bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of DNAH17 Variants in Han-Chinese Patients With Left–Right Asymmetry Disorders
Authors: Yu Xuehui , Yuan Lamei , Deng Sheng , Xia Hong , Tu Xiaolong , Deng Xiong , Huang Xiangjun , Cao Xiao , Deng Hao
Published: May 2022

The formation of left–right asymmetry of the visceral organs is a conserved feature of the human body, and the asymmetry specification of structure and function is precisely orchestrated by multiple regulatory mechanisms. The abnormal results of organ positioning situs arise from defective cilia structure or function during embryogenesis in humans. In this study, we recruited two unrelated Han-Chinese families with left–right asymmetry disorders. The combination of whole-exome sequencing and Sanger sequencing identified two compound heterozygous variants: c.4109C>T and c.9776C>T, and c.612C>G and c.8764C>T in the dynein axonemal heavy chain 17 gene (DNAH17) in two probands with left–right asymmetry disorders. We report for the first time a possible association between DNAH17 gene variants and left–right asymmetry disorders, which is known as a causal gene for asthenozoospermia. Altogether, the findings of our study may enlarge the DNAH17 gene variant spectrum in human left–right asymmetry disorders, pave a way to illustrate the potential pathogenesis of ciliary/flagellar disorders, and provide supplementary explanation for genetic counseling.
Ancient Mitogenomes Reveal the Origins and Genetic Structure of the Neolithic Shimao Population in Northern China
Authors: Xue Jiayang , Wang Wenjun , Shao Jing , Dai Xiangming , Sun Zhouyong , Gardner Jacob D. , Chen Liang , Guo Xiaoning , Di Nan , Pei Xuesong , Wu Xiaohong , Zhang Ganyu , Cui Can , Cao Peng , Liu Feng , Dai Qingyan , Feng Xiaotian , Yang Ruowei , Ping Wanjing , Zhang Lizhao , He Nu , Fu Qiaomei
Published: May 2022

Shimao City is considered an important political and religious center during the Late Neolithic Longshan period of the Middle Yellow River basin. The genetic history and population dynamics among the Shimao and other ancient populations, especially the Taosi-related populations, remain unknown. Here, we sequenced 172 complete mitochondrial genomes, ranging from the Yangshao to Longshan period, from individuals related to the Shimao culture in northern Shaanxi Province and Taosi culture in southern Shanxi Province, Middle Yellow River basin. Our results show that the populations inhabiting Shimao City had close genetic connections with an earlier population in the Middle Neolithic Yangshao period of northern Shaanxi Province, revealing a mostly local origin for the Shimao Society. In addition, among the populations in other regions of the Yellow River basin, the Shimao-related populations had the closest maternal affinity with the contemporaneous Taosi populations from the Longshan period. The Shimao-related populations also shared more affinity with present-day northern Han populations than with the minorities and southern Han in China. Our study provides a new perspective on the genetic origins and structure of the Shimao people and the population dynamics in the Middle Yellow River basin during the Neolithic period.
Engineering Silicon Oxide by Argon Ion Implantation for High Performance Resistance Switching
Authors: Zhao L. , Ng W. H. , Knights A. P. , Stevanovic D. V. , Mannion D. J. , Mehonic A. , Kenyon A. J.
Published: May 2022

We report that implanting argon ions into a film of uniform atomic layer deposition (ALD)-grown SiOx enables electroforming and switching within films that previously failed to electroform at voltages <15 V. We note an implantation dose dependence of electroforming success rate: electroforming can be eliminated when the dosage is high enough. Our devices are capable of multi-level switching during both set and reset operations, and multiple resistance states can be retained for more than 30,000 s under ambient conditions. High endurance of more than 7 million (7.9 × 106) cycles is achieved alongside low switching voltages (±1 V). Comparing SiOx fabricated by this approach with sputtered SiOx we find similar conduction mechanisms between the two materials. Our results show that intrinsic SiOx switching can be achieved with defects created solely by argon bombardment; in contrast to defects generated during deposition, implantation generated defects are potentially more controllable. In the future, noble ion implantation into silicon oxide may allow optimization of already excellent resistance switching devices.
Experimental Investigation of Cavitation-Induced Erosion Using X-Ray Imaging and Tomography
Authors: Moon Chi Young , Magnotti Gina M. , Sforzo Brandon A. , Tekawade Aniket , Kastengren Alan L. , Powell Christopher F.
Published: May 2022

High injection pressure in diesel engines can lead to cavitation-induced erosion in injector nozzles. One important factor affecting the severity of erosion is the fuel and its properties. Traditionally, modeling and simulation studies have used single-component representations of fuels, but realistic fuels feature a multitude of components and can even include volatile additives such as water and alcohol. To provide realistic benchmarks and comparisons, experimental measurements quantifying erosion characteristics were made using ultra-low sulfur diesel (ULSD) and two alternative diesel fuels (ADF). X-ray imaging and computed tomography were used to investigate cavitation-induced erosion onset and progression. Hard X-ray tomography revealed injector internal geometry, including details such as surface marks from the manufacturing process and erosion patterns from repeated injections. Erosion progression was measured using X-ray tomography and imaging performed between injections. The critical erosion site was found to be similar across different fuel blends, while the erosion rate and incubation time were sensitive to the fuel blend. The injector geometry and the erosion characteristics were also prepared for numerical model development and validation.
Differential Effect of Generalized and Abdominal Obesity on the Development and Progression of Diabetic Retinopathy in Chinese Adults With Type 2 Diabetes
Authors: Han Xiaoyan , Wu Huimin , Li Youjia , Yuan Meng , Gong Xia , Guo Xiao , Tan Rongqiang , Xie Ming , Liang Xiaoling , Huang Wenyong , Liu Hua , Wang Lanhua
Published: May 2022

Background

The relationship between obesity and diabetic retinopathy (DR) remains controversial. The aim of this study was to assess the association of generalized obesity [assessed by body mass index (BMI)] and abdominal obesity [assessed by waist to hip ratio (WHR)] with incident DR, and vision-threatening DR (VTDR), and DR progression among Chinese adults with type 2 diabetic mellitus (T2DM).

Method

This prospective cohort study was conducted at the Zhongshan Ophthalmic Center, from November 2017 to December 2020. DR was assessed based on the 7-filed fundus photographs using the modified Airlie House Classification. Multivariable logistic regression models were used to evaluate the associations of BMI and WHR with the development and progression of DR after adjusting for age, sex, traditional risk factors, and mutually for BMI and WHR.

Results

Among the 1,370 eligible participants, 1,195 (87.2%) had no sign of any DR and 175 (12.8%) had DR at baseline examination. During the 2 years follow-up visit, 342 (28.6%) participants had incident DR, 11 (0.8%) participants developed VTDR, 15 (8.6%) demonstrated DR progression. After adjusting for confounders, the BMI was negatively associated with incident DR [relative risk (RR) =0.31; 95% confidence interval (CI), 0.26–0.38; P < 0.001] and incident VTDR (RR = 0.22; 95%CI, 0.11–0.43; P < 0.001), while WHR was positively associated with incident DR (RR = 1.47; 95% CI, 1.27–1.71; P < 0.001). BMI and WHR level were not significantly associated with 2-year DR progression in multivariate models (all P > 0.05).

Conclusions

This study provides longitudinal evidence that generalized obesity confer a protective effect on DR, while abdominal obesity increased the risk of DR onset in Chinese patients, indicating that abdominal obesity is a more clinically relevant risk marker of DR than generalized obesity.
Protocol for a Phase 1, Open-Label, Multiple-Center, Dose-Escalation Study to Evaluate the Safety and Tolerability of ADR-001 in the Treatment of Immunoglobulin A Nephropathy
Authors: Tanaka Akihito , Furuhashi Kazuhiro , Fujieda Kumiko , Maeda Kayaho , Saito Shoji , Mimura Tetsushi , Saka Yosuke , Naruse Tomohiko , Ishimoto Takuji , Kosugi Tomoki , Kinoshita Fumie , Kuwatsuka Yachiyo , Shimizu Shinobu , Nakai Yasuhiro , Maruyama Shoichi
Published: May 2022

Introduction

Immunoglobulin A (IgA) nephropathy is a disease that presents with urinary symptoms such as glomerular hematuria and urinary protein positivity, with predominant deposition of IgA in the mesangial region of the glomerulus. Corticosteroids are mainly used for treatment; however, infection is a serious adverse event, and evidence regarding therapeutic efficacy is insufficient, thus new treatments are strongly desired. Mesenchymal stem cells (MSCs) contribute to the amelioration of inflammation and recovery of organ function in inflammatory environments by converting the character of leukocytes from inflammatory to anti-inflammatory and inducing the proliferation and differentiation of organ component cells, respectively. These properties of MSCs have led to their clinical application in various inflammatory diseases, but this study is the first clinical trial of MSCs for refractory glomerulonephritis in the world. This study is registered and assigned the number, jRCT2043200002 and NCT04342325.

Methods

This will be a phase 1, open-label, multiple-center, dose-escalation study of adult patients with refractory IgA nephropathy resistant to or difficult to treat with existing therapies. ADR-001 will be administered intravenously to from three to six patients at a dose of 1 × 108 cells once in the first cohort and to six patients twice at 2-week intervals in the second cohort, and observation will continue until 52 weeks. The primary endpoint will be the evaluation of adverse events up to 6 weeks after the start of ADR-001 administration. Secondary endpoints will be the respective percentages of patients with adverse events, clinical remission, partial remission, remission of urine protein, remission of hematuria, time to remission, changes in urine protein, hematuria, and estimated glomerular filtration rate.

Results

Following the administration of ADR-001 to patients with IgA nephropathy, the respective percentages of patients with adverse events, asymptomatic pulmonary emboli, clinical remission, partial remission, urine protein remission, hematuria remission, their time to remission, changes in urine protein, hematuria, and glomerular filtration rate will be determined.

Conclusion

This study will evaluate the safety and tolerability of ADR-001 and confirm its therapeutic efficacy in adult patients with refractory IgA nephropathy.
HIV Transmembrane Glycoprotein Conserved Domains and Genetic Markers Across HIV-1 and HIV-2 Variants
Authors: Valadés-Alcaraz Ana , Reinosa Roberto , Holguín África
Published: May 2022

HIV envelope transmembrane glycoproteins gp41 (HIV-1) and gp36 (HIV-2) present high variability and play a key role in the HIV-host cell membrane's fusion, as a target for human broadly neutralizing antibodies (bnAbs) and drugs. Thus, a better knowledge of amino acid (aa) conservation across structural domains and HIV variants can help to identify conserved targets to direct new therapeutic and diagnostic strategies. All available gp41/gp36 nucleotide sequences were downloaded from Los Alamos National Laboratory (LANL) HIV Sequence Database, selecting 17,078 sequences ascribed to HIV-1 and HIV-2 variants with ≥3 sequences. After aligning and translating into aa with MEGAv6.0, an in-house bioinformatics program (EpiMolBio) was used to identify the most conserved aa and the aa changes that were specific for each variant (V-markers) vs. HXB2/BEN (HIV-1/HIV-2) reference sequence. We analyzed the presence of specific aa changes among V-markers affecting infectivity, gp41 structure, function, or resistance to the enfuvirtide viral fusion inhibitor (T-20). We also inferred the consensus sequences per HIV variant, describing in each HIV-1 group (M, N, O, P) the conservation level along the complete gp41 per structural domain and locating in each binding site the anti-gp41 human Abs (bnAbs and non bnAbs) described in LANL. We found 38.3/59.7% highly conserved aa present in ≥90% of the 16,803/275 gp41/gp36 sequences ascribed to 105/3 HIV-1/HIV-2 variants, with 9/12.6% of them showing complete conservation across LANL sequences. The fusion peptide, its proximal region, the N-heptad repeat, and the membrane-proximal external region were the gp41 domains with ≥84% of conserved aa in the HIV-1 consensus sequence, the target of most Abs. No natural major resistance mutations to T-20 were observed. Our results show, for the first time, a complete conservation study of gp41/gp36 per variant in the largest panel of HIV variants analyzed to date, providing useful information for a more rational design of drugs, vaccines, and molecular detection tests targeting the HIV transmembrane glycoprotein.
Rational Framework for the Design of Trp- and Arg-Rich Peptide Antibiotics Against Multidrug-Resistant Bacteria
Authors: Xiang Wenyu , Clemenza Patrice , Klousnitzer Jessie , Chen Jespar , Qin Weiheng , Tristram-Nagle Stephanie , Doi Yohei , Di Y. Peter , Deslouches Berthony
Published: May 2022

The threat of antibiotic resistance warrants the discovery of agents with novel antimicrobial mechanisms. Antimicrobial peptides (AMPs) directly disrupting bacterial membranes may overcome resistance to traditional antibiotics. AMP development for clinical use has been mostly limited to topical application to date. We developed a rational framework for systematically addressing this challenge using libraries composed of 86 novel Trp- and Arg-rich engineered peptides tested against clinical strains of the most common multidrug-resistant bacteria known as ESKAPE pathogens. Structure-function correlations revealed minimum lengths (as low as 16 residues) and Trp positioning for maximum antibacterial potency with mean minimum inhibitory concentration (MIC) of 2–4 μM and corresponding negligible toxicity to mammalian cells. Twelve peptides were selected based on broad-spectrum activity against both gram-negative and -positive bacteria and <25% toxicity to mammalian cells at maximum test concentrations. Most of the selected PAX remained active against the colistin-resistant clinical strains. Of the selected peptides, the shortest (the 16-residue E35) was further investigated for antibacterial mechanism and proof-of-concept in vivo efficacy. E35 killed an extensively-resistant isolate of Pseudomonas aeruginosa (PA239 from the CDC, also resistant to colistin) by irreversibly disrupting the cell membranes as shown by propidium iodide incorporation, using flow cytometry and live cell imaging. As proof of concept, in vivo toxicity studies showed that mice tolerated a systemic dose of up to 30 mg/kg peptide and were protected with a single 5 mg/kg intravenous (IV) dose against an otherwise lethal intraperitoneal injection of PA239. Efficacy was also demonstrated in an immune-compromised Klebsiella pneumoniae infection model using a daily dose of 4mg/kg E35 systemically for 2 days. This framework defines the determinants of efficacy of helical AMPs composed of only cationic and hydrophobic amino acids and provides a path for a potential departure from the restriction to topical use of AMPs toward systemic application.
Current Knowledge on the Role of Cardiolipin Remodeling in the Context of Lipid Oxidation and Barth Syndrome
Authors: Liang Zhuqing , Schmidtke Michael W. , Greenberg Miriam L.
Published: May 2022

Barth syndrome (BTHS, OMIM 302060) is a genetic disorder caused by variants of the TAFAZZIN gene (G 4.5, OMIM 300394). This debilitating disorder is characterized by cardio- and skeletal myopathy, exercise intolerance, and neutropenia. TAFAZZIN is a transacylase that catalyzes the second step in the cardiolipin (CL) remodeling pathway, preferentially converting saturated CL species into unsaturated CLs that are susceptible to oxidation. As a hallmark mitochondrial membrane lipid, CL has been shown to be essential in a myriad of pathways, including oxidative phosphorylation, the electron transport chain, intermediary metabolism, and intrinsic apoptosis. The pathological severity of BTHS varies substantially from one patient to another, even in individuals bearing the same TAFAZZIN variant. The physiological modifier(s) leading to this disparity, along with the exact molecular mechanism linking CL to the various pathologies, remain largely unknown. Elevated levels of reactive oxygen species (ROS) have been identified in numerous BTHS models, ranging from yeast to human cell lines, suggesting that cellular ROS accumulation may participate in the pathogenesis of BTHS. Although the exact mechanism of how oxidative stress leads to pathogenesis is unknown, it is likely that CL oxidation plays an important role. In this review, we outline what is known about CL oxidation and provide a new perspective linking the functional relevance of CL remodeling and oxidation to ROS mitigation in the context of BTHS.
Research Hotspots and Trends of Exercise on Parkinson's Disease: A Global Bibliometric Analysis From 2012 to 2021
Authors: Chen Ji-Wei , Du Shu-Hao , Chen Tian-Cong , Zhu Kun
Published: May 2022

Background

Parkinson's disease is a chronic neurodegenerative disease, which can be alleviated in drug treatment, but with evident side effects. At the same time, increasing evidence shows that exercise can significantly improve the symptoms of patients with Parkinson's disease, with an effect that cannot be achieved by drug treatment. The related research on exercise on Parkinson's disease increases rapidly with the passage of time. However, the research analysis on Parkinson's disease by means of bibliometrics is rare. The purpose of this study is to perform a bibliometric analysis of the research hotspots and development trends of the global movement on Parkinson's disease from 2012 to 2021.

Methods

The literature was derived from the Web of Science core collection database, and the social science citation index was set as SCI-EXPANDED. The language was set to English, and the literature category was set as article and review and published from 2012 to 2021. CiteSpace and other software were used to analyze the relationship among published documents, countries, institutions, journals, authors, references, disciplines, and keywords.

Results

A total of 2,222 articles were included in the analysis. The analysis showed that the publication volume increased with the increase in years, with a total of 76 countries and 546 academic journals published; the largest number was that of the United States. The journals are mainly concentrated in the fields of neurology, sports, and ophthalmology. Rush University and Movement Disorders journals are the main institutions and journals. The cited keywords show that trial, cognition, and interference are the research hotspots and development trends in recent years.

Conclusion

The number of published articles on Parkinson's disease by exercise has increased rapidly in the past 10 years, and the bibliometric analysis can provide useful information for future research teams and researchers.
A Facile Method to Produce N-Terminally Truncated α-Synuclein
Authors: Thrush Rebecca J. , Vadukul Devkee M. , Aprile Francesco A.
Published: May 2022

α-Synuclein is a key protein of the nervous system, which regulates the release and recycling of neurotransmitters in the synapses. It is also involved in several neurodegenerative conditions, including Parkinson’s disease and Multiple System Atrophy, where it forms toxic aggregates. The N-terminus of α-synuclein is of particular interest as it has been linked to both the physiological and pathological functions of the protein and undergoes post-translational modification. One such modification, N-terminal truncation, affects the aggregation propensity of the protein in vitro and is also found in aggregates from patients’ brains. To date, our understanding of the role of this modification has been limited by the many challenges of introducing biologically relevant N-terminal truncations with no overhanging starting methionine. Here, we present a method to produce N-terminally truncated variants of α-synuclein that do not carry extra terminal residues. We show that our method can generate highly pure protein to facilitate the study of this modification and its role in physiology and disease. Thanks to this method, we have determined that the first six residues of α-synuclein play an important role in the formation of the amyloids.
Artesunate Alleviates Paclitaxel-Induced Neuropathic Pain in Mice by Decreasing Metabotropic Glutamate Receptor 5 Activity and Neuroinflammation in Primary Sensory Neurons
Authors: Li Yize , Kang Jiamin , Xu Ying , Li Nan , Jiao Yang , Wang Chenxu , Wang Chunyan , Wang Guolin , Yu Yonghao , Yuan Jingjing , Zhang Linlin
Published: May 2022

Experimental studies on the pathogenetic process of paclitaxel-induced neuropathic pain (PINP) have been initially carried out, but PINP still has no effective therapy. Recently reported studies have highlighted the involvement of glutamate receptors and neuroinflammation in peripheral and central nociceptive transmission in PINP. Artesunate is a first-line antimalarial drug with established efficacy in alleviating pain in a variety of pathologies. The current work assessed whether artesunate inhibits PINP by modulating metabotropic glutamate receptor 5 (mGluR5) and neuroinflammation in mice. The anti-hyperalgesic effect of artesunate was verified by assessing mechanical frequency and thermal latency in the paw withdrawal test as well as spontaneous pain. The expression levels of mGluR5, pain-related receptors and neuroinflammatory markers in dorsal root ganglion (DRG) were examined. In addition, treatment with CHPG and 2-methyl-6-(phenyl ethynyl) pyridine (MPEP) (mGluR5 agonist and antagonist, respectively) was performed to determine mGluR5’s role in the anti-hyperalgesic properties of artesunate. We demonstrated artesunate prevented PINP in a dose-dependent manner, while exerting a clear anti-hyperalgesic effect on already existing PINP. Artesunate normalized paclitaxel-related expression changes in DRG mGluR5, NR1, and GluA2, as well as six paclitaxel related neuroinflammation markers. Intrathecal application of MPEP treated PINP by reversing NR1 and GluA2 expression changes but had no effects on chemokines and inflammatory factors. Furthermore, artesunate treatment reversed acute pain following CHPG application. In conclusion, this study revealed that artesunate alleviates paclitaxel-induced hyperalgesia and spontaneous pain by decreasing DRG mGluR5 expression and neuroinflammation in the mouse model of PINP.
Early-Stage Loss of GALNT6 Predicts Poor Clinical Outcome in Colorectal Cancer
Authors: Ogawa Makiko , Tanaka Atsushi , Namba Kei , Shia Jinru , Wang Julia Y. , Roehrl Michael H.
Published: May 2022

Colorectal adenocarcinomas arise from luminal lining epithelium of the colorectal tract which is covered with highly glycosylated mucins. Mucin O-glycosylation is initiated by a family of polypeptide N-acteylgalactosaminyltransferases (GALNTs). This study examined GALNT6 protein expression in 679 colorectal tumors, including 574 early-stage and 105 late-stage cancers. GALNT6 expression in cancer tissue varied widely between patients ranging from high levels to complete loss. Loss of GALNT6 occurred in 9.9% of early-stage and 15.2% of late-stage cancers and was more prevalent in grade 3 or MSI subtype tumors. Survival analyses revealed that loss of GALNT6 expression is prognostic of reduced overall survival, and univariate and multivariate analyses demonstrated that loss of GALNT6 is an independent risk variable. We also analyzed 508-case TCGA and 63-case CPTAC colorectal cancer cohorts for all members of the GALNT enzyme family, the mucin family, as well as KRAS and BRAF mutations. GLANT6 mRNA expression showed no strong correlation with other GALNTs or mucins but was significantly higher in KRAS mutated or BRAF wild-type early-stage cancers. Using large cohorts of patients and different approaches, this study shows that loss of GALNT6 enzyme in early-stage colorectal cancer predicts poor clinical outcomes.
Association of CT-Based Delta Radiomics Biomarker With Progression-Free Survival in Patients With Colorectal Liver Metastases Undergo Chemotherapy
Authors: Ye Shuai , Han Yu , Pan XiMin , Niu KeXin , Liao YuTing , Meng XiaoChun
Published: May 2022

Predicting the prognosis of patients in advance is conducive to providing personalized treatment for patients. Our aim was to predict the therapeutic efficacy and progression free survival (PFS) of patients with liver metastasis of colorectal cancer according to the changes of computed tomography (CT) radiomics before and after chemotherapy.

Methods

This retrospective study included 139 patients (397 lesions) with colorectal liver metastases who underwent neoadjuvant chemotherapy from April 2015 to April 2020. We divided the lesions into training cohort and testing cohort with a ratio of 7:3. Two - dimensional region of interest (ROI) was obtained by manually delineating the largest layers of each metastasis lesion. The expanded ROI (3 mm and 5 mm) were also included in the study to characterize microenvironment around tumor. For each of the ROI, 1,316 radiomics features were extracted from delineated plain scan, arterial, and venous phase CT images before and after neoadjuvant chemotherapy. Delta radiomics features were constructed by subtracting the radiomics features after treatment from the radiomics features before treatment. Univariate Cox regression and the Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression were applied in the training cohort to select the valuable features. Based on clinical characteristics and radiomics features, 7 Cox proportional-hazards model were constructed to predict the PFS of patients. C-index value and Kaplan Meier (KM) analysis were used to evaluate the efficacy of predicting PFS of these models. Moreover, the prediction performance of one-year PFS was also evaluated by area under the curve (AUC).

Results

Compared with the PreRad (Radiomics form pre-treatment CT images; C-index [95% confidence interval (CI)] in testing cohort: 0.614(0.552-0.675) and PostRad models (Radiomics form post-treatment CT images; 0.642(0.578-0.707), the delta model has better PFS prediction performance (Delta radiomics; 0.688(0.627-0.749). By incorporating clinical characteristics, CombDeltaRad obtains the best performance in both training cohort [C-index (95% CI): 0.802(0.772-0.832)] and the testing cohort (0.744(0.686-0.803). For 1-year PFS prediction, CombDeltaRad model obtained the best performance with AUC (95% CI) of 0.871(0.828-0.914) and 0.745 (0.651-0.838) in training cohort and testing cohort, respectively.

Conclusion

CT radiomics features have the potential to predict PFS in patients with colorectal cancer and liver metastasis who undergo neoadjuvant chemotherapy. By combining pre-treatment radiomics features, post-treatment radiomics features, and clinical characteristics better prediction results can be achieved.
Thyroid Cancer Screening Using Tumor-Associated DN T Cells as Immunogenomic Markers
Authors: Imam Shahnawaz , Paparodis Rodis D. , Rafiqi Shafiya Imtiaz , Ali Sophia , Niaz Azra , Kanzy Abed , Tovar Yara E. , Madkhali Mohammed A. , Elsherif Ahmed , Khogeer Feras , Zahid Zeeshan A. , Sarwar Haider , Karim Tamanna , Salim Nancy , Jaume Juan C.
Published: May 2022

Background

Thyroid nodules are an extremely common entity, and surgery is considered the ultimate diagnostic strategy in those with unclear malignant potential. Unfortunately, strategies aiming to predict the risk of malignancy have inadequate specificity. Our group recently found that the microenvironment of thyroid cancer is characterized by an enhanced immune invasion and activated immune response mediated by double-negative T lymphocytes (DN T) (CD3+CD4-CD8-), which are believed to enable or promote tumorigenesis. In the present work, we try to use the DN T cells’ proportion in thyroid fine-needle aspiration (FNA) material as a predictor of the risk of malignancy.

Methods

We recruited 127 patients and obtained ultrasound-guided FNA samples from subjects with cytology-positive or suspicious for malignancy and from those with benign nodular goiter associated with compressive symptoms (such as dysphagia, shortness of breath, or hoarseness), Hashimoto thyroiditis, and Graves’ disease. Out of 127, we investigated 46 FNA samples of patients who underwent total thyroidectomy and for which postoperative histological diagnosis by the academic pathologists was available. We specifically measured the number of cells expressing CD3+CD4-CD8-(DN T) as a function of total CD3+cells in FNA samples using flow cytometry. We correlated their FNA DN T-cell proportions with the pathological findings.

Results

The DN T cells were significantly more abundant in lymphocytic infiltrates of thyroid cancer cases compared to benign nodule controls (p < 0.0001). When the DN T-cell population exceeded a threshold of 9.14%, of total CD3+cells, the negative likelihood ratio of being cancer-free was 0.034 (96.6% sensitivity, 95% CI, 0.915–1.000, p < 0.0001). DN T cells at <9.14% were not found in any subject with benign disease (specificity 100%). The high specificity of the test is promising, since it abolishes a false-positive diagnosis and in turn unnecessary surgical procedures.

Conclusion

The present study proposes DN T cells’ proportion as a preoperative diagnostic signature for thyroid cancer that with integration of RNA transcriptomics can provide a simplified technology based on the PCR assay for the ease of operation.
Development of a Nomogram for Clinical Risk Prediction of Preterm Neonate Death in Ethiopia
Authors: Hailemeskel Habtamu Shimels , Tiruneh Sofonyas Abebaw
Published: May 2022

Introduction

In 2020, over 6,500 newborn deaths occured every day, resulting in 2.4 million children dying in their 1st month of life. Ethiopia is one of the countries that will need to step up their efforts and expedite progress to meet the 2030 sustainable development goal. Developing prediction models to forecast the mortality of preterm neonates could be valuable in low-resource settings with limited amenities, such as Ethiopia. Therefore, the study aims to develop a nomogram for clinical risk prediction of preterm neonate death in Ethiopia in 2021.

Methods

A prospective follow-up study design was employed. The data were used to analyze using R-programming version 4.0.3 software. The least absolute shrinkage and selection operator (LASSO) regression is used for variable selection to be retained in the multivariable model. The model discrimination probability was checked using the ROC (AUROC) curve area. The model’s clinical and public health impact was assessed using decision curve analysis (DCA). A nomogram graphical presentation created an individualized prediction of preterm neonate risk of mortality.

Results

The area under the receiver operating curve (AUROC) discerning power for five sets of prognostic determinants (gestational age, respiratory distress syndrome, multiple neonates, low birth weight, and kangaroo mother care) is 92.7% (95% CI: 89.9–95.4%). This prediction model was particular (specificity = 95%) in predicting preterm death, with a true positive rate (sensitivity) of 77%. The best cut point value for predicting a high or low risk of preterm death (Youden index) was 0.3 (30%). Positive and negative predictive values at the Youden index threshold value were 85.4 percent and 93.3 percent, respectively.

Conclusion

This risk prediction model provides a straightforward nomogram tool for predicting the death of preterm newborns. Following the preterm neonates critically based on the model has the highest cost-benefit ratio.
Quantum Computing Applications in Future Colliders
Authors: Gray Heather M. , Terashi Koji
Published: May 2022

High-energy physics is facing a daunting computing challenge with the large amount of data expected from the HL-LHC and other future colliders. In addition, the landscape of computation has been expanding dramatically with technologies beyond the standard x86 CPU architecture becoming increasingly available. Both of these factors necessitate an extensive and broad-ranging research and development campaign. As quantum computation has been evolving rapidly over the past few years, it is important to evaluate how quantum computation could be one potential avenue for development for future collider experiments. A wide variety of applications have been considered by different authors. We review here selected applications of quantum computing to high-energy physics, including topics in simulation, reconstruction, and the use of machine learning, and their challenges. In addition, recent advances in quantum computing technology to enhance such applications are briefly highlighted. Finally, we will discuss how such applications might transform the workflows of future collider experiments and highlight other potential applications.
The Impact of the COVID-19 Pandemic on China's Airline Industry
Authors: Zhang Yuan , Zhu LinChuang , Hao Feng
Published: May 2022

Background

The COVID-19 pandemic has posed a great challenge to the development of China's airline industry. Although the existing literature has analyzed the economic impact of the pandemic on the airline industry from different perspectives, it remains to be further studied given the operating characteristics of different types of airlines in China.

Methods

Using a new perspective of heterogeneous airline service models, this study collects high-frequency data on stock prices on six sample airline companies (including both full-service airlines and low-cost airlines) in China over 519 trading days, from August 1, 2019 to September 15, 2021, and identifies structural change points for each company's stock price using the Quandt-Andrews test. The outcome is used to construct an econometric model to quantify the economic impact of the pandemic on different airlines' stock prices under different structural changes.

Results

All results have passed the Quandt-Andrews test. The impact coefficient of full-service airlines is negative, while that of low-cost airlines is positive. Most of them have passed the test at the significance level of 10%.

Conclusions

All Chinese airlines experienced significant sudden changes in stock prices due to the pandemic, but there are sectoral differences in the order of the sudden changes, with full-service airlines experiencing structural changes much earlier than low-cost airlines. In addition, the impact of the pandemic on stock prices varies across airline types, with a negative impact on full-service airlines and a significant positive effect on most low-cost airlines.
Generalized Edema and Pseudothrombocytopenia After ChAdOx1 nCoV-19 COVID-19 Vaccination: A Case Report
Authors: Bokel Joanna , Mendes-de-Almeida Daniela P. , Martins-Gonçalves Remy , Palhinha Lohanna , Vizzoni Alexandre G. , Correa Danusa Ferreira , Brandão Luciana Gomes Pedro , Bozza Patrícia T. , Grinsztejn Beatriz
Published: May 2022

Reports of side effects of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are increasing worldwide. Capillary leak syndrome and vaccine-induced immune thrombotic thrombocytopenia are very rare but life-threatening adverse events that should be identified early and treated. However, isolated thrombocytopenia can indicate pseudothrombocytopenia. In certain people, ethylenediaminetetraacetic acid (EDTA) induces an in vitro platelet aggregation, resulting in misleading underestimation of platelet counts. It is essential to recognize pseudothrombocytopenia to prevent diagnostic errors, overtreatment, anxiety, and unnecessary invasive procedures. We present a case who developed generalized edema and persistent pseudothrombocytopenia after the first dose of the ChAdOx1 nCoV-19 vaccine (AstraZeneca).
How Personality and Communication Patterns Affect Online ad-hoc Teams Under Pressure
Authors: Vinella Federica Lucia , Odo Chinasa , Lykourentzou Ioanna , Masthoff Judith
Published: May 2022

Critical, time-bounded, and high-stress tasks, like incident response, have often been solved by teams that are cohesive, adaptable, and prepared. Although a fair share of the literature has explored the effect of personality on various other types of teams and tasks, little is known about how it contributes to teamwork when teams of strangers have to cooperatead-hoc, fast, and efficiently. This study explores the dynamics between 120 crowd participants paired into 60 virtual dyads and their collaboration outcome during the execution of a high-pressure, time-bound task. Results show that the personality trait of Openness to experience may impact team performance with teams with higher minimum levels of Openness more likely to defuse the bomb on time. An analysis of communication patterns suggests that winners made more use of action and response statements. The team role was linked to the individual's preference of certain communication patterns and related to their perception of the collaboration quality. Highly agreeable individuals seemed to cope better with losing, and individuals in teams heterogeneous in Conscientiousness seemed to feel better about collaboration quality. Our results also suggest there may be some impact of gender on performance. As this study was exploratory in nature, follow-on studies are needed to confirm these results. We discuss how these findings can help the development of AI systems to aid the formation and support of crowdsourced remote emergency teams.
Electromyography of the Multifidus Muscle in Horses Trotting During Therapeutic Exercises
Authors: Ursini Tena , Shaw Karen , Levine David , Richards Jim , Adair Henry Steve
Published: May 2022

Thoracolumbar pain has been identified in both human and equine patients. Rehabilitation and conditioning programs have focused specifically on improving trunk and abdominal muscle function (1–5). Equine exercise programs routinely incorporate ground poles and training devices for the similar goals of increasing spinal and core stability and strength (6–8). The multifidus muscle has been an area of focus due to atrophy associated with disease (9). To date, there have been no reports on the activity of the multifidus muscle in horses in relation to therapeutic exercises. Our objectives were to use electromyography to determine the average work performed and peak muscle activity of the multifidus in horses trotting, trotting over ground poles, trotting while wearing a resistance band-based training device and trotting while wearing the training device over ground poles. We hypothesized that ground poles and the training device would each increase average work performed and peak multifidus muscle activity. Right and left cranial thoracic locations showed significant increased muscle work and peak activation when horses were trotted over ground poles versus without. The peak activation was significantly greater in horses trotting over poles in both lumbar regions, but there was no significant change in peak activation in either location due to the training device. When the influence of the training device was investigated without ground poles, left caudal thoracic muscle work and peak activity, and right lumbar muscle work were significantly lower when using the training device, as compared to without. When the training device was combined with trotting over ground poles, both left and right caudal thoracic regions showed significantly lower muscle work and peak activity when the device was used. There was no significant difference between with and without the device in either left or right lumbar muscle work. In conclusion, implementing ground poles can be an effective strategy to increase the activation of the multifidus muscle, however, caution should be taken when incorporating the use of a resistance band training device as muscle work and peak activation were significantly reduced in most locations. Further study should be performed in regards to the training device to determine its effects on epaxial musculature.
Twelve Threats of Precision Livestock Farming (PLF) for Animal Welfare
Authors: Tuyttens Frank A. M. , Molento Carla F. M. , Benaissa Said
Published: May 2022

Research and development of Precision Livestock Farming (PLF) is booming, partly due to hopes and claims regarding the benefits of PLF for animal welfare. These claims remain largely unproven, however, as only few PLF technologies focusing on animal welfare have been commercialized and adopted in practice. The prevailing enthusiasm and optimism about PLF innovations may be clouding the perception of possible threats that PLF may pose to farm animal welfare. Without claiming to be exhaustive, this paper lists 12 potential threats grouped into four categories: direct harm, indirect harm via the end-user, via changes to housing and management, and via ethical stagnation or degradation. PLF can directly harm the animals because of (1) technical failures, (2) harmful effects of exposure, adaptation or wearing of hardware components, (3) inaccurate predictions and decisions due to poor external validation, and (4) lack of uptake of the most meaningful indicators for animal welfare. PLF may create indirect effects on animal welfare if the farmer or stockperson (5) becomes under- or over-reliant on PLF technology, (6) spends less (quality) time with the animals, and (7) loses animal-oriented husbandry skills. PLF may also compromise the interests of the animals by creating transformations in animal farming so that the housing and management are (8) adapted to optimize PLF performance or (9) become more industrialized. Finally, PLF may affect the moral status of farm animals in society by leading to (10) increased speciesism, (11) further animal instrumentalization, and (12) increased animal consumption and harm. For the direct threats, possibilities for prevention and remedies are suggested. As the direction and magnitude of the more indirect threats are harder to predict or prevent, they are more difficult to address. In order to maximize the potential of PLF for improving animal welfare, the potential threats as well as the opportunities should be acknowledged, monitored and addressed.
Research on Takagi-Sugeno Fuzzy-Model-Based Vehicle Stability Control for Autonomous Vehicles
Authors: Jiao Zeyu , Wu Jian , Chen Zhengfeng , Wang Fengbo , Li Lijun , Kong Qingfeng , Lin Fen
Published: May 2022

Human–machine cooperative driving is an important stage in the development of autonomous driving technology. However, in emergencies, the problem of vehicle stability control for human–computer cooperative autonomous vehicles is still worthy of attention. This paper mainly realizes the stability control of the human–machine cooperative driving vehicle through active steering and considers the influence of the change of vehicle speed on the vehicle stability control performance. Therefore, a vehicle stability control method based on the superposition of steering torque is proposed, in which the Takagi-Sugeno fuzzy model is used to solve the variable parameter problem. Firstly, a vehicle system model with steering moment as input is established to ensure that the driver can participate in the steering control. Secondly, the nonlinear T-S fuzzy model is established by fuzzifying the local linear model. Then, the parallel-distributed-compensation (PDC) method is used to design the vehicle stability controller, and the asymptotic stability of the system in the range of variable parameters is proved by using the Lyapunov stability principle. Finally, the simulation and experimental results show that the control method can improve the handling stability of the human–machine cooperative driving vehicle under the condition of vehicle speed variation.
Effects of Epichloë Endophyte and Transgenerational Effects on Physiology of Achnatherum inebrians under Drought Stress
Authors: Cui Xuelian , Zhang Xingxu , Shi Lielie , Christensen Michael John , Nan Zhibiao , Xia Chao
Published: May 2022

The present study explored the effects of an Epichloë endophyte on growth and physiology parameters of drunken horse grass (DHG, Achnatherum inebrians) under four different soil water content. The possible transgenerational effects (TGE) on the above-mentioned indicators were examined. DHG plants with (EI) and without (EF) this Epichloë endophyte, grown from seed of plants from the same seed line, were used. The seeds had originated in the relatively dry site at Yuzhong [YZ(D)], and also used were seed of plants from this original seed-line grown at the relatively wet site Xiahe [XH(W)]. The growth, photosynthesis, phytohormones, and elements were measured. This study showed that the endophyte increased the aboveground biomass and chlorophyll content, with the increasing of photosynthetic parameters. The presence of endophyte also significantly promoted abscisic acid and indolE−3-acetic acid content but decreased the cytokinin content. The nitrogen and phosphorus content of EI plants was significantly higher than that of EF plants, but the endophyte decreased ratios of C:N and C:P at drought condition. In addition, TGE were present, affecting host growth and the above-mentioned parameters, and which indicated that the plants grown from the seeds in YZ(D) site are more competitive than those in the XH(W) site under water deficiency conditions.
Physicochemical Variables Better Explain Changes in Microbial Community Structure and Abundance under Alternate Wetting and Drying Events
Authors: Abid Abbas Ali , Zou Xiang , Gong Longda , Castellano-Hinojosa Antonio , Afzal Muhammad , Di Hongjie , Zhang Qichun
Published: May 2022

Soil microbial communities play an important role in nutrient cycling; however, their response under repeated long-term fertilization has attracted little attention and needs further appraisal. A 14-day incubation study compared the relative abundance, diversity, and composition of bacterial and fungal microbial communities in soils treated with long-term applications of chemical fertilizer (CF), pig manure plus chemical fertilizer (PMCF), and rice straw plus chemical fertilizer (SRCF) in a paddy field. A high-throughput sequencing approach was applied to assess the diversity and composition of microbial community. Results revealed the Shannon index of the bacterial community decreased with fertilizer addition but increased in case of fungal community. The abundance of the Actinobacteria was higher in the PMCF, while Proteobacteria were higher in the CF and SRCF treatments than those in the unamended control under alternate wetting and drying (AWD) and permanent flooding (PF). In addition, chemical fertilizer history increased the abundance of Firmicutes under AWD. Initially, Nitrospira were found higher in the unamended control than in the amended treatments, but an increase was observed with time in fertilized treatments. Among all genera, Proteobacteria were the most abundant bacterial genus. The main properties that markedly affected the bacterial communities were SOC (R2 = 0.4037, p < 0.02), available P (R2 = 0.3273, p < 0.05), and NO3− (R2 = 0.3096, p < 0.08). Soil physicochemical factors and biogenic factors explained a variation of 46.27% and 29.35%, respectively. At the same time, 4.59% was the combined effect of physicochemical and biogenic factors. Our results suggested that the physicochemical properties had a more significant impact on bacterial activities than water regime by increasing N and organic matter concentrations in the soils.