bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single‐cell profiling of human CD127+ innate lymphoid cells reveals diverse immune phenotypes in hepatocellular carcinoma
Authors: He Yuanlin , Luo Jiajing , Zhang Guannan , Jin Yu , Wang Nanxi , Lu Jinying , Li Changxian , Guo Xiaohuan , Qin Na , Dai Juncheng , Chen Yun 
Published: March 2022

Abstract

Background and Aims
Innate lymphoid cells (ILCs) are tissue‐resident lymphocytes that play critical roles in cytokine‐mediated regulation of homeostasis and inflammation. However, relationships between their immune phenotypic characteristics and HCC remain largely unexplored.

Approach and Results
We performed single‐cell RNA sequencing analysis on sorted hepatic ILC cells from human patients with HCC and validated using flow cytometry, multiplex immunofluorescence staining, and functional experiments. Moreover, we applied selection strategies to enrich ILC populations in HCC samples to investigate the effects of B cells on the immune reaction of inducible T cell costimulator (ICOS)+ ILC2 cells. Dysregulation of ILCs was manifested by the changes in cell numbers or subset proportions in HCC. Seven subsets of 3433 ILCs were identified with unique properties, of which ICOS+ ILC2a were preferentially enriched in HCC and correlated with poor prognosis. Mechanistically, we report that B cells, particularly resting naïve B cells, have a previously unrecognized function that is involved in inflammatory differentiation of ILC2 cells. B cell–derived ICOSL signaling was responsible for exacerbating inflammation through the increased production of IL‐13 in ICOS+ ILC2a cells. Heat shock protein 70 (HSP70) genes Heat Shock Protein Family A Member 1A (HSPA1A) and Heat Shock Protein Family A Member 1B (HSPA1B) were highly expressed in ILC2s in late‐stage HCC, and targeting to ICOS and its downstream effector HSP70 in ILC2s suppressed tumor growth and remodeled the immunosuppressive tumor microenvironment.

Conclusions
This in‐depth understanding sheds light on B cell‐driven innate type 2 inflammation and provides a potential strategy for HCC immunotherapy.
A multi‐analyte cell‐free DNA–based blood test for early detection of hepatocellular carcinoma
Authors: Lin Nan , Lin Yongping , Xu Jianfeng , Liu Dan , Li Diange , Meng Hongyu , Gallant Maxime A. , Kubota Naoto , Roy Dhruvajyoti , Li Jason S. , Gorospe Emmanuel C. , Sherman Morris , Gish Robert G. , Abou‐Alfa Ghassan K. , Nguyen Mindie H. , Taggart David J. , Van Etten Richard A. , Hoshida Yujin , Li Wei 
Published: March 2022

Abstract
The limited performance of guideline‐recommended abdominal ultrasound and serum alpha‐fetoprotein (AFP) highlights the urgent, unmet need for new biomarkers for more accurate detection of early hepatocellular carcinoma (HCC). To this end, we have conducted a prospective clinical validation study to evaluate the performance of the HelioLiver Test, a multi‐analyte blood test combining cell‐free DNA methylation patterns, clinical variables, and protein tumor markers. A blinded, multicenter validation study was performed with 247 subjects, including 122 subjects with HCC and 125 control subjects with chronic liver disease. The performance of the HelioLiver Test was compared with AFP and the GALAD score as established HCC surveillance blood tests. The performance of the HelioLiver Test (area under the receiver operating characteristic curve [AUROC] = 0.944) was superior to both AFP (AUROC = 0.851; p < 0.0001) and GALAD (AUROC = 0.899; p < 0.0001). Using a prespecified diagnostic algorithm, the HelioLiver Test showed sensitivities of 85% (95% confidence interval [CI], 78%–90%) for HCC of any stage and 76% (95% CI, 60%–87%) for early stage (American Joint Committee on Cancer [AJCC] I and II) HCC. In contrast, AFP (≥20 ng/mL) alone and the GALAD score (≥−0.63) showed lower sensitivities of 62% (95% CI, 54%–70%) and 75% (95% CI, 67%‐82%) for HCC overall, and 57% (95% CI, 40%–71%) and 65% (95% CI, 49%–79%) for early stage (AJCC I and II) HCC, respectively. The specificities of the HelioLiver Test (91%; 95% CI, 85%–95%), AFP (97%; 95% CI, 92%–99%), and the GALAD score (94%; 95% CI, 88%–97%) were similar for control subjects. The HelioLiver Test showed superior performance for HCC detection compared to with both AFP and the GALAD score and warrants further evaluation in HCC surveillance settings.
Research progress of the CXCR4 mechanism in Alzheimer's disease
Authors: Wang Qiu‐Lin , Fang Chang‐Le , Huang Xue‐Yan , Xue Lu‐Lu 
Published: March 2022

AbstractAlzheimer's disease (AD) is a degenerative brain disease with complex clinical manifestations and pathogeneses such as abnormal deposition of beta‐amyloid protein and inflammation caused by the excessive activation of microglia. CXC motif chemokine receptor type 4 (CXCR4) is a type of G protein‐coupled receptor that binds to CXC motif ligand 12 (CXCL12) to activate downstream signaling pathways, such as the Janus kinase/signal transducer and activator of transcription and the renin–angiotensin system (Ras)/RAF proto‐oncogene serine (Raf)/mitogen‐activated protein kinase/extracellular‐regulated protein kinase; most of these signaling pathways are involved in inflammatory responses. CXCR4 is highly expressed in the microglia and astrocytes; this might be one of the important causes of inflammation caused by microglia and astrocytes. In this review, we summarize the mechanism and therapeutics of AD, the structures of CXCR4 and the CXCL12 ligand, and the mechanisms of CXCR4/CXCL12 that are involved in the occurrence and development of AD. The possible treatment of AD through microglia and astrocytes is also discussed, with the aim of providing a new method for the treatment of AD.
Renoprotective potential of myo‐inositol on diabetic kidney disease: Focus on the role of the PINK1/Parkin pathway and mitophagy receptors
Authors: Sherkhane Bhoomika , Kalvala Anil Kumar , Arruri Vijay Kumar , Khatri Dharmendra kumar , Singh Shashi Bala 
Published: March 2022

AbstractRecent studies have emphasized the role of mitochondria in renal function as well as in renal injury. Poor mitochondrial quality control mechanisms including mitochondrial fusion, fission and mitophagy are major contributors for progression of diabetic renal injury. The current study is aimed to evaluate the protective role of myo‐inositol (MI) against diabetic nephropathy (DN) by utilizing high glucose exposed NRK 52E cell and streptozotocin (STZ) induced DN model. MI supplementation (at doses 37.5 and 75 mg/kg) ameliorated albuminuria and enhanced the renal function as indicated significant improvement in urinary creatinine and urea levels. On the other hand, the western blot analysis of both in vitro and in vivo studies has revealed poor mitophagy in renal cells which was reversed upon myo‐inositol treatment. Apart from targeting the canonical PINK1/Parkin pathway, we also focused on the role mitophagy receptors prohibitin (PHB) and NIP3‐like protein (NIX). A significant reduction in expression of NIX and PHB2 was observed in renal tissue of diabetic control rats and high glucose exposed NRK 52E cells. Myo‐inositol treatment resulted in positive modulation of PINK1/Parkin pathway as well as PHB2 and NIX. Myo‐inositol also enhanced the mitochondrial biogenesis in renal tissue of diabetic rat by upregulating Nrf2/SIRT1/PGC‐1α axis. The current study thus underlines the renoprotective effect myo‐inositol, upregulation of mitophagy proteins and mitochondrial biogenesis upon myo‐inositol treatment.
Estimation of homocysteine concentration as an indicator of foetal death in pregnant Chinese women with preeclampsia: A case–control study
Authors: Qin Wanyuan , Hu Xuehua , Fu Chunyun , Lu Xiangjun , Deng Zuoxin , Wang Junlong , Jing Junpeng 
Published: March 2022

AbstractIntroductionThis study evaluated whether changes in homocysteine concentrations in pregnant women with preeclampsia (PE) might be useful for predicting foetal death.Materials and methodsThis study evaluated 1,368 PE women at two Chinese centres. Medical records were reviewed to collect data regarding maternal age, homocysteine concentrations and other clinical parameters.ResultsMaternal serum homocysteine concentrations were significantly higher in the group with PE than control. Significant differences (p < 0.05) were also observed between the foetal death and survival groups in terms of body mass index, neonatal weight, previous deliveries, gestation length and adverse pregnancy history. Multivariate logistic regression analysis revealed that upper‐quartile homocysteine concentration was a significant risk factor of foetal death in the group with PE, and overall survival rate of patients with high homocysteine concentrations during pregnancy was significantly lower than those with low level (p < 0.05).ConclusionsOur results indicate that foetal death was associated with upper‐quartile homocysteine concentrations in the group with PE, it can be an indicator of foetal death throughout the pregnancy.
Challenges and opportunities for manureshed management across U.S. dairy systems: Case studies from four regions
Authors: Dell Curtis J. , Baker John M. , Spiegal Sheri , Porter Sarah A. , Leytem April B. , Flynn K. Colton , Rotz C. Alan , Bjorneberg David L. , Bryant Ray B. , Hagevoort G. Robert , Williamson Jeb C. , Slaughter Amalia , Kleinman Peter J. A. 
Published: March 2022

AbstractThe manureshed represents cropland needed to safely assimilate manure nutrients from an animal feeding operation. Dairy manuresheds can be contained on‐farm but may need to involve additional farms that can assimilate excess nutrients. We present case studies reviewing challenges and opportunities to manureshed management in four major dairy‐producing states using available information on local manuresheds. Additionally, geographic information system software was used with data from regulated Minnesota dairies to assess cropland assimilative capacities and transport needs surrounding large dairies. Manureshed requirements vary across regions, but increased import of feed and soil phosphorus accumulation constrain on‐farm manure utilization across the United States. In Minnesota, a growing proportion of Jersey cattle and differences in continuous corn (Zea mays L.) vs. corn–alfafa (Medicago sativa L.) rotations contribute to the amount of land needed to absorb dairy manure nutrients. Farm‐gate budgets reveal that N‐based manuresheds can be contained within Idaho dairies, but P‐based manuresheds extend beyond the farm. In New Mexico, relocation of surplus manure nutrients off the farm is common via informal networks, but incentives to strengthen these networks could ensure sustainable manureshed management. Evaluation of manureshed requirements in Pennsylvania is often complicated by the need for additional nutrient management planning and greater understanding of nutrient balances on the preponderance of small dairies. Nutrient imbalances with highly concentrated dairy production often lead to the need for manure transport off‐farm. However, advances in herd and cropland management offer opportunities to improve on‐farm nutrient efficiencies, and emerging networks and technologies promise to facilitate manure export when needed.
Facile synthesis, antimicrobial, and anti‐inflammatory activities of novel isoxazolyl imidazo[1,2‐b]isoxazoles
Authors: Rama Krishna Saini , Nagaraju Dharavath , Srinivas Reddy Malladi , Rajanarendar Eligeti 
Published: March 2022

AbstractA copper iodide promoted cyclization for the synthesis of isoxazolyl imidazo[1,2‐b]isoxazoles 3 in a one‐pot procedure has been investigated by interaction of 3‐aminoisoxazole 1 with nitrostyrylisoxazoles 2 under aerial oxidation condition. The newly synthesized compounds 3a–l were screened for their in vitro antimicrobial and anti‐inflammatory activities.
Algae‐based biostimulants increase yield and quality of mini tomatoes under protected cultivation
Authors: de Paula Bruno Santos , Feltrim Daniela , Engel Daniele Caroline Hörz , Baptistella João Leonardo Corte , Rodrigues Mayara , Engel Eduardo , Mazzafera Paulo 
Published: March 2022

AbstractBackgroundPlant biostimulants are organic products primarily based on algae, microorganisms, fulvic and humic acids, proteins, and amino acids, which improve physiological plant performance, leading to increased crop productivity. In this work, commercial algae extract of Ascophyllum nodosum were sprayed on Sweet Heaven mini tomato variety [algae extract 0.5 L ha−1 (AE1) and 2 L ha−1 (AE2); aqueous solution prepared with A. nodosum powder at 1% (w/v) (DA1) and 3% (w/v) (DA2)] growing under greenhouse conditions.ResultsAlgae treatment significantly affected the yield, diameter, length, color, and Brix degree of the fruits. Fruit volume and weight and the number of cracked fruits did not change. The treatment of mini tomato plants with DA1 led to a higher fruit yield compared to other treatments and untreated plants.ConclusionTherefore, A. nodosum extract can be an interesting sustainable practice to increase the productivity of mini tomatoes growing under protected conditions.
Assessment of spatiotemporal variations of ecosystem service values and hotspots in a dryland: A case‐study in Pakistan
Authors: Akhtar Mobeen , Zhao Yuanyuan , Gao Guanglei , Gulzar Qudsia , Hussain Azfar 
Published: March 2022

AbstractEcosystem services (ES) provided by dryland ecosystems store nearly half and one‐third of the Earth's terrestrial biomass and biodiversity, respectively. Pakistan is a typical dryland region with significant land degradation and dramatic changes in ES in recent decades, which has not been sufficiently investigated. This study explored the spatiotemporal variations in ecosystem service values (ESV) over Pakistan (2001–2018) by combining land use/cover data, economic modeling, and hotspot analysis. From the achieved results, the total ESV indicated an improvement in ES before 2012 and then showed a declining trend. The largest contribution was attributed to the increase in forest/shrubland by 16.17% (2001–2006) and 10.36% (2006–2012). However, the ESV decreased to 7.76% from 2012 to 2018, which was mainly attributed to the decrease in cropland and grassland. Heterogeneous changes were observed in ESV. The hotspot of ESV change (approximately an area of 32,578 km2) was mainly located in the southern and southeastern parts of Khyber Pakhtunkhwa (KPK), the northeastern part of Balochistan and the central and western parts of Sindh Province. The cold spot (approximately an area of 24,491 km2) showed a distribution in the northern part of KPK and Gilgit Baltistan, northeastern Punjab, coastal regions, and southeastern Sindh Province. We also found that although the total ESV and gross domestic product (GDP) indicated growth, the proportion of ESV from the total ESV and GDP (%ESV) exhibited a negative trend. The Provinces of Punjab and Balochistan retained the highest value of %ESV, while Azad Kashmir and Gilgit Baltistan were much lower. These results reflected the spatial imbalance of ecosystem protection and economic development in Pakistan. We recommend that necessary actions for conserving ES are important to strengthen ecological conservation in Pakistan. Additionally, further interdisciplinary research is needed to fully explore synergies in conserving ES and economical conservation.
Cystic fibrosis lung transplant recipients 10 years of age or younger: Predisposing factors for end‐stage disease
Authors: Melicoff Ernestina , Ruiz Fadel E. , Hosek Kathleen , Mallory George B. 
Published: March 2022

AbstractBackgroundThe largest age group among children and adolescents referred for lung transplantation for cystic fibrosis (CF) have been those in the pubertal or postpubertal age range. However, over 100 younger patients with CF have undergone lung transplantation over the last three decades in the United States.MethodsWe performed a retrospective review of our experience with 18 children with CF who underwent lung transplantation in our center before the age of 11 years and compared them to our older CF lung transplant recipients and our larger CF Center population.ResultsThe transplant population was demographically distinct from our CF center in terms of ethnicity, country of origin, and insurance status. Other notable findings were a high prevalence of methicillin‐resistant Staphylococcus aureus, a high prevalence of CF‐related diabetes mellitus, and a high prevalence of consolidated lobar or whole lung disease. Posttransplant outcomes were comparable to those older than 10 years of age in our center until 5 years after transplant after which the younger cohort showed a superior enduring survival.ConclusionsIn an era of increasingly effective medications modifying the natural history of CF, identification of risk factors for early severe lung disease in CF remains relevant to permit interventions to prevent or postpone the time of future lung transplantation.
Study on the Viscoelastic Damage Properties of NEPE Solid Propellant with Different Cyclic Stress Ratios
Authors: Hu Qinwei , Fang Qin‐Zhi , Sha Baolin , Jin Li 
Published: March 2022

AbstractViscoelastic damage properties of NEPE (Nitrate Ester Plasticized Polyether) solid propellant have been studied in this work. This work focuses on the creep and fatigue damage evolution. Cyclic loading tests for NEPE solid propellants are conducted with different stress ratios. Then a modified model incorporating viscoelasticity and damage evolution is presented and used to fit the experimental data. The fitting results show that the model is suitable to characterize the viscoelastic damage properties of NEPE propellants with different stress ratios. Based on the model with parameters for NEPE propellants, the damage parameter D are obtained. The damage evolution curves under different loading conditions are given. It is shown that, from the predicted damage evolution curves, the critical damage parameter Dcr at the fracture points can be used to predict the fatigue lives under different loading conditions.
Brick Shaped Vanadium Nitride/Graphene Nanocomposite as Highly Efficient Counter Electrode Catalyst for Pt Free Dye‐Sensitized Solar Cell
Authors: Karunagaran Jhanani Raji , Janakiraman Manokaran , Mathew Asha , Natesan Balasubramanian 
Published: March 2022

AbstractA Platinum free hybrid counter electrode (CE) Vanadium nitride/graphene (VNGp) for dye‐sensitized solar cell (DSSC) was synthesized by hydrothermal method. The surface morphology and chemical composition of the as‐prepared VNGp composite were analyzed by X‐ray diffraction (XRD) analysis, Raman spectroscopy, high‐resolution electron transmission microscopy (HR‐TEM), and cyclic voltammetry (CV). The VNGp hybrid counter electrode displayed an adsorption‐controlled process towards the (I−/I3−) redox couple at CE/electrolyte interface and the value was calculated to be 3.16×10−9 mol/s by varying the scan rate. The exchange current density (Jo) was calculated as 6.59 mA/cm2 from the Tafel slope. The VNGp hybrid counter shows a maximum fill factor (FF) of 66.28 with high efficacy of 8.15 % under the illumination of 100 mW/cm2 as compared to the Pt CE for DSSC.
Triflic‐Acid‐Catalyzed Tandem Epoxide Rearrangement and Annulation with Alkynes: An Efficient Approach for Regioselective Synthesis of Naphthalenes
Authors: Rao Chinthu Joginarayana , Sudheer Mokhamatam , Battula Venkateswara Rao 
Published: March 2022

AbstractA facile triflic acid catalyzed method to synthesize 1‐arylnaphthalenes from one‐pot annulation reaction of arylepoxides and arylalkynes has been reported. The annulation reaction involves a successive epoxide to carbonyl rearrangement, electrophilic attack of carbonyl on arylalkyne followed by cyclization catalyzed by triflic acid. The present catalyst effects this transformation at room temperature itself.
Exploring the relationship between refactoring and code debt indicators
Authors: Halepmollasi Rusen , Tosun Ayse 
Published: March 2022

AbstractRefactoring, which aims to improve the internal structure of the software systems preserving their behavior, is the most common payment strategy for technical debt (TD) by removing the code smells. There exist many studies presenting code smell detection approaches/tools or investigating their impact on quality attributes. There are also studies that focus on refactoring techniques, their relation with quality attributes, tool supports, and opportunities for them. Although there are several studies addressing the gap between refactoring and TD indicators, the empirical evidence provided is still limited. In this study, we examine the distribution of 29 refactoring types among the different projects and their relation with code smells or faults. We explore the refactoring types that are most commonly performed together and other activities performed with refactorings. We conduct a large exploratory study with automatically detected 57,528 refactorings, 37,553 smells, 27,340 faults, and 134,812 commits of 33 Java projects. Results show that some refactoring types are more commonly applied by developers. Our analysis indicates that refactorings usually remove or do not affect the code smells, and this contradicts with the previous studies. Also, the commits in which refactoring(s) is performed are three times more fault inducing than those without refactoring.
Enabling the High‐Voltage Operation of Layered Ternary Oxide Cathodes via Thermally Tailored Interphase
Authors: Zhu Zhiqiang , Cao Shengkai , Ge Xiang , Xi Shibo , Xia Huarong , Zhang Wei , Lv Zhisheng , Wei Jiaqi , Chen Xiaodong 
Published: March 2022

AbstractLayered ternary oxides LiNixMnyCozO2 are promising cathode candidates for high‐energy lithium‐ion batteries (LIBs), but they usually suffer from the severe interfacial parasitic reactions at voltages above 4.3 V versus Li+/Li, which greatly limit their practical capacities. Herein, using LiNi1/3Mn1/3Co1/3O2 (NMC111) as the model system, a novel high‐temperature pre‐cycling strategy is proposed to realize its stable cycling in 3.0−4.5 V by constructing a robust cathode/electrolyte interphase (CEI). Specifically, performing the first five cycles of NMC111 at 55 °C helps to yield a uniform CEI layer enriched with fluorine‐containing species, Li2CO3 and poly(CO3), which greatly suppresses the detrimental side reactions during extended cycling at 25 °C, endowing the cell with a capacity retention of 92.3% at 1C after 300 cycles, far surpassing 62.0% for the control sample without the thermally tailored CEI. This work highlights the critical role of temperature on manipulating the interfacial properties of cathode materials, opening a new avenue for developing high‐voltage cathodes for Li‐ion batteries.
Experimental study on the joint bearing behavior of segmented tower structures subjected to normal and bending shear loads
Authors: Klein Fabian , Fürll Florian , Betz Thorsten , Marx Steffen 
Published: March 2022

AbstractThis article deals with the analysis and evaluation of the structural behavior of segmented tower constructions in large‐scale experimental investigations. For this purpose, a tower model with dry horizontal joints on a scale of approximately 1:10 is constructed and loaded. The objective of these large‐scale investigations is to determine the load‐bearing behavior of concrete segment towers subjected to normal force (external prestressing), bending, shear force and torsion and to derive more efficient and realistic design models. The transfer of shear stresses between individual segments is ensured by frictional resistance in the horizontal joints due to prestressing. The current design models are based on plane flange surfaces at the top and bottom of the segments as well as their ideal circular ring shape. This assumes a constant normal stress distribution for the compression connection. Within the large‐scale experimental tests, findings for uneven force distribution in the horizontal joints due to prestressing and shear bending were obtained, that have a significant impact on the design models. However, for the evaluation of the results and the projection onto the real construction components, the scale effects must be urgently taken into account.