bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interleukin‐1β–Activated Microvascular Endothelial Cells Promote DC‐SIGN–Positive Alternatively Activated Macrophages as a Mechanism of Skin Fibrosis in Systemic Sclerosis
Authors: Laurent Paôline , Lapoirie Joelle , Leleu Damien , Levionnois Emeline , Grenier Cyrielle , Jurado‐Mestre Blanca , Lazaro Estibaliz , Duffau Pierre , Richez Christophe , Seneschal Julien , Pellegrin Jean‐Luc , Constans Joel , Schaeverbeke Thierry , Douchet Isabelle , Duluc Dorothée , Pradeu Thomas , Chizzolini Carlo , Blanco Patrick , Truchetet Marie‐Elise , Contin‐Bordes Cécile ,   Fédération Hospitalo‐Universitaire ACRONIM and the Centre National de Référence des Maladies Auto‐Immunes Systémiques Rares de l'Est et du Sud‐Ouest (RESO)
Published: December 2021

ObjectiveTo characterize the role of interleukin‐1β (IL‐1β) and microvascular endothelial cells (MVECs) in the generation of alternatively activated macrophages in the skin, and to explore their role in the development of skin fibrosis in patients with systemic sclerosis (SSc; scleroderma).MethodsConditioned medium prepared with MVECs purified from the skin of healthy donors and the skin of SSc patients was used to generate monocyte‐derived macrophages. Flow cytometry, multiplex protein assessment, real‐time quantitative polymerase chain reaction, and tissue immunofluorescence were used to characterize MVEC‐induced polarization of alternatively activated macrophages. Coculture experiments were conducted to assess the role of MVEC‐induced alternatively activated macrophages in fibroblast activation. Alternatively activated macrophages were characterized in the skin of healthy donors and SSc patients using multiparametric immunofluorescence and multiplex immunostaining for gene expression. Based on our in vitro data, we defined a supervised macrophage gene signature score to assess correlation between the macrophage score and clinical features in patients with SSc, using the Spearman's test.ResultsIL‐1β–activated MVECs from SSc patients induced monocytes to differentiate into DC‐SIGN+ alternatively activated macrophages producing high levels of CCL18, CCL2, and CXCL8 but low levels of IL‐10. DC‐SIGN+ alternatively activated macrophages showed significant enhancing effects in promoting the production of proinflammatory fibroblasts and were found to be enriched in perivascular regions of the skin of SSc patients who had a high fibrosis severity score. A novel skin transcriptomic macrophage signature, defined from our in vitro findings, correlated with the extent of skin fibrosis (Spearman's r = 0.6, P = 0.0018) and was associated with early disease manifestations and lung involvement in patients with SSc.ConclusionOur findings shed new light on the vicious circle implicating unabated IL‐1β secretion, MVEC activation, and the generation of DC‐SIGN+ alternatively activated macrophages in the development of skin fibrosis in patients with SSc.
Impact of age on treatment response in men with prostate cancer treated with radiotherapy
Authors: Bryant Alex K. , Nelson Tyler J. , McKay Rana R. , Kader A. Karim , Parsons J. Kellogg , Einck John P. , Kane Christopher J. , Sandhu Ajay P. , Mundt Arno J. , Murphy James D. , Rose Brent S. 
Published: December 2021

AbstractObjectiveTo analyse the effect of age at diagnosis on clinical outcomes of localized prostate cancer (PCa) treated with radiation therapy.Subjects and methodsWe identified 12 784 patients with intermediate‐ or high‐risk localized PCa treated with radiation therapy (RT) and neoadjuvant androgen deprivation therapy (ADT) between 2000 and 2015 from nationwide Veterans Affairs data. Patients were grouped into three age categories (≤59, 60–69, and ≥70 years old). Outcomes included immediate PSA response (3‐month post‐RT PSA and 2‐year PSA nadir, grouped into <0.10 ng/ml, 0.10–0.49 ng/ml, and ≥0.50 ng/ml), biochemical recurrence, and PCa‐specific mortality. Multivariable regression models included ordinal logistic regression for short‐term PSA outcomes, Cox regression for biochemical recurrence, and Fine‐Gray competing risks regression for PCa‐specific mortality.ResultsA total of 2136 patients (17%) were ≤59 years old at diagnosis, 6107 (48%) were 60–69 years old, and 4541 (36%) were ≥70 years old. Median follow‐up was 6.3 years. Younger age was associated with greater odds of higher 3‐month PSA group (≤59 vs. ≥70: adjusted odds ratio [aOR] 1.90, 95% CI 1.64–2.20; p < 0.001) and higher 2‐year PSA nadir group (≤59 vs. ≥70: aOR 1.89, 95% CI 1.62–2.19, p < 0.001). Younger age was associated with greater risk of biochemical recurrence (≤59 vs. ≥70: adjusted hazard ratio 1.45, 95% CI 1.26–1.67, p < 0.001) but not PCa‐specific mortality (p = 0.16).ConclusionIn a large nationwide sample of US veterans treated with ADT and RT for localized PCa, younger age was associated with inferior short‐term PSA response and higher risk of biochemical recurrence.
Preliminary findings on the effects of medication advocacy and daily behavior ratings on prescriber behavior
Authors: Coon Jodi C. , Rapp John T. , Bush Helena , Ramey Erica S. 
Published: December 2021

AbstractOver a 1‐year period, we trained caregivers to employ a color‐coded daily behavior rating system whereby green denoted a high level of appropriate behavior, yellow denoted a mix of some appropriate behavior and mild problem behavior, and red denoted a high level of problem behavior. We then used these ratings to generate graphs that caregivers brought to their child's prescriber appointments. Preliminary data comparing unconditional and conditional probabilities from 25 prescriber visits with 12 participants indicate prescribers were most likely (a) to decrease psychotropic medication following green ratings, (b) increase psychotropic medication following red ratings, and (c) make no changes following yellow ratings. Across participants, prescribers' decisions matched the color code for 76% of trials. These preliminary findings support continued inclusion of the medication‐advocacy training component to facilitate deprescribing of psychotropic medication within our state‐funded project.
Nanoengineered biomimetic hydrogels: A major advancement to fabricate 3D‐printed constructs for regenerative medicine
Authors: Cernencu Alexandra I. , Dinu Andreea I. , Stancu Izabela C. , Lungu Adriana , Iovu Horia 
Published: December 2021

AbstractNanostructured compounds already validated as performant reinforcements for biomedical applications together with different fabrication strategies have been often used to channel the biophysical and biochemical features of hydrogel networks. Ergo, a wide array of nanostructured compounds has been employed as additive materials integrated with hydrophilic networks based on naturally‐derived polymers to produce promising scaffolding materials for specific fields of regenerative medicine. To date, nanoengineered hydrogels are extensively explored in (bio)printing formulations, representing the most advanced designs of hydrogel (bio)inks able to fabricate structures with improved mechanical properties and high print fidelity along with a cell‐interactive environment. The development of printing inks comprising organic–inorganic hybrid nanocomposites is in full ascent as the impact of a small amount of nanoscale additive does not translate only in improved physicochemical and biomechanical properties of bioink. The biopolymeric nanocomposites may even exhibit additional particular properties engendered by nano‐scale reinforcement such as electrical conductivity, magnetic responsiveness, antibacterial or antioxidation properties. The present review focus on hydrogels nanoengineered for 3D printing of biomimetic constructs, with particular emphasis on the impact of the spatial distribution of reinforcing agents (0D, 1D, 2D). Here, a systematic analysis of the naturally‐derived nanostructured inks is presented highlighting the relationship between relevant length scales and size effects that influence the final properties of the hydrogels designed for regenerative medicine.
Chiral 2‐phenyl‐3‐hydroxypropyl esters as PKC‐alpha modulators: HPLC enantioseparation, NMR absolute configuration assignment, and molecular docking studies
Authors: Linciano Pasquale , Nasti Rita , Listro Roberta , Amadio Marialaura , Pascale Alessia , Potenza Donatella , Vasile Francesca , Minneci Marco , Ann Jihyae , Lee Jeewoo , Zhou Xiaoling , Mitchell Gary A. , Blumberg Peter M. , Rossi Daniela , Collina Simona 
Published: December 2021

AbstractProtein kinase C (PKC) isoforms play a pivotal role in the regulation of numerous cellular functions, making them extensively studied and highly attractive drug targets. In our previous work, we identified in racemate 1–2, based on the 2‐benzyl‐3‐hydroxypropyl ester scaffold, two new potent and promising PKCα and PKCδ ligands, targeting the C1 domain of these two kinases. Herein, we report the resolution of the racemates by enantioselective semi‐preparative HPLC. The attribution of the absolute configuration (AC) of homochirals 1 was performed by NMR, via methoxy‐α‐trifluoromethyl‐α‐phenylacetic acid derivatization (MTPA or Mosher's acid). Moreover, the match between the experimental and predicted electronic circular dichroism (ECD) spectra confirmed the assigned AC. These results proved that Mosher's esters can be properly exploited for the determination of the AC also for chiral primary alcohols. Lastly, homochiral 1 and 2 were assessed for binding affinity and functional activity against PKCα. No significative differences in the Ki of the enantiopure compounds was observed, thus suggesting that chirality does not seem to play a significant role in targeting PKC C1 domain. These results are in accordance with the molecular docking studies performed using a new homology model for the human PKCαC1B domain.
Local to continental‐scale variation in fitness and heritability in common bean
Authors: MacQueen Alice H. , Khoury Colin K. , Miklas Phil , McClean Phillip E. , Osorno Juan M. , Runck Bryan C. , White Jeffrey W. , Kantar Michael B. , Ewing Patrick M. 
Published: December 2021

AbstractSelection during plant domestication and improvement often decreases genetic variation, including variation that confers adaptation to local conditions. We report spatial and temporal variation in fitness (seed yield), local adaptation, and segregating genetic variation within three races of common bean (Phaseolus vulgaris L.) with differing domestication histories and genetic diversities. Three‐hundred and twenty‐seven common bean genotypes had seed yield measured at subsets of 70 sites across North America between 1981 and 2015, as part of the Cooperative Dry Bean Nursery (CDBN). We estimated local adaptation using the metric home field advantage (HFA) and segregating genetic variation using heritability. The Durango and Mesoamerican races (Middle American genepool) had higher‐than‐expected (p = .002) HFA, equal to up to 34 yr of average yield gains. Surprisingly, Nueva Granada (Andean genepool) and Durango yields became more heritable across the study period (p < .001), while Mesoamerican heritability decreased (p < .001). Both metrics detected diversity loss corresponding to the timings of major historical gene introgressions. Local adaptation remains an agronomically important phenomenon within some common bean races. Common bean adaptation to new conditions will be most rapid at locations with large local adaptation benefits and high heritability.
Liquid‐ and Solid‐based Separations Employing Ionic Liquids for the Recovery of Platinum Group Metals Typically Encountered in Catalytic Converters: A Review
Authors: Lanaridi Olga , Schnürch Michael , Limbeck Andreas , Schröder Katharina 
Published: December 2021

AbstractThe wide application range and ascending demand for platinum group metals combined with the progressive depletion of their natural resources renders their efficient recycling a very important and pressing matter. Primarily environmental considerations associated with state‐of‐the‐art recovery processes have shifted the focus of the scientific community toward the investigation of alternative recycling approaches. Within this context, ionic liquids have gained considerable attention in the last two decades chiefly sparked by properties such as tunabilty, low‐volatility, and relatively easy recyclability. In this review an understanding of the state‐of‐the‐art processes, including their drawbacks and limitations, is provided. The core of the discussion is focused on platinum group metal recovery with ionic liquid‐based systems. A brief insight in some environmental considerations related to ionic liquids is also provided while some discussion on research gaps, common misconceptions related to ionic liquids and outlook on unresolved issues could not be absent from this review.
The role of the protein tyrosine phosphatase SHP2 in ossification
Authors: Zhang Yuan , Lu Wei , Zhao Qing , Chen Jindong , Wang Tiancong , Ji Jun 
Published: December 2021

AbstractSHP2, encoded by the PTPN11 gene, participates in multiple cell functions including cell proliferation, movement, and differentiation. PTPN11 loss‐of‐function and gain‐of‐function mutations are both associated with diseases, such as Noonan syndrome, whose manifestations include bone defects, suggesting a crucial role for SHP2 in the skeleton. However, the exact mechanisms by which SHP2 regulates bone development remain unclear. This review focuses on the current understanding of the regulation of SHP2 and highlights the vital roles of SHP2 in skeletal development, especially its roles in ossification. Overall, a better understanding of the functions of SHP2 in ossification will provide a new avenue to treat‐related skeletal diseases.
B‐cell modulation with anti‐CD79b antibodies ameliorates experimental autoimmune encephalitis in mice
Authors: Renner Kerstin , Neumayer Sophia , Talke Yvonne , Buchtler Simone , Schmidbauer Kathrin , Nimmerjahn Falk , Lux Anja , Winter Frederike , Salewski Jan‐Nicklas , Mack Matthias 
Published: December 2021

AbstractB cells play a major role in the pathogenesis of many autoimmune diseases like MS, rheumatoid arthritis, or systemic lupus erythematosus. Depletion of B cells with anti‐CD20 antibodies is an established therapy for MS. However, total B‐cell depletion will also affect regulatory B cells that are known to suppress autoimmune responses. In our studies, we describe an alternative approach based on targeting CD79b that induces only partial B‐cell depletion and achieves therapeutic effects by B‐cell modulation. Prophylactic and therapeutic treatment with an antibody against CD79b and also a deglycosylated variant of this antibody, lacking effector function like antibody‐dependent cellular cytotoxicity or complement activation, significantly reduced the development and progression of EAE in mice. Our data show that modulation of B cells via CD79b is equally effective as almost complete B‐cell depletion with anti‐CD20 antibodies and may constitute an alternative approach to treat MS.
Gold‐Catalyzed Regioselective Oxyfluorination/Oxydifluorination vs. Diketonization of Phthalimido‐Protected Propargylamines with Selectfluor
Authors: Marsicano Vincenzo , Arcadi Antonio , Michelet Véronique 
Published: December 2021

AbstractAlkyl‐ and aryl‐substituted N‐propargyl phthalimides were used as valuable building blocks for the selective formation of the corresponding α‐fluoro, β‐phthalimido ketones, α,α‐difluoro, β‐phthalimido ketones or β‐phthalimido α‐diketones by means of gold‐catalyzed oxyfluorination/oxydifluorination or dioxygenation reactions. The key factors addressing the product selectivity control were determined. The simultaneous assembly of the quinoxaline nucleus and the removal of the phthalimido‐protecting group were tested. Reaction mechanisms of the different reaction pathways are assumed.
Geometry change impact on thermal efficiency with large volumetric sensible heat storage tank
Authors: Kocijel Lino 
Published: December 2021

AbstractBy installation in district heating and cooling systems, large volumetric sensible heat storage tank is a technology that can reduce CO2 emissions into the atmosphere, ensure the integration of renewable energy sources into district heating and cooling systems, overcome the mismatch between production and demand and increase reliability and efficiency of entire systems. Such tanks operate on the principle of temperature stratification. In this paper, the processes of charging and discharging the heat storage tank used in district heating systems depending on the geometric and process parameters are analyzed and the thermal efficiency of each of these processes is calculated. The thermal efficiency of the tank charging process is calculated based on the distribution of the warmer water temperature in the tank after the complete tank charging process and varies between 53.85% and 96.75%. The thermal efficiency of the tank discharging process was calculated based on the warmer water outlet temperature and varies between 87.83% and 96.00%. Validation of mathematical model was achieved by comparing the data obtained by measuring the water temperature in the heat storage tank installed in the city thermal power plant‐heat plant and the results of numerical calculation.
Allometric conservatism in the evolution of bird beaks
Authors: Rombaut Louie M. K. , Capp Elliot J. R. , Cooney Christopher R. , Hughes Emma C. , Varley Zoë K. , Thomas Gavin H. 
Published: December 2021

AbstractEvolution can involve periods of rapid divergent adaptation and expansion in the range of diversity, but evolution can also be relatively conservative over certain timescales due to functional, genetic-developmental, and ecological constraints. One way in which evolution may be conservative is in terms of allometry, the scaling relationship between the traits of organisms and body size. Here, we investigate patterns of allometric conservatism in the evolution of bird beaks with beak size and body size data for a representative sample of over 5000 extant bird species within a phylogenetic framework. We identify clades in which the allometric relationship between beak size and body size has remained relatively conserved across species over millions to tens of millions of years. We find that allometric conservatism is nonetheless punctuated by occasional shifts in the slopes and intercepts of allometric relationships. A steady accumulation of such shifts through time has given rise to the tremendous diversity of beak size relative to body size across birds today. Our findings are consistent with the Simpsonian vision of macroevolution, with evolutionary conservatism being the rule but with occasional shifts to new adaptive zones.
Ultrasound‐controlled drug release and drug activation for cancer therapy
Authors: Tu Li , Liao Zhihuan , Luo Zheng , Wu Yun‐Long , Herrmann Andreas , Huo Shuaidong 
Published: December 2021

AbstractTraditional chemotherapy suffers from severe toxicity and side effects that limit its maximum application in cancer therapy. To overcome this challenge, an ideal treatment strategy would be to selectively control the release or regulate the activity of drugs to minimize the undesirable toxicity. Recently, ultrasound (US)‐responsive drug delivery systems (DDSs) have attracted significant attention due to the non‐invasiveness, high tissue penetration depth, and spatiotemporal controllability of US. Moreover, the US‐induced mechanical force has been proven to be a robust method to site‐selectively rearrange or cleave bonds in mechanochemistry. This review describes the US‐activated DDSs from the fundamental basics and aims to present a comprehensive summary of the current understanding of US‐responsive DDSs for controlled drug release and drug activation. First, we summarize the typical mechanisms for US‐responsive drug release and drug activation. Second, the main factors affecting the ultrasonic responsiveness of drug carriers are outlined. Furthermore, representative examples of US‐controlled drug release and drug activation are discussed, emphasizing their novelty and design principles. Finally, the challenges and an outlook on this promising therapeutic strategy are discussed.
Advanced bioactive nanomaterials for biomedical applications
Authors: Zhao Yu , Zhang Zhanzhan , Pan Zheng , Liu Yang 
Published: December 2021

AbstractBioactive materials are a kind of materials with unique bioactivities, which can change the cellular behaviors and elicit biological responses from living tissues. Bioactive materials came into the spotlight in the late 1960s when the researchers found that the materials such as bioglass could react with surrounding bone tissue for bone regeneration. In the following decades, advances in nanotechnology brought the new development opportunities to bioactive nanomaterials. Bioactive nanomaterials are not a simple miniaturization of macroscopic materials. They exhibit unique bioactivities due to their nanoscale size effect, high specific surface area, and precise nanostructure, which can significantly influence the interactions with biological systems. Nowadays, bioactive nanomaterials have represented an important and exciting area of research. Current and future applications ensure that bioactive nanomaterials have a high academic and clinical importance. This review summaries the recent advances in the field of bioactive nanomaterials, and evaluate the influence factors of bioactivities. Then, a range of bioactive nanomaterials and their potential biomedical applications are discussed. Furthermore, the limitations, challenges, and future opportunities of bioactive nanomaterials are also discussed.
Exploring new battery knowledge by advanced characterizing technologies
Authors: Wang Liguang , Liu Tiefeng , Wu Tianpin , Lu Jun 
Published: December 2021

AbstractExploration of science and technologies represents human's thirst for new knowledge and new life. Presently, we are in a stage of transferring the use of fossil fuels to renewable energy, which urgently calls for new energy materials and techniques beyond the boundary of human knowledge. On the way of scrutinizing these materials and surmounting the bottleneck of their performances, characterizing technologies are of critical importance in enabling the revealing of materials regarding their structural and chemical information, eventually establishing the correlations between microstructures and properties at the multiscale levels. Regrettably, traditional characterizations are hard to simultaneously probe electrochemistry with these chemical and physical structural evolutions, especially under operando conditions, or offer high‐resolution images of materials sensitive to electron‐beam irradiation. To this end, various advanced characterizing and diagnosing technologies recently developed, such as transmission X‐ray microscopy and cryo‐transmission electron microscopy, have demonstrated their benefits in understanding the energy storage behaviors of high‐performance energy materials (such as layered transition oxide cathode and Li metal anode). Benefited from new knowledge, the progress of high‐capacity electroactive materials is significantly accelerated. Here, we timely review the breakthroughs in emerging techniques and discuss how they guide the design of future battery materials to achieve the ultimate carbon neutrality.