bluuebunny/crossref_metadata_2025_split huggingface dataset:
Publishing reproducible dynamic kinetic models
Authors: Porubsky Veronica , Smith Lucian , Sauro Herbert M 
Published: August 2020

Abstract
Publishing repeatable and reproducible computational models is a crucial aspect of the scientific method in computational biology and one that is often forgotten in the rush to publish. The pressures of academic life and the lack of any reward system at institutions, granting agencies and journals means that publishing reproducible science is often either non-existent or, at best, presented in the form of an incomplete description. In the article, we will focus on repeatability and reproducibility in the systems biology field where a great many published models cannot be reproduced and in many cases even repeated. This review describes the current landscape of software tooling, model repositories, model standards and best practices for publishing repeatable and reproducible kinetic models. The review also discusses possible future remedies including working more closely with journals to help reviewers and editors ensure that published kinetic models are at minimum, repeatable. Contact: hsauro@uw.edu
In utero low-protein-diet-programmed type 2 diabetes in adult offspring is mediated by sex hormones in rats†
Authors: Blesson Chellakkan S , Schutt Amy K , Vipin Vidyadharan A , Tanchico Daren T , Mathew Pretty R , Balakrishnan Meena , Betancourt Ancizar , Yallampalli Chandra 
Published: August 2020

Abstract
Sex steroids regulate insulin sensitivity and glucose metabolism. We had characterized a lean type 2 diabetes (T2D) rat model using gestational low-protein (LP) diet programming. Our objective was to identify if endocrine dysfunction leading to decreased sex hormone levels will precede the development of T2D and if steroid replacement will prevent the onset of the disease. Pregnant rats were fed control or isocaloric LP diet from gestational day 4 until delivery. Normal diet was given to all mothers after delivery and to pups after weaning. LP offspring developed glucose intolerance and insulin resistance at 4 months. We measured sex steroid hormone profiles and expression of key genes involved in steroidogenesis in testis and ovary. Furthermore, one-month old rats were implanted with 90-day slow release T and E2 pellets for males and females, respectively. Glucose tolerance test (GTT) and euglycemic hyperinsulinemic clamp was performed at 4 months. LP-programmed T2D males had low T levels and females had low E2 levels due to dysregulated gene expression during steroidogenesis in gonads. GTT and euglycemic hyperinsulinemic clamp showed that LP males and females were glucose intolerant and insulin resistant; however, steroid supplementation prevented the onset of glucose intolerance and insulin resistance. Rats that developed T2D by LP programming have compromised gonadal steroidogenesis leading to low T and E2 in males and females, respectively. Sex steroid supplementation prevented the onset of glucose intolerance and insulin resistance indicating low sex steroid levels could cause compromised glucose metabolism ultimately leading to T2D.
The enigmatic sperm proteins in mammalian fertilization: an overview†
Authors: Gahlay Gagandeep Kaur , Rajput Neha 
Published: August 2020

AbstractMammalian fertilization involves a physical interaction between a sperm and an egg followed by molecular interactions amongst their various cell surface molecules. These interactions are initially mediated on the egg’s outermost matrix, zona pellucida (ZP), and then its plasma membrane. To better understand this process, it is pertinent to find the corresponding molecules on sperm that interact with ZP or the egg’s plasma membrane. Although currently, we have some knowledge about the binding partners for egg’s plasma membrane on sperm, yet the ones involved in an interaction with ZP have remained remarkably elusive. This review provides comprehensive knowledge about the various sperm proteins participating in mammalian fertilization and discusses the possible reasons for not being able to identify the strong sperm surface candidate (s) for ZP adhesion. It also hypothesizes the existence of a multi-protein complex(s), members of which participate in oviduct transport, cumulus penetration, zona adhesion, and adhesion/fusion with the egg’s plasma membrane; with some protein(s) having multiple roles during this process. Identification of these proteins is crucial as it improves our understanding of the process and allows us to successfully treat infertility, develop contraceptives, and improve artificial reproductive technologies.
Effects of Amygdala Lesions on Object-Based Versus Action-Based Learning in Macaques
Authors: Taswell Craig A , Costa Vincent D , Basile Benjamin M , Pujara Maia S , Jones Breonda , Manem Nihita , Murray Elisabeth A , Averbeck Bruno B 
Published: August 2020

Abstract
The neural systems that underlie reinforcement learning (RL) allow animals to adapt to changes in their environment. In the present study, we examined the hypothesis that the amygdala would have a preferential role in learning the values of visual objects. We compared a group of monkeys (Macaca mulatta) with amygdala lesions to a group of unoperated controls on a two-armed bandit reversal learning task. The task had two conditions. In the What condition, the animals had to learn to select a visual object, independent of its location. And in the Where condition, the animals had to learn to saccade to a location, independent of the object at the location. In both conditions choice-outcome mappings reversed in the middle of the block. We found that monkeys with amygdala lesions had learning deficits in both conditions. Monkeys with amygdala lesions did not have deficits in learning to reverse choice-outcome mappings. Rather, amygdala lesions caused the monkeys to become overly sensitive to negative feedback which impaired their ability to consistently select the more highly valued action or object. These results imply that the amygdala is generally necessary for RL.
On-Line Sorbentless Cryogenic Needle Trap and GC–FID Method for the Extraction and Analysis of Trace Volatile Organic Compounds from Soil Samples
Authors: Djozan Djavanshir , Norouzi Jamal , Farajzadeh Mir Ali 
Published: August 2020

Abstract
In this study, an automated sorbentless cryogenic needle trap device (ASCNTD) coupled with a gas chromatograph (GC) was developed with the aim of sampling, pre-concentration and determination of volatile organic compounds (VOCs) from soil sample. This paper describes optimization of relevant parameters, performance evaluation and an illustrative application of ASCNTD. The ASCNTD system consists of a 5 cm stainless steel needle passed through a hollow ceramic rod which is coiled with resistive nichrome wire. The set is placed in a PVC (Polyvinyl chloride) chamber through which liquid nitrogen can flow. The headspace components are circulated with a pump to pass through the needle, and this results in freeze-trapping of the VOCs on the inner surface of the needle. When extraction is completed, the analytes trapped in the inner wall of the needle were thermally desorbed and swept by the carrier gas into the GC capillary column. The parameters being effective on the extraction processes, namely headspace flow rate, the temperature and time of extraction and desorption were optimized and evaluated. The developed technique was compared to the headspace solid-phase microextraction method for the analysis of soil samples containing BTEX (Benzene, Toluene, Ethylbenzene and Xylene). The relative standard deviation values are below 8% and detection limits as low as 1.2 ng g−1 were obtained for BTEX by ASCNTD.
Esophageal cancer surgery in Greece during the era of the financial crisis
Authors: Schizas Dimitrios , Mylonas Konstantinos S , Hasemaki Natasha , Mpaili Efstratia , Ntomi Vasileia , Michalinos Adamantios , Theochari Nikoletta A , Theochari Christina A , Mpoura Maria , Bakopoulos Anargyros , Liakakos Theodoros 
Published: August 2020

Summary
The aim of this study is to describe outcomes of esophageal cancer surgery in a quaternary upper gastrointestinal (GI) center in Athens during the era of the Greek financial crisis. We performed a retrospective analysis of patients that underwent esophagectomy for esophageal or gastroesophageal junction (GEJ) cancer at an upper GI unit of the University of Athens, during the period January 2004–June 2019. Time-to-event analyses were performed to explore trends in survival and recurrence. A total of 146 patients were identified. Nearly half of the patients (49.3%) underwent surgery during the last 4 years of the financial crisis (2015–2018). Mean age at the time of surgery was 62.3 ± 10.3 years, and patients did not present at older ages during the recession (P = 0.50). Most patients were stage III at the time of surgery both prior to the recession (35%) and during the financial crisis (39.8%, P = 0.17). Ivor–Lewis was the most commonly performed procedure (67.1%) across all eras (P = 0.06). Gastric conduit was the most common form of GI reconstruction (95.9%) following all types of surgery (P &lt; 0.001). Pre-recession anastomoses were usually performed using a circular stapler (65%). Both during (88.1%) and following the recession (100%), the vast majority of anastomoses were hand-sewn. R0 resection was achieved in 142 (97.9%) patients. Anastomosis technique did not affect postoperative leak (P = 0.3) or morbidity rates (P = 0.1). Morbidity rates were not significantly different prior to (25%), during (46.9%), and after (62.5%) the financial crisis, P = 0.16. Utilization of neoadjuvant chemotherapy (26.9%, P = 0.90) or radiation (8.4%, P = 0.44) as well as adjuvant chemotherapy (54.8%, P = 0.85) and irradiation (13.7%, P = 0.49) was the same across all eras. Disease-free survival (DFS) and all-cause mortality rates were 41.2 and 47.3%, respectively. Median DFS and observed survival (OS) were 11.3 and 22.7 months, respectively. The financial crisis did not influence relapse (P = 0.17) and survival rates (P = 0.91). The establishment of capital controls also had no impact on recurrence (P = 0.18) and survival (P = 0.94). Austerity measures during the Greek financial crisis did not influence long-term esophageal cancer outcomes. Therefore, achieving international standards in esophagectomy may be possible in resource-limited countries when centralizing care.
Solute Carrier Family 12 Member 2 as a Proteomic and Histological Biomarker of Dysplasia and Neoplasia in Ulcerative Colitis
Authors: Merli Angela-Maria , Vieujean Sophie , Massot Charlotte , Blétard Noella , Quesada Calvo Florence , Baiwir Dominique , Mazzucchelli Gabriel , Servais Laurence , Wéra Odile , Oury Cécile , de Leval Laurence , Sempoux Christine , Manzini Roberto , Bluemel Sena , Scharl Michael , Rogler Gerhard , De Pauw Edwin , Coimbra Marques C , Colard Arnaud , Vijverman Anne , Delvenne Philippe , Louis Edouard , Meuwis Marie-Alice 
Published: August 2020

Abstract

Background and Aims
Ulcerative colitis [UC] patients have a greater risk of developing colorectal cancer through inflammation-dysplasia-carcinoma sequence of transformation. The histopathological diagnosis of dysplasia is therefore of critical clinical relevance, but dysplasia may be difficult to distinguish from inflammatory changes.

Methods
A proteomic pilot study on five UC colorectal dysplastic patients highlighted proteins differentially distributed between paired dysplastic, inflammatory, and normal tissues. The best candidate marker was selected and immunohistochemistry confirmation was performed on azoxymethane/dextran sulphate sodium [AOM/DSS] mouse model lesions, 37 UC-dysplasias, 14 UC-cancers, 23 cases of long-standing UC, 35 sporadic conventional adenomas, 57 sporadic serrated lesions, and 82 sporadic colorectal cancers.

Results
Differential proteomics found 11 proteins significantly more abundant in dysplasia compared with inflammation, including Solute carrier family 12 member 2 [SLC12A2] which was confidently identified with eight specific peptides and was below the limit of quantitation in both inflammatory and normal colon. SLC12A2 immunohistochemical analysis confirmed the discrimination of preneoplastic and neoplastic lesions from inflammatory lesions in mice, in UC, and in sporadic contexts. A specific SLC12A2 staining pattern termed ‘loss of gradient’ reached 89% sensitivity, 95% specificity, and 92% accuracy for UC-dysplasia diagnosis together with an inter-observer agreement of 95.24% [multirater κ free of 0.90; 95% CI: 0.78 - 1.00]. Such discrimination could not be obtained by Ki67 staining. This specific pattern was also associated with sporadic colorectal adenomas and cancers.

Conclusions
We found a specific SLC12A2 immunohistochemical staining pattern in precancerous and cancerous colonic UC lesions which could be helpful for diagnosing dysplasia and cancer in UC and non-UC patients.
General practitioners’ perspectives of the integrated health care system: a cross-sectional study in Wuhan, China
Authors: Chen Fan , Jiang Qingqing , Lu Zuxun , Cao Shiyi 
Published: August 2020

Abstract

Background
In recent years, the Chinese government has introduced a new system called the integrated health care system to deepen health care reform and enhance the capacity of the primary health care services.

Objective
We aimed to investigate the perceptions and opinions of general practitioners (GPs) on the integrated health care system.

Methods
A cross-sectional investigation involving 764 GPs in Hubei province of China was conducted. We used a self-designed questionnaire to collect information on demographics, GPs’ knowledge and attitude of the integrated health care system. Data on 749 GPs with completed questionnaires were analysed descriptively. We conducted Spearman rank correlation analysis to test correlation of grade data.

Results
60.92% of the 749 GPs were familiar with the integrated health care system. 88.25% of the GPs were apt to support its development and 70.09% thought it could promote downward referral of patients. The GPs’ familiarity with the integrated health care system was significantly related to professional guidance from doctors in higher hospitals (P &lt; 0.05), but not job titles of GPs (P &gt; 0.05). 78.0% of GPs thought that the main benefit of the integrated health care system was the reduction of patients’ health care costs; 70.1% believed that the most difficulty was insufficient publicity.

Conclusions
The GPs’ general cognition of the integrated health care system was general. Most of the GPs supported the integrated health care system and believed that it contributed to decrease the patients’ health care costs. Insufficient publicity and the incomplete two-way referral mechanism were regarded to be the main obstacles to its development.
Cell envelope proteases and peptidases of Pseudomonas aeruginosa: multiple roles, multiple mechanisms
Authors: Heywood Astra , Lamont Iain L 
Published: August 2020

ABSTRACT
Pseudomonas aeruginosa is a Gram-negative bacterium that is commonly isolated from damp environments. It is also a major opportunistic pathogen, causing a wide range of problematic infections. The cell envelope of P. aeruginosa, comprising the cytoplasmic membrane, periplasmic space, peptidoglycan layer and outer membrane, is critical to the bacteria's ability to adapt and thrive in a wide range of environments. Over 40 proteases and peptidases are located in the P. aeruginosa cell envelope. These enzymes play many crucial roles. They are required for protein secretion out of the cytoplasm to the periplasm, outer membrane, cell surface or the environment; for protein quality control and removal of misfolded proteins; for controlling gene expression, allowing adaptation to environmental changes; for modification and remodelling of peptidoglycan; and for metabolism of small molecules. The key roles of cell envelope proteases in ensuring normal cell functioning have prompted the development of inhibitors targeting some of these enzymes as potential new anti-Pseudomonas therapies. In this review, we summarise the current state of knowledge across the breadth of P. aeruginosa cell envelope proteases and peptidases, with an emphasis on recent findings, and highlight likely future directions in their study.
Multi-“-Omics” Profiling in Patients With Quiescent Inflammatory Bowel Disease Identifies Biomarkers Predicting Relapse
Authors: Borren Nienke Z , Plichta Damian , Joshi Amit D , Bonilla Gracia , Sadreyev Ruslan , Vlamakis Hera , Xavier Ramnik J , Ananthakrishnan Ashwin N 
Published: August 2020

Abstract

Background
Inflammatory bowel diseases (IBD) are characterized by intermittent relapses, and their course is heterogeneous and unpredictable. Our aim was to determine the ability of protein, metabolite, or microbial biomarkers to predict relapse in patients with quiescent disease.

Methods
This prospective study enrolled patients with quiescent Crohn disease and ulcerative colitis, defined as the absence of clinical symptoms (Harvey-Bradshaw Index ≤ 4, Simple Clinical Colitis Activity Index ≤ 2) and endoscopic remission within the prior year. The primary outcome was relapse within 2 years, defined as symptomatic worsening accompanied by elevated inflammatory markers resulting in a change in therapy or IBD-related hospitalization or surgery. Biomarkers were tested in a derivation cohort, and their performance was examined in an independent validation cohort.

Results
Our prospective cohort study included 164 patients with IBD (108 with Crohn disease, 56 with ulcerative colitis). Upon follow-up for a median of 1 year, 22 patients (13.4%) experienced a relapse. Three protein biomarkers (interleukin-10, glial cell line–derived neurotrophic factor, and T-cell surface glycoprotein CD8 alpha chain) and 4 metabolomic markers (propionyl-L-carnitine, carnitine, sarcosine, and sorbitol) were associated with relapse in multivariable models. Proteomic and metabolomic risk scores independently predicted relapse with a combined area under the curve of 0.83. A high proteomic risk score (odds ratio = 9.11; 95% confidence interval, 1.90-43.61) or metabolomic risk score (odds ratio = 5.79; 95% confidence interval, 1.24-27.11) independently predicted a higher risk of relapse over 2 years. Fecal metagenomics showed an increased abundance of Proteobacteria (P = 0.0019, q = 0.019) and Fusobacteria (P = 0.0040, q = 0.020) and at the species level Lachnospiraceae_bacterium_2_1_58FAA (P = 0.000008, q = 0.0009) among the relapses.

Conclusions
Proteomic, metabolomic, and microbial biomarkers identify a proinflammatory state in quiescent IBD that predisposes to clinical relapse.
A new tool for discovering transcriptional regulators of co-expressed genes predicts gene regulatory networks that mediate ethylene-controlled root development
Authors: Harkey Alexandria F , Sims Kira N , Muday Gloria K 
Published: August 2020

Abstract
Gene regulatory networks (GRNs) are defined by a cascade of transcriptional events by which signals, such as hormones or environmental cues, change development. To understand these networks, it is necessary to link specific transcription factors (TFs) to the downstream gene targets whose expression they regulate. Although multiple methods provide information on the targets of a single TF, moving from groups of co-expressed genes to the TF that controls them is more difficult. To facilitate this bottom-up approach, we have developed a web application named TF DEACoN. This application uses a publicly available Arabidopsis thaliana DNA Affinity Purification (DAP-Seq) data set to search for TFs that show enriched binding to groups of co-regulated genes. We used TF DEACoN to examine groups of transcripts regulated by treatment with the ethylene precursor 1-aminocyclopropane-1-carboxylic acid (ACC), using a transcriptional data set performed with high temporal resolution. We demonstrate the utility of this application when co-regulated genes are divided by timing of response or cell-type-specific information, which provides more information on TF/target relationships than when less defined and larger groups of co-regulated genes are used. This approach predicted TFs that may participate in ethylene-modulated root development including the TF NAM (NO APICAL MERISTEM). We used a genetic approach to show that a mutation in NAM reduces the negative regulation of lateral root development by ACC. The combination of filtering and TF DEACoN used here can be applied to any group of co-regulated genes to predict GRNs that control coordinated transcriptional responses.
ASAS-NANP SYMPOSIUM: RUMINANT/NONRUMINANT FEED COMPOSITION: Challenges and opportunities associated with creating large feed composition tables
Authors: Schlageter-Tello Andres , Fahey George C , Freel Tarra , Koutsos Liz , Miller Phillip S , Weiss William P 
Published: August 2020

Abstract
Traditional feed composition tables have been a useful tool in the field of animal nutrition throughout the last 70 yr. The objective of this paper is to discuss the challenges and opportunities associated with creating large feed ingredient composition tables. This manuscript will focus on three topics discussed during the National Animal Nutrition Program (NANP) Symposium in ruminant and nonruminant nutrition carried out at the American Society of Animal Science Annual Meeting in Austin, TX, on July 11, 2019, namely: 1) Using large datasets in feed composition tables and the importance of standard deviation in nutrient composition as well as different methods to obtain accurate standard deviation values, 2) Discussing the importance of fiber in animal nutrition and the evaluation of different methods to estimate fiber content of feeds, and 3) Description of novel feed sources, such as insects, algae, and single-cell protein, and challenges associated with the inclusion of such feeds in feed composition tables. Development of feed composition tables presents important challenges. For instance, large datasets provided by different sources tend to have errors and misclassifications. In addition, data are in different file formats, data structures, and feed classifications. Managing such large databases requires computers with high processing power and software that are also able to run automated procedures to consolidate files, to screen out outlying observations, and to detect misclassified records. Complex algorithms are necessary to identify misclassified samples and outliers aimed to obtain accurate nutrient composition values. Fiber is an important nutrient for both monogastrics and ruminants. Currently, there are several methods available to estimate the fiber content of feeds. However, many of them do not estimate fiber accurately. Total dietary fiber should be used as the standard method to estimate fiber concentrations in feeds. Finally, novel feed sources are a viable option to replace traditional feed sources from a nutritional perspective, but the large variation in nutrient composition among batches makes it difficult to provide reliable nutrient information to be tabulated. Further communication and cooperation among different stakeholders in the animal industry are required to produce reliable data on the nutrient composition to be published in feed composition tables.