bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety of direct oral anticoagulants in patients with advanced liver disease
Authors: Semmler Georg , Pomej Katharina , Bauer David J. M. , Balcar Lorenz , Simbrunner Benedikt , Binter Teresa , Hartl Lukas , Becker Jeannette , Pinter Matthias , Quehenberger Peter , Trauner Michael , Mandorfer Mattias , Lisman Ton , Reiberger Thomas , Scheiner Bernhard 
Published: June 2021

AbstractBackground & AimsWhile direct oral anticoagulants (DOACs) are increasingly used in patients with liver disease, safety data especially in advanced chronic liver disease (ACLD) are limited.MethodsLiver disease patients receiving DOAC treatment (ACLD: n = 104; vascular liver disease: n = 29) or vitamin K antagonists (VKA)/low‐molecular‐weight heparin (LMWH; ACLD: n = 45; vascular: n = 13) between January 2010 and September 2020 were retrospectively included. Invasive procedures and bleeding events were recorded. Calibrated anti‐Xa peak levels and thrombomodulin‐modified thrombin generation assays (TM‐TGAs) were measured in a subgroup of 35/28 DOAC patients.ResultsAmong patients receiving DOAC, 55 (41.3%) had advanced liver dysfunction (Child‐Pugh‐stage [CPS] B/C) and 66 (49.6%) had experienced decompensation. Overall, 205 procedures were performed in 60 patients and procedure‐related bleedings occurred in 7 (11.7%) patients. Additionally, 38 (28.6%) patients experienced spontaneous (15 minor, 23 major) bleedings during a median follow‐up of 10.5 (IQR: 4.0‐27.8) months. Spontaneous bleedings in ACLD patients were more common in CPS‐B/C (at 12 months: 36.9% vs CPS‐A: 15.9%, subdistribution hazard ratio [SHR]: 3.23 [95% CI: 1.59‐6.58], P < .001), as were major bleedings (at 12 months: 22.0% vs 5.0%, SHR: 5.82 [95% CI: 2.00‐16.90], P < .001). Importantly, CPS (adjusted SHR: 4.12 [91% CI: 1.82‐9.37], P < .001), but not the presence of hepatocellular carcinoma or varices, was independently associated with major bleeding during DOAC treatment. Additionally, ACLD patients experiencing bleeding had worse overall survival (at 12 months: 88.9% vs 95.0% without bleeding; P < .001). Edoxaban anti‐Xa peak levels were higher in patients with CPS‐B/C (345 [95% CI: 169‐395] vs CPS‐A: 137 [95% CI: 96‐248] ng/mL, P = .048) and were associated with lower TM‐TGA. Importantly, spontaneous bleeding rates were comparable to VKA/LMWH patients.ConclusionsAnticoagulants including DOACs should be used with caution in patients with advanced liver disease due to a significant rate of spontaneous bleeding events.
Higher population genetic diversity within the algal symbiontDurusdiniuminPocillopora verrucosafrom Mexican Pacific reefs correlates with higher resistance to bleaching after the El Niño 2015–16 event
Authors: Cárdenas‐Alvarado María Angeles , Nava Héctor , González‐Rodríguez Antonio , Maldonado‐López Yurixhi , Rodríguez‐Lanetty Mauricio 
Published: June 2021

AbstractZooxanthellae are dinoflagellate algae belonging to the family Symbiodiniaceae that provide energy and oxygenation to corals, allowing them to develop a high calcification rate. Additionally, some species of these algal symbionts seem to be related to coral resistance to particular environmental conditions, and such responses have a high potential to cope with climate change and related phenomena. In this study, we examined the role of algal symbiont diversity in the resistance of corals to thermal stress along four coral reefs from the Mexican Pacific after the “El Niño” event of 2015–16. To assess the composition and genetic diversity of the populations of zooxanthellae, the 28S and ITS2 nrRNA genes were amplified and sequenced from a total of 102 fragments ofPocillopora verrucosa. The resulting phylogenetic trees of both molecular markers showed that all sequences were grouped within clade D corresponding to genusDurusdinium, closely related to the subtypes D1.1 and D1.2, respectively. The presence of this genus has been related to the ability of coral hosts to endure thermal stress. Analysis of haplotype networks showed a higher number of haplotypes for the ITS2 in comparison with the 28S marker, with 28 and 5 haplotypes, respectively. With the ITS2 marker, the haplotypes from Islote Zacatoso were differentiated with more mutational steps, showing the highest genetic diversity. This population was associated with corals that suffered a minimum coral bleaching during the El Niño event of 2015–16. Moreover, the population of Playa Las Gatas had the lowest genetic diversity in the area and showed the highest incidence of coral mortality and bleaching. In this way, we discuss the possible relationship between both local and external environmental conditions and current composition of zooxanthellae as modulators of the response of corals to thermal stress: higher genetic diversity of zooxanthellae seems to be related to high resistance to thermal stress.
Two cases of congenital dermatomyofibroma
Authors: Brooks Blake Elizabeth , Robinson‐Bostom Leslie , Telang Gladys , Bercovitch Lionel 
Published: June 2021

AbstractWe present two infants with histologically confirmed congenital dermatomyofibromas. Congenital cases are rare with only one prior case reporting presence since birth. Given the benign nature of the lesions and propensity of dermatomyofibromas to resolve without intervention in young male patients, no additional treatments were pursued.
Psychosocial impact of epidermolysis bullosa on patients: A qualitative study
Authors: Sangha Nimrita , MacLellan A. Nikolas , Pope Elena 
Published: June 2021

AbstractBackgroundEpidermolysis bullosa (EB) is an inherited disorder that results in painful skin blisters requiring daily wound care. The psychosocial impact of EB is one of the most significant concerns for patients, but there is minimal research addressing these concerns or ways to improve patient quality of life (QoL).ObjectiveTo examine the psychosocial impact of EB on affected patients and ways to improve their QoL.MethodsEight EB participants were selected from the 2006 DEBRA Family Conference Day in Toronto. Participants were interviewed by a social worker and a field evaluator. The transcript of each interview was assessed using qualitative content analysis.ResultsFour themes were identified: school interaction, daily life, family interactions, and societal interactions. Participants reported being teased and avoided by peers, and they felt their conditions were misunderstood by the general public. School absenteeism resulted in some patients falling behind in school, which may have been misinterpreted as intellectual impairment. Patients acknowledged significant dependence on others and felt they were contributing to caregiver burden.ConclusionsOur findings highlight the psychosocial impact of EB on patients. As EB awareness and resources to support patients and caregivers have improved since this study was conducted, more studies exploring the current landscape and opportunities to improve quality of life are needed.
Is the demographic dividend diminishing in China? Evidence from population aging and economic growth during 1990–2015
Authors: Ye Jinqi , Chen Ziyan , Peng Bin 
Published: June 2021

AbstractThis paper presents new empirical evidence on the effect of population aging on economic growth in China. Aging is widely assumed to impact economic growth by shaping the labor market performance and human capital. Using an interactive fixed effects model and a provincial panel data set during 1990–2015, and also exploiting the predicted province‐by‐year variation in population aging fraction as an instrument, we examine the impact of population aging on the growth rate of gross domestic product (GDP) per capita, labor force ratio, and labor productivity. The results show that a 10% increase in the fraction of the population aged 65+ decreases the growth rate of GDP per capita by approximately 2%. Furthermore, channel decomposition shows that half of the decrease is due to slower growth of the labor force ratio, whereas the rest may be due to slower productivity growth. In addition, the negative effect of aging on GDP growth is more substantial after the year 2000, and the effect of aging on the labor force ratio and productivity shows different patterns during different periods.
Validation of the Sysmex XN‐V hematology analyzer for canine specimens
Authors: Grebert Margot , Granat Fanny , Braun Jean‐Pierre , Leroy Quentin , Bourgès‐Abella Nathalie , Trumel Catherine 
Published: June 2021

AbstractBackgroundThe Sysmex XN‐V is derived from the new Sysmex XN series of human hematology analyzers. The main changes from the previously validated XT‐2000iV analyzer include an optic‐fluorescent analysis for platelets and nucleated RBC count.ObjectiveWe aimed to validate the Sysmex XN‐V for canine blood according to American College for Veterinary Clinical Pathology and International Council for Standardization in Hematology recommendations.Materials and MethodsCanine EDTA blood specimens and quality control material were analyzed on the Sysmex XN‐V to evaluate imprecision, bias, linearity, a comparison with the XT‐2000iV analyzer, interference effects, carry‐over, and stability. We also verified previously established Sysmex XT‐2000iV reference intervals (RIs).ResultsImprecision and bias were low (<5%) for most variables. Observed total error was lower than allowable total error for most measured variables except lymphocytes and monocytes. Visually determined linearity was excellent for all variables, except for lymphocytes. The correlation between the XN‐V and XT‐2000iV analyzers was high (>0.93) for all variables except MCHC and reticulocyte indices. Correlations between the Sysmex XN‐V and manual differential counts were good for neutrophils and eosinophils, acceptable for lymphocytes, and fair for monocytes. Hemolysis, lipemia, and to a lesser extent icterus, had significant effects on measured hemoglobin concentration and associated variables. Carry‐over was not visually observed for any variable. Changes in the Sysmex XN‐V measurements after storage at 4℃ and 24℃ were similar to those described for the Sysmex XT‐2000iV analyzer. The previously established Sysmex XT‐2000iV RIs can be used to interpret results from the Sysmex XN‐V analyzer for most variables except red blood cell distribution width and mean platelet volume.ConclusionsThe performance of the Sysmex XN‐V analyzer was excellent and compared favorably with the Sysmex XT‐2000iV analyzer.
The Series Elastic Gripper Design, Object Detection, and Recognition by Touch
Authors: Kaya Ozan , Tağlıoğlu Gökçe Burak , Ertuğrul Şeniz 
Published: June 2021

Abstract
In recent years, robotic applications have been improved for better object manipulation and collaboration with human. With this motivation, the detection of objects has been studied with a series elastic parallel gripper by simple touching in case of no visual data available. A series elastic gripper, capable of detecting geometric properties of objects, is designed using only elastic elements and absolute encoders instead of tactile or force/torque sensors. The external force calculation is achieved by employing an estimation algorithm. Different objects are selected for trials for recognition. A deep neural network (DNN) model is trained by synthetic data extracted from standard tessellation language (STL) file of selected objects. For experimental setup, the series elastic parallel gripper is mounted on a Staubli RX160 robot arm and objects are placed in pre-determined locations in the workspace. All objects are successfully recognized using the gripper, force estimation, and the DNN model. The best DNN model is capable of recognizing different objects with the average prediction value ranging from 71% to 98%. Hence, the proposed design of the gripper and the algorithm achieved the recognition of selected objects without the need for additional force/torque or tactile sensors.
In Situ Monitoring of Optical Emission Spectra for Microscopic Pores in Metal Additive Manufacturing
Authors: Sun Wenbo , Zhang Zhenhao , Ren Wenjing , Mazumder Jyoti , Jin Jionghua (Judy) 
Published: June 2021

AbstractQuality assurance techniques are increasingly demanded in additive manufacturing. Going beyond most of the existing research that focuses on the melt pool temperature monitoring, we develop a new method that monitors the in situ optical emission spectra signals. Optical emission spectra signals have been showing a potential capability of detecting microscopic pores. The concept is to extract features from the optical emission spectra via deep auto-encoders and then cluster the features into two quality groups to consider both unlabeled and labeled samples in a semi-supervised manner. The method is integrated with multitask learning to make it adaptable for the samples collected from multiple processes. Both a simulation example and a case study are performed to demonstrate the effectiveness of the proposed method.
The impact of a tear in the subducted Indian plate on the Miocene geology of the Himalayan-Tibetan orogen
Authors: Wang Rui , Weinberg Roberto F. , Zhu Di-Cheng , Hou Zeng-Qian , Yang Zhi-Ming 
Published: June 2021

Abstract
The Yadong-Gulu Rift, cutting across the Gangdese belt and Himalayan terranes, is currently associated with a thermal anomaly in the mantle and crustal melting at 15–20 km depth. The rift follows the trace of a tear in the underthrusted Indian continental lithospheric slab recognized by high resolution geophysical methods. The Miocene evolution of a 400-km-wide band following the trace of the tear and the rift, records differences interpreted as indicative of a higher heat flow than its surroundings. In the Gangdese belt, this band is characterized by high-Sr/Y granitic magmatism that lasted 5 m.y. longer than elsewhere and by the highest values of εHf(i) and association with the largest porphyry Cu-Mo deposits in the Gangdese belt. Anomalously young magmatic rocks continue south along the rift in the Tethyan and Higher Himalayas. Here, a 300-km-wide belt includes some of the youngest Miocene Himalayan leucogranites; the only occurrence of mantle-derived mafic enclaves in a leucogranite; young mantle-derived lamprophyre dikes; and the youngest and hottest migmatites in the Higher Himalayas. These migmatites record a history of rapid exhumation contemporaneous with the exhumation of Miocene mafic eclogite blocks, which are unique to this region and which were both heated to &gt;800 °C at ca. 15–13 Ma, followed by isothermal decompression. We suggest that the prominent tear in the Indian lithosphere, sub-parallel to the rift, is the most likely source for these tectono-thermal anomalies since the Miocene.
Caveolin-1 expression predicts favourable outcome and correlates withPDGFRAmutations in gastrointestinal stromal tumours (GISTs)
Authors: Bertero Luca , Gambella Alessandro , Barreca Antonella , Osella-Abate Simona , Chiusa Luigi , Francia di Celle Paola , Lista Patrizia , Papotti Mauro , Cassoni Paola 
Published: June 2021

AimsNovel prognostic markers are warranted for gastrointestinal stromal tumours. Caveolin-1 is a multifunctional protein that proved to be associated with outcome in multiple tumour types. Aim of this study was to investigate Caveolin-1 expression and prognostic efficacy in a series of gastrointestinal stromal tumours.MethodsCaveolin-1 expression was assessed by immunohistochemistry in a retrospective series of 66 gastrointestinal stromal tumours representative of the different molecular subtypes. Correlations with clinical, histopathological and molecular features were investigated. Statistical analyses were performed as appropriate.ResultsThirty-five cases out of 66 (53.0%) expressed Caveolin-1. Presence of Caveolin-1 expression correlated with favourable histopathologic and clinical traits, including a lower mitotic count (p=0.003) and lower relapse rate (p=0.005). Caveolin-1 expression also resulted associated with the presence ofPDGFRAmutations (p=0.010). Outcome analyses showed a favourable prognostic significance of Caveolin-1 expression in terms of relapse-free survival (HR=0.14; 95% CI=0.03 to 0.63) and overall survival (HR=0.29; 95% CI=0.11 to 0.74), even after adjusting for the mutational subgroup (relapse-free survival: HR=0.14, 95% CI=0.04 to 0.44; overall survival: HR=0.29, 95% CI=0.11 to 0.51) and imatinib treatment (relapse-free survival: HR=0.14, 95% CI=0.02 to 0.81; overall survival: HR=0.29, 95% CI=0.17 to 0.48).ConclusionCaveolin-1 represents a novel prognostic marker in gastrointestinal stromal tumours. Further studies are warranted to validate these results and to explore the mechanisms linking Caveolin-1 expression with thePDGFRAoncogenic pathway.
Castration-Induced Downregulation of SPARC in Stromal Cells Drives Neuroendocrine Differentiation of Prostate Cancer
Authors: Enriquez Claudia , Cancila Valeria , Ferri Renata , Sulsenti Roberta , Fischetti Irene , Milani Matteo , Ostano Paola , Gregnanin Ilaria , Mello-Grand Maurizia , Berrino Enrico , Bregni Marco , Renne Giuseppe , Tripodo Claudio , Colombo Mario P. , Jachetti Elena 
Published: June 2021

AbstractFatal neuroendocrine differentiation (NED) of castration-resistant prostate cancer is a recurrent mechanism of resistance to androgen deprivation therapies (ADT) and antiandrogen receptor pathway inhibitors (ARPI) in patients. The design of effective therapies for neuroendocrine prostate cancer (NEPC) is complicated by limited knowledge of the molecular mechanisms governing NED. The paucity of acquired genomic alterations and the deregulation of epigenetic and transcription factors suggest a potential contribution from the microenvironment. In this context, whether ADT/ARPI induces stromal cells to release NED-promoting molecules and the underlying molecular networks are unestablished. Here, we utilized transgenic and transplantable mouse models and coculture experiments to unveil a novel tumor-stroma cross-talk that is able to induce NED under the pressure of androgen deprivation. Castration induced upregulation of GRP78 in tumor cells, which triggers miR29-b–mediated downregulation of the matricellular protein SPARC in the nearby stroma. SPARC downregulation enabled stromal cells to release IL6, a known inducer of NED. A drug that targets GRP78 blocked NED in castrated mice. A public, human NEPC gene expression dataset showed that Hspa5 (encoding for GRP78) positively correlates with hallmarks of NED. Finally, prostate cancer specimens from patients developing local NED after ADT showed GRP78 upregulation in tumor cells and SPARC downregulation in the stroma. These results point to GRP78 as a potential therapeutic target and to SPARC downregulation in stromal cells as a potential early biomarker of tumors undergoing NED.Significance:Tumor–stroma cross-talk promotes neuroendocrine differentiation in prostate cancer in response to hormone therapy via a GRP78/SPARC/IL6 axis, providing potential therapeutic targets and biomarkers for neuroendocrine prostate cancer.
Abstract 140: Magnesium Lithospermate B Inhibits Blood Coagulation and Platelet Aggregation: Novel Mechanism of a Traditional Drug for Cardiovascular Diseases
Authors: Wang Yiming , Zhang Dan , Xu Xiaohong , Lei Xi , Wang Yiping , Xuan Lijiang , Ding Jian , Ni Heyu 
Published: June 2021

Magnesium lithospermate B (MLB) is one of the major components of Salvia miltiorrhiza root (Danshen). Danshen extracts have been used to control cardiovascular disease for centuries. In 2005, intravenous injection of Danshen depside salt was approved in China for treatment of chronic angina. Although clinical observations have suggested that Danshen extracts inhibited thrombosis, the exact mechanism has not been adequately explored.

Using an
in vitro
whole blood clotting assay, we observed that MLB (250 μM) significantly reduced clot size. Both the clot wet and dry weights were decreased following treatment (108.3 mg
vs.
63.5 mg, and 32.8 mg
vs.
18.5 mg, p<0.05, respectively). Using thromboelastography, we found that MLB markedly decreased the mechanical strength of the clot and modestly delayed initiation of coagulation in cell-free blood plasma prepared by centrifugation (10,000 хg, 10 min). Under confocal microscopy, we further observed that MLB significantly reduced the density of the fibrin network formed in plasma following thrombin treatment, suggesting that MLB targets coagulation factors to inhibit coagulation.

Recent network pharmacology analyses predict that MLB may interact with VWF, factor XIII (FXIII), or thrombin in the coagulation cascade. We found that MLB did not inhibit VWF-dependent platelet agglutination induced by botrocetin. ELISA revealed that MLB also did not significantly alter the binding of activated FXIII (FXIIIa) to fibrinogen. However, when native FXIII from blood plasma was used for the same assay, MLB significantly reduced the binding of FXIIIa to fibrinogen. Since generation of FXIIIa from FXIII is thrombin-dependent, these data suggest that MLB inhibits thrombin activity or thrombin generation. Indeed, we found that MLB markedly inhibited thrombin-induced gel-filtered human and mouse platelet aggregation.
These data demonstrated a novel role for MLB in the inhibition of blood coagulation and platelet aggregation, likely through direct inhibition of thrombin function, although we cannot exclude its additional anti-thrombotic activities. Thus, purified MLB may represent an efficient, low-cost agent for treatment of artery and deep vein thrombosis.
Abstract 197: A Novel Association Between High Density Lipoprotein Levels and the Risk of Postoperative Acute Kidney Injury
Authors: Smith Loren E , Smith Derek K , Linton MacRae F , Billings Frederic T 
Published: June 2021

Acute kidney injury (AKI) after cardiac surgery occurs in up to 30% of patients and is an independent predictor of death. HDL may attenuate mechanisms of AKI. We hypothesized that a high preoperative HDL cholesterol concentration is protective against postoperative AKI.
We analyzed data from a prospective, 393-subject trial of perioperative atorvastatin to prevent post-cardiac surgery AKI. Statin-using patients were randomized to placebo or 80mg atorvastatin the morning of surgery and 40mg on postoperative day 1. Stain-naïve patients were randomized to placebo or 80mg the day prior to surgery and 40mg daily thereafter during hospitalization. The association between HDL level and maximum serum creatinine change from baseline in the first 48 postoperative hours was assessed using a two-component latent variable mixture model and AKI risk factors. Regression analyses assessed interactions of chronic statin use, perioperative atorvastatin treatment, and HDL level on AKI risk.

Postoperative AKI occurred in 99 patients (25.2%). Median (10
th
, 90
th
percentile) preoperative HDL was 37.6 (25.0, 54.0) mg/dL and postoperative creatinine change 0.09 (-0.11, 0.59) mg/dL. Lower HDL levels were independently associated with increased creatinine rise (p=0.02) (Figure 1A). Regression analysis showed this association was present in statin-using but not statin-naïve patients (p=0.008) (1B). The protective effect of high HDL in chronic statin users was enhanced with perioperative atorvastatin treatment (p=0.004) (1C) and with increasing chronic statin dose (p=0.003) (1D). Similar analyses using LDL found no association with AKI risk (p=0.51).

Conclusions:
Higher preoperative HDL was associated with less risk of AKI. Statin exposure modified this association. Specifically, subjects with higher HDL levels on chronic statin therapy had less creatinine rise and appeared to further benefit from higher chronic statin dose and perioperative atorvastatin therapy.