bluuebunny/crossref_metadata_2025_split huggingface dataset:
One-Hour Oral Glucose Tolerance Tests for the Prediction and Diagnostic Surveillance of Type 1 Diabetes
Authors: Simmons Kimber M , Sosenko Jay M , Warnock Megan , Geyer Susan , Ismail Heba M , Elding Larsson Helena , Steck Andrea K 
Published: August 2020

Abstract

Context
Once islet autoantibody–positive individuals are identified, predicting which individuals are at highest risk for type 1 diabetes (T1D) is important. A metabolic risk score derived from 2-hour oral glucose tolerance test (OGTT) data, the Diabetes Prevention Trial-Type 1 risk score (DPTRS), can accurately predict T1D. However, 2-hour OGTTs are time-consuming and costly.

Objective
We aimed to determine whether a risk score derived from 1-hour OGTT data can predict T1D as accurately as the DPTRS. Secondarily, we evaluated whether a 1-hour glucose value can be used for diagnostic surveillance.

Methods
The DPTRS was modified to derive a 1-hour OGTT risk score (DPTRS60) using fasting C-peptide, 1-hour glucose and C-peptide, age, and body mass index. Areas under receiver operating curves (ROCAUCs) were used to compare prediction accuracies of DPTRS60 with DPTRS in Diabetes Prevention Trial–Type 1 (DPT-1) (n = 654) and TrialNet Pathway to Prevention (TNPTP) (n = 4610) participants. Negative predictive values (NPV) for T1D diagnosis were derived for 1-hour glucose thresholds.

Results
ROCAUCs for T1D prediction 5 years from baseline were similar between DPTRS60 and DPTRS (DPT-1: 0.805 and 0.794; TNPTP: 0.832 and 0.847, respectively). DPTRS60 predicted T1D significantly better than 2-hour glucose (P &lt; .001 in both cohorts). A 1-hour glucose of less than 180 mg/dL had a similar NPV, positive predictive value, and specificity for T1D development before the next 6-month visit as the standard 2-hour threshold of less than 140 mg/dL (both ≥ 98.5%).

Conclusion
A 1-hour OGTT can predict T1D as accurately as a 2-hour OGTT with minimal risk of missing a T1D diagnosis before the next visit.
New Therapeutic Horizons for Graves’ Hyperthyroidism
Authors: Lane Laura C , Cheetham Tim D , Perros Petros , Pearce Simon H S 
Published: August 2020

Abstract
Graves’ hyperthyroidism is characterized by the presence of autoantibodies that stimulate the thyroid-stimulating hormone receptor (TSHR), resulting in uncontrolled secretion of excessive thyroid hormone. Conventional treatments, including antithyroid medication, radioiodine, or surgery have remained largely unchanged for the past 70 years and either lack efficacy for many patients, or result in lifelong thyroid hormone replacement therapy, in the case of the latter 2 options. The demand for new therapeutic options, combined with greater insight into basic immunobiology, has led to the emergence of novel approaches to treat Graves’ hyperthyroidism. The current therapies under investigation include biologics, small molecules, and peptide immunomodulation. There is a growing focus on TSHR-specific treatment modalities, which carry the advantage of eliciting a specific, targeted approach, with the aim of avoiding disruption of the functioning immune system. These therapies present a new opportunity to supersede the inadequate treatments currently available for some Graves’ patients, offering hope of successful restoration of euthyroidism without the need for ongoing therapy. Several of these therapeutic options have the potential to translate into clinical practice in the near future. This review provides a comprehensive summary of the recent advances and various stages of development of the novel therapeutic approaches to treat Graves’ hyperthyroidism.
Understanding Research Culture: What researchers think about the culture they work in
Authors: Moran Helene , Karlin Lena , Lauchlan Elsie , Rappaport Sarah J. , Bleasdale Ben , Wild Lucy , Dorr Josh 
Published: August 2020

Background: The current performance of UK research can be presented as highly successful, but evidence has emerged about issues with working culture in research and the impact this may have on people and their work. Wellcome commissioned market research agency Shift Learning to investigate current perceptions and experiences of research culture among the research community. Methods: This article presents key findings from two phases of this project: 94 qualitative interviews and a quantitative e-survey with 4267 usable responses. Interview invitations were sent out to UK-based research staff at various career stages. The survey was open to international respondents, but the majority of responses came from the UK. Respondents came predominantly from academia and the sample was intentionally skewed towards biological and biomedical sciences. Results: While participants considered the quality of research outputs to have generally remained high, many felt that issues impacting research culture were becoming more apparent and there was real concern about the future of research professions and the high personal cost for individuals. Factors identified as disruptive to research culture included chasing impact, increased competition, proliferation of metrics, job insecurity and rigid career pathways. Poor research culture manifested in workplace behaviours and practices, including problems with management and leadership and unhealthy power dynamics, such as patronage, bullying and harassment, discrimination and exploitation. These conditions were linked to a range of negative impacts on the researchers and the research outputs. Conclusions: The research ecosystem is characterised by increased levels of competition, lack of job security and insufficient career flexibility. A key takeaway is that the conditions in which research takes place are not inclusive and lack sufficient support mechanisms, which is negatively affecting researchers’ wellbeing, and work-life balance. Such research culture was perceived as unsustainable.
Does diametrical clearance influence the wear of Pinnacle hip implants?
Authors: Bergiers Sean , Hothi Harry , Henckel Johann , Eskelinen Antti , Skinner John , Hart Alister 
Published: August 2020

Aims The optimum clearance between the bearing surfaces of hip arthroplasties is unknown. Theoretically, to minimize wear, it is understood that clearances must be low enough to maintain optimal contact pressure and fluid film lubrication, while being large enough to allow lubricant recovery and reduce contact patch size. This study aimed to identify the relationship between diametrical clearance and volumetric wear, through the analysis of retrieved components. Methods A total of 81 metal-on-metal Pinnacle hips paired with 12/14 stems were included in this study. Geometrical analysis was performed on each component, using coordinate and roundness measuring machines. The relationship between their as-manufactured diametrical clearance and volumetric wear was investigated. The Mann-Whitney U test and unpaired t-test were used, in addition to calculating the non-parametric Spearman's correlation coefficient, to statistically evaluate the acquired data. Results The hips in this study were found to have had a median unworn diametrical clearance of 90.31 μm (interquartile range (IQR) 77.59 to 97.40); 32% (n = 26) were found to have been below the manufacturing tolerance. There was no correlation found between clearance and bearing (rs = -0.0004, p = 0.997) or taper (rs = 0.0048, p = 0.966) wear rates. The wear performance of hips manufactured within and below these specifications was not significantly different (bearing: p = 0.395; taper: p = 0.653). Pinnacles manufactured from 2007 onwards had a greater prevalence of bearing clearance below tolerance (p = 0.004). Conclusion The diametrical clearance of Pinnacle hips did not influence their wear performance, even when below the manufacturing tolerance. The optimum clearance for minimizing hip implant wear remains unclear. Cite this article: Bone Joint Res 2020;9(8):515–523.
Promising targets and drugs in rheumatoid arthritis
Authors: Li Xingyan , Yang Yejing , Sun Guili , Dai Wanwu , Jie Xuri , Du Yongjun , Huang Runjie , Zhang Jiaming 
Published: August 2020

Aims Rheumatoid arthritis (RA) is a systematic autoimmune disorder, characterized by synovial inflammation, bone and cartilage destruction, and disease involvement in multiple organs. Although numerous drugs are employed in RA treatment, some respond little and suffer from severe side effects. This study aimed to screen the candidate therapeutic targets and promising drugs in a novel method. Methods We developed a module-based and cumulatively scoring approach that is a deeper-layer application of weighted gene co-expression network (WGCNA) and connectivity map (CMap) based on the high-throughput datasets. Results Four noteworthy RA-related modules were identified, revealing the immune- and infection-related biological processes and pathways involved in RA. HLA-DMA, HLA-DMB, HLA-DPA1, HLA-DPB1, HLA-DQB1, HLA-DRA, HLA-DRB1, BLNK, BTK, CD3D, CD4, IL2RG, INPP5D, LCK, PTPRC, RAC2, SYK, and VAV1 were recognized as the key hub genes with high connectivity in gene regulation networks and gene pathway networks. Moreover, the long noncoding RNAs (lncRNAs) in the RA-related modules, such as FAM30A and NEAT1, were identified as the indispensable interactors with the hub genes. Finally, candidate drugs were screened by developing a cumulatively scoring approach based on the selected modules. Niclosamide and the other compounds of T-type calcium channel blocker, IKK inhibitor, and PKC activator, HIF activator, and proteasome inhibitor, which harbour the similar gene signature with niclosamide, were promising drugs with high specificity and broad coverage for the RA-related modules. Conclusion This study provides not only the promising targets and drugs for RA but also a novel methodological insight into the target and drug screening. Cite this article: Bone Joint Res 2020;9(8):501–514.
Enzyme Production From Cassava Peels by Aspergillus Awamori KT-11: The Making of Natural Sweetener From Several Tubbers
Authors: Melliawati Ruth , Rahman Farida 
Published: August 2020

The use of cassava (Manihot esculenta Crantz) peel for enzyme production has not been widely used. The purpose of this study was to produce complex amylase enzymes from cassava peel by A. awamori KT-11 and apply them in the manufacture of natural sweeteners. Enzyme production is carried out on red and white cassava peel. Media of cassava peel sterilized, inoculated with 1% A. awamori KT-11, incubated for 5 days, then dried at 50°C and mashed. Making sugar is done on cassava flour, sweet potato ( Ipomoea batatas L), taro (Colocasia esculenta) and cocoyam (Xanthosoma sagittifolium) with different concentrations of 10%, 15%, 20%, and 15% and 20% enzyme concentrations. The hydrolysis process is carried out for 3 days at 60°C. The enzyme activity in red cassava peel was 405,006 U/mL and white cassava peel was 321,239 U/ml. The sugar produced in cassava, taro, sweet potato, and Cocoyam was 101.38 mg/mL, 81.18 mg/mL, 55.929 mg/mL, and 42.874 mg/mL, respectively. The results of TLC showed that cassava and taro sugar contain maltose, lactose and glucose, sweet potatoes contained glucose and dextrin and Cocoyam containing fructose. The sweetness level of sugar from cassava, taro, sweet potato and Cocoyam is 14 brix, 12 brix, 9 brix and 9 brix, respectively.
The Use of NACSELD and EASL-CLIF Classification Systems of ACLF in the Prediction of Prognosis in Hospitalized Patients With Cirrhosis
Authors: Cao Zhujun , Liu Yuhan , Cai Minghao , Xu Yumin , Xiang Xiaogang , Zhao Gangde , Cai Wei , Wang Hui , Wang Weijing , Xie Qing 
Published: August 2020

INTRODUCTION:
Acute-on-chronic liver failure (ACLF) is defined by the European Association for the Study of the Liver-Chronic Liver Failure (EASL-CLIF) consortium and the North American Consortium for the Study of End-Stage Liver Disease (NACSELD) as an acute deterioration of cirrhosis with multiple organ failures and high short-term mortality. However, their diagnostic criteria differ. We aimed to compare these 2 criteria in the prediction of prognosis in hospitalized cirrhosis.

METHODS:
This was a prospective study of nonelectively hospitalized patients with cirrhosis (N = 468) from a single tertiary hospital between 2016 and 2018. Baseline characteristics, incidence, and types of organ failure and survival data at 7, 28, and 90 days were collected. Prognostic utilities of the 2 criteria were compared.

RESULTS:
One hundred thirty-seven of 468 patients (29.3%) had EASL-CLIF ACLF, and 35 of 468 (7.4%) had NACSELD ACLF. The 28-day transplant-free survival of ACLF was 58.4% using EASL-CLIF and 37.1% using the NACSELD criteria. In predicting 28-day mortality, the NACSELD criteria demonstrated significantly higher overall accuracy (92.0% vs 85.3%, P < 0.01), specificity (99.7% vs 84.0%, P < 0.001), and positive predictive value (97.1% vs 50.4%, P < 0.001) but lower sensitivity (49.3% vs 92.5%, P < 0.001) and negative predictive value (91.6% vs 98.5%, P < 0.001) than those of EASL-CLIF. The results were similar in predicting 7-day outcome. However, the overall accuracy became similar between NACSELD and EASL-CLIF ACLF criteria in predicting 90-day mortality (86.3% vs 88.7%, P = 0.27) because of the decrease of sensitivity and negative predictive value of NACSELD ACLF criteria. The prognostic performance of these 2 ACLF criteria was similar when applied to patients with or without hepatitis B virus infection as an etiology of cirrhosis.

DISCUSSION:
There are both caveats and utilities of NACSELD and EASL-CLIF ACLF criteria in prognosis prediction in patients with cirrhosis. NACSED criteria is highly accurate in predicting morality, whereas the EASL-CLIF criteria is more sensitive to identify patients who would benefit from liver transplantation.
Normal Lactate and Unenhanced CT-Scan Result in Delayed Diagnosis of Acute Mesenteric Ischemia
Authors: Nuzzo Alexandre , Joly Francisca , Ronot Maxime , Castier Yves , Huguet Audrey , Paugam-Burtz Catherine , Cazals-Hatem Dominique , Tran-Dinh Alexy , Becq Aymeric , Panis Yves , Bouhnik Yoram , Maggiori Leon , Corcos Olivier ,   on behalf of the SURVI group
Published: August 2020

INTRODUCTION:
To investigate the factors associated with a delayed diagnosis (DD) of acute mesenteric ischemia (AMI).

METHODS:
An observational cohort study from an intestinal failure center. The primary outcome was DD >24 hours.

RESULTS:
Between 2006 and 2015, 74 patients with AMI were included and 39 (53%) had a DD. Plasma lactate <2 mmol/L (odd ratio: 3.2; 95% confidence interval: 1.1–9.1; P = 0.03) and unenhanced computed tomography scan (odds ratio: 5.9; 95% confidence interval: 1.4–25.8; P = 0.01) were independently associated with DD.

DISCUSSION:
Suspicion of AMI should no longer be affected by normal plasma lactate levels and should prompt evaluation by a contrast-enhanced computed tomography-scan.
VALIDA project: Validation of allergy in vitro diagnostics assays (Tools and recommendations for the assessment of in vitro tests in the diagnosis of allergy)
Authors: Casas María L. , Esteban Ángel , González-Muñoz Miguel , Labrador-Horrillo Moisés , Pascal Mariona , Teniente-Serra Aina 
Published: August 2020

Abstract

In vitro allergen-specific immunoglobulin E (IgE) detection and quantification tests are routinely performed in clinical laboratories to diagnose patients with a suspected allergy. Numerous commercial assays are available to test for allergies, but the results can vary widely, thereby influencing both diagnosis and treatment. Given the challenges posed by differences in the various assays for in vitro determination of specific IgE, a group of experts has compiled in a document a series of recommendations on the implications that the use of a certain in vitro technique may have and the impact on the management of the allergic patient that the differences between the various techniques represent. The reading and analysis of this consensus document will help to understand the implications of the change of in vitro diagnostic method in the management of the patient with allergy, in the quality of life and in the socioeconomic costs associated with the disease.
NUDT15 polymorphism explains serious toxicity to azathioprine in Indian patients with chronic immune thrombocytopenia and autoimmune hemolytic anemia: a case series
Authors: Devasia Anup J. , Illangeswaran Raveen Stephen Stallon , Raj Infencia Xavier , George Biju , Balasubramanian Poonkuzhali 
Published: August 2020

Abstract

Objectives
Azathioprine (AZA) is a commonly used immunosuppressant in patients with autoimmune diseases. The toxic side effect to AZA (myelosuppression, hair loss, and oral ulcers) are highly unpredictable which can be life threatening if not identified earlier and dose adjustments made or the drug is withdrawn.

Case presentation
Here we report a case series of five patients with severe toxicity while on treatment with AZA for autoimmune hemolytic anemia (n=1) and Immune thrombocytopenia (n=4). The common thiopurine methyltransferase (TPMT) variants (TPMT*2, *3A, *3B) were not present in these patients. However, all these patients had the NUDT15 415C>T variant that has been reported to explain serious toxicity to thioguanine in Asian patients.

Conclusions
Our report suggests pre-emptive genotype-based dosing of AZA could reduce adverse toxicity and hence better outcome.
Formal Institutions and Informal Entrepreneurial Activity: Panel Data Evidence from Latin American Countries
Authors: Salinas Aldo , Ortiz Cristian , Muffatto Moreno , Changoluisa Javier 
Published: August 2020

AbstractThe objective of this work is to examine the influence of formal institutions on the level of informal entrepreneurial activity in Latin American countries. We use a panel dataset for 18 countries during the 2004–2017 periods. This dataset has not been widely used for longitudinal research by academics in the field of entrepreneurship in developing countries. Using the percentage of the adult population identified as self-employed as a proxy for informal entrepreneurial activity, our results suggest that informal entrepreneurial activity is lower in Latin American countries that have stronger property rights and lighter business regulation. However, countries with more flexible labor regulation show higher informal entrepreneurial activity. Therefore, we believe there is margin for policy intervention to reduce informal entrepreneurial activities in Latin America.
The COVID-19 and bond spreads
Authors: Esteves Rui , Sussman Nathan 
Published: August 2020

Abstract
Financial markets reacted with a vengeance to the COVID-19 pandemic. We argue that while the spread of the pandemic is statistically significant in explaining changes to bond spreads, it has little additional explanatory power over variables that capture financial stress. Financial markets reacted as in any international financial crisis by penalizing emerging economies exposing existing vulnerabilities. This finding highlights the need for credible, but flexible, sovereign currencies and the need to build up liquidity reserves.
Construction of Pressure Tunnels
Authors: Zabuski Lesław 
Published: August 2020

Abstract
The paper focuses on two pressure tunnels in the design of “Kąty-Myscowa” water reservoir. One of them serves as a discharge conduit, whereas the other plays an energetic role. Their depths range between 0 and 75 metres and their diameters equal 5 m. Tunnels are located in the rock mass of Carpathian flysch which is anisotropic and heterogeneous, composed of layers of sandstone and clay shales and intersected with interbedding fissures and numerous joints. The paper is divided in two parts. The first part focuses on methods of excavating and supporting, as well as injecting and sealing (i.e. waterproofing) the tunnel. In the second part, a numerical analysis using the FLAC2D code based on the finite difference method was carried for calculating displacements and internal forces in the preliminary support and in permanent lining. Results of the analysis allow for the assessment of conditions in the tunnel during its excavation and exploitation stages.
Ships and Boats in David Jones’s Tristan ac Essyllt
Authors: Field P. J. C. 
Published: August 2020

Abstract
David Jones’s last important painting, Tristan ac Essylt, shows its central figures surrounded by other people, beset by dangers, and being carried inexorably towards their meeting with King Mark, to all of which they are sublimely unconscious. Jones renders the world in which the lovers are set, and particularly the ships in which they travel, with a mixture of historical authenticity (whose full extent has often eluded commentators) and non-naturalistic freedom that suggest simultaneously a powerful physicality and the possible presence of hidden forces working to other ends.
Dynamic routing and wavelength assignment for efficient traffic grooming
Authors: Mohan Neeraj , Kaushal Priyanka 
Published: August 2020

Abstract
The routing and wavelength assignment (RWA) schemes play an important role in all computer networks. The performance of a computer network and resource utilization largely depend on the RWA. The demand for higher bandwidth is increasing with each passing day, so more efficient RWA schemes need to be devolved to cater the increasing requirements. RWA becomes more challenging for dynamic traffic as the nature and flow of data are not known in advance. In this paper, a dynamic RWA scheme has been proposed for establishing a path in optical networks. The proposed scheme is based upon dynamic conversion sensing algorithm. It can be applied on a number of different network topologies. The proposed scheme is dynamic in nature, which is significantly useful for dynamic traffic grooming. The proposed scheme has been applied on 14 nodes National Science Foundation Network (NFSNet). Simulation results have shown that the blocking probability of this scheme is very low as compared to the existing schemes. So, the proposed dynamic RWA scheme enhances the network efficiency. It is useful for congestion hit networks. The reduced blocking probability in wavelength division multiplexing optical networks leads to better resource utilization and enhanced performance.
How useful are anthropometric measurements as predictive markers for elevated blood pressure in adolescents in different gender?
Authors: Erdal İzzet , Yalçin Songül S. , Aksan Ayşegül , Gençal Didem , Kanbur Nuray 
Published: August 2020

AbstractBackgroundObesity and obesity-related diseases are one of the common health problems worldwide and have also been proposed to be important predictors of blood pressure and cardiovascular disease risk. The aim of our study is to determine the utility of different anthropometric measurements (body mass index [BMI], skinfold thickness [SFT], waist circumference [WC], mid-upper arm circumference [MUAC], arm circumference-height ratio [AHtR], and waist circumference-height ratio [WHtR]) as markers of hypertension (HT) risk in adolescents.MethodsIn this cross-sectional study, 544 participants aged between 12 and 13 years were included. Anthropometric measurements and blood pressure of participants were measured. The association of different anthropometric measurements with blood pressure was evaluated.ResultsThe frequency of both elevated blood pressure and HT was 30.2%. Biceps, triceps, and suprailiac SFT have an impact on HT in girls but only suprailiac SFT in boys. WC measurements above the 85th percentile were strongly correlated with HT conditions, and this relationship was stronger in boys than in girls (3.3 vs. 2.6 fold). MUAC, WHtR, and AHtR measurements also have strong correlation with HT in boys but only WHtR has a poor relation in girls. In boys and girls with obesity, there was a positive association between obesity and blood pressures.ConclusionsNot only age-related BMI z scores but also a number of other anthropometric measurements, such as WC, SFT, MUAC, WHtR, and AHtR, could have an influence on high blood pressure. The influence changes with gender during adolescence.