bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long‐Term Safety and Efficacy of Subcutaneous Tanezumab Versus Nonsteroidal Antiinflammatory Drugs for Hip or Knee Osteoarthritis: A Randomized Trial
Authors: Hochberg Marc C. , Carrino John A. , Schnitzer Thomas J. , Guermazi Ali , Walsh David A. , White Alexander , Nakajo Satoru , Fountaine Robert J. , Hickman Anne , Pixton Glenn , Viktrup Lars , Brown Mark T. , West Christine R. , Verburg Kenneth M. 
Published: February 2021

ObjectiveTo assess the long‐term safety and 16‐week efficacy of subcutaneous tanezumab in patients with hip or knee osteoarthritis (OA).MethodsThis was a phase III randomized, double‐blind, active treatment–controlled (using nonsteroidal antiinflammatory drugs [NSAIDs] as the active treatment control) safety trial of tanezumab (56‐week treatment/24‐week posttreatment follow‐up) in adults who were receiving stable‐dose NSAID therapy at the time of screening and who had Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and physical function scores of ≥5; patient global assessment (PtGA) of OA of fair, poor, or very poor; history of inadequate pain relief with standard analgesics; and no history or radiographic evidence of prespecified bone/joint conditions beyond OA. Patients received oral naproxen, celecoxib, or diclofenac twice daily (NSAID group; n = 996) or tanezumab 2.5 mg (n = 1,002) or 5 mg (n = 998) subcutaneously every 8 weeks. Coprimary efficacy end points at week 16 were changes in WOMAC pain and physical function scores and changes in PtGA. The primary joint safety end point over 80 weeks comprised adjudicated rapidly progressive OA type 1 or 2, primary osteonecrosis, subchondral insufficiency fracture, or pathologic fracture. Mean values, least squares mean values, and least squares mean differences between groups (with 95% confidence intervals [95% CIs]) were calculated.ResultsOf 3,021 randomized patients, 2,996 received ≥1 treatment dose. Adverse events (AEs) were similar between patients treated with tanezumab 2.5 mg and those treated with NSAIDs, and were more prevalent in those treated with tanezumab 5 mg. Composite joint safety events were significantly more prevalent with tanezumab 2.5 mg and tanezumab 5 mg than with NSAIDs (observation time–adjusted rate/1,000 patient‐years 38.3 [95% CI 28.0, 52.5] and 71.5 [95% CI 56.7, 90.2], respectively, versus 14.8 [95% CI 8.9, 24.6]; P = 0.001 for tanezumab 2.5 mg versus NSAIDs; P < 0.001 for tanezumab 5 mg versus NSAIDs). Tanezumab 5 mg significantly improved pain and physical function but did not improve PtGA at week 16 when compared to NSAIDs; corresponding differences between the tanezumab 2.5 mg and NSAID groups were not statistically significant.ConclusionIn patients previously receiving a stable dose of NSAIDs, tanezumab administered subcutaneously resulted in more joint safety events than continued NSAIDs, with differences being dose dependent. Pain and physical function improved with both doses of tanezumab compared to NSAIDs, reaching statistical significance with tanezumab 5 mg at 16 weeks.
A stability analysis of the static Einstein‐Klein‐Gordon Boson Stars
Authors: Suarez Fontanella Duvier , de Oca Alenjandro Cabo Montes 
Published: February 2021

AbstractThe stability of the recently proposed static solutions for boson stars is analyzed. These solutions of Einstein‐Klein‐Gordon (EKG) equations are obtained by considering the interaction of a real scalar field with matter. We assume that the inclusion of the scalar field in addition to matter allows one to justify that stability implies that the total mass of the solution should grow when the initial condition for the density of matter at the origin is also increased. Employing numerical values for the static boson star based on a linear relation between the source and the energy density and between this and the pressure, we found the relation that linked the scalar field at the origin with the matter energy density at the same point. We also determine the behavior of the total mass with the matter energy density in the origin by obtaining through this and the weak energy condition two possible ranges for stable solutions of static boson stars.
Hybrid star properties from an extended linear sigma model
Authors: Takátsy János , Kovács Péter , Wolf György 
Published: February 2021

AbstractThe equation of state provided by effective models of strongly interacting matter should comply with the restrictions imposed by current astrophysical observations on compact stars. Using the equation of state given by the (axial‐)vector meson extended linear sigma model, we determine the mass–radius relation and study whether these restrictions are satisfied under the assumption that most of the star is filled with quark matter. We study the dependence of the mass–radius relation on the parameters of the model.
A test of the fermionic dark matter nature of the supermassive compact object at the center of our galaxy
Authors: Becerra‐Vergara E. A. , Rueda J. A. , Ruffini R. 
Published: February 2021

AbstractThe extensive and continuous monitoring of the closest stars to the Galactic center has been producing over decades a large amount of high‐quality data of their positions and velocities. The explanation of these data, especially the S2 star motion, reveals the presence of a compact source, Sagittarius A* (Sgr A*), whose mass must be about 4 × 106 M⊙. This result has been protagonist of the awarded Nobel Prize in Physics 2020 to Reinhard Genzel and Andrea Ghez “for the discovery of a supermassive compact object at the centre of our galaxy.” Traditionally, the nature of Sgr A* has been attributed to a supermassive black hole (SMBH), even though a proof of its existence is absent. Further, recent data on the motion of the G2 cloud show that its post‐peripassage velocity is lower than the expected one from a Keplerian orbit around the hypothesized SMBH. An attempt to overcome this difficulty has used a friction force, produced (arguably) by an accretion flow whose presence is also observationally unconfirmed. We advance an alternative scenario that identifies the nature of the supermassive compact object in a highly concentrated core of dark matter (DM) made of fermions, that is, inos, which we here refer to as darkinos. This DM concentration is predicted by the core‐halo profile obtained from the Ruffini‐Argüelles‐Rueda fermionic DM model, which also fits the Galactic‐halo rotation curves. We show that the sole DM core, for 56 keV darkinos, explains the orbits of S2 and G2. No drag force or other external agents are needed, that is, their motion is purely geodesic. A core made of these darkinos becomes unstable against gravitational collapse into a BH for a mass of ∼108M⊙; hence, they can provide the BH seeds from which grow the observed central SMBHs in active galaxies, for example, M87.
Thyroglobulin determination on silane–antibody functionalized interdigitated dielectrode surface to diagnose thyroid tumor
Authors: Wang Yujie , Sun Xia , Gopinath Subash C.B. , Saheed Mohamed Shuaib Mohamed , Wang Xiaofei 
Published: February 2021

AbstractThyroid cancer appears in endocrine glands and specific to thyroid glands has been reported widely. This work was targeted to identify and quantify thyroglobulin by using antithyroglobulin antibody complexed silane surface on interdigitated electrode (IDE) sensing surface. (3‐Aminopropyl)triethoxysilane linker was used to make silane‐coupling with antibody and attached on the hydroxylated IDE. This electroanalytical IDE revealed the dose‐dependent responses with thyroglobulin concentrations. By getting increments with the thyroglobulin concentrations, the current responses were enhanced concomitantly and the thyroglobulin detection limit was noted as 1 pM on the linear curve [y = 0.1311x + 0.5386; R² = 0.9707] with the sensitivity at lower picomolar range. Moreover, the control experiments with thyroid peroxidase and nonimmune antibody cannot yield any response of current, confirming the specific detection of thyroglobulin. This research set‐up is useful to determine and quantify the thyroglobulin and diagnose thyroid cancer.
Wärmemarktstudie für das Großherzogtum Luxemburg
Authors: Bechtel Steffen , Scholzen Frank 
Published: February 2021

AbstractIn 2020 hat Luxemburg seinen Klimaplan für den Zeitraum 2021 bis 2030 beschlossen, welcher ehrgeizige Ziele für den Wärmesektor enthält. Die Datenlage im Wärmesektor, vor allem bei der Schlüsseltechnologie Wärmepumpe, ist jedoch unzureichend, zum Nachteil aller beteiligten Akteure. Die Universität Luxemburg hat deshalb eine Wärmemarktstudie erstellt, die Verkaufszahlen nationaler Hersteller und Händler im Zeitraum von 2014 bis 2018 auswertet und auf diese Weise wesentliche Trends im Hinblick auf die Klimaziele aufzeigt. Die Auswertung zeigt signifikante Unterschiede zur bisherigen Datenlage bei Wärmepumpen, die sich aufgrund der Nichtinanspruchnahme der staatlichen Förderung ergeben. Insgesamt werden deutlich mehr Anlagen installiert als bisher angenommen Der Absatz fossiler Heizkessel ist konstant, wobei eine Verschiebung des Energieträgers von Öl zu Erdgas zu verzeichnen ist. Der allgemeine Trend bewegt sich in Richtung der gesteckten Ziele. Dennoch besteht signifikanter Handlungsbedarf, da zum Erreichen der nationalen Klimaziele u. a. ein jährliches Wachstum des Luxemburger Wärmepumpenmarktes von 16 % bis 2030 angenommen wurde.
Recent advances in the integrated biorefinery concept for the valorization of algal biomass through sustainable routes
Authors: Katiyar Richa , Banerjee Shivali , Arora Amit 
Published: February 2021

AbstractMicroalgae have garnered significant interest among researchers and industries as a potential source of valuable products that can find applications in the food, feed, biofuels, cosmetics, pharmaceuticals, and nutraceuticals industries. Microalgae can remediate various waste streams. This review discusses the current trends in the valorization of algal biomass and proposes integrated biorefinery approaches to produce high‐value products by sustainable routes. In such processes, the waste streams can be used as a source of nutrients for the production of microalgal biomass, rich in high‐quality lipids, digestible proteins and bioactive compounds. The integrated approaches presented in this study offer cost‐effective and environment‐friendly processing techniques while expanding the bioproducts portfolio in the food and therapeutics sector. The simultaneous or sequential extraction of valuable compounds from microalgae makes the biorefinery proposition appealing for waste minimization, revenue diversification, and complete feedstock utilization. The systematic exploration of microalgae on a large scale is required to evaluate its future as a favorable resource for biorefinery products. This would also necessitate detailed techno‐economic, environmental, and lifecycle assessment for the biorefinery processes. © 2021 Society of Chemical Industry and John Wiley & Sons, Ltd
M1a prostate cancer: Results of a Dutch multidisciplinary consensus meeting
Authors: Aluwini Shafak , Oprea‐Lager Daniela E. , de Barros Hilda , Mehra Niven , Stoevelaar Herman , Yakar Derya , van der Poel Henk ,   Dutch M1a Prostate Cancer Working Group
Published: February 2021

AbstractObjectivesTo determine the consensus of a Dutch multidisciplinary expert panel on the diagnostic evaluation and treatment of de novo and recurrent metastatic prostate cancer (PCa) limited to non‐regional lymph nodes (M1a) in daily clinical practice.Materials and methodsThe panel consisted of 37 Dutch specialists from disciplines involved in the management of M1a PCa (urology, medical and radiation oncology, radiology, and nuclear medicine). We used a modified Delphi method consisting of two voting rounds and a consensus meeting (video conference). Consensus (good agreement) was defined as the situation in which ≥ 75% of the panelists chose the same option.ResultsConsensus existed for 57% of the items. The panel agreed that prostate‐specific membrane antigen positron emission tomography/computed tomography (PSMA‐PET/CT) is the most appropriate standard imaging modality to identify de novo (100%) and recurrent (97%) M1a PCa. Androgen deprivation therapy (ADT) combined with radiotherapy to the prostate ± the M1a lesion(s) was most frequently considered an option for de novo M1a PCa. For M1a as recurrent disease, ADT alone, deferring treatment, or local radiotherapy to the M1a lesion(s) were judged to be the most important treatment options. However, no specific indications for treatment choice in relation to disease characteristics could be formulated.ConclusionsThe Dutch consensus panel preferred PSMA‐PET/CT as the standard diagnostic modality to detect M1a PCa. Although potential treatment options were identified, explicit recommendations could not be formulated. This might (partly) be explained by the absence of high‐level clinical evidence in this subset of patients. Further research is, therefore, strongly encouraged.
Exkursionen als Beitrag zur praxisorientierten akademischen Lehre – Wilhelm Kählers Besichtigungen der pommerschen Wirtschaft in der Weimarer Zeit
Authors: Grube Klemens 
Published: February 2021

AbstractIn the German Weimar Republic of the 1920s, the field of economic science found itself in a crisis environment beyond the limits of its understanding. Very few contributions from academia found their way into practice, and thus the limited interplay between the two was of little consequence. During this era, universities responded by introducing various new approaches to make the teaching of economics more relevant to practice. In many universities, this included the participation of practitioners as lecturers and examiners. In addition, Professor Wilhelm Kähler of the University of Greifswald organised field trips within the province of Pomerania so that students could see economics in practice and better grasp its real‐world peculiarities. In this paper, the historical records of these excursions, as recorded in a log, are analysed and insights gained from the numerous teaching visits to companies, welfare institutions, organisations and associations as well as to municipalities, housing developments and infrastructural establishments. The paper concludes with an examination of how practical relevance in university teaching subsequently shifted during the Nazi era.
Why do cancer cells break from host circadian rhythm? Insights from unicellular organisms
Authors: Alamoudi Aliaa A. 
Published: February 2021

AbstractIt is not clear why cancer cells choose to disrupt their circadian clock rhythms, and whether such disruption governs a selective fitness and a survival advantage. In this review, I focus on understanding the impacts of clock gene disruption on a simpler model, such as the unicellular cyanobacterium, in order to explain how cancer cells may alter the circadian rhythm to reprogram their metabolism based on their needs and status. It appears to be that the activation of the oxidative pentose phosphate pathway (OPPP) and production of NADPH, the preferred molecule for detoxification of reactive oxygen species, is a critical process for night survival in unicellular organisms. The circadian clock acts as a gatekeeper that controls how the organism will utilize its sugar, shifting sugar influx between glycolysis and OPPP. The circadian clock can thus act as a gatekeeper between an anabolic, proliferative mode and a homeostatic, survival mode.
Environmental sustainability engagement of firms: The roles of social capital, resources, and managerial entrepreneurial orientation of small and medium enterprises in Vietnam
Authors: Roxas Banjo 
Published: February 2021

AbstractHow firms in transition economies demonstrate their strategic engagement in sustainable environmental management given their limited resources and capabilities is less understood in the literature. This study explores how small and medium enterprises (SMEs) in Vietnam, an exemplar of a country in transition from a closed and socialist economy to an open and liberal market, draw on their external social capital to access critical resources that are leveraged by the entrepreneurial orientation or capabilities of the firms' top management towards engagement in business‐wide environmentally sustainable practices. Drawing on a database of more than 2000 firms from a large‐scale survey of firms in Vietnam, this study tests the relationships between two facets of social capital, environmental management resources and environmental sustainability engagement. This study further contends that managerial entrepreneurial orientation moderates by enhancing the strategic utilisation of resources to enable firms in Vietnam to engage in environmental sustainability. The results offer novel theoretical insights and timely managerial or practical implications as well as promising directions for future research on the resources, strategies and capabilities of firms in transition economies.
Risk–need–responsivity: Evaluating need‐to‐service matching with reach, effectiveness, adoption, implementation, maintenance
Authors: Drawbridge Dara C. , Truong Debbie , Nguyen Ngoc T. , Lorenti Vincent L. , Vincent Gina M. 
Published: February 2021

AbstractWith a sample of 125 adults under community supervision (71.20% male, 76.00% White, mean age = 33.17 years), this study evaluated need‐to‐service matching using an evaluation framework from implementation science. Need‐to‐service matching is a case management strategy intended to align service referrals in case plans with justice‐involved persons' criminogenic needs. The results indicated that need‐to‐service matching reached a high percentage of its target population at 81.70%. Within criminogenic need areas, good match frequencies ranged from 80.00% in family/marital problems to 98.29% in alcohol/drug problems. Clinical staff also met the adherence benchmark applied by the current study, which required a 75.00% match between individuals' criminogenic needs and the services they received. Justice‐involved persons had, on average, 90.46% of their criminogenic needs matched with at least one service referral. Over‐prescription of services (i.e., recommendation of services that were not needed) was high, with frequencies in need areas ranging from 60.98% in education/employment to 82.21% in antisocial patterns. Methods from implementation science are useful for structuring evaluations of need‐to‐service matching, understanding implementation success and failure, and generating recommendations for improving implementation practice. The field would benefit greatly from benchmarks for need‐to‐service matching evaluation elements.
Safety, tolerability, and pharmacokinetics of BAT8001 in patients with HER2‐positive breast cancer: An open‐label, dose‐escalation, phase I study
Authors: Hong Ruoxi , Xia Wen , Wang Liye , Lee Kaping , Lu Qianyi , Jiang Kuikui , Li Shengfeng , Yu Jinquan , Wei Jin , Tang Weijia , Zhou Danyang , An Xin , Huang Jiajia , Xue Cong , Bi Xiwen , Shi Yanxia , Yuan Zhongyu , Xu Fei , Wang Shusen 
Published: February 2021

AbstractBackgroundThe introductions of anti‐ human epidermal growth factor receptor‐2 (HER2) agents have significantly improved the treatment outcome of patients with HER2‐positive breast cancer. BAT8001 is a novel antibody‐drug conjugate targeting human epidermal growth factor receptor‐2 (HER2)‐expressing cells composed of a trastuzumab biosimilar linked to the drug‐linker Batansine. This dose‐escalation, phase I study was designed to assess the safety, tolerability, pharmacokinetics, and preliminary anti‐tumor activity of BAT8001 in patients with HER2‐positive locally advanced or metastatic breast cancer.MethodsThis trial was conducted in subjects with histologically confirmed HER2‐positive breast cancer (having evaluable lesions and an Eastern Cooperative Oncology Group performance status of 0 or 1) using a 3 + 3 design of escalating BAT8001 doses. Patients received BAT8001 intravenously in a 21‐day cycle, with dose escalation in 5 cohorts: 1.2, 2.4, 3.6, 4.8, and 6.0 mg/kg. The primary objective was to evaluate the safety and tolerability of BAT8001. Preliminary activity of BAT8001 was also assessed as a secondary objective.ResultsBetween March 2017 to May 2018, 29 HER2‐positive breast cancer patients were enrolled. The observed dose‐limiting toxicities were grade 4 thrombocytopenia and grade 3 elevated transaminase. The maximum tolerated dose was determined to be 3.6 mg/kg. Grade 3 or greater adverse events (AEs) occurred in 14 (48.3%) of 29 patients, including thrombocytopenia in 12 (41.4%) patients, aspartate aminotransferase increased in 4 (13.8%) patients, γ‐glutamyl transferase increased in 2 (6.9%) patients, alanine aminotransferase increased in 2 (6.9%) patients, diarrhea in 2 (6.9%) patients. Objective response was observed in 12 (41.4%; 95% confidence interval [CI] = 23.5%‐61.1%) and disease control (including patients achieving objective response and stable disease) was observed in 24 (82.8%; 95% CI = 64.2%‐94.2%) patients.ConclusionsBAT8001 demonstrated favorable safety profiles, with promising anti‐tumor activity in patients with HER2‐positive locally advanced or metastatic breast cancer. BAT8001 has the potential to provide a new therapeutic option in patients with metastatic HER2‐positive breast cancer.
Tuning the Transglycosylation Reaction of a GH11 Xylanase by a Delicate Enhancement of its Thumb Flexibility
Authors: Marneth Kim , van den Elst Hans , Cramer‐Blok Anneloes , Codee Jeroen , Overkleeft Hermen S. , Aerts Johannes M. F. G. , Ubbink Marcellus , Ben Bdira Fredj 
Published: February 2021

AbstractGlycoside hydrolases (GHs) are attractive tools for multiple biotechnological applications. In conjunction with their hydrolytic function, GHs can perform transglycosylation under specific conditions. In nature, oligosaccharide synthesis is performed by glycosyltransferases (GTs); however, the industrial use of GTs is limited by their instability in solution. A key difference between GTs and GHs is the flexibility of their binding site architecture. We have used the xylanase from Bacillus circulans (BCX) to study the interplay between active‐site flexibility and transglycosylation. Residues of the BCX “thumb” were substituted to increase the flexibility of the enzyme binding site. Replacement of the highly conserved residue P116 with glycine shifted the balance of the BCX enzymatic reaction toward transglycosylation. The effects of this point mutation on the structure and dynamics of BCX were investigated by NMR spectroscopy. The P116G mutation induces subtle changes in the configuration of the thumb and enhances the millisecond dynamics of the active site. Based on our findings, we propose the remodelling of the GH enzymes glycon site flexibility as a strategy to improve the transglycosylation efficiency of these biotechnologically important catalysts.