bluuebunny/crossref_metadata_2025 huggingface dataset:
Massive Right Atrial Thrombosis: Are You Brave Enough to Start Anticoagulation? A Case Report
Authors: Bergonti Marco , Ascione Ciro , Agostoni Piergiuseppe , Castelli Roberto , Vignati Carlo
Published: July 2021

Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell disorder with overlapping myelodysplastic and myeloproliferative features. The disease is generally characterized by blood monocytosis, bone marrow dysplasia, cytopenia, and hepatosplenomegaly. While malignant blood diseases are frequently associated with a high risk of thromboembolism, CMML is often accompanied by immune-mediated hemorrhagic diathesis. Indeed, very few reports in literature report thrombotic complications of CMML patients. We will briefly present here the case of a patient with CMML who developed a massive right atrial thrombus. We aim to highlight the non-negligible thrombotic burden of the disease, and we will get through the differential diagnosis of right atrial masses and the management of right atrial thrombi, which are a rare and poorly known entity.
Risk Factors, Prognostic Factors, and Nomograms for Distant Metastasis in Patients With Newly Diagnosed Osteosarcoma: A Population-Based Study
Authors: Chen Bo , Zeng Yuan , Liu Bo , Lu Gaoxiang , Xiang Zhouxia , Chen Jiyang , Yu Yan , Zuo Ziyi , Lin Yangjun , Ma Jinfeng
Published: July 2021

Background

Osteosarcoma is the most common bone cancer, mainly occurring in children and adolescents, among which distant metastasis (DM) still leads to a poor prognosis. Although nomogram has recently been used in tumor areas, there are no studies focused on diagnostic and prognostic evaluation of DM in primary osteosarcoma patients.

Methods

The data of osteosarcoma patients diagnosed between 2004 and 2015 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate logistic regression analyses were used to identify independent risk factors for DM in osteosarcoma patients, and univariate and multivariate Cox proportional hazards regression analyses were used to determine independent prognostic factors of osteosarcoma patients with DM. We then established two novel nomograms and the results were evaluated by receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA).

Result

A total of 1,657 patients with osteosarcoma were included, and 267 patients (16.11%) had DM at the time of diagnosis. The independent risk factors for DM in patients with osteosarcoma include age, grade, T stage, and N stage. The independent prognostic factors for osteosarcoma patients with DM are age, chemotherapy and surgery. The results of ROC curves, calibration, DCA, and Kaplan–Meier (K-M) survival curves in the training, validation, and expanded testing sets, confirmed that two nomograms can precisely predict occurrence and prognosis of DM in osteosarcoma patients.

Conclusion

Two nomograms are expected to be effective tools for predicting the risk of DM for osteosarcoma patients and personalized prognosis prediction for patients with DM, which may benefit clinical decision-making.
Optimal Sequential Distribution Planning for Low-Voltage Network With Electric Vehicle Loads
Authors: Sangob Surasit , Sirisumrannukul Somporn
Published: July 2021

There has been a growing presence of electric vehicles in many countries including Thailand, where many forms of incentives have been provided to build integrated infrastructure, and to encourage drivers to switch to electric vehicles (EVs). Because the immediate entry of EVs unavoidably can alter household load profiles, reinforcement on the existing system based on traditional planning may not be sufficient and can introduce over or under capital and operating expenditure over the time horizon. Therefore, if distribution systems are unreadily prepared for such an uptake, three obvious problems can be expected: 1) voltage regulation, 2) overloads of the distribution feeders and the distribution transformers, and 3) high energy loss. In this paper, an activity-based, time-sequential Monte Carlo Simulation algorithm was comprehensively developed for uncontrollable and smart charging, given annually updated information of EV locations and number of EVs, their energy consumption, hourly average vehicle speed, number of daily trips, travel distance per trip, size of EV batteries, time to arrive home and time to leave home. Minimizing the annual sum of investment and operating costs over a planning period could then be sequentially solved by a Particle Swarm Optimization (PSO) algorithm. The results from a practical 122-bus, 24 kV/400 V distribution system with different scenarios of uncontrollable and smart charging show that the sequential optimization embedded with deterministic decision can help improve customer voltage profile, keep feeder and transformer loading within acceptable operating limits and offer significant cost savings from energy loss. As far as a large number of low-voltage networks, and the associated large sum of cost savings are concerned, the proposed planning framework is practical to be applied and expected to be served as a new guideline for future implementation in Thailand.
LncRNA SOX2-OT/miR-30d-5p/PDK1 Regulates PD-L1 Checkpoint Through the mTOR Signaling Pathway to Promote Non-small Cell Lung Cancer Progression and Immune Escape
Authors: Chen Zhoumiao , Chen Zhao , Xu Shaohua , Zhang Qiang
Published: July 2021

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. Currently, treatment methods generally cause poor prognosis. Therefore, in order to seek new treatment options, we explored the internal mechanism of NSCLC. Firstly, the SOX2-OT/miR-30d-5p/PDK1 axis regulated by lncRNA SOX2-OT was predicted by bioinformatics methods, and the expression of SOX2-OT, miR-30d-5p, and PDK1 mRNA in cells were detected by qRT-PCR while PDK1 protein expression was detected by western blot. The results expressed that in NSCLC, SOX2-OT, and PDK1 were notably overexpressed while miR-30d-5p was markedly under-expressed. The interaction between them was verified by dual-luciferase reporter and RNA binding protein immunoprecipitation assays. Subsequently, through CCK8, scratch healing, cell invasion and flow cytometry assays, we revealed that inhibiting the expression of SOX2-OT could inhibit the proliferation, migration and invasion of NSCLC cells and promote cell apoptosis; while simultaneous overexpression of PDK1 or inhibition of miR-30d-5p expression could reverse the inhibitory effect of SOX2-OT silence-mediated malignant progression of NSCLC cells. Then, the combined application of overexpressed PDK1 and rapamycin verified that PDK1 could regulate the expression of PD-L1 in NSCLC cells through the mTOR signaling pathway. Co-culture of CD8+ T cells verified that silencing SOX2-OT could inhibit the apoptosis of CD8+ T cells through miR-30d-5p/PDK1. Finally, tumor formation assay in animals confirmed that overexpression of SOX2-OT could promote the growth of NSCLC tumor in vivo. In this study, assays in vitro and in vivo were conducted to elucidate the mechanism by which SOX2-OT/miR-30d-5p/PDK1 drives PD-L1 through the mTOR signaling pathway to promote the malignant progression and immune escape of NSCLC.
An Analysis of Pharmacogenomic-Guided Pathways and Their Effect on Medication Changes and Hospital Admissions: A Systematic Review and Meta-Analysis
Authors: David Victoria , Fylan Beth , Bryant Eleanor , Smith Heather , Sagoo Gurdeep S. , Rattray Marcus
Published: July 2021

Ninety-five percent of the population are estimated to carry at least one genetic variant that is discordant with at least one medication. Pharmacogenomic (PGx) testing has the potential to identify patients with genetic variants that puts them at risk of adverse drug reactions and sub-optimal therapy. Predicting a patient's response to medications could support the safe management of medications and reduce hospitalization. These benefits can only be realized if prescribing clinicians make the medication changes prompted by PGx test results. This review examines the current evidence on the impact PGx testing has on hospital admissions and whether it prompts medication changes. A systematic search was performed in three databases (Medline, CINAHL and EMBASE) to search all the relevant studies published up to the year 2020, comparing hospitalization rates and medication changes amongst PGx tested patients with patients receiving treatment-as-usual (TAU). Data extracted from full texts were narratively synthesized using a process model developed from the included studies, to derive themes associated to a suggested workflow for PGx-guided care and its expected benefit for medications optimization and hospitalization. A meta-analysis was undertaken on all the studies that report the number of PGx tested patients that had medication change(s) and the number of PGx tested patients that were hospitalized, compared to participants that received TAU. The search strategy identified 5 hospitalization themed studies and 5 medication change themed studies for analysis. The meta-analysis showed that medication changes occurred significantly more frequently in the PGx tested arm across 4 of 5 studies. Meta-analysis showed that all-cause hospitalization occurred significantly less frequently in the PGx tested arm than the TAU. The results show proof of concept for the use of PGx in prescribing that produces patient benefit. However, the review also highlights the opportunities and evidence gaps that are important when considering the introduction of PGx into health systems; namely patient involvement in PGx prescribing decisions, thus a better understanding of the perspective of patients and prescribers. We highlight the opportunities and evidence gaps that are important when considering the introduction of PGx into health systems.
Case Report: Novel Biallelic Mutations in ARMC4 Cause Primary Ciliary Dyskinesia and Male Infertility in a Chinese Family
Authors: Gao Yang , Xu Chuan , Tan Qing , Shen Qunshan , Wu Huan , Lv Mingrong , Li Kuokuo , Tang Dongdong , Song Bing , Xu Yuping , Zhou Ping , Wei Zhaolian , Tao Fangbiao , Cao Yunxia , He Xiaojin
Published: July 2021

Primary ciliary dyskinesia (PCD) is a clinically and genetically heterogeneous ciliopathy affecting the cilia and sperm flagella. Mutations in genes related to the structural and functional defects of respiratory ciliary axoneme have been reported to be the predominant cause of this symptom; however, evidence regarding male infertility and genotype–phenotype associations between some of these genes and flagellar axoneme remains unclear. Here, we reported a male patient from a non-consanguineous Chinese family who exhibited left/right body asymmetry and oligoasthenoterazoospermia factor infertility. Novel compound heterozygous mutations in ARMC4 (NM:018076: c.2095C>T: p. Gln699*; c.1679C>T: p. Ala560Val) were identified in this patient, and his parents were a heterozygous carrier for the mutations. Morphological and ultrastructural analysis of the spermatozoa from the man showed aberrant sperm flagella with axonemal disorganization and outer dynein arm (ODA) loss. In addition, immunofluorescence analysis of the spermatozoa from the proband and a control man revealed a significant lower expression of ARMC4 protein due to pathogenic mutations. Therefore, our findings help to expand the spectrum of ARMC4 pathogenic mutations and linked biallelic ARMC4 mutations to male infertility for the first time.
Sequential Vaccination With Heterologous Acinetobacter baumannii Strains Induces Broadly Reactive Antibody Responses
Authors: Kamuyu Gathoni , Suen Cheng Yat , Willcocks Sam , Kewcharoenwong Chidchamai , Kiratisin Pattarachai , Taylor Peter W. , Wren Brendan W. , Lertmemongkolchai Ganjana , Stabler Richard A. , Brown Jeremy
Published: July 2021

Antibody therapy may be an alternative treatment option for infections caused by the multi-drug resistant (MDR) bacterium Acinetobacter baumannii. As A. baumannii has multiple capsular serotypes, a universal antibody therapy would need to target conserved protein antigens rather than the capsular polysaccharides. We have immunized mice with single or multiple A. baumannii strains to induce antibody responses to protein antigens, and then assessed whether these responses provide cross-protection against a collection of genetically diverse clinical A. baumannii isolates. Immunized mice developed antibody responses to multiple protein antigens. Flow cytometry IgG binding assays and immunoblots demonstrated improved recognition of both homologous and heterologous clinical strains in sera from mice immunized with multiple strains compared to a single strain. The capsule partially inhibited bacterial recognition by IgG and the promotion of phagocytosis by human neutrophils. However, after immunization with multiple strains, serum antibodies to protein antigens promoted neutrophil phagocytosis of heterologous A. baumannii strains. In an infection model, mice immunized with multiple strains had lower bacterial counts in the spleen and liver following challenge with a heterologous strain. These data demonstrate that antibodies targeting protein antigens can improve immune recognition and protection against diverse A. baumannii strains, providing support for their use as an antibody therapy.
A Synthesis of the Ecology, Human-Related Threats and Conservation Perspectives for the Endangered Franciscana Dolphin
Authors: Secchi Eduardo R. , Cremer M. J. , Danilewicz D. , Lailson-Brito J.
Published: July 2021

The franciscana is endemic to subtropical coastal waters of Brazil, Uruguay, and Argentina, and is the only living species of the family Pontoporiidae. It is regarded as the most endangered cetacean in the western South Atlantic. Five management units are recognized (Franciscana Management Areas, FMAs – sensuSecchi et al., 2003a), with abundance estimates ranging from a few hundred to around 15,000 dolphins. Low reproductive potential and short life span make this species highly susceptible to current non-natural removal rates. Bycatch in gillnet fisheries occurs in high levels since the 1960s in Uruguay and 1980s in Brazil and Argentina. Although other threats exist, such as habitat degradation that includes physical (noise) and chemical pollution, depletion of fish stocks and climate change, incidental mortality in gillnets is currently the greatest threat to franciscanas. Fishing-related mortality ranges from approximately 100, in FMA I, to more than 1,000 in FMA III, and exceed from near two (in FMA IV) to more than five times (in FMA III) the maximum allowed sustainable mortality rate, based on potential biological removal (PBR) approach. These numbers indicate that the species is unlikely to cope with the current levels of bycatch and that urgent and extreme reduction on fishing practice and effort are required to avoid collapse of the franciscana and to lower its risk of extinction. Current mortality levels and projected declines resulted in the listing of the franciscana as “Vulnerable” in the IUCN Red List. Recent fisheries regulations were implemented in areas with extensive bycatch in Brazil and were expected to improve the species’ conservation status. There is evidence, however, that this regulation is insufficient to reduce fishing-related mortality to sustainable levels due to either or both lack of compliance and inadequate regulation strategies. Here we provide a comprehensive review on the franciscana ecology and threats and discuss perspectives for its conservation.
The Efficacy of Management Measures to Reduce Vessel Noise in Critical Habitat of Southern Resident Killer Whales in the Salish Sea
Authors: Burnham Rianna E. , Vagle Svein , O’Neill Caitlin , Trounce Krista
Published: July 2021

The inland waters around southern Vancouver Island and northern Washington State, known as the Salish Sea, host critical habitat for endangered southern resident killer whales (SRKW). This is, however, a highly traversed area, with approaches to industrial ports and coastal cities, international shipping lanes, ferry routes, and considerable recreational vessel traffic. Vessel noise is a key threat to SRKW prosperity, and so conservation measures directed to mitigate its effects have been explored annually since 2017. Here, we describe trials undertaken in 2020, which included spatially limited slowdown zones, exclusion areas as Interim whale Sanctuary Zones (ISZs), and a lateral displacement of tug transits to increase the distance between their route and SRKW foraging areas. To assess each of the measures we first considered the level of mariner participation using data from the Automated Identification Systems (AIS), mandatory for commercial vessels. Knowing this, the changes in soundscape were examined, focused on impacts on broadband (10 Hz to 100 kHz) ambient noise and the frequencies used by SRKW for communication (500 Hz to 15 kHz) and echolocation (15 to 100 kHz). A control period of two-months prior to trial initiation was used to quantify the changes. High levels (> 80%) of compliance were found for each measure, except ISZs, where observance was low. Median reduction in speeds ranged from 0.2–3.5 knots. Resulting sound reductions were most notable in the lower frequencies, although reductions were also recorded in SRKW pertinent ranges. Tug displacement also reduced ambient noise in these frequencies, despite making up a small portion of the overall traffic. The management trials were effective in reducing potential impacts singularly and in concert. Greater awareness and stakeholder engagement may increase compliance and, therefore, the efficacy of measures in the future.
Molecular Characterization and Expression Analysis of a Novel Glutaredoxin 3 Gene in Pacific White Shrimp (Litopenaeus vannamei)
Authors: Zheng Peihua , Zhang Xiuxia , Wang Dongmei , Li Juntao , Zhang Zelong , Lu Yaopeng , Xian Jianan , Wang Anli , Wang Lei
Published: July 2021

Glutaredoxins (Grxs), small heat-stable oxidoreductases, are key members of the thioredoxin (Trx) superfamily. Recently, an emerging subclass of Grxs with a cysteine residue in the active site was found in shrimps. However, molecular functions of Grx-related proteins in decapods were rarely reported. In this study, a novel full-length Grx 3 (LvGrx 3) complementary DNA (cDNA) was identified in Pacific white shrimp (Litopenaeus vannamei), which had a 975-bp open reading frame (ORF) encoding a polypeptide of 324 amino acids. The nucleic acid sequence of Pacific white shrimp glutaredoxin 3 (LvGrx 3) showed 99.59% identity with genomic DNA (gDNA) sequence and 63.49% coverage. Sequence alignment showed that the amino acid sequence of LvGrx 3 shared 97% identity with black tiger shrimp (Penaeus monodon) Grx 3 and 62% identity with amphipod (Hyalella azteca) Grx 3. LvGrx 3 showed higher expression in the intestine, gill, and hepatopancreas, and lower expression in epithelium and abdominal nerve. In response to ammonia-N stress, LvGrx 3 was significantly upregulated in both the hepatopancreas and gill, and the peak value appeared after 24 h exposure. After lipopolysaccharide (LPS) injection, expression levels of LvGrx 3 in the hepatopancreas were increased in the middle stage, and LvGrx 3 in gill was upregulated in the middle and later periods (24 and 48 h). These results indicate that LvGrx 3 can participate in immune responses against ammonia-N stress and pathogen infection. However, RNA interference (RNAi) assay showed that LvGrx 3 silencing in ammonia-N-challenged shrimp could significantly induce the gene expression of antioxidant enzymes and aggravate the oxidative damage of protein and lipid. These results suggest that LvGrx 3 is involved in regulating the antioxidant system and plays a vital role in defense responses against environmental stress.
Microstructure and Oxidation Behavior of NiCoCrAlY Coating With Different Sm2O3 Concentration on TiAl Alloy
Authors: Gong X. , Chen R. R. , Wang Y. , Su Y. Q. , Guo J. J. , Fu H. Z.
Published: July 2021

In order to improve the oxidation resistance of TiAl alloys, NiCoCrAlY coatings with different amounts of Sm2O3 were prepared by laser cladding on TiAl alloys. The microstructure and oxidation behavior of the coatings were investigated by isothermal oxidation tests at 900°C. The results indicated that the grains of the coatings were refined by Sm2O3. The fine grain reduced the crack sensitivity of the doped coatings and promoted the transformation of θ-Al2O3 to α-Al2O3. Therefore, the internal oxidation of the coatings and the growth rate of the oxide films were reduced. The segregation of Sm at grain boundary inhibited the outward diffusion of Ti, thus reducing the excessive oxidation of Ti. In addition, the oxidation mechanism of the coating was changed from simultaneous diffusion of Al and O to predominant inward diffusion of O. The oxidation resistance of the doped coatings was significantly improved. However, excessive Sm2O3 is detrimental to the improvement of the oxidation resistance. The oxidation resistance of 3 wt% Sm2O3 is the best.
Lung Transplant Improves Survival and Quality of Life Regardless of Telomere Dysfunction
Authors: Planas-Cerezales Lurdes , Arias-Salgado Elena G. , Berastegui Cristina , Montes-Worboys Ana , González-Montelongo Rafaela , Lorenzo-Salazar José. M. , Vicens-Zygmunt Vanesa , Garcia-Moyano Marta , Dorca Jordi , Flores Carlos , Perona Rosario , Román Antonio , Molina-Molina María
Published: July 2021

Introduction: Fibrotic interstitial lung diseases (ILDs) are the first indication for lung transplantation (LT). Telomere dysfunction has been associated with poor post-transplant outcomes. The aim of the study was to evaluate the morbi-mortality and quality of life in fibrotic ILDs after lung transplant depending on telomere biology.

Methods: Fibrotic ILD patients that underwent lung transplant were allocated to two arms; with or without telomere dysfunction at diagnosis based on the telomere length and telomerase related gene mutations revealed by whole-exome sequencing. Post-transplant evaluation included: (1) short and long-term mortality and complications and (2) quality of life.

Results: Fifty-five percent of patients that underwent LT carried rare coding mutations in telomerase-related genes. Patients with telomere shortening more frequently needed extracorporeal circulation and presented a higher rate of early post-transplant hematological complications, longer stay in the intensive care unit (ICU), and a higher number of long-term hospital admissions. However, post-transplant 1-year survival was higher than 80% regardless of telomere dysfunction, with improvement in the quality of life and oxygen therapy withdrawal.

Conclusions: Post-transplant morbidity is higher in patients with telomere dysfunction and differs according to elapsed time from transplantation. However, lung transplant improves survival and quality of life and the associated complications are manageable.
Soil pH and Organic Carbon Properties Drive Soil Bacterial Communities in Surface and Deep Layers Along an Elevational Gradient
Authors: Tian Qiuxiang , Jiang Ying , Tang Yanan , Wu Yu , Tang Zhiyao , Liu Feng
Published: July 2021

Elevational gradients strongly affect the spatial distribution and structure of soil bacterial communities. However, our understanding of the effects and determining factors is still limited, especially in the deep soil layer. Here, we investigated the diversity and composition of soil bacterial communities in different soil layers along a 1,500-m elevational gradient in the Taibai Mountain. The variables associated with climate conditions, plant communities, and soil properties were analyzed to assess their contributions to the variations in bacterial communities. Soil bacterial richness and α-diversity showed a hump-shaped trend with elevation in both surface and deep layers. In the surface layer, pH was the main factor driving the elevational pattern in bacterial diversity, while in the deep layer, pH and soil carbon (C) availability were the two main predictors. Bacterial community composition differed significantly along the elevational gradient in all soil layers. In the surface layer, Acidobacteria, Delta-proteobacteria, and Planctomycetes were significantly more abundant in the lower elevation sites than in the higher elevation sites; and Gemmatimonadetes, Chloroflexi, and Beta-proteobacteria were more abundant in the higher elevation sites. In the deep layer, AD3 was most abundant in the highest elevation site. The elevational pattern of community composition co-varied with mean annual temperature, mean annual precipitation, diversity and basal area of trees, pH, soil C availability, and soil C fractions. Statistical results showed that pH was the main driver of the elevational pattern of the bacterial community composition in the surface soil layer, while soil C fractions contributed more to the variance of the bacterial composition in the deep soil layer. These results indicated that changes in soil bacterial communities along the elevational gradient were driven by soil properties in both surface and deep soil layers, which are critical for predicting ecosystem functions under future climate change scenarios.
β-Glucosidase VmGlu2 Contributes to the Virulence of Valsa mali in Apple Tree
Authors: Huang Yan , Yu Chunlei , Sun Cuicui , Saleem Muhammad , Li Pingliang , Li Baohua , Wang Caixia
Published: July 2021

The apple tree canker is caused by Valsa mali, which produces major pathogenic factors involving multiple cell wall-degrading enzymes (CWDEs) and toxins. The β-glucosidases are among the main CWDEs, and thus, they play important roles in the virulence of necrotrophic pathogens. However, the specific roles of β-glucosidases in the virulence of V. mlai remain largely unknown. In this study, we identified a β-glucosidase gene, VmGlu2, which was upregulated during the V. mali infection. We found that VmGlu2 protein had high enzyme activity of β-glucosidase using p-nitrophenyl-β-D-glucopyranoside (pNPG) as a substrate, while the VmGlu2 could convert phloridzin to phloretin with the release of glucose. The deletion and overexpression of VmGlu2 showed no effect on vegetative growth, but gene deletion mutants of V. mlai showed significantly reduced pycnidia formation. The gene deletion mutants had lower β-glucosidase activities and toxin levels as compared to the wild-type strain. Therefore, these mutants showed a reduced virulence. Moreover, the overexpression of VmGlu2 did not affect toxin levels, but it significantly enhanced β-glucosidase activities, which resulted in an increased pathogenicity. Thus, we conclude that VmGlu2 is required for the full virulence of V. mali. These results provide valuable evidence to the complex role of CWDEs in the fungal pathogenicity.
Full Genome Evolutionary Studies of Wheat Streak Mosaic-Associated Viruses Using High-Throughput Sequencing
Authors: Redila Carla Dizon , Phipps Savannah , Nouri Shahideh
Published: July 2021

Wheat streak mosaic (WSM), a viral disease affecting cereals and grasses, causes substantial losses in crop yields. Wheat streak mosaic virus (WSMV) is the main causal agent of the complex, but mixed infections with Triticum mosaic virus (TriMV) and High plains wheat mosaic emaravirus (HPWMoV) were reported as well. Although resistant varieties are effective for the disease control, a WSMV resistance-breaking isolate and several potential resistance-breaking isolates have been reported, suggesting that viral populations are genetically diverse. Previous phylogenetic studies of WSMV were conducted by focusing only on the virus coat protein (CP) sequence, while there is no such study for either TriMV or HPWMoV. Here, we studied the genetic variation and evolutionary mechanisms of natural populations of WSM-associated viruses mainly in Kansas fields and fields in some other parts of the Great Plains using high-throughput RNA sequencing. In total, 28 historic and field samples were used for total RNA sequencing to obtain full genome sequences of WSM-associated viruses. Field survey results showed WSMV as the predominant virus followed by mixed infections of WSMV + TriMV. Phylogenetic analyses of the full genome sequences demonstrated that WSMV Kansas isolates are widely distributed in sub-clades. In contrast, phylogenetic analyses for TriMV isolates showed no significant diversity. Recombination was identified as the major evolutionary force of WSMV and TriMV variation in KS fields, and positive selection was detected in some encoding genomic regions in the genome of both viruses. Furthermore, the full genome sequence of a second Kansas HPWMoV isolate was reported. Here, we also identified previously unknown WSMV isolates in the Great Plains sharing clades and high nucleotide sequence similarities with Central Europe isolates. The findings of this study will provide more insights into the genetic structure of WSM-associated viruses and, in turn, help in improving strategies for disease management.
Free Triiodothyronine Connected With Metabolic Changes in Patients With Coronary Artery Disease by Interacting With Other Functional Indicators
Authors: Tian Xiao-xue , Zheng Shu-fen , Liu Ju-e , Wu Yuan-yuan , Lin Lu , Chen Hong-mei , Li Li-wen , Qin Min , Wang Zi-xian , Zhu Qian , Lai Wei-hua , Zhong Shilong
Published: July 2021

This study aims to evaluate the association between free triiodothyronine (FT3) and outcomes of coronary artery disease (CAD) patients, as well as to assess the predictive power of FT3 and related functional markers from the perspective of potential mechanism. A total of 5104 CAD patients with an average follow-up of three years were enrolled into our study. Multivariate Cox regression was used to evaluate the associations between FT3, FT4 (free thyroxin), FT3/FT4 and death, MACE. We developed and validated an age, biomarker, and clinical history (ABC) model based on FT3 indicators to predict the prognosis of patients with CAD. In the multivariable Cox proportional hazards model, FT3 and FT3/FT4 were independent predictors of mortality (Adjusted HR = 0.624, 95% CI = 0.486–0.801; adjusted HR = 0.011, 95% CI = 0.002–0.07, respectively). Meanwhile, emerging markers pre-brain natriuretic peptide, fibrinogen, and albumin levels are significantly associated with low FT3 (p < 0.001). The new risk death score based on biomarkers can be used to well predict the outcomes of CAD patients (C index of 0.764, 95% CI = 0.731–0.797). Overall, our findings suggest that low levels of FT3 and FT3/FT4 are independent predictors of death and MACE risk in CAD patients. Besides, the prognostic model based on FT3 provides a useful tool for the death risk stratification of CAD patients.
Calcitriol Alleviates MPP+- and MPTP-Induced Parthanatos Through the VDR/PARP1 Pathway in the Model of Parkinson’s Disease
Authors: Hu Junjie , Wu Jiawei , Wan Fang , Kou Liang , Yin Sijia , Sun Yadi , Li Yunna , Zhou Qiulu , Wang Tao
Published: July 2021

The pathogenesis of Parkinson’s disease (PD) is currently unclear. Recent studies have suggested a correlation between vitamin D and PD. Vitamin D and its analogs have protective effects in animal models of PD, but these studies have not clarified the mechanism. Parthanatos is a distinct type of cell death caused by excessive activation of poly (ADP-ribose) polymerase-1 (PARP1), and the activation of PARP1 in PD models suggests that parthanatos may exist in PD pathophysiology. 1,25-Dihydroxyvitamin D3 (calcitriol) is a potential inhibitor of PARP1 in macrophages. This study aimed to investigate whether calcitriol treatment improves PD models and its effects on the parthanatos pathway. A 1-methyl-4-phenylpyridinium (MPP+)-induced cell model and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) subacute animal model were selected as the in vitro and in vivo PD models, and calcitriol was applied in these models. Results showed that parthanatos existed in the MPP+-induced cell model and pretreatment with calcitriol improved cell viability, reduced the excessive activation of PARP1, and relieved parthanatos. The application of calcitriol in the MPTP subacute animal model also improved behavioral tests, restored the damage to dopamine neurons, and reduced the activation of PARP1-related signaling pathways. To verify whether calcitriol interacts with PARP1 through its vitamin D receptor (VDR), siRNA, and overexpression plasmids were used to downregulate or overexpress VDR. Following the downregulation of VDR, the expression and activation of PARP1 increased and PARP1 was inhibited when VDR was overexpressed. Coimmunoprecipitation verified the combination of VDR and PARP1. In short, calcitriol can substantially improve parthanatos in the MPP+-induced cell model and MPTP model, and the protective effect might be partly through the VDR/PARP1 pathway, which provides a new possibility for the treatment of PD.
An Autism-Associated de novo Mutation in GluN2B Destabilizes Growing Dendrites by Promoting Retraction and Pruning
Authors: Bahry Jacob A. , Fedder-Semmes Karlie N. , Sceniak Michael P. , Sabo Shasta L.
Published: July 2021

Mutations in GRIN2B, which encodes the GluN2B subunit of NMDA receptors, lead to autism spectrum disorders (ASD), but the pathophysiological mechanisms remain unclear. Recently, we showed that a GluN2B variant that is associated with severe ASD (GluN2B724t) impairs dendrite morphogenesis. To determine which aspects of dendrite growth are affected by GluN2B724t, we investigated the dynamics of dendrite growth and branching in rat neocortical neurons using time-lapse imaging. GluN2B724t expression shifted branch motility toward retraction and away from extension. GluN2B724t and wild-type neurons formed new branches at similar rates, but mutant neurons exhibited increased pruning of dendritic branches. The observed changes in dynamics resulted in nearly complete elimination of the net expansion of arbor size and complexity that is normally observed during this developmental period. These data demonstrate that ASD-associated mutant GluN2B interferes with dendrite morphogenesis by reducing rates of outgrowth while promoting retraction and subsequent pruning. Because mutant dendrites remain motile and capable of growth, it is possible that reducing pruning or promoting dendrite stabilization could overcome dendrite arbor defects associated with GRIN2B mutations.
Nutritional Supplementation of Naturally Occurring Vitamin D to Improve Hemorrhagic Stroke Outcomes
Authors: Ashouri Rani , Fangman Madison , Brielmaier Jordan , Fields Zoe A. , Campo Natalie , Doré Sylvain
Published: July 2021

Vitamin D deficiency, if left untreated, is associated with bone disorders, cardiovascular damage, and an increased risk of ischemic stroke. While there are various nutritional options for the natural intake of vitamin D, we hope to elucidate the potential mechanisms dietary vitamin D may play in hemorrhagic stroke pathology. This scoping review outlines findings from studies relevant to the biochemical activity of vitamin D, the impact of vitamin D deficiency on hemorrhagic stroke outcomes, and the potential benefit of nutritional vitamin D on hemorrhagic stroke outcomes. Here, we analyze the relevant factors that can lead to vitamin D deficiency, and subsequently, a higher risk of hemorrhagic stroke incidence with worsened subsequent outcomes. The neuroprotective mechanisms through which vitamin D works to attenuate hemorrhagic stroke onset and post-stroke outcomes have not yet been thoroughly examined. However, researchers have proposed several potential protective mechanisms, including reduction of blood brain barrier disturbance by inhibiting the production of reactive oxygen species, mitigation of inflammation through a reduction of levels of proinflammatory cytokines, and prevention of cerebral vasospasm and delayed cerebral ischemia following subarachnoid hemorrhage and intracerebral hemorrhage. While more research is needed and there are limitations to vitamin D supplementation, vitamin D as a whole may play a significant role in the dynamics of hemorrhagic stroke. Further research should focus on expanding our understanding of the neuroprotective capacity and mechanisms of vitamin D, as well as how vitamin D supplementation could serve as an effective course of treatment of hemorrhagic strokes.
Deep Neuro-Vision Embedded Architecture for Safety Assessment in Perceptive Advanced Driver Assistance Systems: The Pedestrian Tracking System Use-Case
Authors: Rundo Francesco , Conoci Sabrina , Spampinato Concetto , Leotta Roberto , Trenta Francesca , Battiato Sebastiano
Published: July 2021

In recent years, the automotive field has been changed by the accelerated rise of new technologies. Specifically, autonomous driving has revolutionized the car manufacturer's approach to design the advanced systems compliant to vehicle environments. As a result, there is a growing demand for the development of intelligent technology in order to make modern vehicles safer and smarter. The impact of such technologies has led to the development of the so-called Advanced Driver Assistance Systems (ADAS), suitable to maintain control of the vehicle in order to avoid potentially dangerous situations while driving. Several studies confirmed that an inadequate driver's physiological condition could compromise the ability to drive safely. For this reason, assessing the car driver's physiological status has become one of the primary targets of the automotive research and development. Although a large number of efforts has been made by researchers to design safety-assessment applications based on the detection of physiological signals, embedding them into a car environment represents a challenging task. These mentioned implications triggered the development of this study in which we proposed an innovative pipeline, that through a combined less invasive Neuro-Visual approach, is able to reconstruct the car driver's physiological status. Specifically, the proposed contribution refers to the sampling and processing of the driver PhotoPlethysmoGraphic (PPG) signal. A parallel enhanced low frame-rate motion magnification algorithm is used to reconstruct such features of the driver's PhotoPlethysmoGraphic (PPG) data when that signal is no longer available from the native embedded sensor platform. A parallel monitoring of the driver's blood pressure levels from the PPG signal as well as the driver's eyes dynamics completes the reconstruction of the driver's physiological status. The proposed pipeline has been tested in one of the major investigated automotive scenarios i.e., the detection and monitoring of pedestrians while driving (pedestrian tracking). The collected performance results confirmed the effectiveness of the proposed approach.
Ear-Specific Hemispheric Asymmetry in Unilateral Deafness Revealed by Auditory Cortical Activity
Authors: Han Ji-Hye , Lee Jihyun , Lee Hyo-Jeong
Published: July 2021

Profound unilateral deafness reduces the ability to localize sounds achieved via binaural hearing. Furthermore, unilateral deafness promotes a substantial change in cortical processing to binaural stimulation, thereby leading to reorganization over the whole brain. Although distinct patterns in the hemispheric laterality depending on the side and duration of deafness have been suggested, the neurological mechanisms underlying the difference in relation to behavioral performance when detecting spatially varied cues remain unknown. To elucidate the mechanism, we compared N1/P2 auditory cortical activities and the pattern of hemispheric asymmetry of normal hearing, unilaterally deaf (UD), and simulated acute unilateral hearing loss groups while passively listening to speech sounds delivered from different locations under open free field condition. The behavioral performances of the participants concerning sound localization were measured by detecting sound sources in the azimuth plane. The results reveal a delayed reaction time in the right-sided UD (RUD) group for the sound localization task and prolonged P2 latency compared to the left-sided UD (LUD) group. Moreover, the RUD group showed adaptive cortical reorganization evidenced by increased responses in the hemisphere ipsilateral to the intact ear for individuals with better sound localization whereas left-sided unilateral deafness caused contralateral dominance in activity from the hearing ear. The brain dynamics of right-sided unilateral deafness indicate greater capability of adaptive change to compensate for impairment in spatial hearing. In addition, cortical N1 responses to spatially varied speech sounds in unilateral deaf people were inversely related to the duration of deafness in the area encompassing the right auditory cortex, indicating that early intervention would be needed to protect from maladaptation of the central auditory system following unilateral deafness.
The Role of Long Noncoding RNA AL161431.1 in the Development and Progression of Pancreatic Cancer
Authors: Ma Gang , Li Guichen , Fan Wufeng , Xu Yuanhong , Song Shaowei , Guo Kejian , Liu Zhe
Published: July 2021

Pancreatic cancer is known for its notorious fast progression and poor prognosis. Long noncoding RNA (lncRNA) AL161431.1 has been reported to be involved in the pathogenesis of different cancers. In this study, we explored the role of lncRNA AL161431.1 in the development and progression of pancreatic cancer by bioinformatic analysis, in vitro and in vivo experiments in pancreatic cancer BxPC-3 and SW1990 cells, as well as clinical samples. We found that lncRNA AL161431.1 was highly expressed in pancreatic cancer cells and tissues. Knock down of lncRNA AL161431.1 led to increased cancer cell death and cell cycle arrest. Xenograft growth of SW1990 cells with stable knockdown of lncRNA AL161431.1 in mice was significantly slower than that of SW1990 cells with scrambled control shRNA. Finally, we showed the involvement of lncRNA AL161431.1 in pancreatic cancer was related to its promotion of epithelial mesenchymal transition process.
MitoTracker Deep Red (MTDR) Is a Metabolic Inhibitor for Targeting Mitochondria and Eradicating Cancer Stem Cells (CSCs), With Anti-Tumor and Anti-Metastatic Activity In Vivo
Authors: Sargiacomo Camillo , Stonehouse Sophie , Moftakhar Zahra , Sotgia Federica , Lisanti Michael P.
Published: July 2021

MitoTracker Deep Red (MTDR) is a relatively non-toxic, carbocyanine-based, far-red, fluorescent probe that is routinely used to chemically mark and visualize mitochondria in living cells. Previously, we used MTDR at low nano-molar concentrations to stain and metabolically fractionate breast cancer cells into Mito-high and Mito-low cell sub-populations, by flow-cytometry. Functionally, the Mito-high cell population was specifically enriched in cancer stem cell (CSC) activity, i) showing increased levels of ESA cell surface expression and ALDH activity, ii) elevated 3D anchorage-independent growth, iii) larger overall cell size (>12-μm) and iv) Paclitaxel-resistance. The Mito-high cell population also showed enhanced tumor-initiating activity, in an in vivo preclinical animal model. Here, we explored the hypothesis that higher nano-molar concentrations of MTDR could also be used to therapeutically target and eradicate CSCs. For this purpose, we employed an ER(+) cell line (MCF7) and two triple negative cell lines (MDA-MB-231 and MDA-MB-468), as model systems. Remarkably, MTDR inhibited 3D mammosphere formation in MCF7 and MDA-MB-468 cells, with an IC-50 between 50 to 100 nM; similar results were obtained in MDA-MB-231 cells. In addition, we now show that MTDR exhibited near complete inhibition of mitochondrial oxygen consumption rates (OCR) and ATP production, in all three breast cancer cell lines tested, at a level of 500 nM. However, basal glycolytic rates in MCF7 and MDA-MB-468 cells remained unaffected at levels of MTDR of up to 1 μM. We conclude that MTDR can be used to specifically target and eradicate CSCs, by selectively interfering with mitochondrial metabolism, by employing nano-molar concentrations of this chemical entity. In further support of this notion, MTDR significantly inhibited tumor growth and prevented metastasis in vivo, in a xenograft model employing MDA-MB-231 cells, with little or no toxicity observed. In contrast, Abemaciclib, an FDA-approved CDK4/6 inhibitor, failed to inhibit metastasis. Therefore, in the future, MTDR could be modified and optimized via medicinal chemistry, to further increase its potency and efficacy, for its ultimate clinical use in the metabolic targeting of CSCs for their eradication.
The Clinical Experiences of Urine Metabolomics of Genitourinary Urothelial Cancer in a Tertiary Hospital in Taiwan
Authors: Juang Horng-Heng , Chen Shao-Ming , Lin Gigin , Chiang Meng-Han , Hou Chen-Pang , Lin Yu-Hsiang , Yang Pei-Shan , Chang Phei-Lang , Chen Chien-lun , Lin Kuo-Yen , Tsui Ke-Hung
Published: July 2021

Few studies have addressed the impact of diagnostic urine metabolites and the clinical outcomes associated with genitourinary urothelial (GU) cancer to date. Furthermore, longitudinal analysis of the dynamics of urine metabolites contributing to the detection of GU cancer has not yet been fully investigated; therefore, the discovery of novel diagnostic urine biomarkers is of enormous interest. We explored the correlation of the urine metabolomic profiles to GU cancers. The aqueous metabolites of the GU cancer and the control were also identified and analyzed through high-resolution1H nuclear magnetic resonance (NMR) spectroscopy. Compared with the control, the urine metabolites of the tumor were studied in relation to changes over time in a linear mixed model for repeated measures. The urine metabolites of sixty-three (44 male and 19 female) patients with GU cancers were systemically analyzed. The urine metabolite profile in GU cancer was significantly higher than those in the control group (p<0.05). Sevenurine metabolites including histidine, propylene glycol, valine, leucine, acetylsalicylate, glycine, and isoleucine as well as other pathways were identified statistically and were significantly associated with GU cancer detection with longitudinal analysis. We discovered that histidine, propylene glycol, valine, leucine, acetylsalicylate, glycine, isoleucine, succinic acid, lysine2-aminobutyric acid, and acetic acid are involved significantly in all types of male patients in whom the type (upper tract) of urine metabolites were found to be statistically significant compared with the control. We did not find any statistical significance in urine biomarkers between female and male patients. However, a statistically insignificant correlation was found among the grade and stage with the metabolites.