bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biomarkers for the diagnosis and post-Kasai portoenterostomy prognosis of biliary atresia: a systematic review and meta-analysis
Authors: He Lin , Ip Dennis Kai Ming , Tam Greta , Lui Vincent Chi Hang , Tam Paul Kwong Hang , Chung Patrick Ho Yu 
Published: June 2021

AbstractTo evaluate the accuracy of biomarkers for the early diagnosis of biliary atresia (BA) and prognostic stratification after Kasai portoenterostomy (KPE). We conducted a systematic review of PubMed, Web of Science, Embase, Scopus and OVID for English literature reporting BA biomarkers published before August 2020. Screening, data extraction, and quality assessment were performed in duplicate. A total of 51 eligible studies were included in the systematic review, and data from 12 (4182 subjects) were extracted for meta-analysis regarding the following 2 domains: (1) serum matrix metallopeptidase-7 (MMP-7), interleukin33 (IL-33) and γ-glutamyl transferase (GGT) to differentiate BA from non-BA; (2) the aspartate aminotransferase to platelet ratio index (APRi) to predict post-KPE liver fibrosis/cirrhosis. The summary sensitivity, specificity and area under the curve (AUC) of MMP-7 for diagnosing BA were 96%, 91% and 0.9847, respectively, and those of GGT were 80%, 79% and 0.9645, respectively. The summary sensitivity and specificity of IL-33 for diagnosing BA were 77% and 85%, respectively. The summary sensitivity and specificity of APRi for predicting post-KPE liver fibrosis were 61% and 80%, respectively, and the summary sensitivity, specificity and AUC of APRi for predicting post-KPE cirrhosis were 78%, 83% and 0.8729, respectively. Moreover, good evidence was shown in investigations of serum IL-18 and IL-33 in distinguishing BA from healthy controls, serum IL-18 for prognosis of post-KPE persistent jaundice, and serum hyaluronic acid and MMP-7 for prognosis of post-KPE significant liver fibrosis. MMP-7, IL-33 and GGT are useful biomarkers to assist in the diagnosis of BA. APRi might be used to predict post-KPE significant liver fibrosis and cirrhosis. These noninvasive biomarkers can be integrated into the management protocol of BA.
Detecting pelvic fracture on 3D-CT using deep convolutional neural networks with multi-orientated slab images
Authors: Ukai Kazutoshi , Rahman Rashedur , Yagi Naomi , Hayashi Keigo , Maruo Akihiro , Muratsu Hirotsugu , Kobashi Syoji 
Published: June 2021

AbstractPelvic fracture is one of the leading causes of death in the elderly, carrying a high risk of death within 1 year of fracture. This study proposes an automated method to detect pelvic fractures on 3-dimensional computed tomography (3D-CT). Deep convolutional neural networks (DCNNs) have been used for lesion detection on 2D and 3D medical images. However, training a DCNN directly using 3D images is complicated, computationally costly, and requires large amounts of training data. We propose a method that evaluates multiple, 2D, real-time object detection systems (YOLOv3 models) in parallel, in which each YOLOv3 model is trained using differently orientated 2D slab images reconstructed from 3D-CT. We assume that an appropriate reconstruction orientation would exist to optimally characterize image features of bone fractures on 3D-CT. Multiple YOLOv3 models in parallel detect 2D fracture candidates in different orientations simultaneously. The 3D fracture region is then obtained by integrating the 2D fracture candidates. The proposed method was validated in 93 subjects with bone fractures. Area under the curve (AUC) was 0.824, with 0.805 recall and 0.907 precision. The AUC with a single orientation was 0.652. This method was then applied to 112 subjects without bone fractures to evaluate over-detection. The proposed method successfully detected no bone fractures in all except 4 non-fracture subjects (96.4%).
A novel piperazine derivative that targets hepatitis B surface antigen effectively inhibits tenofovir resistant hepatitis B virus
Authors: Kiruthika S. , Bhat Ruchika , Dash Rozaleen , Rathore Anurag S. , Vivekanandan Perumal , Jayaram B. 
Published: June 2021

AbstractChronic hepatitis B virus (HBV) infection is a global problem. The loss of hepatitis B surface antigen (HBsAg) in serum is a therapeutic end point. Prolonged therapy with nucleoside/nucleotide analogues targeting the HBV-polymerase may lead to resistance and rarely results in the loss of HBsAg. Therefore, inhibitors targeting HBsAg may have potential therapeutic applications. Here, we used computational virtual screening, docking, and molecular dynamics simulations to identify potential small molecule inhibitors against HBsAg. After screening a million molecules from ZINC database, we identified small molecules with potential anti-HBV activity. Subsequently, cytotoxicity profiles and anti-HBV activities of these small molecules were tested using a widely used cell culture model for HBV. We identified a small molecule (ZINC20451377) which binds to HBsAg with high affinity, with a KD of 65.3 nM, as determined by Surface Plasmon Resonance spectroscopy. Notably, the small molecule inhibited HBsAg production and hepatitis B virion secretion (10 μM) at low micromolar concentrations and was also efficacious against a HBV quadruple mutant (CYEI mutant) resistant to tenofovir. We conclude that this small molecule exhibits strong anti-HBV properties and merits further testing.
Transport current and magnetization of Bi-2212 wires above liquid Helium temperature for cryogen-free applications
Authors: Leveratto A. , Armenio A. Angrisani , Traverso A. , De Marzi G. , Celentano G. , Malagoli A. 
Published: June 2021

AbstractSince the discovery of high temperature superconductors, a possible cryogen-free scenario has always been wished. Nowadays, liquid Helium is running out, and it is likely that the cooling by will be a large part of the costs of any superconducting system. Bi-2212 wires at temperature higher than 4.2 K still show a very high irreversibility field and thus a deep investigation of their properties in such a range of temperature is very useful in order to assess the applicability in high field cryogen-free magnets. Here electrical transport and magnetic properties characterization at variable temperature and magnetic field on our “GDG—processed” wires are reported together with a well-described original approach to calculate the irreversibility field Hirr. This study is devoted to provide reference data on the behaviour of the only isotropic wire for high field application with an eye to the performances at temperatures above 4.2 K.
Differential effects of heat-not-burn and conventional cigarettes on coronary flow, myocardial and vascular function
Authors: Ikonomidis Ignatios , Vlastos Dimitrios , Kostelli Gavriela , Kourea Kallirhoe , Katogiannis Konstantinos , Tsoumani Maria , Parissis John , Andreadou Ioanna , Alexopoulos Dimitrios 
Published: June 2021

AbstractWe compared the effects of Heat-not-Burn cigarette (HNBC) to those of tobacco cigarette (Tcig), on myocardial, coronary and arterial function as well as on oxidative stress and platelet activation in 75 smokers. In the acute study, 50 smokers were randomised into smoking a single Tcig or a HNBC and after 60 min were crossed-over to the alternate smoking. For chronic phase, 50 smokers were switched to HNBC and were compared with an external group of 25 Tcig smokers before and after 1 month. Exhaled carbon monoxide (CO), pulse wave velocity (PWV), malondialdehyde (MDA) and thromboxane B2 (TxB2) were assessed in the acute and chronic study. Global longitudinal strain (GLS), myocardial work index (GWI), wasted myocardial work (GWW), coronary flow reserve (CFR), total arterial compliance (TAC) and flow-mediated dilation (FMD) were assessed in the chronic study. Acute HNBC smoking caused a smaller increase of PWV than Tcig (change 1.1 vs 0.54 m/s, p < 0.05) without change in CO and biomarkers in contrast to Tcig. Compared to Tcig, switching to HNBC for 1-month improved CO, FMD, CFR, TAC, GLS, GWW, MDA, TxB2 (differences 10.42 ppm, 4.3%, 0.98, 1.8 mL/mmHg, 2.35%, 19.72 mmHg%, 0.38 nmol/L and 45 pg/mL respectively, p < 0.05). HNBCs exert a less detrimental effect on vascular and cardiac function than tobacco cigarettes.Trial registration Registered on https://clinicaltrials.gov/ (NCT03452124, 02/03/2018).
Denosumab versus romosozumab for postmenopausal osteoporosis treatment
Authors: Kobayakawa Tomonori , Miyazaki Akiko , Saito Makoto , Suzuki Takako , Takahashi Jun , Nakamura Yukio 
Published: June 2021

AbstractDenosumab and romosozumab, a recently approved new drug, are effective and widely known molecular-targeted drugs for postmenopausal osteoporosis treatment. However, no studies have directly compared their therapeutic effects or safety in postmenopausal osteoporosis. This retrospective observational registry study compared the efficacy of 12-month denosumab or romosozumab treatment in postmenopausal osteoporosis patients. The primary outcome was the change in bone mineral density (BMD) at the lumbar spine. Secondary outcomes included BMD changes at the total hip and femoral neck, changes in bone turnover markers, and adverse events. Propensity score matching was employed to assemble patient groups with similar baseline characteristics. Sixty-nine patients each received either denosumab or romosozumab for 12 months. The mean 12-month percentage change from baseline in lumbar spine BMD was 7.2% in the denosumab group and 12.5% in the romosozumab group, indicating a significant difference between the groups. The percentage changes in BMD at both the total hip and femoral neck were also significantly higher at 12 months in the romosozumab group than in the denosumab group. In denosumab patients, bone formation and bone resorption markers were significantly decreased at 6 and 12 months from baseline. In the romosozumab group, the bone formation marker was significantly increased at 6 months and then returned to baseline, while the bone resorption marker was significantly decreased at both time points. Adverse events were few and predominantly minor in both groups, with no remarkable difference in the incidence of new vertebral fractures. Romosozumab showed a higher potential for improving BMD than denosumab in this clinical study of postmenopausal osteoporosis patient treatment.
Accelerating deployment of offshore wind energy alter wind climate and reduce future power generation potentials
Authors: Akhtar Naveed , Geyer Beate , Rockel Burkhardt , Sommer Philipp S. , Schrum Corinna 
Published: June 2021

AbstractThe European Union has set ambitious CO2 reduction targets, stimulating renewable energy production and accelerating deployment of offshore wind energy in northern European waters, mainly the North Sea. With increasing size and clustering, offshore wind farms (OWFs) wake effects, which alter wind conditions and decrease the power generation efficiency of wind farms downwind become more important. We use a high-resolution regional climate model with implemented wind farm parameterizations to explore offshore wind energy production limits in the North Sea. We simulate near future wind farm scenarios considering existing and planned OWFs in the North Sea and assess power generation losses and wind variations due to wind farm wake. The annual mean wind speed deficit within a wind farm can reach 2–2.5 ms−1 depending on the wind farm geometry. The mean deficit, which decreases with distance, can extend 35–40 km downwind during prevailing southwesterly winds. Wind speed deficits are highest during spring (mainly March–April) and lowest during November–December. The large-size of wind farms and their proximity affect not only the performance of its downwind turbines but also that of neighboring downwind farms, reducing the capacity factor by 20% or more, which increases energy production costs and economic losses. We conclude that wind energy can be a limited resource in the North Sea. The limits and potentials for optimization need to be considered in climate mitigation strategies and cross-national optimization of offshore energy production plans are inevitable.
Outcome after kidney transplantation in hepatitis B surface antigen-positive patients
Authors: Mo Hyejin , Min Sangil , Han Ahram , Jung In Mok , Ha Jongwon 
Published: June 2021

AbstractFew reports detail the actual outcome of Hepatitis B Surface Antigen-positive patients after kidney transplant. HBsAg-positive patients who underwent kidney transplant between January, 1999, and December, 2018, were reviewed retrospectively. Outcomes including hepatitis B reactivation rate, risk factors for reactivation, and patient and graft survival rates were analyzed. Seventy-seven patients were enrolled (47.1 ± 11.5 years old). Patients received ABO-incompatible (n = 5), crossmatch positive transplant (n = 2), and re-transplant (n = 4). Forty-six patients received prophylactic; 19, medication at least 3 months before the transplant; and 12, did not receive medication. Seventeen out of 76 patients developed reactivation post-transplant. 52.9% of HBV reactivation was accompanied by hepatitis. Inappropriate, other than lifelong prophylactic, antiviral agents (HR = 7.34, 95% CI 1.51–35.69, P = 0.01) and high hepatitis DNA (≥ 1000 IU/ml) pre-transplant (HR = 4.39, 95% CI 1.08–17.81, P = 0.04) increased reactivation risk. There was no significant difference in patient and graft survival between antigen positive patients who received antiviral agent and propensity score matched negative patients. HBsAg positivity in kidney transplant recipients is associated with substantial HBV reactivation rate. Lifelong antiviral therapy is mandatory, and patients with high preop HBV titer should be monitored closely for HBV reactivation.
Risk of herpes zoster in psoriasis patients receiving systemic therapies: a nationwide population-based cohort study
Authors: Ting Sze-Wen , Ting Sze-Ya , Lin Yu-Sheng , Lin Ming-Shyan , Kuo George 
Published: June 2021

AbstractThe incidence of herpes zoster in psoriasis patients is higher than in the general population. However, the association between herpes zoster risk and different systemic therapies, especially biologic agents, remains controversial. This study investigated the association between herpes zoster risk and several systemic antipsoriasis therapies. This prospective open cohort study was conducted using retrospectively collected data from the Taiwan National Health Insurance Research Database. We included 92,374 patients with newly diagnosed psoriasis between January 1, 2001, and December 31, 2013. The exposure of interest was the “on-treatment” effect of systemic antipsoriasis therapies documented by each person-quarter. The outcome was the occurrence of newly diagnosed herpes zoster. During a mean follow-up of 6.8 years, 4834 (5.2%) patients were diagnosed with herpes zoster after the index date. Among the systemic antipsoriasis therapies, etanercept (hazard ratio [HR] 4.78, 95% confidence interval [CI] 1.51–15.17), adalimumab (HR 5.52, 95% CI 1.72–17.71), and methotrexate plus azathioprine (HR 4.17, 95% CI 1.78–9.82) were significantly associated with an increased risk of herpes zoster. By contrast, phototherapy (HR 0.76, 95% CI 0.60–0.96) and acitretin (HR 0.39, 95% CI 0.24–0.64) were associated with a reduced risk of herpes zoster. Overall, this study identified an association of both etanercept and adalimumab with an increased risk of herpes zoster among psoriasis patients. Acitretin and phototherapy were associated with a reduced risk.
3D architecture and structural flexibility revealed in the subfamily of large glutamate dehydrogenases by a mycobacterial enzyme
Authors: Lázaro Melisa , Melero Roberto , Huet Charlotte , López-Alonso Jorge P. , Delgado Sandra , Dodu Alexandra , Bruch Eduardo M. , Abriata Luciano A. , Alzari Pedro M. , Valle Mikel , Lisa María-Natalia 
Published: June 2021

AbstractGlutamate dehydrogenases (GDHs) are widespread metabolic enzymes that play key roles in nitrogen homeostasis. Large glutamate dehydrogenases composed of 180 kDa subunits (L-GDHs180) contain long N- and C-terminal segments flanking the catalytic core. Despite the relevance of L-GDHs180 in bacterial physiology, the lack of structural data for these enzymes has limited the progress of functional studies. Here we show that the mycobacterial L-GDH180 (mL-GDH180) adopts a quaternary structure that is radically different from that of related low molecular weight enzymes. Intersubunit contacts in mL-GDH180 involve a C-terminal domain that we propose as a new fold and a flexible N-terminal segment comprising ACT-like and PAS-type domains that could act as metabolic sensors for allosteric regulation. These findings uncover unique aspects of the structure-function relationship in the subfamily of L-GDHs.
Exosome loaded immunomodulatory biomaterials alleviate local immune response in immunocompetent diabetic mice post islet xenotransplantation
Authors: Mohammadi M. Rezaa , Rodriguez Samuel Mathew , Luong Jennifer Cam , Li Shiri , Cao Rui , Alshetaiwi Hamad , Lau Hien , Davtyan Hayk , Jones Mathew Blurton , Jafari Mahtab , Kessenbrock Kai , Villalta S. Armando , de Vos Paul , Zhao Weian , Lakey Jonathan R. T. 
Published: June 2021

AbstractForeign body response (FBR) to biomaterials compromises the function of implants and leads to medical complications. Here, we report a hybrid alginate microcapsule (AlgXO) that attenuated the immune response after implantation, through releasing exosomes derived from human Umbilical Cord Mesenchymal Stem Cells (XOs). Upon release, XOs suppress the local immune microenvironment, where xenotransplantation of rat islets encapsulated in AlgXO led to >170 days euglycemia in immunocompetent mouse model of Type 1 Diabetes. In vitro analyses revealed that XOs suppressed the proliferation of CD3/CD28 activated splenocytes and CD3+ T cells. Comparing suppressive potency of XOs in purified CD3+ T cells versus splenocytes, we found XOs more profoundly suppressed T cells in the splenocytes co-culture, where a heterogenous cell population is present. XOs also suppressed CD3/CD28 activated human peripheral blood mononuclear cells (PBMCs) and reduced their cytokine secretion including IL-2, IL-6, IL-12p70, IL-22, and TNFα. We further demonstrate that XOs mechanism of action is likely mediated via myeloid cells and XOs suppress both murine and human macrophages partly by interfering with NFκB pathway. We propose that through controlled release of XOs, AlgXO provide a promising new platform that could alleviate the local immune response to implantable biomaterials.
Lithium in NGC 2243 and NGC 104
Authors: Aoki M. , Primas F. , Pasquini L. , Weiss A. , Salaris M. , Carollo D. 
Published: June 2021

Aims.Our aim was to determine the initial Li content of two clusters of similar metallicity but very different ages, the old open cluster NGC 2243 and the metal-rich globular cluster NGC 104.Methods.We compared the lithium abundances derived for a large sample of stars (from the turn-off to the red giant branch) in each cluster. For NGC 2243 the Li abundances are from the catalogues released by theGaia-ESO Public Spectroscopic Survey, while for NGC 104 we measured the Li abundance using FLAMES/GIRAFFE spectra, which include archival data and new observations. We took the initial Li of NGC 2243 to be the lithium measured in stars on the hot side of the Li dip. We used the difference between the initial abundances and the post first dredge-up Li values of NGC 2243, and by adding this amount to the post first dredge-up stars of NGC 104 we were able to infer the initial Li of this cluster. Moreover, we compared our observational results to the predictions of theoretical stellar models for the difference between the initial Li abundance and that after the first dredge-up.Results.The initial lithium content of NGC 2243 was found to be A(Li)i= 2.85 ± 0.09 dex by taking the average Li abundance measured from the five hottest stars with the highest lithium abundance. This value is 1.69 dex higher than the lithium abundance derived in post first dredge-up stars. By adding this number to the lithium abundance derived in the post first dredge-up stars in NGC 104, we infer a lower limit of its initial lithium content of A(Li)i= 2.34 ± 0.13 dex. Stellar models predict similar values. Therefore, our result offers important insights for further theoretical developments.
Extracellular Vesicles and Citrullinated Histone H3 in Coronavirus Disease 2019 Patients
Authors: Traby Ludwig , Kollars Marietta , Kussmann Manuel , Karer Matthias , Šinkovec Hana , Lobmeyr Elisabeth , Hermann Alexander , Staudinger Thomas , Schellongowski Peter , Rössler Bernhard , Burgmann Heinz , Kyrle Paul A. , Eichinger Sabine 
Published: June 2021

AbstractObjectives Pulmonary thrombus formation is a hallmark of coronavirus disease 2019 (COVID-19). A dysregulated immune response culminating in thromboinflammation has been described, but the pathomechanisms remain unclear.Methods We studied 41 adult COVID-19 patients with positive results on reverse-transcriptase polymerase-chain-reaction assays and 37 sex- and age-matched healthy controls. Number and surface characteristics of extracellular vesicles (EVs) and citrullinated histone H3 levels were determined in plasma upon inclusion by flow cytometry and immunoassay.Results In total, 20 patients had severe and 21 nonsevere disease. The number of EV (median [25th, 75th percentile]) was significantly higher in patients compared with controls (658.8 [353.2, 876.6] vs. 435.5 [332.5, 585.3], geometric mean ratio [95% confidence intervals]: 2.6 [1.9, 3.6]; p < 0.001). Patients exhibited significantly higher numbers of EVs derived from platelets, endothelial cells, leukocytes, or neutrophils than controls. EVs from alveolar-macrophages and alveolar-epithelial cells were detectable in plasma and were significantly higher in patients. Intercellular adhesion molecule-1-positive EV levels were higher in patients, while no difference between tissue factor-positive and angiotensin-converting enzyme-positive EV was seen between both groups. Levels of EV did not differ between patients with severe and nonsevere COVID-19. Citrullinated histone H3 levels (ng/mL, median [25th, 75th percentile]) were higher in patients than in controls (1.42 [0.6, 3.4] vs. 0.31 [0.1, 0.6], geometric mean ratio: 4.44 [2.6, 7.7]; p < 0.001), and were significantly lower in patients with nonsevere disease compared with those with severe disease.Conclusion EV and citrullinated histone H3 are associated with COVID-19 and could provide information regarding pathophysiology of the disease.
Chiral Phosphoric Acid Catalyzed Enantioselective [4+3]-Cyclization Reaction of Indol-4-ylmethanols and Quinone Esters
Authors: Lin Xufeng , Chen Zhouli , Wang Lei , Qian Yiheng 
Published: June 2021

AbstractAn asymmetric [4+3]-cyclization reaction of racemic indol-4-ylmethanols and quinone esters catalyzed by chiral phosphoric acids has been developed. This method provides efficient access to biologically important [1]benzoxepino[5,4,3-cd]indoles featuring both axial and central chirality in good yields and up to 98% ee, as essentially single diastereomers, under mild reaction conditions.