bluuebunny/crossref_metadata_2025_split huggingface dataset:
Generation of a potent anti-PD-L1-CD47 bispecific antibody with a strong therapeutic and safety profile for cancer immunotherapy
Authors: Tang Irene , Schwimmer Lauren , Gu Shenda , Wei Prior Wei , Tran Hieu Van , Chan Allan , McClain Anna , Fraser Christopher C. , Sun Chunyan , Si Meimei , Wang Guijiang , Zhao Yunxia , Zhang Ning , Fu Jiayu , Liu Mengxin , Cao Chuanzeng , Chen Shihao 
Published: May 2023

Cell surface molecules PD-L1 and CD47 are potent inhibitors of adaptive and innate anti-cancer immunity. We sought to generate a safe, therapeutic, bispecific antibody specifically targeting, and blocking both PD-L1 and CD47 inhibitory activity. Novel anti-PDL-1 and anti-CD47 antibodies with favorable inhibitory activity, were humanized and constructed into a unique bi-specific antibody intended for clinical use. Previous pre-clinical and clinical studies using anti-CD47 antibodies indicated anemia and thrombocytopenia as potential risks. QL401 is a PD-L1 x CD47 bispecific antibody engineered to reduce effect on red blood cells while retaining potent phagocytic activation of macrophages in vitro and delayed tumor growth in vivo. QL401 comprises three functional components: a PD-L1 binding Fab arm, a CD47 binding scFv arm, and a human IgG4 backbone. The PD-L1 binding arm provides both tumor targeting and blocking of PD-1 for reactivating T cells. The CD47 arm blocks the binding of SIRPα, while the IgG4 Fc retains Fc gamma receptor binding to provide a phagocytic signal. In preclinical efficacy studies, QL401 potently blocked SIRPα to promote phagocytosis of tumor cells with sub-nanomolar potency. In vivo efficacy studies in mouse xenograft tumor models showed QL401 to be comparable or superior to PD-L1 or CD47 monoclonal antibodies alone or in combination. In vitro safety evaluation of QL401 showed significantly reduced binding and phagocytosis of red blood cells, in contrast to CD47 monoclonal antibodies. In addition, QL401 did not induce hemagglutination. In non-human primates, QL401 was well tolerated up to 100 mg/kg without reduction of red blood cells or platelets below the normal range. QL401 is presently in a human phase I safety study.
Prehistoric Hunter-Gatherers in the Philippines—Subsistence strategies, adaptation, and behaviour in maritime environments
Authors: Pawlik Alfred F. , Fuentes Riczar B. 
Published: May 2023

Archaeological research in the Philippines has produced a timeline of currently over 700,000 years of human occupation. However, while an initial presence of early hominins has been securely established through several radiometric dates between 700 ka to 1 ma from Luzon Island, there is currently little evidence for the presence of hominins after those episodes until c. 67 to 50 ka for Luzon or any of the other Philippine islands. At approximately 40 ka, anatomically modern humans had arrived in the Philippines. Early sites with fossil and/or artifactual evidence are Tabon Cave in Palawan and Bubog 1 in Occidental Mindoro, the latter situated in the Wallacean part of the archipelago. This paper presents an overview of the archaeological research on the prehistory of the Philippines from the Pleistocene until the Late Holocene and the arrival of the first farmers, presumably from Austronesian language groups approximately 4,000 years ago. Research on this topic has significantly intensified over the past 20 years and is providing a variety of evidence for the successful adaptation of those first islanders to maritime environments, the diversity of technological and subsistence strategies, and increasingly complex interrelationships across Island Southeast Asia.
Assessing the impacts of future urban expansion on multiple ecosystem services in the transnational area of Changbai Mountain
Authors: Chen Ruikang , Zhang Da , Nan Ying , Feng Hengdong , Geng Xin 
Published: May 2023

Introduction: An assessment of the potential impacts of future urban expansion on multiple ecosystem services (ESs) represents an essential contribution to the sustainable development of the transnational area of Changbai Mountain (TACM). However, the potential ES losses attributed to future urban expansion have been assessed in few studies.Methods: In this study, we evaluated the potential ES losses attributable to urban expansion in the TACM over the period from 2015 to 2050. To achieve this objective, we initially quantified multiple ESs (namely, food production (FP), carbon storage (CS), water retention (WR), and air purification (AP)) based on 1992 data, and subsequently simulated urban expansion from 2015 to 2050 by coupling Shared Socioeconomic Pathways scenarios (SSPs) with the zoned Land Use Scenario Dynamics-urban model. Finally, the potential impacts of future urban expansion on ESs were evaluated on multiple scales.Results: The results indicated that during the period from 2015 to 2050, the extent of urban land will grow by between 157.59 and 517.77 km2, resulting in FP, CS, WR, and AP losses of 193.76–684.39 thousand tons, 1.47–5.24 million tons, 8.74–30.00 million tons, and 0.34–1.18 thousand tons, respectively.Discussion: The subregion falling within the Democratic People’s Republic of Korea (DPRK) will experience the most severe future losses of ESs, with losses of FP, CS, WR, and AP being 1.06–3.77-fold, 1.15–3.46-fold, 1.10–3.54-fold, and 1.08–3.21-fold higher, respectively than those that occurred in this subregion the period of 1992–2015. Specifically, the encroachment of new urban land onto cropland and woodland will be the main contributing factor in these future declines in ESs. Furthermore, the reductions in ESs attributable to urban expansion in this subregion will have serious effects on human wellbeing. By 2050, the loss of FP will affect approximately 9.58%–30.00% of the population. Moreover, among the residents of this subregion, the loss of AP will contribute to the need for additional expenditures of 6.63–19.81 million euros on air purification measures. On the basis of these findings, we suggest that effective policies and regulations should be implemented to promote the sustainable development of the TACM.
Flexural-slip folding in buckling phases of orogenic belts: Insight into the tectonic evolution of fault splays in the East Iran orogen
Authors: Rashidi Ahmad , Shafieibafti Shahram , Nemati Majid , Ezati Maryam , Gholami Ebrahim , Mousavi Seyed Morteza , Derakhshani Reza 
Published: May 2023

Introduction: The East Iran orogen has experienced multiple buckling phases resulting in the formation of strike-slip fault splays. The geometric and kinematic characteristics of these splays are influenced by folding mechanisms. This study focuses on investigating the structural characteristics and tectonic evolution model of the Khousf splay, located in the northern terminus of the Nehbandan right-lateral strike-slip fault system.Methods: Field visits and geometrical properties from map views were used to analyze the structural features of the Khousf splay. The splay was found to consist of a multi-plunging anticline and syncline, referred to as the Khousf anticline and Khousf syncline, respectively. Flexural slip was identified as a significant mechanism for the formation of these structures. Structural evidence, including parasitic folds, active folds, and strike-slip duplexes, suggested that flexural slip occurred on discrete movement horizons among the rock units.Results: Analysis of the parasitic folds in the cores and limbs of the Khousf anticline and syncline revealed M, W, Z, and S shapes, with complex slicken-line patterns observed on faults parallel to the beds at the limbs. The analysis results indicated strain partitioning and inclined left- and right-lateral transpressional zones. Shortening estimates obtained from profiles in the Shekarab inclined transpressional zone were approximately 33%, 65%, and 68% for NE-SW, N-S, and NW-SE profiles, respectively. In the Arc area, which is the core of the anticline, shortening estimates from NE-SW and N-S profiles ranged from 14% to 10%. Structural analysis of the folds in this area revealed broad, close, semi-elliptical, and parabolic shapes, suggesting that secondary folds with NW-SE axis directions have been superimposed on the first-generation folds with E-W axis directions in the Khousf refolded splay.Discussion: The findings of this study highlight the structural characteristics and tectonic evolution model of the Khousf splay in the northern terminus of the Nehbandan right-lateral strike-slip fault system. The results suggest that flexural slip played a crucial role in the formation of the multi-plunging anticline and syncline in the Khousf splay. The presence of parasitic folds and complex slicken-line patterns on faults indicate the complexity of deformation processes. The observed strain partitioning and inclined transpressional zones suggest a complex tectonic history in the study area. The superimposition of secondary folds with different axis directions on first-generation folds adds further complexity to the structural evolution of the Khousf refolded splay. Overall, this study provides new insights into the structural characteristics and tectonic evolution of the Khousf splay in the East Iran orogen.
Basic characteristics and environmental impact of iron ore tailings
Authors: Wang Changlong , Jing Jianlin , Qi Yang , Zhou Yongxiang , Zhang Kaifan , Zheng Yongchao , Zhai Yuxin , Liu Feng 
Published: May 2023

Introduction: In our study, various test methods were adopted to explore the mineralogical characteristics, grindability, particle morphology, particle size distribution, and environmental leaching toxicity of iron ore tailings (lOTs).Methods: The methods include petrographic analysis, X-ray diffraction (XRD), scanning electronic microscopy (SEM), synchronous thermal analyzer (DSC-TGA), electron probe X-ray microanalyser (EPMA), and synthetic precipitation leaching Procedure (SPLP).Results: The results show that the used IOTs contained 14.54% iron which was mainly stored in magnetite and pyrite. The content of iron silicate accounted for 11.82% of the total iron content. Most of it existed in silicate minerals, including grunerite and hornblende. A small amount of iron was contained in biotite, chlorite and augite. Besides, the grindability of lOTs was much better than that of granulated blast furnace slag (GBFS). After grinding for 140 min, the mass fraction of lOTs particles with the particle size less than 5 um was 44.19%. These particles could be used to fill in the voids in the cement-powder-packed structure. lOTs also contained a large number of submicron and nanoscale particles.Discussion: With great strength and environmental friendliness, the composite cementitious material (CCM) prepared from lOTs can be well applied to the building material field and environmental remediation.
The clinical and genetic features in patients coexisting primary breast and thyroid cancers
Authors: Fu Jingyao , He Miao , Wu Qiong , Zhang Xiangkai , Qi Xin , Shen Keyu , Wang Xiaochun , Zhang Guang 
Published: May 2023

BackgroundWe attempted to examine the clinical characteristics in patients with breast cancer (BC) and thyroid cancer (TC); explore the potential mechanisms of tumorigenesis and progression.MethodsUsing the Surveillance, Epidemiology, and End Result Program-9 (SEER-9) database, a retrospective study (1975-2017) was conducted on patients with BC and TC. We identified the common differentially expressed genes involved in BC and TC using the Gene Expression Omnibus database (GEO). Immunohistochemical staining (IHC) was performed to verify the expression of the hit gene in patients with co-occurrence of BC and TC. Using The Cancer Genome Atlas (TCGA) database, the relationship between gene expression and clinicopathological characters was determined. Gene set enrichment analysis (GSEA) was used to identify the pathways enriched in BC and TC.ResultsBC patients had a higher predisposition to develop TC (standardized incidence ratio, SIR: 1.29) and vice-versa (SIR: 1.12). Most of these patients were differentiated thyroid carcinoma (DTC) and hormone receptor (HR) - positive BC. The mRNA expression of COMP (Cartilage oligomeric matrix protein) was significantly overexpressed in BC and TC by analyzing the GEO database. The protein expression of COMP was increased in both BC and TC tissues obtained from the same patients validated by IHC. COMP was correlated with worse OS in BC (stage II-IV) and TC; it was the independent factor for prognosis of BC. GSEA indicated that the estrogen response and epithelial-mesenchymal transition (EMT) pathways were significantly enriched in both TC- and BC- COMP overexpressed groups.ConclusionThe co-occurrence risk of BC and TC in the same individual is higher than in the general population. Overexpression of COMP could promote oncogenesis and progression in patients with BC and TC through estrogen signaling and EMT pathways.
Interrelations between clinical-psychological features and bone mineral density changes in post-menopausal women undergoing anti-osteoporotic treatment: a two-year follow-up
Authors: Martino Gabriella , Bellone Federica , Vicario Carmelo Mario , Gaudio Agostino , Corica Francesco , Squadrito Giovanni , Lund-Jacobsen Trine , Schwarz Peter , Lo Coco Gianluca , Morabito Nunziata , Catalano Antonino 
Published: May 2023

IntroductionPsychological features have been bidirectionally associated with osteoporosis, but it is still unclear whether patient’s anxiety fluctuations during the anti-osteoporotic treatment can have an impact on bone mineral density (BMD) variation. The aim of this study was to investigate the interrelations between psychological distress features, such as anxiety, depression, health-related QoL (HRQoL) and bone health in women receiving anti-osteoporotic treatment.Methods192 post-menopausal osteoporotic women were treated with alendronate or risedronate according to the standard procedure. The levels of anxiety, depression, and perceived HRQoL, along with BMD, were assessed at baseline and at a 2-year follow-up.ResultsAt the end of the study, the patients showed a statistically significant increase of both psychic and somatic anxiety (p&lt;0.0001) and exhibited a worsening of depressive symptoms (p&lt;0.0001), whereas HRQoL showed no change. BMD improved and no incident fractures occurred. BMD variation (ΔBMD) at lumbar spine was significantly associated with anxiety levels (r=0.23, p=0.021). Multiple regression analysis showed that both patients’ worsening anxiety levels (β = -0.1283, SE=0.06142, p=0.04) and their treatment adherence (β=0.09, SE=0.02, p=0.0006) were independently associated with ΔBMD.DiscussionThe findings of the current follow-up study suggest that BMD in post-menopausal women undergoing anti-osteoporotic treatment was predicted by treatment adherence and anxiety change over time.
The effects of sucrose and arsenic on muscular insulin signaling pathways differ between the gastrocnemius and quadriceps muscles
Authors: Pánico Pablo , Velasco Myrian , Salazar Ana María , Ostrosky-Wegman Patricia , Hiriart Marcia 
Published: May 2023

IntroductionInsulin resistance in muscle can originate from a sedentary lifestyle, hypercaloric diets, or exposure to endocrine-disrupting pollutants such as arsenic. In skeletal muscle, insulin stimulates glucose uptake by translocating GLUT4 to the sarcolemma. This study aimed to evaluate the alterations induced by sucrose and arsenic exposure in vivo on the pathways involved in insulinstimulated GLUT4 translocation in the quadriceps and gastrocnemius muscles.MethodsMale Wistar rats were treated with 20% sucrose (S), 50 ppm sodium arsenite (A), or both (A+S) in drinking water for 8 weeks. We conducted an intraperitoneal insulin tolerance (ITT) test on the seventh week of treatment. The quadriceps and gastrocnemius muscles were obtained after overnight fasting or 30 min after intraperitoneal insulin injection. We assessed changes in GLUT4 translocation to the sarcolemma by cell fractionation and abundance of the proteins involved in GLUT4 translocation by Western blot.ResultsMale rats consuming S and A+S gained more weight than control and Atreated animals. Rats consuming S, A, and A+S developed insulin resistance assessed through ITT. Neither treatments nor insulin stimulation in the quadriceps produced changes in GLUT4 levels in the sarcolemma and Akt phosphorylation. Conversely, A and A+S decreased protein expression of Tether containing UBX domain for GLUT4 (TUG), and A alone increased calpain-10 expression. All treatments reduced this muscle’s protein levels of VAMP2. Conversely, S and A treatment increased basal GLUT4 levels in the sarcolemma of the gastrocnemius, while all treatments inhibited insulin-induced GLUT4 translocation. These effects correlated with lower basal levels of TUG and impaired insulin-stimulated TUG proteolysis. Moreover, animals treated with S had reduced calpain-10 protein levels in this muscle, while A and A+S inhibited insulin-induced Akt phosphorylation.ConclusionArsenic and sucrose induce systemic insulin resistance due to defects in GLUT4 translocation induced by insulin. These defects depend on which muscle is being analyzed, in the quadriceps there were defects in GLUT4 retention and docking while in the gastrocnemius the Akt pathway was impacted by arsenic and the proteolytic pathway was impaired by arsenic and sucrose.
A novel large-scale EV charging scheduling algorithm considering V2G and reactive power management based on ADMM
Authors: Zhang Chen , Sheinberg Rachel , Narayana Gowda Shashank , Sherman Michael , Ahmadian Amirhossein , Gadh Rajit 
Published: May 2023

Electric vehicle aggregators (EVAs) that utilize vehicle-to-grid (V2G) technologies can function as both controllable loads and virtual power plants, providing key energy management services to the distribution system operator (DSO). EVAs can also balance the grid’s reactive power as a virtual static VAR compensator (SVC) and provide voltage stability by utilizing advanced electric vehicle (EV) chargers that are capable of four-quadrant operations to provide reactive power management. Finally, managed charging can benefit EVAs themselves by minimizing power factor penalties in their electricity bills. In this paper, we propose a novel EV charging scheduling algorithm based on a hierarchical distributed optimization framework that minimizes peak load and provides reactive power compensation for the DSO by collaboration with EVAs that manage both the active and the reactive charging and discharging power of participating EVs. Utilizing the alternative direction method of multipliers (ADMM), the proposed distributed optimization approach scales well with increased EV charging infrastructure by balancing active and reactive power while decreasing computational burden. In our proposed hierarchical approach, each EVA schedules the active and reactive EV charging and discharging power for 1) reactive power compensation in order to minimize power factor penalty and electricity cost accrued by the EVA, 2) satisfaction of each EV’s energy demand at minimal charging cost, and 3) peak shaving and load management for the DSO. When compared with an uncoordinated charging model, the efficacy of this proposed model is successfully demonstrated through a 300% decreased peak EV load for the DSO, 28% lower electricity costs for EV users, and 98.55% smaller power factor penalty, along with 17.58% lower overall electricity costs, for EVAs. The performance of our approach is validated in a case study with 50 EVs at multiple EVAs in an IEEE 13-bus test case and compared the results with uncoordinated EV charging.
Morphology and phase state of PM2.5 in urban and coastal-rural areas during summer
Authors: Gaikwad Sanjit , Kim Daeun , Jeong Rani , Lee Ji Yi , Lee Kwangyul , Ahn Junyoung , Jang Kyoung-Soon , Kim Changhyuk , Song Mijung 
Published: May 2023

The morphology and phase state are critical physical properties of aerosol particles. However, studies related to the analysis of these properties primarily focus on laboratory experiments, and studies on real aerosol particles are limited. Herein, fine particulate matter (PM2.5) filter samples were obtained to investigate and compare the morphology and phase state of ambient aerosol particles in South Korea. The PM2.5 samples were collected in the summer of June 2021 from two different environments: Seoul (urban) and Seosan (coastal-rural). Optical microscopy was combined with the poke-and-flow technique to determine the morphology and phase state of the PM2.5 as a function of relative humidity (RH) at 293 ± 1 K. At both sites, the PM2.5 droplets, which were extracted in purified water, showed a multiphase nature that was dependent on the RH and chemical composition. Based on the results and ambient average RH in Seoul, most of the PM2.5 was observed in a liquid state on polluted days under an inorganic-dominant condition, but in a semisolid state on clean days under an organic carbon-rich condition. In Seosan, the PM2.5 predominantly existed in a liquid state, due to the high RH caused by proximity to the Yellow Sea. Our study provides fundamental physical properties of PM2.5 for both urban and coastal-rural environments. The results have strong applications for atmospheric chemistry and predicting particle size distributions.
BVLOS UAV missions for vegetation mapping in maritime Antarctic
Authors: Zmarz Anna , Karlsen Stein Rune , Kycko Marlena , Korczak-Abshire Małgorzata , Gołębiowska Izabela , Karsznia Izabela , Chwedorzewska Katarzyna 
Published: May 2023

Polar areas are among the regions where climate change occurs faster than on most of the other areas on Earth. To study the effects of climate change on vegetation, there is a need for knowledge on its current status and properties. Both classic field observation methods and remote sensing methods based on manned aircraft or satellite image analysis have limitations. These include high logistic operation costs, limited research areas, high safety risks, direct human impact, and insufficient resolution of satellite images. Fixed-wing unmanned aerial vehicle beyond the visual line of sight (UAV BVLOS) missions can bridge the scale gap between field-based observations and full-scale airborne or satellite surveys. In this study the two operations of the UAV BVLOS, at an altitude of 350 m ASL, have been successfully performed in Antarctic conditions. Maps of the vegetation of the western shore of Admiralty Bay (King George Island, South Shetlands, Western Antarctic) that included the Antarctic Specially Protected Area No. 128 (ASPA 128) were designed. The vegetation in the 7.5 km2 area was mapped in ultra-high resolution (&lt;5 cm and DEM of 0.25 m GSD), and from the Normalized Difference Vegetation Index (NDVI), four broad vegetation units were extracted: “dense moss carpets” (covering 0.14 km2, 0.8% of ASPA 128), “Sanionia uncinata moss bed” (0.31 km2, 1.7% of ASPA 128), “Deschampsia antarctica grass meadow” (0.24 km2, 1.3% of ASPA 128), and “Deschampsia antarctica–Usnea antarctica heath” (1.66 km2, 9.4% of ASPA 128). Our results demonstrate that the presented UAV BVLOS–based surveys are time-effective (single flight lasting 2.5 h on a distance of 300 km) and cost-effective when compared to classical field-based observations and are less invasive for the ecosystem. Moreover, unmanned airborne vehicles significantly improve security, which is of particular interest in polar region research. Therefore, their development is highly recommended for monitoring areas in remote and fragile environments.