bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of a Reliable Surgical Quality Assurance System for 2-stage Esophagectomy in Randomized Controlled Trials
Authors: Harris Alexander , Butterworth James , Boshier Piers R. , MacKenzie Hugh , Tokunaga Masanori , Sunagawa Hideki , Mavroveli Stella , Ni Melody , Mikhail Sameh , Yeh Chi-Chuan , Blencowe Natalie S. , Avery Kerry N. L. , Hardwick Richard , Hoelscher Arnulf , Pera Manuel , Zaninotto Giovanni , Law Simon , Low Donald E. , van Lanschot Jan J. B. , Berrisford Richard , Barham Christopher Paul , Blazeby Jane M. , Hanna George B.
Published: March 2020

Objective:

The aim was to develop a reliable surgical quality assurance system for 2-stage esophagectomy. This development was conducted during the pilot phase of the multicenter ROMIO trial, collaborating with international experts.

Summary of Background Data:

There is evidence that the quality of surgical performance in randomized controlled trials influences clinical outcomes, quality of lymphadenectomy and loco-regional recurrence.

Methods:

Standardization of 2-stage esophagectomy was based on structured observations, semi-structured interviews, hierarchical task analysis, and a Delphi consensus process. This standardization provided the structure for the operation manual and video and photographic assessment tools. Reliability was examined using generalizability theory.

Results:

Hierarchical task analysis for 2-stage esophagectomy comprised fifty-four steps. Consensus (75%) agreement was reached on thirty-nine steps, whereas fifteen steps had a majority decision. An operation manual and record were created. A thirty five-item video assessment tool was developed that assessed the process (safety and efficiency) and quality of the end product (anatomy exposed and lymphadenectomy performed) of the operation. The quality of the end product section was used as a twenty seven-item photographic assessment tool. Thirty-one videos and fifty-three photographic series were submitted from the ROMIO pilot phase for assessment. The overall G-coefficient for the video assessment tool was 0.744, and for the photographic assessment tool was 0.700.

Conclusions:

A reliable surgical quality assurance system for 2-stage esophagectomy has been developed for surgical oncology randomized controlled trials.

Ethical approval:

11/NW/0895 and confirmed locally as appropriate, 12/SW/0161, 16/SW/0098.

Trial registration number: ISRCTN59036820, ISRCTN10386621.
Oncological Resection for Liver Malignancies
Authors: Yoh Tomoaki , Cauchy François , Soubrane Olivier
Published: March 2020

Laparoscopic surgery has become an increasingly popular alternative approach to open surgery, resulting in a paradigm shift in liver surgery. Although laparoscopic liver resection (LLR) was initially indicated for small benign and peripheral tumors, at present more than half of LLRs are performed in malignant tumors. Several studies have reported the feasibility of LLR in malignant disease and suggested various short-term benefits compared to open liver resection, including decreased blood loss and postoperative complications and a shorter hospital stay. Although these benefits are important to surgeons, patients, and providers, the main goal of surgery for malignancies is to achieve a maximum oncologic benefit.

The relevance of the laparoscopic approach must be assessed in relation to the possibility of respecting basic oncological rules and the expertise of the center. Easy LLRs can be safely performed by most surgeons with minimum expertise in liver surgery and laparoscopy, and can therefore probably provide an oncological benefit. On the other hand, intermediate or difficult LLRs require technical expertise and an oncological benefit can only be achieved in expert centers. Technical standardization is the only way to obtain an oncological benefit with this type of resection, and many problems must still be solved.
Minimally Invasive Donor Hepatectomy for Adult Living Donor Liver Transplantation
Authors: Soubrane Olivier , Eguchi Susumu , Uemoto Shinji , Kwon Choon Hyuck David , Wakabayashi Go , Han Ho-Seong , Kim Ki-Hun , Troisi Roberto Ivan , Cherqui Daniel , Rotellar Fernando , Cauchy François , Soyama Akihiko , Ogiso Satoshi , Choi Gyu-Seong , Takahara Takeshi , Cho Jai Young , Cho Hwui-Dong , Vanlander Aude , Pittau Gabriella , Scatton Olivier , Pardo Fernando , Baker Talia
Published: March 2020

Objective:

Evaluating the perioperative outcomes of minimally invasive (MIV) donor hepatectomy for adult live donor liver transplants in a large multi-institutional series from both Eastern and Western centers.

Background:

Laparoscopic liver resection has become standard practice for minor resections in selected patients in whom it provides reduced postoperative morbidity and faster rehabilitation. Laparoscopic approaches in living donor hepatectomy for transplantation, however, remain controversial because of safety concerns. Following the recommendation of the Jury of the Morioka consensus conference to address this, a retrospective study was designed to assess the early postoperative outcomes after laparoscopic donor hepatectomy. The collective experience of 10 mature transplant teams from Eastern and Western countries was reviewed.

Methods:

All centers provided data from prospectively maintained databases. Only left and right hepatectomies performed using a MIV technique were included in this study. Primary outcome was the occurrence of complications using the Clavien-Dindo graded classification and the Comprehensive Complication Index during the first 3 months. Logistic regression analysis was used to identify risk factors for complications.

Results:

In all, 412 MIV donor hepatectomies were recorded including 164 left and 248 right hepatectomies. Surgical technique was either pure laparoscopy in 175 cases or hybrid approach in 237. Conversion into standard laparotomy was necessary in 17 donors (4.1%). None of the donors died. Also, 108 experienced 121 complications including 9.4% of severe (Clavien-Dindo 3–4) complications. Median Comprehensive Complication Index was 5.2.

Conclusions:

This study shows favorable early postoperative outcomes in more than 400 MIV donor hepatectomy from 10 experienced centers. These results are comparable to those of benchmarking series of open standard donor hepatectomy.
Donating a Kidney to a Stranger
Authors: Maple Hannah , Draper Heather , Gogalniceanu Petrut , Burnapp Lisa , Chilcot Joseph , Mamode Nizam
Published: March 2020

Summary of Background Data:

Unspecified kidney donation (UKD) describes living donation of a kidney to a stranger. The practice is playing an increasingly important role within the transplant programme in the United Kingdom, where these donors are commonly used to trigger a chain of transplants; thereby amplifying the benefit derived from their donation. The initial reluctance to accept UKD was in part due to uncertainty about donor motivations and whether the practice was morally and ethically acceptable.

Objectives:

This article provides an overview of UKD and answers common questions regarding the ethical considerations, clinical assessment, and how UKD kidneys are used to maximize utility. Existing literature on outcomes after UKD is also discussed, along with current controversies.

Conclusions:

We believe UKD is an ethically acceptable practice which should continue to grow, despite its controversies. In our experience, these donors are primarily motivated by a desire to help others and utilization of their kidney as part of a sharing scheme means that many more people seek to benefit from their very generous donation.
Intraoperative Near-infrared Fluorescence (NIR) Imaging With Indocyanine Green (ICG) Can Identify Bone and Soft Tissue Sarcomas Which May Provide Guidance for Oncological Resection
Authors: Nicoli Fabio , Saleh Daniel B. , Baljer Bence , Chan Corey D. , Beckingsale Tom , Ghosh Kanishka M. , Ragbir Maniram , Rankin Kenneth S.
Published: March 2020

Background:

Complete excision of sarcomas to maximize function without compromising the oncological outcome can be challenging. The aim of this study was to investigate the feasibility and potential drawbacks of near-infrared (NIR) fluorescence imaging with indocyanine green during resection of bone and soft tissue sarcomas.

Methods:

Eleven patients with high-grade sarcomas were enrolled in the study. All patients received intravenous indocyanine green (75 mg) between 16 and 24 hours before the resection. Sarcomas were resected under NIR guidance and specimens were sent for routine histopathological analysis.

Results:

Majority of treatment naive tumors demonstrated fluorescence. There were no adverse events from the indocyanine green administration. In 3 cases, the fluorescence was reported by the surgeon to have been of definite guidance leading to further tissue resection to improve the margin.

Conclusion:

This is the first report of NIR fluorescence guidance in the setting of open sarcoma surgery. The technique is acceptable to patients and surgeons and was able to guide resection. Multicenter studies are required to assess the utility of this technique in a large cohort of patients with regards to quantification of fluorescence, resection guidance, and longer follow-up period.
Bariatric Surgery is Associated With Decreased Progression of Nonalcoholic Fatty Liver Disease to Cirrhosis
Authors: Wirth Keith M. , Sheka Adam C. , Kizy Scott , Irey Ryan , Benner Ashley , Sieger Gretchen , Simon Gyorgy , Ma Sisi , Lake John , Aliferis Constantin , Leslie Daniel , Marmor Schelomo , Ikramuddin Sayeed
Published: March 2020

Objective:

This study sought to compare trends in the development of cirrhosis between patients with NAFLD who underwent bariatric surgery and a well-matched group of nonsurgical controls.

Summary of Background Data:

Patients with NAFLD who undergo bariatric surgery generally have improvements in liver histology. However, the long-term effect of bariatric surgery on clinically relevant liver outcomes has not been investigated.

Methods:

From a large insurance database, patients with a new NAFLD diagnosis and at least 2 years of continuous enrollment before and after diagnosis were identified. Patients with traditional contraindications to bariatric surgery were excluded. Patients who underwent bariatric surgery were identified and matched 1:2 with patients who did not undergo bariatric surgery based on age, sex, and comorbid conditions. Kaplan-Meier analysis and Cox proportional hazards modeling were used to evaluate differences in progression from NAFLD to cirrhosis.

Results:

A total of 2942 NAFLD patients who underwent bariatric surgery were identified and matched with 5884 NAFLD patients who did not undergo surgery. Cox proportional hazards modeling found that bariatric surgery was independently associated with a decreased risk of developing cirrhosis (hazard ratio 0.31, 95% confidence interval 0.19–0.52). Male gender was associated with an increased risk of cirrhosis (hazard ratio 2.07, 95% confidence interval 1.31–3.27).

Conclusions:

Patients with NAFLD who undergo bariatric surgery are at a decreased risk for progression to cirrhosis compared to well-matched controls. Bariatric surgery should be considered as a treatment strategy for otherwise eligible patients with NAFLD. Future bariatric surgery guidelines should include NAFLD as a comorbid indication when determining eligibility.
Environmental Enrichment in Postoperative Pain and Surgical Care
Authors: Yeung Sung Ching , Irwin Michael G. , Cheung Chi Wai
Published: March 2020

Background:

Holistic biopsychosocial care has been underemphasized in perioperative pathway designs. The importance and a cost-effective way of implementing biopsychosocial care to improve postoperative pain and facilitate surgical convalescence are not well established, despite the recent popularization of Enhanced Recovery After Surgery (ERAS) programs.

Objective:

We have explored the evidence and rationale of environmental enrichment (EE) as a complementary multimodal psychosocial care pathway to reduce postoperative pain, optimize patient recovery and improve existing weaknesses in surgical care.

Methods:

We conducted a database search to identify and grade potential EE techniques for their evidence quality and consistency in the management of acute postoperative pain, perioperative anxiety and the etiologically comparable acute procedural or experimental pain.

Findings and Conclusions:

The introduction of music, virtual reality, educational information, mobile apps, or elements of nature into the healthcare environment can likely improve patients’ experience of surgery. Compared with traditional psychological interventions, EE modalities are voluntary, therapist-sparing and more economically sustainable. We have also discussed practical strategies to integrate EE within the perioperative workflow. Through a combination of sensory, motor, social and cognitive modalities, EE is an easily implementable patient-centered approach to alleviate pain and anxiety in surgical patients, create a more homelike recovery environment and improve quality of life.
Important Issues to Severe Trauma Survivors
Authors: James Arthur , Tran Viet-Thi , Gauss Tobias , Hamada Sophie , Roquet Florian , Bitot Valérie , Boutonnet Mathieu , Raux Mathieu , Ravaud Philippe
Published: March 2020

Objective:

Identify issues that are important to severe trauma survivors up to 3 years after the trauma.

Background:

Severe trauma is the first cause of disability-adjusted life years worldwide, yet most attention has focused on acute care and the impact on long-term health is poorly evaluated.

Method:

We conducted a large-scale qualitative study based on semi-structured phone interviews. Qualitative research methods involve the systematic collection, organization, and interpretation of conversations or textual data with patients to explore the meaning of a phenomenon experienced by individuals themselves. We randomly selected severe trauma survivors (abbreviated injury score ≥3 in at least 1 body region) who were receiving care in 6 urban academic level-I trauma centers in France between March 2015 and March 2018. We conducted double independent thematic analysis. Issues reported by patients were grouped into overarching domains by a panel of 5 experts in trauma care. Point of data saturation was estimated with a mathematical model.

Results:

We included 340 participants from 3 months to 3 years after the trauma [median age: 41 years (Q1–Q3 24–54), median injury severity score: 17 (Q1–Q3 11–22)]. We identified 97 common issues that we grouped into 5 overarching domains: body and neurological issues (29 issues elicited by 277 participants), biographical disruption (23 issues, 210 participants), psychological and personality issues (21 issues, 147 participants), burden of treatment (14 issues, 145 participants), and altered relationships (10 issues, 87 participants). Time elapsed because the trauma, injury location, or in-hospital trauma severity did not affect the distribution of these domains across participants’ answers.

Conclusions:

This qualitative study explored trauma survivors’ experiences of the long-term effect of their injury and allowed for identifying a set of issues that they consider important, including dimensions that seem overlooked in trauma research. Our findings confirm that trauma is a chronic medical condition that demands new approaches to post-discharge and long-term care.
Short-term Outcomes of Single-port Versus Multiport Laparoscopic Surgery for Colon Cancer
Authors: Lee Yoon Suk , Kim Ji Hoon , Kim Hyung Jin , Lee Sang Chul , Kang Byung Mo , Kim Chang Woo , Lim Sang Woo , Lee Suk-Hwan , Kim Jun Gi
Published: March 2020

Objective:

To compare short-term perioperative outcomes of single-port laparoscopic surgery (SPLS) and multiport laparoscopic surgery (MPLS) for colon cancer.

Summary Background Data:

Although many studies reported short- and long-term outcomes of SPLS for colon cancer compared with MPLS, few have reported results of randomized controlled trials.

Methods:

This was a multicenter, prospective, randomized controlled trial with a noninferiority design. It was conducted between August 2011 and June 2017 at 7 sites in Korea. A total of 388 adults (aged 19–85 yrs) with clinical stage I, II, or III adenocarcinoma of the ascending or sigmoid colon were enrolled and randomized. The primary endpoint was 30-day postoperative complication rates. Secondary endpoints were the number of harvested lymph nodes, length of the resection margin, postoperative pain, and time to functional recovery (bowel movement and diet). Patients were followed for 30 days after surgery.

Results:

Among 388 patients, 359 (92.5%) completed the study (SPLS, n = 179; MPLS, n = 180). The 30-day postoperative complication rate was 10.6% in the SPLS group and 13.9% in the MPLS group (95% confidence interval, −10.05 to 3.05 percentage points; P < 0.0001). Total incision length was shorter in the SPLS group than in the MPLS group (4.6 cm vs 7.2 cm, P < 0.001), whereas the length of the specimen extraction site did not differ (4.4 cm vs 4.6 cm, P = 0.249). There were no significant differences between groups for all secondary endpoints and all other outcomes.

Conclusions:

Even though there was no obvious benefit to SPLS over MPLS when performing colectomy for cancer, our data suggest that SPLS is noninferior to MPLS and can be considered an option in selected patients, when performed by experienced surgeons.

Trial registration: ClinicalTrials.gov Identifier: NCT01480128.
Genome sequences of both organelles of the grapevine rootstock cultivar ‘Börner’
Authors: Frommer Bianca , Holtgräwe Daniela , Hausmann Ludger , Viehöver Prisca , Huettel Bruno , Töpfer Reinhard , Weisshaar Bernd
Published: March 2020

Genomic long reads of the interspecific grapevine rootstock cultivar ‘Börner’ (Vitis ripariaGM183 xVitis cinereaArnold) were used to assemble its chloroplast and mitochondrion genome sequences. We annotated 133 chloroplast and 172 mitochondrial genes including the RNA-editing sites. The organellar genomes were maternally inherited to ‘Börner’ fromVitis riparia.
Broad anti-coronaviral activity of FDA approved drugs against SARS-CoV-2in vitroand SARS-CoVin vivo
Authors: Weston Stuart , Coleman Christopher M. , Haupt Rob , Logue James , Matthews Krystal , Frieman Matthew B.
Published: March 2020

SARS-CoV-2 emerged in China at the end of 2019 and has rapidly become a pandemic with roughly 2.7 million recorded COVID-19 cases and greater than 189,000 recorded deaths by April 23rd, 2020 (www.WHO.org). There are no FDA approved antivirals or vaccines for any coronavirus, including SARS-CoV-2. Current treatments for COVID-19 are limited to supportive therapies and off-label use of FDA approved drugs. Rapid development and human testing of potential antivirals is greatly needed. A quick way to test compounds with potential antiviral activity is through drug repurposing. Numerous drugs are already approved for human use and subsequently there is a good understanding of their safety profiles and potential side effects, making them easier to fast-track to clinical studies in COVID-19 patients. Here, we present data on the antiviral activity of 20 FDA approved drugs against SARS-CoV-2 that also inhibit SARS-CoV and MERS-CoV. We found that 17 of these inhibit SARS-CoV-2 at a range of IC50 values at non-cytotoxic concentrations. We directly follow up with seven of these to demonstrate all are capable of inhibiting infectious SARS-CoV-2 production. Moreover, we have evaluated two of these, chloroquine and chlorpromazine,in vivousing a mouse-adapted SARS-CoV model and found both drugs protect mice from clinical disease.
Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia
Authors: Brann David H. , Tsukahara Tatsuya , Weinreb Caleb , Lipovsek Marcela , Van den Berge Koen , Gong Boying , Chance Rebecca , Macaulay Iain C. , Chou Hsin-jung , Fletcher Russell , Das Diya , Street Kelly , de Bezieux Hector Roux , Choi Yoon-Gi , Risso Davide , Dudoit Sandrine , Purdom Elizabeth , Mill Jonathan S. , Hachem Ralph Abi , Matsunami Hiroaki , Logan Darren W. , Goldstein Bradley J. , Grubb Matthew S. , Ngai John , Datta Sandeep Robert
Published: March 2020

Altered olfactory function is a common symptom of COVID-19, but its etiology is unknown. A key question is whether SARS-CoV-2 (CoV-2) – the causal agent in COVID-19 – affects olfaction directly by infecting olfactory sensory neurons or their targets in the olfactory bulb, or indirectly, through perturbation of supporting cells. Here we identify cell types in the olfactory epithelium and olfactory bulb that express SARS-CoV-2 cell entry molecules. Bulk sequencing revealed that mouse, non-human primate and human olfactory mucosa expresses two key genes involved in CoV-2 entry, ACE2 and TMPRSS2. However, single cell sequencing and immunostaining demonstrated ACE2 expression in support cells, stem cells, and perivascular cells; in contrast, neurons in both the olfactory epithelium and bulb did not express ACE2 message or protein. These findings suggest that CoV-2 infection of non-neuronal cell types leads to anosmia and related disturbances in odor perception in COVID-19 patients.
Markerless tracking of an entire insect colony
Authors: Bozek Katarzyna , Hebert Laetitia , Portugal Yoann , Stephens Greg J.
Published: March 2020

We present a comprehensive, computational method for tracking an entire colony of the honey beeApis melliferausing high-resolution video on a natural honeycomb background. We adapt a convolutional neural network (CNN) segmentation architecture to automatically identify bee and brood cell positions, body orientations and within-cell states. We achieve high accuracy (~10% body width error in position, ~10° error in orientation, and true positive rate > 90%) and demonstrate months-long monitoring of sociometric colony fluctuations. We combine extracted positions with rich visual features of organism-centered images to track individuals over time and through challenging occluding events, recovering ~79% of bee trajectories from five observation hives over a span of 5 minutes. The resulting trajectories reveal important behaviors, including fast motion, comb-cell activity, and waggle dances. Our results provide new opportunities for the quantitative study of collective bee behavior and for advancing tracking techniques of crowded systems.
Inflated citations and metrics of journals discontinued from Scopus for publication concerns: the GhoS(t)copus Project
Authors: Cortegiani Andrea , Ippolito Mariachiara , Ingoglia Giulia , Manca Andrea , Cugusi Lucia , Severin Anna , Strinzel Michaela , Panzarella Vera , Campisi Giuseppina , Manoj Lalu , Gregoretti Cesare , Einav Sharon , Moher David , Giarratano Antonino
Published: March 2020

Background

Scopus is a leading bibliometric database. It contains the largest number of articles cited in peer-reviewed publications. The journals included in Scopus are periodically re-evaluated to ensure they meet indexing criteria and some journals might be discontinued for publication concerns. These journals remain indexed and can be cited. Their metrics have yet to be studied. This study aimed to evaluate the main features and metrics of journals discontinued from Scopus for publication concerns, before and after their discontinuation, and to determine the extent of predatory journals among the discontinued journals.

Methods

We surveyed the list of discontinued journals from Scopus (July 2019). Data regarding metrics, citations and indexing were extracted from Scopus or other scientific databases, for the journals discontinued for publication concerns.

Results

A total of 317 journals were evaluated. Ninety-three percent of the journals (294/318) declared they published using an Open Access model. The subject areas with the greatest number of discontinued journals wereMedicine(52/317; 16%),Agriculture and Biological Science(34/317; 11%), andPharmacology, Toxicology and Pharmaceutics(31/317; 10%). The mean number of citations per year after discontinuation was significantly higher than before (median of difference 64 citations, p<0.0001), and so was the number of citations per document (median of difference 0.4 citations, p<0.0001). Twenty-two percent (72/317) were included in the Cabell’s blacklist. The DOAJ currently included only 9 journals while 61 were previously included and discontinued, most for “suspected editorial misconduct by the publisher’.Conclusions:The citation count of journals discontinued for publication concerns increases despite discontinuation and predatory behaviors seemed common. This paradoxical trend can inflate scholars’ metrics prompting artificial career advancements, bonus systems and promotion. Countermeasures should be taken urgently to ensure the reliability of Scopus metrics both at the journal- and author-level for the purpose of scientific assessment of scholarly publishing.
Burkholderia pseudomalleiclinical isolates are highly susceptiblein vitroto cefiderocol, a novel siderophore cephalosporin
Authors: Burnard Delaney , Robertson Gemma , Henderson Andrew , Falconer Caitlin , Bauer-Leo Michelle , Cottrell Kyra , Gassiep Ian , Norton Robert , Paterson David L. , Harris Patrick N. A.
Published: March 2020

Cefiderocol is a novel cephalosporin designed to treat multidrug resistant Gram-negative infections. By forming a chelated complex with ferric iron, cefiderocol is transported into the periplasmic space via bacterial iron transport systems and primarily binds to penicillin-binding protein 3 (PBP3) to inhibit peptidoglycan synthesis. This mode of action results in cefiderocol having greaterin vitroactivity against many Gram-negative bacilli than currently used carbapenems, β-lactam/β-lactamase inhibitor combinations, and cephalosporins. Thus, we investigated thein vitroactivity of cefiderocol (S-649266) against a total of 271 clinical isolates ofBurkholderia pseudomalleifrom Australia. The collection was comprised of primary isolates (92.3%) and subsequent isolates (7.7%). Minimum inhibitory concentrations (MIC) of cefiderocol ranged from ≤0.03 to 32 mg/L, where the MIC90was 1 mg/L and 16 mg/L for primary and subsequent isolates, respectively. Based upon non-species specific (Gram-negative bacilli) clinical breakpoints for cefiderocol (MIC ≤ 4 mg/L), twelve isolates (4.4%) would be classified as non-susceptible. Further testing for co-resistance to meropenem, ceftazidime, trimethoprim-sulfamethoxazole, amoxicillin-clavulanate and doxycycline was performed on a subset of isolates with elevated cefiderocol MICs (≥2 mg/L, 4.8%) and 84.6% of these isolates exhibited resistance to at least one of these antimicrobials. Cefiderocol was found to be highly activein vitroagainstB. pseudomalleiprimary clinical isolates. This novel compound shows great potential for the treatment of melioidosis in endemic countries and should be explored further.
Anaerobic metabolism of Foraminifera thriving below the seafloor
Authors: Orsi William D. , Morard Raphaël , Vuillemin Aurele , Eitel Michael , Wörheide Gert , Milucka Jana , Kucera Michal
Published: March 2020

Foraminifera are single-celled eukaryotes (protists) of large ecological importance, as well as environmental and paleoenvironmental indicators and biostratigraphic tools. In addition, they are capable of surviving in anoxic marine environments where they represent a major component of the benthic community. However, the cellular adaptations of Foraminifera to the anoxic environment remain poorly constrained. We sampled an oxic-anoxic transition zone in marine sediments from the Namibian shelf, where the generaBolivinaandStainforthiadominated the Foraminifera community, and use metatranscriptomics to characterize Foraminifera metabolism across the different geochemical conditions. The relative abundance of Foraminifera gene expression in anoxic sediment depths increased an order of magnitude, which was confirmed in a ten-day incubation experiment where the development of anoxia coincided with a 27-fold increase in the relative abundance of Foraminifera protein encoding transcripts. This indicates that many Foraminifera were not only surviving, but thriving under the anoxic conditions. The anaerobic energy metabolism of these active Foraminifera was characterized by fermentation of sugars and amino acids, dissimilatory nitrate reduction, fumarate reduction, and dephosphorylation of creatine phosphate. This was co-expressed alongside genes involved in production of reticulopodia, phagocytosis, calcification, and clathrin-mediated-endocytosis (CME). Thus, Foraminifera may use CME under anoxic conditions to utilize dissolved organic matter as a carbon and energy source, in addition to ingestion of prey cells via phagocytosis. These mechanisms help explain how some Foraminifera can thrive under anoxia, which would help to explain their ecological success documented in the fossil record since the Cambrian period more than 500 million years ago.
DeeReCT-APA: Prediction of Alternative Polyadenylation Site Usage Through Deep Learning
Authors: Li Zhongxiao , Li Yisheng , Zhang Bin , Li Yu , Long Yongkang , Zhou Juexiao , Zou Xudong , Zhang Min , Hu Yuhui , Chen Wei , Gao Xin
Published: March 2020

Alternative polyadenylation (APA) is a crucial step in post-transcriptional regulation. Previous bioinformatic works have mainly focused on the recognition of polyadenylation sites (PAS) in a given genomic sequence, which is a binary classification problem. Recently, computational methods for predicting the usage level of alternative PAS in a same gene have been proposed. However, all of them cast the problem as a non-quantitative pairwise comparison task and do not take the competition among multiple PAS into account. To address this, here we propose a deep learning architecture, DeeReCT-APA, to quantitatively predict the usage of all alternative PAS of a given gene. To accommodate different genes with potentially different numbers of PAS, DeeReCT-APA treats the problem as a regression task with a variable-length target. Based on a CNN-LSTM architecture, DeeReCT-APA extracts sequence features with CNN layers, uses bidirectional LSTM to explicitly model the interactions among competing PAS, and outputs percentage scores representing the usage levels of all PAS of a gene. In addition to the fact that only our method can predict quantitatively the usage of all the PAS within a gene, we show that our method consistently outperforms other existing methods on three different tasks for which they are trained: pairwise comparison task, highest usage prediction task and ranking task. Finally, we demonstrate that our method can be used to predict the effect of genetic variations on APA patterns and shed light on future mechanistic understanding in APA regulation. Our code and data are available athttps://github.com/lzx325/DeeReCT-APA-repo.
Maternal DNMT3A-dependent de novo methylation of the zygotic paternal genome inhibits gene expression in the early embryo
Authors: Albert Julien Richard , Yeung Wan Kin Au , Toriyama Keisuke , Kobayashi Hisato , Hirasawa Ryutaro , Brind’Amour Julie , Bogutz Aaron , Sasaki Hiroyuki , Lorincz Matthew
Published: March 2020

De novo DNA methylation (DNAme) during mammalian spermatogenesis yields a densely methylated genome, with the exception of CpG islands (CGIs), which are hypomethylated in sperm. Following fertilization, the paternal genome undergoes widespread DNAme loss before the first S-phase. Paradoxically, recent mass spectrometry analysis revealed that a low level of de novo DNAme occurs exclusively on the zygotic paternal genome. However, the loci involved and impact on genic transcription was not addressed. Here, we employ allele-specific analysis of wholegenome bisulphite sequencing (WGBS) data and show that a number of genomic regions, including several dozen CGI promoters, are de novo methylated on the paternal genome in 2-cell embryos. A subset of these promoters maintains DNAme through development to the blastocyst stage. Consistent with zygotic paternal DNAme acquisition (PDA), many of these loci are hypermethylated in androgenetic blastocysts but hypomethylated in parthenogenetic blastocysts. Strikingly, PDA is lost following maternal deletion ofDnmt3a. Furthermore, a subset of promoters showing PDA which are normally transcribed from the paternal allele in blastocysts show premature transcription at the 4-cell stage in maternalDnmt3aknockout embryos. These observations uncover an unexpected role for maternal DNMT3A activity in postfertilization epigenetic reprogramming and transcriptional silencing of the paternal genome.
Large-scale Phenotypic Drug Screen Identifies Neuroprotectants in Zebrafish and Mouse Models of Retinitis Pigmentosa
Authors: Zhang Liyun , Chen Conan , Fu Jie , Lilley Brendan , Berlinicke Cynthia , Hansen Baranda , Ding Ding , Wang Guohua , Wang Tao , Shou Daniel , Ye Ying , Saxena Meera T. , Hall Kelsi R. , Sharrock Abigail V. , Brandon Carlene , Shim Joong Sup , Hanes Justin , Ji Hongkai , Liu Jun O. , Qian Jiang , Ackerley David F. , Rohrer Baerbel , Zack Donald J. , Mumm Jeff S.
Published: March 2020

Retinitis pigmentosa (RP) and associated inherited retinal diseases (IRDs) are caused by rod photoreceptor degeneration, necessitating therapeutics promoting rod photoreceptor survival. To address this, we tested compounds for neuroprotective effects in zebrafish and mouse RP models, reasoning drugs effective across species may translate better clinically. We first performed a large-scale phenotypic drug screen using a larval zebrafish model of inducible RP. 2,934 compounds, mostly human-approved drugs, were tested across six concentrations. Statistically, 113 compounds achieved “hit” status. Secondary tests of 42 high-priority hits confirmed eleven lead compounds. Nine leads were then evaluated in mouse RP models, with six exhibiting neuroprotective effects. An analysis of potential mechanisms of action suggested complementary activities. Paired lead compound assays in zebrafish showed additive neuroprotective effects for the majority. These results highlight the value of cross-species phenotypic drug discovery and suggest combinatorial drug therapies may provide enhanced therapeutic benefits for patients with RP and IRDs.
Pancreatlas™: applying an adaptable framework to map the human pancreas in health and disease
Authors: Saunders Diane C. , Messmer James , Kusmartseva Irina , Beery Maria L. , Yang Mingder , Atkinson Mark A. , Powers Alvin C. , Cartailler Jean-Philippe , Brissova Marcela
Published: March 2020

Human tissue phenotyping generates complex spatial information from numerous imaging modalities, yet images typically become static figures for publication and original data and metadata are rarely available. While comprehensive image maps exist for some organs, most resources have limited support for multiplexed imaging or have non-intuitive user interfaces. Therefore, we built a Pancreatlas™ resource that integrates several technologies into a novel interface, allowing users to access richly annotated web pages, drill down to individual images, and deeply explore data online. The current version of Pancreatlas contains over 800 unique images acquired by whole-slide scanning, confocal microscopy, and imaging mass cytometry, and is available athttps://www.pancreatlas.org. To create this human pancreas-specific biological imaging resource, we developed a React-based web application and Python-based application programming interface, collectively called Flexible Framework for Integrating and Navigating Data (FFIND), which can be adapted beyond Pancreatlas to meet countless imaging or other structured data management needs.
Structure of the Cytoplasmic Ring of theXenopus laevisNuclear Pore Complex
Authors: Huang Gaoxingyu , Zhang Yanqing , Zhu Xuechen , Zeng Chao , Wang Qifan , Zhou Qiang , Tao Qinghua , Liu Minhao , Lei Jianlin , Yan Chuangye , Shi Yigong
Published: March 2020

Nuclear pore complex (NPC) exhibits structural plasticity and has only been characterized at local resolutions of up to 15 Å for the cytoplasmic ring (CR). Here we present a single-particle cryo-electron microscopy (cryo-EM) structure of the CR fromXenopus laevisNPC at average resolutions of 5.5-7.9 Å, with local resolutions reaching 4.5 Å. Improved resolutions allow identification and placement of secondary structural elements in the majority of the CR components. The two Y complexes in each CR subunit interact with each other and associate with those from flanking subunits, forming a circular scaffold. Within each CR subunit, the Nup358-containing region wraps around the stems of both Y complexes, likely stabilizing the scaffold. Nup205 connects the short arms of the two Y complexes and associates with the stem of a neighbouring Y complex. The Nup214-containing region uses an extended coiled-coil to link Nup85 of the two Y complexes and protrudes into the axial pore of the NPC. These previously uncharacterized structural features reveal insights into NPC assembly.
Characterization of theCorynebacterium glutamicumdehydroshikimate dehydratase QsuB and its potential for microbial production of protocatechuic acid
Authors: Shmonova Ekaterina A. , Voloshina Olga V. , Ovsienko Maksim V. , Smirnov Sergey V. , Doroshenko Vera G.
Published: March 2020

The dehydroshikimate dehydratase (DSD) fromCorynebacterium glutamicumencoded by theqsuBgene is related to the previously described QuiC1 protein (39.9% identity) fromPseudomonas putida. QuiC1 and QsuB are both two-domain bacterial DSDs. The N-terminal domain provides dehydratase activity, while the C-terminal domain has sequence identity with 4-hydroxyphenylpyruvate dioxygenase. Here, the QsuB protein and its DSD domain (N-QsuB) were expressed in the T7 system, purified and characterized. QsuB was present mainly in octameric form (60%), while N-QsuB had a predominantly monomeric structure (80%) in solution. Both proteins possessed DSD activity with one of the following cofactors (listed in order of decreasing activity): Co2+, Mg2+, Mn2+or Ca2+. The Kmand kcatvalues for QsuB were two and three times higher, respectively (Km~ 1 mM, kcat~ 61 s−1) than those for N-QsuB. Notably, 3,4-DHBA inhibited both enzymes via an uncompetitive mechanism. QsuB and N-QsuB were tested for 3,4-DHBA production from glucose inE. coli. MG1655ΔaroEPlac–qsuBproduced at least two times more 3,4-DHBA than MG1655ΔaroEPlac–n-qsuBin the presence of isopropyl β-D-1-thiogalactopyranoside.
EphA7 Isoforms Differentially Regulate Cortical Dendrite Development
Authors: Leonard Carrie E. , Baydyuk Maryna , Stepler Marissa A. , Burton Denver A. , Donoghue Maria J.
Published: March 2020

The shape of a neuron reflects its cellular function and ultimately, how it operates in neural circuits. Dendrites receive and integrate incoming signals, including excitatory input onto dendritic spines, so understanding how dendritic development proceeds is fundamental for discerning neural function. Using loss- and gain-of-function paradigms, we previously demonstrated that EphA7 receptor signaling during cortical development impacts dendrites in two ways: restricting growth early and promoting spine formation later. Here, the molecular basis for this shift in EphA7 function is defined. Expression analyses reveal that both full-length (EphA7-FL) and truncated (EphA7-T1; lacking kinase domain) isoforms of EphA7 are expressed in the developing cortex, with peak expression of EphA7-FL overlapping with dendritic elaboration and highest levels of EphA7-T1 coinciding with spine formation. Overexpression studies in cultured neurons demonstrate that EphA7-FL inhibits both dendritic growth and spine formation, while EphA7-T1 increases spine density. Furthermore, signaling downstream of EphA7 varies during development;in vivoinhibition of kinase-dependent mTOR by rapamycin in EphA7 mutant neurons rescues the dendritic branching, but not the dendritic spine phenotypes. Finally, interaction and signaling modulation was examined. In cells in culture, direct interaction between EphA7-FL and EphA7-T1 is demonstrated which results in EphA7- T1-based modulation of EphA7-FL phosphorylation.In vivo, both isoforms are colocalized to cortical synapses and levels of phosphorylated EphA7-FL decrease as EphA7-T1 levels rise. Thus, the phenotypes of EphA7 during cortical dendrite development are explained by divergent functions of two variants of the receptor.
Identification of genes required for enzalutamide resistance in castration-resistant prostate cancer cellsin vitro
Authors: Kohrt Sarah E. , Awadallah Wisam N. , Phillips Robert A. , Case Thomas C. , Jin Renjie , Nanda Jagpreet S. , Yu Xiuping , Clark Peter E. , Yi Yajun , Matusik Robert J. , Anderson Philip D. , Grabowska Magdalena M.
Published: March 2020

Castration-resistant prostate cancer can be treated with the anti-androgen enzalutamide, but responses and duration of response are variable. To identify genes that support enzalutamide resistance, we performed a short hairpin RNA (shRNA) screen in the bone-homing, castration-resistant prostate cancer cell line, C4-2B. We identified eleven genes (TFAP2C, CAD, SPDEF, EIF6, GABRG2, CDC37, PSMD12, COL5A2, AR, MAP3K11, andACAT1), whose loss resulted in decreased cell survival in response to enzalutamide. To validate our screen, we performed transient knockdowns in C4-2B and 22Rv1 cells and evaluated cell survival in response to enzalutamide. Through these studies, we validated three genes (ACAT1, MAP3K11, andPSMD12) as supporters of enzalutamide resistancein vitro. AlthoughACAT1expression is lower in metastatic castration-resistant prostate cancer samples versus primary prostate cancer samples, knockdown ofACAT1was sufficient to reduce cell survival in C4-2B and 22Rv1 cells.MAP3K11expression increases with Gleason grade, and the highest expression is observed in metastatic castration-resistant disease. Knockdown ofMAP3K11reduced cell survival and pharmacologic inhibition of MAP3K11 with CEP-1347 in combination with enzalutamide resulted in a dramatic increase in cell death. This was associated with decreased phosphorylation of AR-Serine650, which is required for maximal AR activation. Finally, whilePSMD12expression did not change during disease progression, knockdown ofPSMD12resulted in decreased AR and AR splice variant expression, likely contributing to the C4-2B and 22Rv1 decrease in cell survival. Our study has therefore identified at least three new supporters of enzalutamide resistance in castration-resistant prostate cancer cellsin vitro.

Financial support

The authors would like to acknowledge funding from the Joe C. Davis Foundation (to RJM), the Vanderbilt Institute for Clinical and Translational Research (VICTR, to YY, PEC, and RJM). The Vanderbilt Institute for Clinical and Translational Research (VICTR) is funded by the National Center for Advancing Translational Sciences (NCATS) Clinical Translational Science Award (CTSA) Program, Award Number 5UL1TR002243. The content of this manuscript solely the responsibility of the authors and does not necessarily represent the official views of the NIH. We would also like to acknowledge the Case Research Institute, a joint venture between University Hospitals and Case Western Reserve University, start-up funds (to MMG), and the Cell and Molecular Biology Training Program (T32 GM 008056 to SEK).
O-GlcNAc regulates gene expression by controlling detained intron splicing
Authors: Tan Zhi-Wei , Fei George , Paulo Joao A. , Bellaousov Stanislav , Martin Sara E.S. , Duveau Damien Y. , Thomas Craig J. , Gygi Steven P. , Boutz Paul L. , Walker Suzanne
Published: March 2020

Intron detention in precursor RNAs serves to regulate expression of a substantial fraction of genes in eukaryotic genomes. How detained intron (DI) splicing is controlled is poorly understood. Here we show that a ubiquitous post-translational modification called O-GlcNAc, which is thought to integrate signaling pathways as nutrient conditions fluctuate, controls detained intron splicing. Using specific inhibitors of the enzyme that installs O-GlcNAc (O-GlcNAc transferase, or OGT) and the enzyme that removes O-GlcNAc (O-GlcNAcase, or OGA), we first show that O-GlcNAc regulates splicing of the highly conserved detained introns inOGTandOGAto control mRNA abundance in order to buffer O-GlcNAc changes. We show thatOGTandOGArepresent two distinct paradigms for how DI splicing can control gene expression. We also show that when DI splicing of the O-GlcNAc-cycling genes fails to restore O-GlcNAc homeostasis, there is a global change in detained intron levels. Strikingly, almost all detained introns are spliced more efficiently when O-GlcNAc levels are low, yet other alternative splicing pathways change minimally. Our results demonstrate that O-GlcNAc controls detained intron splicing to tune system-wide gene expression, providing a means to couple nutrient conditions to the cell’s transcriptional regime.
Trade credit in emerging economies: an interorganizational power perspective
Authors: Liu Bai , Wang Yibo , Shou Yongyi
Published: March 2020

Purpose

The extant literature recognizes that trade credit is influenced by the power imbalance between buyers and suppliers but most studies focus on either buyer power or supplier power. The purpose of this study is to investigate how buyer power and supplier power interact and jointly influence trade credit. Moreover, this study examines the moderating effects of political ties in an emerging economy context.

Design/methodology/approach

A research framework was developed by combining resource dependence theory and institutional theory to investigate the interactive effects of market power (i.e. market share and supplier concentration) and non-market power (i.e. political ties) on trade credit. The proposed hypotheses were empirically tested by a fixed effects model using secondary data from 2,433 listed firms in China.

Findings

The results show that a buyer firm's market share promotes trade credit but this effect is weakened by supplier concentration. Moreover, the buyer's political ties enhance the impact of market share on trade credit and attenuate the negative moderating effect of supplier concentration.

Originality/value

This study contributes to the trade credit and supply chain power literature by identifying the interactive effects of market share, supplier concentration and political ties in trade credit. It advances our understanding of how trade credit is jointly determined by a variety of factors in emerging economies.