bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circulating Exosomal PD-L1 at Initial Diagnosis Predicts Outcome and Survival of Patients with Osteosarcoma
Authors: Wang Jun , Guo Wei , Wang Xiaofang , Tang Xiaodong , Sun Xin , Ren Tingting 
Published: November 2022

Abstract

Purpose:
It is difficult to predict prognosis of patients with osteosarcoma at initial diagnosis due to lack of efficient prognostic parameters. We evaluated the relationship between level of circulating serum exosomal PD-L1 (Sr-exosomal PD-L1) at initial diagnosis and oncologic outcome during the follow-up.

Experimental Design:
Sixty-seven patients with newly diagnosed osteosarcoma were prospectively recruited. Fasting blood was collected and exosome isolation was performed using ultracentrifugation method. Evaluation of Sr-exosomal PD-L1 was performed respectively by immunogold labeling and ELISA method. Correlation between level of Sr-exosomal PD-L1 at initial diagnosis and clinical risk factors was assessed.

Results:
Mean follow-up was 46.7 months. Two-year and 5-year overall survival (OS) rates were respectively 96.9% and 62.5%. Two-year and 5-year disease-free survival (DFS) rates were respectively 85.0% and 31.4%. Results revealed a significantly positive association between high PD-L1 cargo of circulating exosomes and clinicopathologic disease markers such as pulmonary metastasis, multiple metastasis, and death. Patients who died of disease at final follow-up had higher level of Sr-exosomal PD-L1 at initial diagnosis, which compared with patients who were still alive at last follow-up. Patients in group of ≥14.23 pg/mL Sr-exosomal PD-L1 at initial diagnosis had inferior DFS compared with patients in group of &lt;14.23 pg/mL at initial diagnosis. Patients in group of ≥25.96 pg/mL at initial diagnosis had poor OS compared with patients in group of &lt;25.96 pg/mL at initial diagnosis.

Conclusions:
Use of liquid biopsy of circulating exosomal PD-L1 at initial diagnosis provides a robust means of predicting prognosis for patients with a newly diagnosed osteosarcoma.
Simplification Is Not Dominant in the Evolution of Chinese Characters
Authors: Han Simon J. , Kelly Piers , Winters James , Kemp Charles 
Published: November 2022

AbstractLinguistic systems are hypothesised to be shaped by pressures towards communicative efficiency that drive processes of simplification. A longstanding illustration of this idea is the claim that Chinese characters have progressively simplified over time. Here we test this claim by analyzing a dataset with more than half a million images of Chinese characters spanning more than 3,000 years of recorded history. We find no consistent evidence of simplification through time, and contrary to popular belief we find that modern Chinese characters are higher in visual complexity than their earliest known counterparts. One plausible explanation for our findings is that simplicity trades off with distinctiveness, and that characters have become less simple because of pressures towards distinctiveness. Our findings are therefore compatible with functional accounts of language but highlight the diverse and sometimes counterintuitive ways in which linguistic systems are shaped by pressures for communicative efficiency.
The Animal-Riding Lute Player: a Lens on Gender and Ethnicity in Art and Texts
Authors: Furniss Ingrid 
Published: November 2022

Abstract
This paper explores the theme of the horse- and camel-riding lute player appearing in Chinese art and texts as early as the Han dynasty (206 BCE-220 CE). Such works reflect the expansion of trade with Central Asian peoples in late Han, when texts first mention the introduction of lutes by steppe peoples who themselves played them on horseback. Many subsequent texts, poems, and works of art, particularly during the Tang dynasty (618-907), expand on this idea, highlighting not only the instrument’s steppe origins and association with non-Han men but also elite Han women, particularly those sent to the border regions as diplomatic brides. Drawing primarily on Tang writings and works of art, this paper examines issues of gender, social status, ethnicity and the complex meanings of the lute-playing, camel-riding theme and its depiction in art.
Agricultural Domestic Support Reforms at the wto: An Assessment of the Proportional Reduction Approach
Authors: Sharma Sachin Kumar , Das Abhijit , Mathur Paavni , Lahiri Teesta , Neogi Suvayan 
Published: November 2022

Abstract
Domestic support reforms remain an unresolved and contentious issue in the wto agricultural negotiations. There are proposals to halve the current global trade-distorting domestic support entitlements by 2030, where members would have to undertake reductions proportionate to their existing domestic support entitlements. This study critically examines the implications of the proportional reduction approach on the policy space of 164 wto members to support their farmers. The results show that this approach fails to address the issues and concerns of developing members regarding domestic support reforms, and these members would be required to undertake higher reduction commitments than their developed counterparts. Additionally, the per-farmer entitlement for developed members would remain massive under this approach. Contrary to general belief, the least developed countries would lose half of their flexibility to support their farmers. Further, the proposed approach would dilute the existing special and differential treatment for developing, and least developed, members.
Between Reality and Society: Lee Kuohsiu’s Far Away from Home
Authors: Wang Wei-chih 
Published: November 2022

Abstract
This paper presents the argument that the practice of modern theatre constitutes a crucial method for reorienting the particular traumas of the Chinese diaspora in contemporary Taiwan. In particular, it offers a close reading of Far Away from Home (西出陽關, Xichu yangguan, 1988) by Taiwanese playwright Lee Kuohsiu (李國修, 1955‒2013) and its performance archive of 2004. Lee deploys theatre as a negotiating space in which to reflect the social formations, identities, and history of Taiwan in the late 1980s—a period that saw Taiwan’s complicated relationship with China become the subject of intense scrutiny as the Cold War came to an end and the pressures of rapid globalisation mounted.
Relationship Between Serum Endocan Levels and Other Predictors of Endothelial Dysfunction in Obese Women
Authors: Mercantepe Filiz , Baydur Sahin Serap , Cumhur Cure Medine , Karadag Zakir 
Published: November 2022

Endocan, or endothelial cell-specific molecule-1 (ESM-1), is a potential inflammatory marker implicated in endothelial dysfunction. The purpose of this study was to determine the correlation between serum endocan levels and the presence and severity of endothelial dysfunction, and the relationships with serum intracellular adhesion molecule-1 (ICAM-1), adiponectin (a marker of inflammation), high sensitivity C-reactive protein (hsCRP) levels, and carotid intima-media thickness (cIMT) in obese subjects. Serum endocan, ICAM-1, adiponectin, hsCRP levels, and cIMT were evaluated in 76 obese women (BMI > 30 kg/m2) and 53 controls (BMI < 25 kg/m2). ICAM-1 ( P = .01), hs-CRP (p < 0.001), and cIMT ( p < .001) were significantly higher, while adiponectin ( P = .006) was significantly lower, in obese women compared with the controls. Serum endocan levels were similar between the obese (470.5 ± 171.3 pg/mL) and controls (471.9 ± 146.3 pg/mL) ( P = .732). There was no correlation between serum endocan values and the endothelial dysfunction markers, hsCRP (r = −.021), ICAM-1 (r = −.054), adiponectin (r = .113), or cIMT (r = −.060) in obesity. Endocan is not a suitable marker of endothelial dysfunction in the context of obesity. More research is required to evaluate the role of endocan in the regulation of inflammatory processes in obesity.
Derivation of the toxicological threshold of silicon element in the extractables and leachables from the pharmaceutical packaging and process components
Authors: Hao Pengchao , Wang Yingying , Sun Xiongfei , Wang Jinhui , Zhang Leshuai W. 
Published: November 2022

Silicon is one of the most monitored elements in extractables and leachables studies of pharmaceutical packaging systems and related components. There is a need to review and evaluate toxicological thresholds of silicon because of its direct contact with drug products (DP) especially a liquid form of DP with the widely used pharmaceutical packaging systems made of silicon materials like glass and silicone. It is required by regulatory authorities to test silicon content in DP; however, there are no official guidelines on the toxicology of silicon that are currently available, yet the knowledge of toxicological thresholds of silicon is critical to justify the analytical limit of quantification (LOQ). Therefore, we reviewed the toxicity of silicon to derive a toxicological threshold by literature review of toxicity studies of both inorganic and organic silicon compounds. Oral toxicity is low for inorganic silicon like silicon dioxide or organic silicon polymers such as silicone tube/silicone oil (polydimethylsiloxane, or namely, PDMS as the major ingredient). In comparison, inhalational toxicity of silicon dioxide leads to pulmonary silicosis or even lung cancer. When orally administered, the toxicity of silicon dioxide, glass, polymers, or PDMS oligomers varies depending on their morphology, molecular weight (MW), and degrees of polymerization. PDMS with high MW has minimal toxic symptoms with non-detectable degradation/elimination by both intraperitoneal and subcutaneous administration routes, while exposure to either PDMS or small molecule dimethyl silicone compounds by the intravenous administration route may lead to death. We here determined a general parenteral permitted daily exposure (PDE) of 93 μg/day for inorganic silicon element and 100 μg/day for organic silicon element by reviewing toxicological data of both forms of silicon. In conclusion, this work provides evidence for pharmaceutical companies and regulatory agencies on the PDEs of silicon elements in pharmaceutical packaging and process components through a variety of administration routes.
Mitral Valve Re-Repair Due to Chordal Pseudo-Elongation Through Repeated Right Anterior Minithoracotomy
Authors: Celmeta Bleri , Miceli Antonio , Ferrarini Matteo , Glauber Mattia 
Published: November 2022

Objective: We aim to show the step-by-step surgical technique of mitral valve re-repair by means of a repeated right anterior minithoracotomy in a case of a procedure-related early mitral valve repair failure due to left ventricular positive remodeling and chordal pseudo-elongation. Methods: The patient was readdressed to our institution for an early severe mitral valve regurgitation, less than a year after performing a right minithoracotomy mitral valve repair (42-mm annular ring implantation, P2 triangular resection, and P2 neochord positioning). The mechanism was attributed to a positive left ventricle remodeling and neochordal pseudo-elongation. Therefore, we decided to perform a mitral valve re-repair in a redo minimally invasive cardiac surgery. We describe in a video-guided step-by-step fashion the surgical procedure, from the reopening of the right anterior minithoracotomy to the surgical strategy chosen to address the re-repair, guided by the mechanism of the previous repair failure. Results: We replaced the previously implanted ring with a smaller one and positioned a new polytetrafluoroethylene 4-0 neochord at the P2 level. The patient was discharged home on the fifth postoperative day after an uneventful hospital stay. Predischarge echocardiogram demonstrated undetectable residual mitral valve regurgitation. At 3-month follow-up, echocardiographic and clinical data were encouraging. At 9-month follow-up, the patient endorsed no recurrence of cardiologic symptoms. Conclusions: Redo minimally invasive cardiac surgery is a viable option even in case of a mitral valve re-repair due to previous repair failure, especially when procedure related in degenerative mitral disease. Combining the benefits of mitral valve re-repair with those of a minimally invasive surgery may optimize short-term and long-term outcomes.
The maraca plot: A novel visualization of hierarchical composite endpoints
Authors: Karpefors Martin , Lindholm Daniel , Gasparyan Samvel B 
Published: November 2022

Background: Hierarchical composite endpoints are complex endpoints combining outcomes of different types and different clinical importance into an ordinal outcome that prioritizes the clinically most important (e.g. most severe) event of a patient. Hierarchical composite endpoint can be analysed with the win odds, an adaptation of win ratio to include ties. One of the difficulties in interpreting hierarchical composite endpoint is the lack of proper tools for visualizing the treatment effect captured by hierarchical composite endpoint, given the complex nature of the endpoint which combines events of different types. Methods: Hierarchical composite endpoints usually combine time-to-event outcomes and continuous outcomes into a composite; hence, it is important to capture not only the shift from more severe categories to less severe categories in the active group in comparison to the control group (as in any ordinal endpoint), but also changes occurring within each category. We introduce the novel maraca plot which combines violin plots (with nested box plots) to visualize the density of the distribution of the continuous outcome and Kaplan–Meier plots for time-to-event outcomes into a comprehensive visualization. Conclusion: The novel maraca plot is suggested for visualization of hierarchical composite endpoints consisting of several time-to-event outcomes and a continuous outcome. It has a very simple structure and therefore easily communicates both the overall treatment effect and the effect on individual components.
Dyslipidemia is Associated with an Increased Risk of Achilles Tendinopathy and Tendon Rupture to a Greater Extent in Underweight Than in Obese Subjects
Authors: Choi Jun Young 
Published: November 2022

Category: Ankle Introduction/Purpose: The association between dyslipidemia and Achilles tendinopathy (AT) or Achilles tendon rupture (ATR) remains controversial, although some studies have been reported on the subject. This study aimed to evaluate the correlation of dyslipidemia and the risk of AT or ATR, and its association with body mass index (BMI), by assessing data from a nationwide population-based cohort. Methods: We used the National Health Insurance database, which includes the entire South Korean population to follow-up subjects who participated in the National Health Screening Program (NHSP) from January 2009 to December 2010. Participants diagnosed with AT or ATR before December 31, 2017, were selected. The variables were age, sex, frequency of high-intensity exercise per week, BMI, waist circumference, low-density lipoprotein cholesterol (LDL-C) levels, triglyceride (TG) levels, high- density lipoprotein cholesterol (HDL-C) levels, fasting blood glucose levels, and systolic blood pressure. Multivariate Cox proportional hazards regression was used for data analysis. Results: A total of 16,830,532 subjects were included. Of these, 125,814 and 31,424 subjects developed AT and ATR, respectively. A higher level of LDL-C was associated with an increased risk of both AT (adjusted hazard ratio [HR], 1.16) and ATR (adjusted HR, 1.18). A slightly increased risk of AT was observed in subjects with higher TG levels (adjusted HR, 1.03), whereas higher HDL-C level was associated with a slight risk reduction for AT (adjusted HR, 0.95). However, no significant association was observed between higher TG or HDL-C levels and ATR. In the underweight group (BMI < 18.5 kg/m2), a higher LDL-C level was associated with an increased risk of AT and ATR by 37 and 116%, respectively, compared with lower LDL-C. Higher LDL-C levels was associated with an increased risk of AT and ATR by 10 and 16%, respectively, in the obese group (BMI >= 25 kg/m2). Conclusion: Our results support the hypothesis that dyslipidemia was related to the development of AT and ATR. The association of higher LDL-C levels with AT and ATR risk was more pronounced in underweight than in overweight and obese subjects.
Impact of COVID-19 on emergency department visits among palliative home care recipients: a retrospective population-based cohort study in the Piedmont region, Italy
Authors: Scacchi Alessandro , Conti Alessio , Politano Gianfranco , Dalmasso Marco , Ostellino Sofia , Gianino Maria Michela 
Published: November 2022

Background: Integrated palliative home care (IHPC) is delivered to patients with progressive end-stage diseases. During the COVID-19 pandemic, IHPC needed to provide high-quality home care services for patients who were treated at home, with the goal of avoiding unnecessary care, hospital admissions, and emergency department (ED) visits. This study aimed to compare the ED visits of IHPC recipients in a large Italian region before and during the first two waves of the COVID-19 pandemic and to find sociodemographic or clinical characteristics associated with changes in ED visits during the first two waves of COVID-19 pandemic, compared with the period before. Methods: Administrative databases were used to identify sociodemographic and clinical variables of IHPC recipients admitted before and during the pandemic. The obtained data were balanced by applying a propensity score. The average number of ED visits before and during the pandemic was calculated by using the Welch’s t test and stratified by all the variables. Results: Before and during the pandemic, 5155 and 3177 recipients were admitted to IHPC, respectively. These individuals were primarily affected by neoplasms. ED visits of IHPC recipients reduced from 1346 to 467 before and during the pandemic, respectively. A reduced mortality among IHCP patients who had at least one ED visit during the pandemic (8% during the pandemic versus 15% before the pandemic) was found. The average number of ED visits decreased during the pandemic [0.143, confidence interval (CI) = (0.128–0.158) versus 0.264, CI = (0.242–0.286) before the pandemic; p < 0.001] for all ages and IHPC duration classes. The presence of a formal caregiver led to a significant decrease in ED use. Medium and high emergency ED admissions showed no difference, whereas a decrease in low-level emergency ED admissions during the pandemic [1.27, CI = (1.194–1.345) versus 1.439, CI = (1.3–1.579) before the pandemic; p = 0.036] was found. Conclusion: ED visits among IHPC recipients were significantly decreased during the first two waves of the COVID-19 pandemic, especially in those individuals characterized by a low level of emergency. This did not result in an increase in mortality among IHPC recipients. These findings could inform the reorganization of home care services after the pandemic.
Eco-friendly hybrid materials made from Tunisian clay and natural flowers
Authors: Amraoui Amira , Gamoudi Safa , Baenas Nieves , Periago Maria Jesus , Srasra Ezzeddine 
Published: November 2022

AbstractClay minerals are used widely in health products both as cosmetic and pharmaceutical ingredients. To optimize use, natural compounds are mixed with clay powder. The aim of the present study was to synthesize new, coloured hybrids based on purified Tunisian clay and powders of natural flowers: Malva sylvestris, Chrysanthemum coronarium, Silene dioica, Anagallis monellin and Pelargonium × hortorum. The floral pigments in Tunisian flowers were studied. The chlorophylls (a and b), total flavonoids (TF), total phenolic compounds (TPC), and carotenoids were analyzed using UV-Vis spectrophotometry and high-performance liquid chromatography (HPLC-DAD). In addition, the antioxidant capacity was determined using the oxygenated radical absorption capacity assay (ORAC) and the antioxidant capacity to reduce ferric ion assay (FRAP). The properties of the studied clay were evaluated by means of pharmaceutical and microbiological tests. The coloured hybrids were prepared by solid–solid reaction and analyzed using X-ray diffraction (XRD) and Fourier transform infrared (FTIR) spectroscopy. Chlorophyll a is present in large quantities in the Malva flower which presents the smallest antioxidant capacity. Chlorophyll b and the TPC are more abundant in the Pelargonium × hortorum. The TF appears in large quantities in the Anagallis flower. The carotenoids are present in the largest amounts in the Chrysanthemum. The results of the clay characterization justify its use as a pharmaceutical and cosmetic agent. The mixture of dried flowers and purified clay is used in the synthesis of new and biocoloured hybrids; these can be used as biocosmetic products without negative side effects on human health or the environment.
Targeting platelet GPVI with glenzocimab: a novel mechanism for inhibition
Authors: Billiald Philippe , Slater Alexandre , Welin Martin , Clark Joanne C. , Loyau Stéphane , Pugnière Martine , Jiacomini Isabella G. , Rose Nadia , Lebozec Kristell , Toledano Elie , François Déborah , Watson Steve P. , Jandrot-Perrus Martine 
Published: November 2022

Abstract
Platelet glycoprotein VI (GPVI) is attracting interest as a potential target for the development of new antiplatelet molecules with a low bleeding risk. GPVI binding to vascular collagen initiates thrombus formation and GPVI interactions with fibrin promote the growth and stability of the thrombus. In this study, we show that glenzocimab, a clinical stage humanized antibody fragment (Fab) with a high affinity for GPVI, blocks the binding of both ligands through a combination of steric hindrance and structural change. A cocrystal of glenzocimab with an extracellular domain of monomeric GPVI was obtained and its structure determined to a resolution of 1.9 Å. The data revealed that (1) glenzocimab binds to the D2 domain of GPVI, GPVI dimerization was not observed in the crystal structure because glenzocimab prevented D2 homotypic interactions and the formation of dimers that have a high affinity for collagen and fibrin; and (2) the light variable domain of the GPVI-bound Fab causes steric hindrance that is predicted to prevent the collagen-related peptide (CRP)/collagen fibers from extending out of their binding site and preclude GPVI clustering and downstream signaling. Glenzocimab did not bind to a truncated GPVI missing loop residues 129 to 136, thus validating the epitope identified in the crystal structure. Overall, these findings demonstrate that the binding of glenzocimab to the D2 domain of GPVI induces steric hindrance and structural modifications that drive the inhibition of GPVI interactions with its major ligands.