bluuebunny/crossref_metadata_2025_split huggingface dataset:
Delayed graft function is correlated with graft loss in recipients of expanded-criteria rather than standard-criteria donor kidneys: a retrospective, multicenter, observation cohort study
Authors: Han Fei , Lin Min-Zhuan , Zhou Hong-Lan , Li Heng , Sun Qi-Peng , Huang Zheng-Yu , Hong Liang-Qing , Wang Gang , Cai Rui-Ming , Sun Qi-Quan 
Published: February 2020

Abstract

Background:
Although the use of expanded-criteria donors (ECDs) alleviates the problem of organ shortage, it significantly increases the incidence of delayed graft function (DGF). DGF is a common complication after kidney transplantation; however, the effect of DGF on graft loss is uncertain based on the published literature. Hence, the aim of this study was to determine the relationship between DGF and allograft survival.

Methods:
We conducted a retrospective, multicenter, observation cohort study. A total of 284 deceased donors and 541 recipients between February 2012 and March 2017 were included. We used logistic regression analysis to verify the association between clinical parameters and DGF, and Cox proportional hazards models were applied to quantify the hazard ratios of DGF for kidney graft loss.

Results:
Among the 284 deceased donors, 65 (22.8%) donors were ECD. Of the 541 recipients, 107 (19.8%) recipients developed DGF, and this rate was higher with ECD kidneys than with standard-criteria donor (SCD) kidneys (29.2% vs. 17.1%; P = 0.003). The 5-year graft survival rate was not significantly different between SCD kidney recipients with and without DGF (95.8% vs. 95.4%; P = 0.580). However, there was a significant difference between ECD kidney recipients with and without DGF (71.4% vs. 97.6%; P = 0.001), and the adjusted hazard ratio (HR) for graft loss for recipients with DGF was 1.885 (95% confidence interval [CI] = 1.305–7.630; P = 0.024). Results showed that induction therapy with anti-thymocyte globulin was protective against DGF (odds ratio = 0.359; 95% CI = 0.197–0.652; P = 0.001) with all donor kidneys and a protective factor for graft survival (HR = 0.308; 95% CI = 0.130–0.728; P = 0.007) with ECD kidneys.

Conclusion:
DGF is an independent risk factor for graft survival in recipients with ECD kidneys, but not SCD kidneys.
Cannabinoid type 2 receptor agonist JWH133 decreases blood pressure of spontaneously hypertensive rats through relieving inflammation in the rostral ventrolateral medulla of the brain
Authors: Shi He-Kai , Guo Hui-Cai , Liu Hou-Yue , Zhang Zi-Lin , Hu Mei-Yu , Zhang Yi , Li Qian 
Published: February 2020

Objective:
Neuroinflammation in the rostral ventrolateral medulla (RVLM) has been reported to be associated with hypertension. The upregulation and activation of the cannabinoid type 2 (CB2) receptor may be part of the active process of limiting or downregulating the inflammatory process. This study was designed to determine the role of the CB2 receptor in blood pressure (BP) through relieving neuroinflammation in the RVLM in spontaneously hypertensive rats (SHRs).

Methods:
The long-term effects of intracerebroventricular injection of JWH133, a selective CB2 receptor agonist, on BP, heart rate (HR) and renal sympathetic nerve activity (RSNA) in SHR and Wistar–Kyoto (WKY) rats were determined. ELISA was used to measure the levels of proinflammatory cytokines, and western blotting was employed to detect protein expression of the CB2 receptor. Immunofluorescence staining was used to localize the CB2 receptor. Gene silencing of the CB2 receptor was realized by injecting adeno-associated virus (AAV) expressing CB2-specific shRNA (AAV2-r-CB2shRNA) into the RVLM.

Results:
We found that SHRs exhibited higher levels of basal BP, HR, RSNA and proinflammatory cytokines (TNFα, IL-6 and IL-1β) than those in WKY rats. The protein level of the CB2 receptor in the RVLM was robustly increased in SHRs. In addition, the CB2 receptor was mainly expressed on microglia cells of SHRs but not in WKY rats. No expression of the CB2 receptor was found on neurons of either WKY rats or SHRs. Furthermore, intracerebroventricular injection of JWH133 (1 mmol/l, 10 μl) for 28 days decreased the BP, HR, RSNA and proinflammatory cytokines significantly in SHRs, but it had no such effects in WKY rats. These effects were abolished by microinjection of 300 nl AAV2-r-CB2shRNA into the RVLM to knock down the CB2 receptor.

Conclusion:
Taken together, our results suggest that exciting the CB2 receptor relieves proinflammatory cytokine levels in the RVLM to decrease the BP, HR and RSNA in SHRs.
Stage 1 hypertension defined by the 2017 American College of Cardiology/American Heart Association guideline and risk of adverse birth outcomes in Eastern China
Authors: Liu Jieyu , Tao Linghua , Cao Yingying , Teng Haoyue , Wang Jiaxiang , Wang Min , Li Fang , Wang Yumei , Yang Luoqi , Zhao Xiaoyan , Qin Liqiang , Yin Jieyun , Zhang Yonghong 
Published: February 2020

Objective:
The 2017 American College of Cardiology/American Heart Association (ACC/AHA) guideline recommended a lower threshold (130/80 mmHg) for hypertension in nonpregnant adults. However, the influence of this guideline in Chinese pregnant women is not well characterized.

Methods:
Data of 32 742 and 14 479 mothers who had blood pressure (BP) less than 130/80 mmHg and no proteinuria before 20 gestational weeks and delivered live singletons between 1 January 2014 and 30 November 2019 were extracted from Taizhou and Taicang register-based cohorts, respectively. The average measured BP in the third trimester was obtained and categorized according to the 2017 ACC/AHA guideline. The association between BP and risk of adverse birth outcomes was assessed by multivariate logistic regression analysis.

Results:
In the third trimester, 331 (1.01%) and 378 (2.61%) women had mean BP at least 140/90 mmHg, but 2435 (7.44%) and 1054 (7.28%) had stage 1 hypertension (130–139/80–89 mmHg) in Taizhou and Taicang, respectively. Significant associations between stage 1 hypertension and small for gestational age [odds ratio (OR) = 1.32, 95% confidence interval (CI) = 1.14–1.52] and low birth weight (OR = 1.81, 95% CI = 1.46–2.25) were observed in the Taizhou population. Consistent results were also shown in the Taicang population [OR (95% CI), of 1.46 (1.18–1.79) and 1.50 (1.07–2.11), respectively].

Conclusion:
Stage 1 hypertension in the third trimester defined by the 2017 ACC/AHA guideline was associated with an increased risk for adverse birth outcomes in Eastern Chinese pregnant women, suggesting that this guideline may improve the detection of high BP and surveillance of adverse neonatal outcomes in China.
Efficacy and Safety of Monoclonal Antibodies Against Clostridioides difficile Toxins for Prevention of Recurrent Clostridioides difficile Infection
Authors: Akiyama Shintaro , Yamada Akihiro , Komaki Yuga , Komaki Fukiko , Micic Dejan , Sakuraba Atsushi 
Published: February 2020

Background:

Clostridioides difficile infection is one of the most common health care-associated infections. To reduce the recurrent Clostridioides difficile infection (rCDI), monoclonal antibodies against Clostridioides difficile toxin A (actoxumab) and toxin B (bezlotoxumab) were developed. In the present study, we performed a systematic review and meta-analysis to assess their efficacy and safety.

Materials and Methods:
An electronic database was searched for relevant randomized controlled trials assessing bezlotoxumab and/or actoxumab. Outcomes included rate of rCDI and adverse events including cardiovascular and gastrointestinal events.

Results:
Four randomized controlled trials comparing antitoxin antibodies (n=1916) versus placebo (n=889) were identified. rCDI was significantly reduced by bezlotoxumab plus actoxumab (risk ratio=0.54, 95% confidence interval=0.41-0.70, P<0.001) and bezlotoxumab monotherapy (risk ratio=0.62, 95% confidence interval=0.51-0.76, P<0.001) compared with placebo. Subgroup analysis showed that bezlotoxumab plus actoxumab was remarkably preventive for patients with the following high-risk features: inpatients, vancomycin treatment, and BI/NAP/027 strain. Regarding safety, there was no difference in cardiovascular and gastrointestinal events as well as all-cause mortality between bezlotoxumab-treated patients and placebo.

Conclusions:
The results of our meta-analysis demonstrated the effectiveness and safety of bezlotoxumab for the prevention of rCDI. Bezlotoxumab may be a good therapeutic option for severe C. difficile infection rather than mild cases.
Indirectly Activated Treg Allow Dominant Tolerance to Murine Skin-grafts Across an MHC Class I Mismatch After a Single Donor-specific Transfusion
Authors: Zhang Geoff Yu , Hu Min , Watson Debbie , Wang Yuan Min , Knight John F. , Alexander Stephen I. 
Published: February 2020

Background.
Tolerance induced in stringent animal transplant models using donor-specific transfusions (DST) has previously required additional immunological manipulation. Here, we demonstrate a dominant skin-allograft tolerance model induced by a single DST across an major histocompatibility class I mismatch in an unmanipulated B6 host.

Methods.
C57BL/6 (H-2b) (B6) mice were injected intravenously with splenocytes from B6.C.H-2bm1 (H-2kbm1) (bm1) or F1 (B6 × bm1) mice before skin transplantation. Mice were transplanted 7 days postinjection with donor (bm1 or F1) and third-party B10.BR (H-2k) skin grafts.

Results.
B6 hosts acutely rejected skin grafts from B6.C.H-2bm1 (bm1) and F1 (B6 × bm1) mice. A single transfusion of F1 splenocytes into B6 mice without any additional immune modulation led to permanent acceptance of F1 skin grafts. This graft acceptance was associated with persistence of donor cells long-term in vivo. The more rapid removal of DST bm1 cells than F1 cells was reduced by natural killer-cell depletion. Tolerant grafts survived an in vivo challenge with naive splenocytes. Both CD4+CD25+ and CD4+CD25− T cells from F1 DST treated B6 mice suppressed alloproliferation in vitro. Tolerance was associated with expansion of peripheral Foxp3+CD4+CD25+ regulatory T cells (Treg) and increased forkhead box P3 (Foxp3) expression in tolerant grafts. In tolerant mice, Foxp3+ Treg arises from the proliferation of indirectly activated natural Foxp3+ Treg (nTreg) and depletion of Foxp3+ Treg abrogates skin-graft tolerance.

Conclusions.
This study demonstrates that the persistence of transfused semiallogeneic donor cells mismatched at major histocompatibility class I can enhance tolerance to subsequent skin allografts through indirectly expanded nTreg leading to dominant tolerance without additional immunological manipulation.
Serial interval of novel coronavirus (COVID-19) infections
Authors: Nishiura Hiroshi , Linton Natalie M. , Akhmetzhanov Andrei R. 
Published: February 2020

AbstractObjectiveTo estimate the serial interval of novel coronavirus (COVID-19) from information on 28 infector-infectee pairs.MethodsWe collected dates of illness onset for primary cases (infectors) and secondary cases (infectees) from published research articles and case investigation reports. We subjectively ranked the credibility of the data and performed analyses on both the full dataset (n=28) and a subset of pairs with highest certainty in reporting (n=18). In addition, we adjusting for right truncation of the data as the epidemic is still in its growth phase.ResultsAccounting for right truncation and analyzing all pairs, we estimated the median serial interval at 4.0 days (95% credible interval [CrI]: 3.1, 4.9). Limiting our data to only the most certain pairs, the median serial interval was estimated at 4.6 days (95% CrI: 3.5, 5.9).ConclusionsThe serial interval of COVID-19 is shorter than its median incubation period. This suggests that a substantial proportion of secondary transmission may occur prior to illness onset. The COVID-19 serial interval is also shorter than the serial interval of severe acute respiratory syndrome (SARS), indicating that calculations made using the SARS serial interval may introduce bias.Highlights-The serial interval of novel coronavirus (COVID-19) infections was estimated from a total of 28 infector-infectee pairs.-The median serial interval is shorter than the median incubation period, suggesting a substantial proportion of pre-symptomatic transmission.-A short serial interval makes it difficult to trace contacts due to the rapid turnover of case generations.
Glycopeptide antibiotic teicoplanin inhibits cell entry of SARS-CoV-2 by suppressing the proteolytic activity of cathepsin L
Authors: Yu Fei , Pan Ting , Huang Feng , Ying Ruosu , Liu Jun , Fan Huimin , Zhang Junsong , Liu Weiwei , Lin Yingtong , Yuan Yaochang , Yang Tao , Li Rong , Zhang Xu , Lv Xi , Chen Qianyu , Liang Anqi , Zou Fan , Liu Bingfeng , Hu Fengyu , Tang Xiaoping , Li Linghua , Deng Kai , He Xin , Zhang Hui , Zhang Yiwen , Ma Xiancai 
Published: February 2020

AbstractSince the outbreak of the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the public health worldwide has been greatly threatened. The development of an effective treatment for this infection is crucial and urgent but is hampered by the incomplete understanding of the viral infection mechanism and the lack of specific antiviral agents. We previously reported that teicoplanin, a glycopeptide antibiotic that has been commonly used in the clinic to treat bacterial infection, significantly restrained the cell entry of Ebola virus, SARS-CoV and MERS-CoV by specifically inhibiting the activity of cathepsin L (CTSL). Here, we found that the cleavage sites of CTSL on the Spike of SARS-CoV-2 were highly conserved among all the variants. The treatment with teicoplanin suppressed the proteolytic activity of CTSL on Spike and prevented the cellular infection of different pseudotyped SARS-CoV-2 viruses. Teicoplanin potently prevented the entry of authentic SARS-CoV-2 into the cellular cytoplasm with an IC50of 2.038 μM for the Wuhan-Hu-1 reference strain and an IC50of 2.116 μM for the SARS-CoV-2 (D614G) variant. The pre-treatment of teicoplanin also prevented SARS-CoV-2 infection in hACE2 mice. In summary, our data reveal that CTSL is required for both SARS-CoV-2 and SARS-CoV infection and demonstrate the therapeutic potential of teicoplanin for universal anti-CoVs intervention.ImportanceDisease prevention and treatment are two important countermeasures to end the coronavirus disease 2019 (COVID-19). However, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, evolves all the time, resulting in the emerging of many epidemic SARS-CoV-2 mutants, which significantly impairs the effectiveness of early strain-based vaccines and antibodies. Developing universal vaccines and broad-spectrum antiviral drugs are essential to confront SARS-CoV-2 mutants including those may emerge in the future. Our study reported here showed that the cleavage sites of cellular cathepsin L (CTSL) are highly conserved among all the SARS-CoV-2 mutants and SARS-CoV. The CTSL inhibitor teicoplanin not only inhibited the cell entry of two live SARS-CoV-2 strains and various pseudotyped viruses but also prevented live virus infection in animal models. Based on our previous finding that teicoplanin also inhibited SARS-CoV and MERS-CoV infection, we believe that teicoplanin possesses the potential to become a universal anti-CoVs drug.
Evidence of recombination in coronaviruses implicating pangolin origins of nCoV-2019
Authors: Wong Matthew C. , Javornik Cregeen Sara J. , Ajami Nadim J. , Petrosino Joseph F. 
Published: February 2020

SUMMARYA novel coronavirus (nCoV-2019) was the cause of an outbreak of respiratory illness detected in Wuhan, Hubei Province, China in December of 2019. Genomic analyses of nCoV-2019 determined a 96% resemblance with a coronavirus isolated from a bat in 2013 (RaTG13); however, the receptor binding motif (RBM) of these two genomes share low sequence similarity. This divergence suggests a possible alternative source for the RBM coding sequence in nCoV-2019. We identified high sequence similarity in the RBM between nCoV-2019 and a coronavirus genome reconstructed from a viral metagenomic dataset from pangolins possibly indicating a more complex origin for nCoV-2019.
The immune vulnerability landscape of the 2019 Novel Coronavirus, SARS-CoV-2
Authors: Zhu James , Kim Jiwoong , Xiao Xue , Wang Yunguan , Luo Danni , Jiang Shuang , Chen Ran , Xu Lin , Zhang He , Moise Lenny , Gutierrez Andres H. , De Groot Anne S. , Xiao Guanghua , Schoggins John W. , Zhan Xiaowei , Wang Tao , Xie Yang 
Published: February 2020

ABSTRACTThe outbreak of the 2019 Novel Coronavirus (SARS-CoV-2) rapidly spread from Wuhan, China to more than 150 countries, areas, or territories, causing staggering numbers of infections and deaths. In this study, bioinformatics analyses were performed on 5,568 complete genomes of SARS-CoV-2 virus to predict the T cell and B cell immunogenic epitopes of all viral proteins, which formed a systematic immune vulnerability landscape of SARS-CoV-2. The immune vulnerability and genetic variation profiles of SARS-CoV were compared with those of SARS-CoV and MERS-CoV. In addition, a web portal was developed to broadly share the data and results as a resource for the research community. Using this resource, we showed that genetic variations in SARS-CoV-2 are associated with loss of B cell immunogenicity, an increase in CD4+T cell immunogenicity, and a minimum loss in CD8+T cell immunogenicity, indicating the existence of a curious correlation between SARS-CoV-2 genetic evolutions and the immunity pressure from the host. Overall, we present an immunological resource for SARS-CoV-2 that could promote both therapeutic/vaccine development and mechanistic research.
Bilateral Sequential Theta Burst Stimulation for Multiple-Therapy-Resistant Depression: a naturalistic observation study
Authors: Burhan Amer M. , Patience James A. , Teselink Johannes G.P. , Marlatt Nicole M. , Babapoor-Farokhran Sahand , Palaniyappan Lena 
Published: February 2020

AbstractDepression is a significant health issue with treatment resistance reported in about one third of patients. Treatment resistance results in significant disability, impaired quality of life, and increased healthcare costs. Repetitive transcranial magnetic stimulation (rTMS) is a treatment option for treatment resistant depression (TRD) with an average response rate of around 30%. Theta-burst is a novel rTMS paradigm that has shown promise as a treatment for TRD in some preliminary studies. In a naturalistic design, we evaluated the efficacy and tolerability of bilateral sequential (right then left) prefrontal theta-burst rTMS (bsTBS) in 50 patients with TRD (600 pulses/session, 20 sessions, 100% of resting motor threshold (two patients treated at 80% due to intolerance of 100%), F4/F3 of 10-20-20 EEG localization). Data was collected over 36 months from a specialized academic TMS clinic. Patients had multiple-treatment resistance with at least two failed trials of different antidepressants with 20% also having failed electroconvulsive therapy and 66% having received professional therapy. We found a 28% remission rate (HAMD-17 score of ≤ 7) and a 52% response rate (≥ 50% reduction in HAMD-17) with a 42% reduction in average HAMD-17 score. The treatment was well tolerated, with muscle contractions, mild pain or discomfort, headache, scalp irritation, and changes to vitals being captured as occasional adverse events with two instances of syncope (0.22% of treatments). This naturalistic study shows that bsTBS is a promising paradigm for a multiple-TRD patient population with approximately one-third of treatments achieving remission and over half achieving significant response.Previous PublicationAbstract accepted and study presented at the 2018 Canadian Psychiatric Association Annual Conference, Toronto, Ontario, Canada, September 29, 2018.
corto: a lightweight R package for Gene Network Inference and Master Regulator Analysis
Authors: Mercatelli Daniele , Lopez-Garcia Gonzalo , Giorgi Federico M. 
Published: February 2020

AbstractMotivationGene Network Inference and Master Regulator Analysis (MRA) have been widely adopted to define specific transcriptional perturbations from gene expression signatures. Several tools exist to perform such analyses, but most require a computer cluster or large amounts of RAM to be executed.ResultsWe developed corto, a fast and lightweight R package to infer gene networks and perform MRA from gene expression data, with optional corrections for Copy Number Variations (CNVs) and able to run on signatures generated from RNA-Seq or ATAC-Seq data. We extensively benchmarked it to infer context-specific gene networks in 39 human tumor and 27 normal tissue datasets.AvailabilityCross-platform and multi-threaded R package on CRAN (stable version)https://cran.rproject.org/package=cortoand Github (development release)https://github.com/federicogiorgi/corto.Contactfederico.giorgi@unibo.it
Demonstration of resistance to satyrization behavior inAedes aegypti(Linnaeus) from La Réunion island
Authors: Maïga Hamidou , Gilles Jérémie R. L. , Lees Rosemary Susan , Yamada Hanano , Bouyer Jérémy 
Published: February 2020

AbstractAedes aegyptiandAedes albopictusare competent vectors of arboviruses such as dengue and chikungunya viruses which co-exist in some areas including La Réunion island. A kind of reproductive interference called satyrization has been described in sympatric species where a dominant species tends to control the spread of the other species. Here, we investigated satyrization in laboratory experiments to provide insights on the potential impact onAe. aegyptiof a control campaign including a sterile insect technique component againstAe. albopictus. Different mating crosses were used to test sympatric, conspecific-interspecific and allopatric effects of irradiated and non-irradiated maleAe. albopictuson femaleAe. aegypti, including in a situation of skewed male ratio. Our results suggest that there was only a low level of satyrization between sympatric populations ofAe. aegyptiandAe. albopictuscolonised from La Réunion island. A maleAe. albopictusto femaleAe. aegyptiratio of 3:1 did not increase the level of satyrization. FemaleAe. aegyptipreviously mated to maleAe. albopictuswere not prevented from being inseminated by conspecific maleAe. aegypti. A satyrization effect was not seen between allopatricAe. albopictusandAe. aegyptistrains from La Réunion Island either. The testedAe. aegyptistrain from La Réunion island has therefore developed full resistance to satyrization and so releasing sterile maleAe. albopictusmay not suppressAe. aegyptipopulations if an overflooding of irradiated maleAe. albopictusleads to similar results. The management strategy of two competent species in a sympatric area is discussed.