bluuebunny/crossref_metadata_2025_split huggingface dataset:
Precipitation Changes in Semi-arid Regions in East Asia Under Global Warming
Authors: Guan Xiaodan , Zhu Kaiwei , Huang Xiaoqian , Zeng Xinrui , He Yongli 
Published: November 2021

The semi-arid regions of East Asia are located in the transition area between regions dominated by the monsoon system and by westerly winds; their interaction is the key to understand precipitation changes, especially in the summer. Our results show that the enhancement of both the monsoon and westerly winds occurs in wet years, leading to stronger convergence and more rainfall. Weakening of both the monsoon and westerly winds occurs in dry years and results in less rainfall. Such interaction between the monsoon and westerlies is not constant; the boundary of their effects is changing all the time. As the monsoon strengthens, it shifts to the west in wet years and covers most of the semi-arid regions, and the negative effect of the El Niño-Southern Oscillation (ENSO) system on precipitation in the semi-arid regions becomes obvious. However, westward expansion has not been evident over the past 70 years in historic data. In the future, the monsoon will obviously expand westward, and the precipitation over the Loess Plateau will gradually increase as the monsoon boundary expand westward until the end of the 21st century. This change indicates that more rainfall will occur in the semi-arid regions of East Asia, which could dramatically change the ecological environment, especially over the Loess Plateau.
Immunosuppressants in Liver Transplant Recipients With Coronavirus Disease 2019: Capability or Catastrophe?—A Systematic Review and Meta-Analysis
Authors: Yadav Dipesh Kumar , Adhikari Vishnu Prasad , Ling Qi , Liang Tingbo 
Published: November 2021

Background: The probable impact of a maintenance immunosuppressant (IS) on liver transplant (LT) recipients with coronavirus disease 2019 (COVID-19) remains unexplored. Our specific aim was to approximate the prognosis of LT recipients with COVID-19 on the standard maintenance IS.Method: We searched separate databases for the qualified studies in between December 2019 and June 25, 2021. Ultimately, a meta-analysis was carried out using a fixed-effect or random-effect model based on the heterogeneity.Results: In a total of eight studies and 509 LT recipients with COVID-19, the pooled rates of severity and mortality during all the combined immunosuppressive therapies were 22.4 and 19.5%, respectively. Our study sufficiently showed that an immunosuppressive therapy in LT recipients with COVID-19 was significantly associated with a non-severe COVID-19 [odds ratio (OR): 11.49, 95% CI: 4.17–31.65; p &lt; 0.001] and the survival of the patients (OR: 17.64, 95% CI: 12.85–24.22; p &lt; 0.001). Moreover, mammalian target of rapamycin inhibitor (mTORi) typically had the lowest rate of severity and mortality compared to other ISs such as calcineurin inhibitors (CNIs), steroids, and antimetabolites, i.e., severity (13.5 vs. 21.1, 24.7, and 26.3%) and mortality (8.3 vs. 15, 17.2, and 12.1%), respectively. Contrary to the general opinions, our meta-analysis showed comorbidities such as diabetes, hypertension, cardiopulmonary disorders, chronic kidney disease (CKD), age &gt;60, the duration of LT to the diagnosis of COVID-19, primary disease for LT, and obesity were not significantly associated with the severity and mortality in LT recipients with COVID-19 under an immunosuppressive therapy. However, our pooled analysis found that LT recipients with COVID-19 and without comorbidities have a less severe disease and low mortality rate compared to those with both COVID-19 and comorbidities.Conclusions: In conclusion, LT recipients with COVID-19 undergoing immunosuppressive therapies are not significantly associated with the severity and mortality. Therefore, taking the risk of organ rejection into a key consideration, a complete withdrawal of the IS may not be wise. However, mycophenolate mofetil (MMF) might be discontinued or replaced from an immunosuppressive regimen with the CNIs- or mTORis-based immunosuppressive therapy in some selected LT recipients with COVID-19, depending upon the severity of the disease.
A Type I Collagen-Targeted MR Imaging Probe for Staging Fibrosis in Crohn’s Disease
Authors: Li Zhoulei , Lu Baolan , Lin Jinjiang , He Shaofu , Huang Li , Wang Yangdi , Meng Jixin , Li Ziping , Feng Shi-Ting , Lin Shaochun , Mao Ren , Li Xue-Hua 
Published: November 2021

Fibrostenosis is a serious complication of Crohn’s disease (CD), affecting approximately one-half of all patients. Surgical resection is the typical clinical end due to ineffective antifibrotic therapy mainly through anti-inflammatory treatment and fibrosis can be reverted only at early stages. Mover, human fibrotic disorders is known to be associated with aging process. Thus, accurate monitoring of the progression of fibrosis is crucial for CD management as well as can be benefit to aging related fibrosis. The excessive deposition of type I collagen (ColI) is the core point in major complications of fibrosis, including that in patients with CD and aging related fibrosis. Therefore, a MR imaging probe (EP-3533) targeted ColI was employed to stage bowel fibrosis in CD using a rat model and to compare its efficiency with the common MR imaging contrast medium gadopentetatedimeglumine (Gd-DTPA). The bowel fibrotic rat model was established with different degrees of bowel fibrosis, were scanned using a 3.0-T MRI scanner with a specialized animal coil. MRI sequence including T1 mapping and T1-weighed imaging were performed before and after injecting the MRI probe (EP-3533 or Gd-DTPA). The T1 relaxation time (T1 value) and change in the contrast-to-noise ratio (ΔCNR) were measured to evaluate bowel fibrosis. Masson’s trichrome staining was performed to determine the severity of fibrosis. EP-3533 offered a better longitudinal relaxivity (r1) with 67.537 L/mmol·s, which was approximately 13 times that of Gd-DTPA. The T1 value on bowel segments was reduced in the images from EP-3533 compared to that from Gd-DTPA (F = 16.478; p &lt; 0.001). Additionally, a better correlation between ΔCNR calculated from EP-3533 imaging and bowel fibrosis (AUC = 0.846) was determined 10 min after enhanced media administration than with Gd-DTPA (AUC = 0.532). The 10th-minute ΔCNR performed using the ColI probe showed the best correlation with the severity of bowel fibrosis (r = 0.538; p = 0.021). Our results demonstrates that targeted MRI probe (EP-3533) supplies a better enhanced effect compared to Gd-DTPA and could be a promising method to evaluate the progression and monitor the therapeutic response of bowel fibrosis.
Navigation-Guided Transnasal Endoscopic Delineation of the Posterior Margin for Maxillary Sinus Cancers: A Preclinical Study
Authors: Taboni Stefano , Ferrari Marco , Daly Michael J. , Chan Harley H. L. , Eu Donovan , Gualtieri Tommaso , Jethwa Ashok R. , Sahovaler Axel , Sewell Andrew , Hasan Wael , Berania Ilyes , Qiu Jimmy , de Almeida John , Nicolai Piero , Gilbert Ralph W. , Irish Jonathan C. 
Published: November 2021

BackgroundThe resection of advanced maxillary sinus cancers can be challenging due to the anatomical proximity to surrounding critical anatomical structures. Transnasal endoscopy can effectively aid the delineation of the posterior margin of resection. Implementation with 3D-rendered surgical navigation with virtual endoscopy (3D-SNVE) may represent a step forward. This study aimed to demonstrate and quantify the benefits of this technology.Material and MethodFour maxillary tumor models with critical posterior extension were created in four artificial skulls (Sawbones®). Images were acquired with cone-beam computed tomography and the tumor and carotid were contoured. Eight head and neck surgeons were recruited for the simulations. Surgeons delineated the posterior margin of resection through a transnasal approach and avoided the carotid while establishing an adequate resection margin with respect to tumor extirpation. Three simulations were performed: 1) unguided: based on a pre-simulation study of cross-sectional imaging; 2) tumor-guided: guided by real-time tool tracking with 3D tumor and carotid rendering; 3) carotid-guided: tumor-guided with a 2-mm alert cloud surrounding the carotid. Distances of the planes from the carotid and tumor were classified as follows and the points of the plane were classified accordingly: “red”: through the carotid artery; “orange”: &lt;2 mm from the carotid; “yellow”: &gt;2 mm from the carotid and within the tumor or &lt;5 mm from the tumor; “green”: &gt;2 mm from the carotid and 5–10 mm from the tumor; and “blue”: &gt;2 mm from the carotid and &gt;10 mm from the tumor. The three techniques (unguided, tumor-guided, and carotid-guided) were compared.Results3D-SNVE for the transnasal delineation of the posterior margin in maxillary tumor models significantly improved the rate of margin-negative clearance around the tumor and reduced damage to the carotid artery. “Green” cuts occurred in 52.4% in the unguided setting versus 62.1% and 64.9% in the tumor- and carotid-guided settings, respectively (p &lt; 0.0001). “Red” cuts occurred 6.7% of the time in the unguided setting versus 0.9% and 1.0% in the tumor- and carotid-guided settings, respectively (p &lt; 0.0001).ConclusionsThis preclinical study has demonstrated that 3D-SNVE provides a substantial improvement of the posterior margin delineation in terms of safety and oncological adequacy. Translation into the clinical setting, with a meticulous assessment of the oncological outcomes, will be the proposed next step.
Warthy-Basaloid Squamous Cell Carcinoma of Penile – Case Report
Authors: Domian Natalia , Młynarczyk Grzegorz , Kasacka Irena 
Published: November 2021

ObjectiveThe aim of the study was to present a case of penile squamous cell carcinoma and immunohistochemical identification and evaluation of E-cadherin and β-catenin expression.MethodsWe are presenting a 70-year old man with a variant of penile squamous cell carcinoma with mixed warty and basaloid features. After diagnosis, the patient underwent partial penectomy. Samples taken from the material after surgery were subjected to basic histological staining and immunohistochemical identification of E-cadherin and β-catenin. A Real-time PCR study was conducted to investigate the expression of E-cadherin and β-catenin.ResultsRoutine histopathological examinations revealed the characteristic features of warty-basaloid squamous cell carcinoma. In the case studied, a positive immunohistochemical reaction was observed for E-cadherin and β-catenin. QRT-PCR analysis showed a statistically significant decrease in E-cadherin expression in tumor samples compared to healthy tissue. In contrast, expression of the gene encoding β-catenin was slightly higher in tumor samples compared to normal tissue.ConclusionsThe reduced level of the complex of adhesive elements, E-cadherin-β-catenin, disturbs cell differentiation, promotes a more invasive phenotype-stromal infiltration and the formation of distant metastases. In the described case of the penile tumor, a decrease in E-cadherin expression was noted, which could be related to the occurrence of neoplastic infiltration of the spongy body space. In summary, E-cadherin and β-catenin expression and the immunoreactivity of these proteins are expressed at different levels in tumor cells and in penile interstitial cells. Regulation of expression during various physiological and pathophysiological processes indicates a potentially important role of E-cadherin and β-catenin in cell proliferation and adhesion.
Heparan Sulfate Biosynthesis and Sulfation Profiles as Modulators of Cancer Signalling and Progression
Authors: Marques Catarina , Reis Celso A. , Vivès Romain R. , Magalhães Ana 
Published: November 2021

Heparan Sulfate Proteoglycans (HSPGs) are important cell surface and Extracellular Matrix (ECM) maestros involved in the orchestration of multiple cellular events in physiology and pathology. These glycoconjugates bind to various bioactive proteins via their Heparan Sulfate (HS) chains, but also through the protein backbone, and function as scaffolds for protein-protein interactions, modulating extracellular ligand gradients, cell signalling networks and cell-cell/cell-ECM interactions. The structural features of HS chains, including length and sulfation patterns, are crucial for the biological roles displayed by HSPGs, as these features determine HS chains binding affinities and selectivity. The large HS structural diversity results from a tightly controlled biosynthetic pathway that is differently regulated in different organs, stages of development and pathologies, including cancer. This review addresses the regulatory mechanisms underlying HS biosynthesis, with a particular focus on the catalytic activity of the enzymes responsible for HS glycan sequences and sulfation motifs, namely D-Glucuronyl C5-Epimerase, N- and O-Sulfotransferases. Moreover, we provide insights on the impact of different HS structural epitopes over HSPG-protein interactions and cell signalling, as well as on the effects of deregulated expression of HS modifying enzymes in the development and progression of cancer. Finally, we discuss the clinical potential of HS biosynthetic enzymes as novel targets for therapy, and highlight the importance of developing new HS-based tools for better patients’ stratification and cancer treatment.
Safety Evaluation for Restorin® NMN, a NAD+ Precursor
Authors: Turner John , Licollari Albert , Mihalcea Emil , Tan Aimin 
Published: November 2021

NAD+ is an abundant molecule in the body and vital to all living cells. NAD+ levels decline with age, and this decline correlates with age-related diseases. Therefore, sustaining NAD+ levels offers potential benefits to healthspan and longevity. Here we conducted toxicity studies to evaluate the safety of Restorin® NMN, a high purity form of the direct NAD+ precursor, β-nicotinamide mononucleotide (NMN). Based on the preliminary toxicity study and a 14-days repeated dose toxicity study at a higher dose level exposure, Restorin® NMN was administered orally to Sprague-Dawley rats for 91 days followed by a 14-days recovery period. The oral doses of 500, 1,000, and 2000 mg/kg/day were compared. There were no test item-related findings that could be considered adverse events in animals dosed at 500 mg/kg/day. The findings in the Restorin® NMN high dose group (2000 mg/kg/day) were similar to the reference item (Nicotinamide Riboside Chloride) dosed at 1740 mg/kg/day: reduced body weight, reductions in body weight gains, and diminished food consumption. In conclusion, the No-Observed-Adverse-Effect-Level (NOAEL) for Restorin® NMN is 1,000 mg/kg/day in female rats and 500 mg/kg/day in male rats, and the Low-Observed-Adverse-Effect-Level (LOAEL) for Resotrin® NMN is 2000 mg/kg/day.
Yerba Mate Modulates Tumor Cells Functions Involved in Metastasis in Breast Cancer Models
Authors: Rocio Soledad Garcia-Lazaro , Lorena Gisel Caligiuri , Norailys Lorenzo , Humberto Lamdan , Daniel Fernando Alonso , Hernan Gabriel Farina 
Published: November 2021

Breast cancer (BC) is the most frequent cancer in women and tumor metastasis is a major cause of cancer-related deaths. Our aim was to evaluate anti-metastatic properties of yerba mate extract (YMe) in BC models. 4T1, F3II, MCF-7, and MDA-MB231 cell lines were used to perform in vitro assays. The F3II syngeneic mammary carcinoma model in BALB/c mice was used to evaluate tumor progression, BC metastasis and survival. Cells were inoculated subcutaneously into the flank for the heterotopic model and into the mammary fat pad for the orthotopic model. YMe was administered p.o. in a dose of 1.6 g/kg/day. In vitro YMe inhibited cell proliferation and reduced tumor cell adhesion, migration and invasion. These biological effects were cell-line dependent. In vivo YMe reduced tumor metastasis and increased mice survival in both models. Our preclinical results suggest that YMe could modulate tumor progression and metastasis in BC models.
Optimization of the Cryogenic Light-Emitting Diodes for High-Performance Broadband Terahertz Upconversion Imaging
Authors: Bai Peng , Zhang Yueheng , Shen Wenzhong , Yang Ning , Chu Weidong 
Published: November 2021

High-performance terahertz (THz) imaging devices have drawn wide attention due to their significant application in a variety of application fields. Recently, the upconversion device based on the integrated homo-junction interfacial workfunction internal photoemission detector and light-emitting diode (HIWIP-LED) has emerged as a promising candidate for broadband THz upconversion pixelless imaging device. In this paper, systematical investigations on the cryogenic-temperature performances of the LED part in HIWIP-LED devices, including electroluminescence (EL) spectra and the EL efficiency, have been carried out by elaborating the radiative recombination mechanism in the quantum well, internal quantum efficiency, and the light extraction efficiency (LEE) both experimentally and theoretically. On this basis, we have further studied the operation mode of the HIWIP-LED and concluded that the LEE could directly determine the upconversion efficiency. A numerical simulation has been performed to optimize the LEE. Numerical results show that the device with a micro-lens geometry structure could significantly improve the LEE of the LED thereby increasing the upconversion efficiency. An optimal upconversion efficiency value of 0.12 W/W and a minimum noise equivalent power (NEP) of 14 pW/Hz1/2 are achieved using the micro-lens structure together with anti-reflection coating. This work gives a precise description of cryogenic LED performance in the HIWIP-LED device and provides an optimization method for the broadband HIWIP-LED THz upconversion pixelless imaging device.
Identification of a Novel Gene Correlated With Vascular Smooth Muscle Cells Proliferation and Migration in Chronic Thromboembolic Pulmonary Hypertension
Authors: Wang Feng , Sun Congrui , Lv Xiaoshuo , Sun Mingsheng , Si Chaozeng , Zhen Yanan , Guo Jing , Sun Weiliang , Ye Zhidong , Wen Jianyan , Liu Peng 
Published: November 2021

Objective: Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by thrombofibrotic obstruction of the proximal pulmonary arteries, which result in vascular remodeling of the distal pulmonary artery. While the cellular and molecular mechanisms underlying CTEPH pathogenesis remain incompletely understood, recent evidence implicates vascular remodeling. Here, we identify the molecular mechanisms that contribute to vascular remodeling in CTEPH.Methods: Microarray data (GSE130391) for patients with CTEPH and healthy controls were downloaded from the Gene Expression Omnibus (GEO) and screened for differentially expressed genes (DEGs). DEGs were functionally annotated using Gene Ontology (GO) functional analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. A protein–protein interaction (PPI) network was constructed to identify hub genes. Finally, pulmonary artery samples were harvested from patients with CTEPH (n = 10) and from controls (n = 10) and primary vascular smooth muscle cells (VSMCs) were cultured. Effects of the proto-oncogene FOS on VSMC proliferation and migration were assessed using expression and knockdown studies.Results: We detected a total of 292 DEGs, including 151 upregulated and 141 downregulated genes. GO analysis revealed enrichment of DEGs in biological processes of signal transduction, response to lipopolysaccharide, signal transduction, and myeloid dendritic cell differentiation. Molecular function analysis revealed enrichment in tumor necrosis factor (TNF)-activated receptor activity, transcriptional activator activity, and protein homodimerization activity. The expression of TNF-α and its receptor (sTNFR1 and sTNFR2) were significantly higher in CTEPH group, compared with control group. KEGG pathway analysis revealed enrichment in salmonella infection, pathways in cancer, osteoclast differentiation, and cytokine-cytokine receptor interaction. Hub genes in the PPI included FOS, suggesting an important role for this gene in vascular remodeling in CTEPH. Primary VSMCs derived from patients with CTEPH showed increased FOS expression and high proliferation and migration, which was attenuated by FOS inhibition. In control VSMCs, TNF-α treatment increased proliferation and migration, which FOS inhibition likewise attenuated.Conclusion: TNF-α drives CTEPH pathogenesis by promoting VSMC proliferation and migration via increased FOS expression. These results advance our understanding of the molecular mechanisms of vascular remodeling in CTEPH, and may inform the development of new therapeutic targets.
EEG Signal Complexity Is Reduced During Resting-State in Fragile X Syndrome
Authors: Proteau-Lemieux Mélodie , Knoth Inga Sophia , Agbogba Kristian , Côté Valérie , Barlahan Biag Hazel Maridith , Thurman Angela John , Martin Charles-Olivier , Bélanger Anne-Marie , Rosenfelt Cory , Tassone Flora , Abbeduto Leonard J. , Jacquemont Sébastien , Hagerman Randi , Bolduc François , Hessl David , Schneider Andrea , Lippé Sarah 
Published: November 2021

Introduction: Fragile X syndrome (FXS) is a genetic disorder caused by a mutation of the fragile X mental retardation 1 gene (FMR1). FXS is associated with neurophysiological abnormalities, including cortical hyperexcitability. Alterations in electroencephalogram (EEG) resting-state power spectral density (PSD) are well-defined in FXS and were found to be linked to neurodevelopmental delays. Whether non-linear dynamics of the brain signal are also altered remains to be studied.Methods: In this study, resting-state EEG power, including alpha peak frequency (APF) and theta/beta ratio (TBR), as well as signal complexity using multi-scale entropy (MSE) were compared between 26 FXS participants (ages 5–28 years), and 77 neurotypical (NT) controls with a similar age distribution. Subsequently a replication study was carried out, comparing our cohort to 19 FXS participants independently recorded at a different site.Results: PSD results confirmed the increased gamma, decreased alpha power and APF in FXS participants compared to NT controls. No alterations in TBR were found. Importantly, results revealed reduced signal complexity in FXS participants, specifically in higher scales, suggesting that altered signal complexity is sensitive to brain alterations in this population. The replication study mostly confirmed these results and suggested critical points of stagnation in the neurodevelopmental curve of FXS.Conclusion: Signal complexity is a powerful feature that can be added to the electrophysiological biomarkers of brain maturation in FXS.