm Franziska , Rabiger Friederike V. , Alber Gottfried , Pompe Tilo , Müller Uwe , Roßner Steffen
Published: September 2020

Neurodegenerative disorders are characterised by the activation of brain‐resident microglia cells and by the infiltration of peripheral T cells. However, their interplay in disease has not been clarified yet. It is difficult to investigate complex cellular dynamics in living animals, and simple two‐dimensional (2D) cell culture models do not resemble the soft 3D structure of brain tissue. Therefore, we developed a biomimetic 3D in vitro culture system for co‐cultivation of microglia and T cells. As the activation and/or migration of immune cells in the brain might be affected by components of the extracellular matrix, defined 3D fibrillar collagen I‐based matrices were constructed and modified with hyaluronan and/or chondroitin sulphate, resembling aspects of brain extracellular matrix. Murine microglia and spleen‐derived T cells were cultured alone or in co‐culture on the constructed matrices. Microglia exhibited in vivo‐like morphology and T cells showed enhanced survival when co‐cultured with microglia or to a minor degree in the presence of glia‐conditioned medium. The open and porous fibrillar structure of the matrix allowed for cell invasion and direct cell‐cell interaction, with stronger invasion of T cells. Both cell types showed no dependence on the matrix modifications. Microglia could be activated on the matrices by lipopolysaccharide resulting in interleukin‐6 and tumour necrosis factor‐α secretion. The findings herein indicate that biomimetic 3D matrices allow for co‐cultivation and activation of primary microglia and T cells and provide useful tools to study their interaction in vitro.
Science, institutions, and values
Authors: Mantzavinos C.
Published: September 2020

This paper articulates and defends three interconnected claims: firstly, that the debate on the role of values for science misses a crucial dimension, the institutional one; secondly, that institutions occupy the intermediate level between scientific activities and values and that they are to be systematically integrated into the analysis; thirdly, that the appraisal of the institutions of science with respect to values should be undertaken within the premises of a comparative approach rather than an ideal approach. Hence, I defend the view that the issue be framed in reference to the following question: “What kind of institutional rules should be in place in order for the scientific process to unfold in such a way that the values that we deem more important come to the fore?” Addressing this concern is equivalent to conducting a debate on institutions and their role for science.
Diffuse brain connectivity changes in Charcot–Marie–Tooth type 1a patients: a resting‐state functional magnetic resonance imaging study
Authors: Pontillo G. , Tozza S. , Perillo T. , Cocozza S. , Dubbioso R. , Severi D. , Iodice R. , Tedeschi E. , Elefante A. , Brunetti A. , Manganelli F. , Quarantelli M.
Published: September 2020

Background and purpose

Changes of brain structure and function have been described in peripheral neuropathies. The aim of our study was to systematically investigate possible modifications of major large‐scale brain networks using resting‐state functional magnetic resonance imaging (RS‐fMRI) in Charcot–Marie–Tooth disease type 1A (CMT1A) patients.

Methods

In this cross‐sectional study, 3‐T MRI brain scans were acquired of right‐handed genetically confirmed CMT1A patients and age‐ and sex‐comparable healthy controls. Patients also underwent clinical and electrophysiological examinations assessing neurological impairment. RS‐fMRI data were analysed using a seed‐based approach, with 32 different seeds sampling the main hubs of default mode, sensorimotor, visual, salience (SN), dorsal attention, frontoparietal, language and cerebellar networks. Between‐group differences in terms of functional connectivity (FC) with the explored seeds were tested voxelwise, correcting for local grey matter density to account for possible structural abnormalities, whilst the relationship between FC modifications and neurological impairment was investigated using robust correlation analyses.

Results

Eighteen CMT1A patients (34.0 ± 11.4 years; M/F 11/7) were enrolled, along with 20 healthy controls (30.1 ± 10.2 years; M/F 11/9). In the CMT group compared to controls, clusters of increased FC with the visual cortex (P = 0.001), SN (P < 6 × 10−4), dorsal attention network (P < 8 × 10−5) and language network (P < 7 × 10–4) were found, along with a single cluster of reduced FC with the visual cortex in the left lentiform nucleus (P = 10–6). A significant correlation emerged between neurophysiological impairment and increased FC with right temporal language areas (r = 0.655, P = 0.006), along with an association between walking ability and increased FC with the left supramarginal gyrus (SN) (r = 0.620, P = 0.006).

Conclusions

Our data show evidence of diffuse functional reorganization involving multiple large‐scale networks in the CMT1A brain, independent of structural modifications and partially correlating with peripheral nerve damage and functional impairment.
Dynamic analysis of fMRI activation during epileptic spikes can help identify the seizure origin
Authors: Kowalczyk Magdalena A. , Omidvarnia Amir , Dhollander Thijs , Jackson Graeme D.
Published: September 2020

Objective

We use the dynamic electroencephalography–functional magnetic resonance imaging (EEG‐fMRI) method to incorporate variability in the amplitude and field of the interictal epileptic discharges (IEDs) into the fMRI analysis. We ask whether IED variability analysis can (a) identify additional activated brain regions during the course of IEDs, not seen in standard analysis; and (b) demonstrate the origin and spread of epileptic activity. We explore whether these functional changes recapitulate the structural connections and propagation of epileptic activity during seizures.

Methods

Seventeen patients with focal epilepsy and at least 30 IEDs of a single type during simultaneous EEG‐fMRI were studied. IED variability and EEG source imaging (ESI) analysis extracted time‐varying dynamic changes. General linear modeling (GLM) generated static functional maps. Dynamic maps were compared to static functional maps. The dynamic sequence from IED variability was compared to the ESI results. In a subset of patients, we investigated structural connections between active brain regions using diffusion‐based fiber tractography.

Results

IED variability distinguished the origin of epileptic activity from its propagation in 15 of 17 (88%) patients. This included two cases where no result was obtained from the standard GLM analysis. In both of these cases, IED variability revealed activation in line with the presumed epileptic focus. Two cases showed no result from either method. Both had very high spike rates associated with dysplasia in the postcentral gyrus. In all 15 cases with dynamic activation, the observed dynamics were concordant with ESI. Fiber tractography identified specific white matter pathways between brain regions that were active at IED onset and propagation.

Significance

Dynamic techniques involving IED variability can provide additional power for EEG‐fMRI analysis, compared to standard analysis, revealing additional biologically plausible information in cases with no result from the standard analysis and gives insight into the origin and spread of IEDs.
A semantic‐enabled and context‐aware monitoring system for the internet of medical things
Authors: Rhayem Ahlem , Mhiri Mohamed Ben Ahmed , Drira Khalil , Tazi Said , Gargouri Faiez
Published: September 2020

The emergence of the Internet of Things (IoT) in the medical field has led to the massive deployment of a myriad of medical connected objects (MCOs). These MCOs are being developed and implemented for remote healthcare monitoring purposes including elderly patients with chronic diseases, pregnant women, and patients with disabilities. Accordingly, different associated challenges are emerging and include the heterogeneity of the gathered health data from these MCOs with ever‐changing contexts. These contexts are relative to the continuous change of constraints and requirements of the MCOs deployment (time, location, state). Other contexts are related to the patient (medical record, state, age, sex, etc.) that should be taken into account to ensure a more precise and appropriate treatment of the patient. These challenges are difficult to address due to the absence of a reference model for describing the health data and their sources and linking these data with their contexts. This article addresses this problem and introduces a semantic‐based context‐aware system (IoT Medicare system) for patient monitoring with MCOs. This system is based on a core domain ontology (HealthIoT‐O), that is, designed to describe the semantic of heterogeneous MCOs and their data. Moreover, an efficient interpretation and management of this knowledge in diverse contexts are ensured through SWRL rules such as the verification of the proper functioning of the MCOs and the analysis of the health data for diagnosis and treatment purposes. A case study of gestational diabetes disease management is proposed to evaluate the effectiveness of the implemented IoT Medicare system. An evaluation phase is provided and focuses on the quality of the elaborated semantic model and the performance of the system.
Pollock and “the Blob”: Impacts of a marine heatwave on walleye pollock early life stages
Authors: Rogers Lauren A. , Wilson Matthew T. , Duffy‐Anderson Janet T. , Kimmel David G. , Lamb Jesse F.
Published: September 2020

The North Pacific marine heatwave of 2014–2016 (nicknamed “The Blob”) impacted marine ecosystems from California to Alaska, USA, with cascading effects on fisheries and fishing communities. We investigated the effects of this anomalous ocean warming on early life stages of walleye pollock (Gadus chalcogrammus) in the Gulf of Alaska. In spring of 2015, pollock larvae were caught at record low levels relative to a 30‐year time series. Survival rates were low during the summer, and by late summer, numbers were further reduced, with very low abundances of juvenile (age‐0) pollock. Our analyses suggested multiple mechanisms for this decline: (a) Low‐saline conditions may have impacted egg buoyancy and survival; (b) population densities of zooplankton nauplii may have been too low to support first‐feeding larvae; (c) body condition of age‐0 pollock was poor and a bioenergetics model indicated that reduced quality of zooplankton prey, coupled with warmer temperatures, increased the ration required for positive growth by up to 19%, at a time when prey abundance was likely reduced. Thus, walleye pollock experienced a cascade of poor conditions for growth and survival through early life stages, resulting in the near disappearance of the 2015 year class in the population by the end of their first year. These impacts differ from previous warm years and emphasize the importance of looking beyond simple temperature–abundance relationships when predicting species responses to climate warming.
The problem of scale in predicting biological responses to climate
Authors: Bütikofer Luca , Anderson Karen , Bebber Daniel P. , Bennie Jonathan J. , Early Regan I. , Maclean Ilya M. D.
Published: September 2020

Many analyses of biological responses to climate rely on gridded climate data derived from weather stations, which differ from the conditions experienced by organisms in at least two respects. First, the microclimate recorded by a weather station is often quite different to that near the ground surface, where many organisms live. Second, the temporal and spatial resolutions of gridded climate datasets derived from weather stations are often too coarse to capture the conditions experienced by organisms. Temporally and spatially coarse data have clear benefits in terms of reduced model size and complexity, but here we argue that coarse‐grained data introduce errors that, in biological studies, are too often ignored. However, in contrast to common perception, these errors are not necessarily caused directly by a spatial mismatch between the size of organisms and the scale at which climate data are collected. Rather, errors and biases are primarily due to (a) systematic discrepancies between the climate used in analysis and that experienced by organisms under study; and (b) the non‐linearity of most biological responses in combination with differences in climate variance between locations and time periods for which models are fitted and those for which projections are made. We discuss when exactly problems of scale can be expected to arise and highlight the potential to circumvent these by spatially and temporally down‐scaling climate. We also suggest ways in which adjustments to deal with issues of scale could be made without the need to run high‐resolution models over wide extents.
Black servants and Captain's slaves: James Cook and the death of George Rupee
Authors: Parsons Harriet
Published: September 2020

Captain James Cook's first voyage of Pacific exploration on the Endeavour, from 1768 to 1771, with the naturalist Joseph Banks, was one of the 18th century's most ambitious scientific ventures. Two of Banks' servants, Thomas Richmond and George Dorlton, were black men, and close reading of the records of their deaths in January 1769, suggests that one of them, Dorlton, was the Captain's slave, George ‘Rupee’. The Admiralty had banned slavery on Royal Navy ships and Rupee's accidental death had unforeseen consequences for the expedition. Cook's role as captain required him to investigate, and potentially dole out punishment if a member of the crew was culpable. However, his personal interest in the judgement as Rupee's master, compromised his impartiality. Networks of personal loyalty were integral to the social architecture of command in the Georgian Navy, and Rupee's death threatened to upset this fragile equilibrium. In the following days, half truths burgeoned into lies and deception in the Endeavour's reporting systems. The escalating ‘bad language’ put the crew's confidence in Cook's command in jeopardy, until the Master, Robert Molyneux, took decisive action to stop its spread.
Overlap between hemophagocytic lymphohistiocytosis and drug reaction and eosinophilia with systemic symptoms: a review
Authors: Yang Jason J. , Lei Donald K. , Ravi Vignesh , Maloney Nolan J. , Crew Ashley , Worswick Scott
Published: September 2020

Drug reaction and eosinophilia with systemic symptoms (DRESS), also known as drug‐induced hypersensitivity syndrome (DIHS), shares features with hemophagocytic lymphohistiocytosis (HLH), most notably fever, rash, and internal organ involvement. However, there is increasing recognition of drug‐induced (secondary) HLH and biopsy‐proven hemophagocytosis in DRESS, suggesting that HLH and DRESS not only overlap but also may be diseases on the same spectrum of immune dysfunction. To characterize existing literature on HLH/DRESS overlap, we queried the PubMed/MEDLINE database for 23 cases of HLH‐DRESS codiagnosis. Average time‐to‐onset of rash after exposure to inciting drug was 2.7 weeks. Fourteen cases (61%) clinically worsened despite initial therapy, prompting a workup with diagnosis of HLH on average 2.3 weeks after diagnosing DRESS. Nine cases met HLH diagnostic criteria and had a RegiSCAR score ≥4. Nine cases met one set of criteria with a presentation suggestive of the other. Five cases met neither criteria. A patient presenting with fever, generalized rash, bicytopenia, and internal organ involvement after drug exposure was most predictive of meeting diagnostic criteria for both HLH and DRESS. Treatment was highly variable, although most initiated systemic corticosteroids with/without IVIG, plasmapheresis, or etoposide. Patients with poor outcomes in this review were treated using steroid monotherapy and had viral reactivation. Dermatologists should consider the possibility of HLH in any patient presenting with fever, rash, internal organ involvement, and cytopenia. Additional studies will be necessary to further characterize HLH and DRESS overlap and determine optimal management.
Coordination mechanisms for scheduling games with machine modification
Authors: He Chaoyu , Tan Zhiyi
Published: September 2020

This paper studies scheduling games with machine modification. A set of jobs is to be processed on a set of identical machines. An initial schedule before the modification of machines is given as a prior. Then some machines are removed and some new machines are added. Each job has the right either to stay on its original machine if the machine is not removed, or to move to another machine. The choices of all jobs after the machine modification constitute a new schedule. The individual cost of each job is its completion time, which is determined by the scheduling policy that the machines follow. We present properties of the Nash equilibriums under generalizations of the classical scheduling policies such as LPT, SPT and Makespan. For the social cost of minimizing the makespan, we establish the Price of Anarchy and Price of Stability of the games, and majorities of the parametric bounds are tight for each combination of the number of final machines, the number of added machines and the number of removed machines.