bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of the pellet injection system on the J-TEXT tokamak
Authors: JIANG Yingzhou , CHEN Zhongyong , LI You , YAN Wei , LUKIN A , VINYAR I , LI Feng , XU Xin , CHEN Zhipeng , YANG Zhoujun , WANG Nengchao , DING Yonghua , PAN Yuan 
Published: April 2022

Abstract
Pellet injection is an attractive technology for core-fueling and magnetohydrodynamic study in magnetic-confinement fusion devices like tokamaks and stellarators. It can inject solid hydrogen/deuterium pellets into the plasma with deeper density deposition compared with other fueling methods, such as gas puffing. A three-barrel H2 pellet injection system was installed on the J-TEXT tokamak and experiments were carried out. The pellets are formed in three barrels cooled by a cryocooler and compressor system at around 9 K, and are 0.8 mm/1 mm diameter and 0.8 mm length. The pellet is launched by helium propellant gas and injected from the low-field side of the plasma. The normal range of pellet speed is 210–310 m s−1 for different propellant gas pressures. Due to the three-barrel structure, the number of injected pellets can be adjusted between one and three. Pellets can be launched sequentially with arbitrary time intervals, which enables flexible applications. The results of the experiments show that pellet fueling efficiency can reach 50%. The energy confinement time increased by about 7.5‒10 ms after pellet injection.
Field-free approaches for deterministic spin–orbit torque switching of the perpendicular magnet
Authors: Wu Hao , Zhang Jing , Cui Baoshan , Razavi Seyed Armin , Che Xiaoyu , Pan Quanjun , Wu Di , Yu Guoqiang , Han Xiufeng , Wang Kang L 
Published: April 2022

Abstract
All-electrical driven magnetization switching attracts much attention in next-generation spintronic memory and logic devices, particularly in magnetic random-access memory (MRAM) based on the spin–orbit torque (SOT), i.e. SOT-MRAM, due to its advantages of low power consumption, fast write/read speed, and improved endurance, etc. For conventional SOT-driven switching of the magnet with perpendicular magnetic anisotropy, an external assisted magnetic field is necessary to break the inversion symmetry of the magnet, which not only induces the additional power consumption but also makes the circuit more complicated. Over the last decade, significant effort has been devoted to field-free magnetization manipulation by using SOT. In this review, we introduce the basic concepts of SOT. After that, we mainly focus on several approaches to realize the field-free deterministic SOT switching of the perpendicular magnet. The mechanisms mainly include mirror symmetry breaking, chiral symmetry breaking, exchange bias, and interlayer exchange coupling. Furthermore, we show the recent progress in the study of SOT with unconventional origin and symmetry. The final section is devoted to the industrial-level approach for potential applications of field-free SOT switching in SOT-MRAM technology.
findPC: An R package to automatically select the number of principal components in single-cell analysis
Authors: Zhuang Haotian , Wang Huimin , Ji Zhicheng 
Published: April 2022

Abstract

Summary
Principal component analysis is widely used in analyzing single-cell genomic data. Selecting the optimal number of principal components (PCs) is a crucial step for downstream analyses. The elbow method is most commonly used for this task, but it requires one to visually inspect the elbow plot and manually choose the elbow point. To address this limitation, we developed six methods to automatically select the optimal number of PCs based on the elbow method. We evaluated the performance of these methods on real single-cell RNA-seq data from multiple human and mouse tissues and cell types. The perpendicular line method with 30 PCs has the best overall performance, and its results are highly consistent with the numbers of PCs identified manually. We implemented the six methods in an R package, findPC, that objectively selects the number of PCs and can be easily incorporated into any automatic analysis pipeline.

Availability and Implementation
findPC R package is freely available at https://github.com/haotian-zhuang/findPC.

Supplementary information
Supplementary data are available at Bioinformatics online.
Maturation of hiPSC-derived cardiomyocytes promotes adult alternative splicing of SCN5A and reveals changes in sodium current associated with cardiac arrhythmia
Authors: Campostrini Giulia , Kosmidis Georgios , Ward-van Oostwaard Dorien , Davis Richard Paul , Yiangou Loukia , Ottaviani Daniele , Veerman Christiaan Cornelis , Mei Hailiang , Orlova Valeria Viktorovna , Wilde Arthur Arnold Maria , Bezzina Connie Rose , Verkerk Arie Otto , Mummery Christine Lindsay , Bellin Milena 
Published: April 2022

AbstractAimsHuman-induced pluripotent stem cell-cardiomyocytes (hiPSC-CMs) are widely used to study arrhythmia-associated mutations in ion channels. Among these, the cardiac sodium channel SCN5A undergoes foetal-to-adult isoform switching around birth. Conventional hiPSC-CM cultures, which are phenotypically foetal, have thus far been unable to capture mutations in adult gene isoforms. Here, we investigated whether tri-cellular cross-talk in a three-dimensional (3D) cardiac microtissue (MT) promoted post-natal SCN5A maturation in hiPSC-CMs.Methods and resultsWe derived patient hiPSC-CMs carrying compound mutations in the adult SCN5A exon 6B and exon 4. Electrophysiological properties of patient hiPSC-CMs in monolayer were not altered by the exon 6B mutation compared with isogenic controls since it is not expressed; further, CRISPR/Cas9-mediated excision of the foetal exon 6A did not promote adult SCN5A expression. However, when hiPSC-CMs were matured in 3D cardiac MTs, SCN5A underwent isoform switch and the functional consequences of the mutation located in exon 6B were revealed. Up-regulation of the splicing factor muscleblind-like protein 1 (MBNL1) drove SCN5A post-natal maturation in microtissues since its overexpression in hiPSC-CMs was sufficient to promote exon 6B inclusion, whilst knocking-out MBNL1 failed to foster isoform switch.ConclusionsOur study shows that (i) the tri-cellular cardiac microtissues promote post-natal SCN5A isoform switch in hiPSC-CMs, (ii) adult splicing of SCN5A is driven by MBNL1 in these tissues, and (iii) this model can be used for examining post-natal cardiac arrhythmias due to mutations in the exon 6B.Translational perspectiveThe cardiac sodium channel is essential for conducting the electrical impulse in the heart. Postnatal alternative splicing regulation causes mutual exclusive inclusion of fetal or adult exons of the corresponding gene, SCN5A. Typically, immature hiPSCCMs fall short in studying the effect of mutations located in the adult exon. We describe here that an innovative tri-cellular three-dimensional cardiac microtissue culture promotes hiPSC-CMs maturation through upregulation of MBNL1, thus revealing the effect of a pathogenic genetic variant located in the SCN5A adult exon. These results help advancing the use of hiPSC-CMs in studying adult heart disease and for developing personalized medicine applications.
Eosinophils protect pressure overload- and β-adrenoreceptor agonist-induced cardiac hypertrophy
Authors: Yang Chongzhe , Li Jie , Deng Zhiyong , Luo Songyuan , Liu Jing , Fang Wenqian , Liu Feng , Liu Tianxiao , Zhang Xian , Zhang Yuanyuan , Meng Zhaojie , Zhang Shuya , Luo Jianfang , Liu Conglin , Yang Dafeng , Liu Lijun , Sukhova Galina K , Sadybekov Anastasiia , Katritch Vsevolod , Libby Peter , Wang Jing , Guo Junli , Shi Guo-Ping 
Published: April 2022

AbstractAimsBlood eosinophil (EOS) counts and EOS cationic protein (ECP) levels associate positively with major cardiovascular disease (CVD) risk factors and prevalence. This study investigates the role of EOS in cardiac hypertrophy.Methods and resultsA retrospective cross-section study of 644 consecutive inpatients with hypertension examined the association between blood EOS counts and cardiac hypertrophy. Pressure overload- and β-adrenoreceptor agonist isoproterenol-induced cardiac hypertrophy was produced in EOS-deficient ΔdblGATA mice. This study revealed positive correlations between blood EOS counts and left ventricular (LV) mass and mass index in humans. ΔdblGATA mice showed exacerbated cardiac hypertrophy and dysfunction, with increased LV wall thickness, reduced LV internal diameter, and increased myocardial cell size, death, and fibrosis. Repopulation of EOS from wild-type (WT) mice, but not those from IL4-deficient mice ameliorated cardiac hypertrophy and cardiac dysfunctions. In ΔdblGATA and WT mice, administration of ECP mEar1 improved cardiac hypertrophy and function. Mechanistic studies demonstrated that EOS expression of IL4, IL13, and mEar1 was essential to control mouse cardiomyocyte hypertrophy and death and cardiac fibroblast TGF-β signalling and fibrotic protein synthesis. The use of human cardiac cells yielded the same results. Human ECP, EOS-derived neurotoxin, human EOS, or murine recombinant mEar1 reduced human cardiomyocyte death and hypertrophy and human cardiac fibroblast TGF-β signalling.ConclusionAlthough blood EOS counts correlated positively with LV mass or LV mass index in humans, this study established a cardioprotective role for EOS IL4 and cationic proteins in cardiac hypertrophy and tested a therapeutic possibility of ECPs in this human CVD.
Phenome-wide screening of the putative causal determinants of depression using genetic data
Authors: Aman Asma M , García-Marín Luis M , Thorp Jackson G , Campos Adrian I , Cuellar-Partida Gabriel , Martin Nicholas G , Rentería Miguel E 
Published: April 2022

AbstractDepression is one of the most common mental health disorders and one of the top causes of disability throughout the world. The present study sought to identify putative causal associations between depression and hundreds of complex human traits through a genome-wide screening of genetic data and a hypothesis-free approach. We leveraged genome-wide association studies summary statistics for depression and 1504 complex traits and investigated potential causal relationships using the latent causal variable method. We identified 559 traits genetically correlated with depression risk at FDR &lt; 5%. Of these, 46 were putative causal genetic determinants of depression, including lifestyle factors, diseases of the nervous system, respiratory disorders, diseases of the musculoskeletal system, traits related to the health of the gastrointestinal system, obesity, vitamin D levels and the use of prescription medications, among others. No phenotypes were identified as potential outcomes of depression. Our results suggest that genetic liability to multiple complex traits may contribute to a higher risk for depression. In particular, we show a putative causal genetic effect of pain, obesity and inflammation on depression. These findings provide novel insights into the potential causal determinants of depression and should be interpreted as testable hypotheses for future studies to confirm, which may facilitate the design of new prevention strategies to reduce depression’s burden.
Autoclaving time-related reduction in metabolizable energy of poultry meal is greater in growing pigs compared with broiler chickens
Authors: Sung Jung Yeol , Wiltafsky-Martin Markus K , Caroline González-Vega J , Adeola Olayiwola 
Published: April 2022

Abstract
The objective of this study was to determine the energy utilization responses of growing pigs and broiler chickens to poultry meal that was autoclaved at 134 °C for 0 to 180 min. Poultry meal from the same batch was autoclaved at 134 °C for 7 autoclaving times of 0, 30, 60, 90, 120, 150, or 180 min to generate 7 samples. Eight experimental diets consisting of a basal diet based on corn and soybean meal, and seven test diets in which 15% of energy-contributing ingredients in the basal diet were replaced with each of the seven poultry meal samples were used. In experiment 1, there were 64 barrows (initial body weight = 19.4 ± 1.0 kg) allotted to 8 experimental diets in a randomized complete block design with body weight as a blocking factor. Each pig received an experimental diet during 5 d of adaptation followed by 5 d of quantitative total, but separate, collection of urine and feces. In experiment 2, a total of 512 male broiler chickens at day 17 post-hatching (initial body weight = 660 ± 80 g) in 8 replicate cages were allotted to 8 experimental diets in a randomized complete block design with body weight as a blocking factor. Excreta were collected from days 20 to 22 post-hatching, and birds were euthanized by CO2 asphyxiation for ileal digesta collection. Data from experiments 1 and 2 were pooled together for statistical analysis as a 2 × 7 factorial treatment arrangement with the effect of species (pigs or broiler chickens) and autoclaving time of poultry meal (7 autoclaving times between 0 and 180 min). An interaction between species and their linear effect of autoclaving time was observed (P &lt; 0.05) in metabolizable energy (ME) of poultry meal. Specifically, linear decrease in ME values in poultry meal with increasing autoclaving time was greater (P &lt; 0.05) in growing pigs (4,792 to 3,897 kcal/kg dry matter) compared with broiler chickens (3,591 to 3,306 kcal/kg dry matter). The ME value of unautoclaved poultry meal was greater (P &lt; 0.01) for pigs than broiler chickens at 4,792 vs. 3,591 kcal/kg dry matter. Although decrease in ME values with autoclaving time of poultry meal was greater in growing pigs than in broiler chickens, the ME in autoclaved poultry meal fed to pigs was greater than ME in non-autoclaved poultry meal fed to broiler chickens. Furthermore, the ratio of cysteine to crude protein concentration is a potential indicator for estimating the ratio of ME to gross energy in poultry meal for growing pigs (r2 = 0.81) and broiler chickens (r2 = 0.84).
Entrectinib in children and young adults with solid or primary CNS tumors harboring NTRK, ROS1, or ALK aberrations (STARTRK-NG)
Authors: Desai Ami V , Robinson Giles W , Gauvain Karen , Basu Ellen M , Macy Margaret E , Maese Luke , Whipple Nicholas S , Sabnis Amit J , Foster Jennifer H , Shusterman Suzanne , Yoon Janet , Weiss Brian D , Abdelbaki Mohamed S , Armstrong Amy E , Cash Thomas , Pratilas Christine A , Corradini Nadège , Marshall Lynley V , Farid-Kapadia Mufiza , Chohan Saibah , Devlin Clare , Meneses-Lorente Georgina , Cardenas Alison , Hutchinson Katherine E , Bergthold Guillaume , Caron Hubert , Chow Maneval Edna , Gajjar Amar , Fox Elizabeth 
Published: April 2022

Abstract

Background
Entrectinib is a TRKA/B/C, ROS1, ALK tyrosine kinase inhibitor approved for the treatment of adults and children aged ≥12 years with NTRK fusion-positive solid tumors and adults with ROS1 fusion-positive non–small-cell lung cancer. We report an analysis of the STARTRK-NG trial, investigating the recommended phase 2 dose (RP2D) and activity of entrectinib in pediatric patients with solid tumors including primary central nervous system tumors.

Methods
STARTRK-NG (NCT02650401) is a phase 1/2 trial. Phase 1, dose-escalation of oral, once-daily entrectinib, enrolled patients aged &lt;22 years with solid tumors with/without target NTRK1/2/3, ROS1, or ALK fusions. Phase 2, basket trial at the RP2D, enrolled patients with intracranial or extracranial solid tumors harboring target fusions or neuroblastoma. Primary endpoints: phase 1, RP2D based on toxicity; phase 2, objective response rate (ORR) in patients harboring target fusions. Safety-evaluable patients: ≥1 dose of entrectinib; response-evaluable patients: measurable/evaluable baseline disease and ≥1 dose at RP2D.

Results
At data cutoff, 43 patients, median age of 7 years, were response-evaluable. In phase 1, 4 patients experienced dose-limiting toxicities. The most common treatment-related adverse event was weight gain (48.8%). Nine patients experienced bone fractures (20.9%). In patients with fusion-positive tumors, ORR was 57.7% (95% CI 36.9-76.7), median duration of response was not reached, and median (interquartile range) duration of treatment was 10.6 months (4.2-18.4).

Conclusions
Entrectinib resulted in rapid and durable responses in pediatric patients with solid tumors harboring NTRK1/2/3 or ROS1 fusions.
Dichotomous Role of Jasmonic Acid in Modulating Sorghum Defense Against Aphids
Authors: Grover Sajjan , Puri Heena , Xin Zhanguo , Sattler Scott E. , Louis Joe 
Published: April 2022

The precursors and derivatives of jasmonic acid (JA) contribute to plant protective immunity to insect attack. However, the role of JA in sorghum ( Sorghum bicolor) defense against sugarcane aphid (SCA) ( Melanaphis sacchari), which is considered a major threat to sorghum production, remains elusive. Sorghum SC265, previously identified as a SCA-resistant genotype among the sorghum nested association mapping founder lines, transiently increased JA at early stages of aphid feeding and deterred aphid settling. Monitoring of aphid feeding behavior using electropenetrography, a technique to unveil feeding process of piercing-sucking insects, revealed that SC265 plants restricted SCA feeding from the phloem sap. However, exogenous application of JA attenuated the resistant phenotype and promoted improved aphid feeding and colonization on SC265 plants. This was further confirmed with sorghum JA-deficient plants, in which JA deficiency promoted aphid settling, however, it also reduced aphid feeding from the phloem sap and curtailed SCA population. Exogenous application of JA caused enhanced feeding and aphid proliferation on JA-deficient plants, suggesting that JA promotes aphid growth and development. SCA feeding on JA-deficient plants altered the sugar metabolism and enhanced the levels of fructose and trehalose compared with wild-type plants. Furthermore, aphid artificial diet containing fructose and trehalose curtailed aphid growth and reproduction. Our findings underscore a previously unknown dichotomous role of JA, which may have opposing effects by deterring aphid settling during the early stage and enhancing aphid proliferative capacity during later stages of aphid colonization on sorghum plants. [Formula: see text] Copyright © 2022 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Stereotactic Body Radiation Therapy (SBRT) for Spinal Metastases
Authors: Singh Raj , Valluri Anisha , Jenkins Jan , Davis Joanne , Vargo John A. , Sharma Sanjeev 
Published: April 2022

Objective:
The objective of this study was to compare clinical outcomes following single fraction versus fractionated stereotactic body radiotherapy (SBRT) for spinal metastases.

Materials and Methods:
A multi-institutional registry was queried for patients with spinal metastases treated with single-fraction or fractionated SBRT. Potential predictive factors of local control (LC) and overall survival were evaluated. Pretreatment and posttreatment Visual Analog Scale scores were analyzed to examine initial and durable pain responses and complete response (CR) rates. Logistic regression was utilized to assess potential correlations between pain response, biologically effective dose (BED), and fractionation.

Results:
Four hundred sixty-six patients with 514 lesions treated with SBRT were identified; 209 and 104 lesions had information on LC and pain, respectively. The median pain score of patients with symptoms was 6 (range: 3 to 10). The median follow-up was 8.9 months (range: 0.4 to 125.5 mo). Utilizing Karnofsky Performance Score, age, and primary site (lung and/or nonbreast), 1-year overall survival rates were 76.1%, 59.1%, 54.9%, 37.2%, and 23.5% for patients with 0 to 4 of these factors, respectively (P<0.0001). One- and 2-year LC rates were 79.9% and 73.6%, respectively. Eighty-six patients (82.7%) had an initial pain response with a median decline of 3.5 and a CR rate of 47.1%. Sixty-five patients (62.5%) had a durable pain response with a median decline of 2 and a CR rate of 20.2%. Higher initial CR rates were observed with BED10 ≥51 Gy10 (58.7% vs. 37.9%; P=0.04).

Conclusions:
Following SBRT, encouraging palliative responses with >80% and 60% of patients having initial and durable pain responses, respectively. Dose escalation may result in improved initial CR rates. Performance status, age, and primary histology are factors to consider in the absence of pain.
Incretin-Based Drugs and the Incidence of Prostate Cancer Among Patients With Type 2 Diabetes
Authors: Lu Sally , Yin Hui , Yu Oriana H. Y. , Azoulay Laurent 
Published: April 2022

Background:
There is some evidence that glucagon-like peptide 1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors have chemopreventive effects on prostate cancer cells but real-world evidence for this possible effect is lacking. Thus, the objective of this study was to estimate whether use of GLP-1 receptor agonists and DPP-4 inhibitors, separately, is associated with a decreased risk of prostate cancer among patients with type 2 diabetes.

Methods:
We assembled two new-user, active-comparator cohorts using the UK Clinical Practice Research Datalink (2007 to 2019). The first cohort included 5,063 initiators of GLP-1 receptor agonists and 112,955 of sulfonylureas. The second cohort included 53,529 initiators of DPP-4 inhibitors and 114,417 of sulfonylureas. We fit Cox proportional hazards models to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for prostate cancer. We weighted the models using propensity score fine stratification, which considered over 50 potential confounders.

Results:
GLP-1 receptor agonists were associated with a decreased risk of prostate cancer when compared with sulfonylureas (incidence rates = 156.4 vs. 232.0 per 100,000 person-years, respectively; HR = 0.65; 95% CI = 0.43, 0.99). DPP-4 inhibitors were also associated with a decreased risk of prostate cancer when compared with sulfonylureas (incidence rates = 316.2 vs. 350.5 events per 100,000 person-years, respectively; HR = 0.90; 95% CI = 0.81, 1.00).

Conclusions:
The results of this study are consistent with the hypothesis that the use of GLP-1 receptor agonists and DPP-4 inhibitors, separately, may decrease the risk of prostate cancer when compared with the use of sulfonylureas.
Effects of a Modified Chitosan Compound Combined with Lung Lavage after Inhalation of Depleted Uranium Dust
Authors: Xiao Yao , Zeng Feng , Fu Weilin , Zhang Yi , Chen Xiangyu , Liang Yi , Li Rong , Liu Minghua 
Published: April 2022

Abstract
When exposed to depleted uranium (DU), the respiratory tract is the main route for DU to enter the body. At present, lung lavage is considered to be a method for removing DU from the lung. However, there is still room for improvement in the efficiency of lung lavage. In this work, a model of DU dust inhalation injury was established in beagle dogs so that chitosan-diethylenetriaminepentaacetic nanoparticles (CS-DTPA NP) could be synthesized. The purpose of this work was to evaluate the removal efficiency of CS-DTPA NP combined with lung lavage in dogs. Results showed that 7 d after DU exposure, the diethylenetriaminepentaacetic (DTPA) and CS-DTPA NP groups showed lower U content in kidney tissue compared with the normal saline (NS) group. In the left lung tissue (lavage fluid and recovery rate of lavage fluid), the U content in the CS-DTPA NP group was higher than in the NS and DTPA groups. In terms of blood levels, the CS-DPTA NP group increased over time at 1, 3 and 7 d of DU exposure without lavage; however, the U levels in the 3 and 7 d lavage groups were significantly lower than in the non-lavage groups. IL-1 in the lavage fluid of the CS-DPTA NP and CS NPs group were lower than in the NS group. In summary, after respiratory exposure to DU, early inhalation of CS-DPTA NP may block insoluble DU particles in the lung, and if combined with lung lavage, the clearance efficiency of DU from lung tissue improves.