bluuebunny/crossref_metadata_2025 huggingface dataset:
Membrane Protein Structures in Lipid Bilayers; Small-Angle Neutron Scattering With Contrast-Matched Bicontinuous Cubic Phases
Authors: Conn Charlotte E. , de Campo Liliana , Whitten Andrew E. , Garvey Christopher J. , Krause-Heuer Anwen M. , van 't Hag Leonie
Published: February 2021

This perspective describes advances in determining membrane protein structures in lipid bilayers using small-angle neutron scattering (SANS). Differentially labeled detergents with a homogeneous scattering length density facilitate contrast matching of detergent micelles; this has previously been used successfully to obtain the structures of membrane proteins. However, detergent micelles do not mimic the lipid bilayer environment of the cell membrane in vivo. Deuterated vesicles can be used to obtain the radius of gyration of membrane proteins, but protein-protein interference effects within the vesicles severely limits this method such that the protein structure cannot be modeled. We show herein that different membrane protein conformations can be distinguished within the lipid bilayer of the bicontinuous cubic phase using contrast-matching. Time-resolved studies performed using SANS illustrate the complex phase behavior in lyotropic liquid crystalline systems and emphasize the importance of this development. We believe that studying membrane protein structures and phase behavior in contrast-matched lipid bilayers will advance both biological and pharmaceutical applications of membrane-associated proteins, biosensors and food science.
Overview of Current International Recommendations for Echocardiography Exams During the Covid-19 Pandemic and Its Local Implementation in Austria
Authors: Lichtenauer Michael , Prinz Erika , Granitz Christina , Wernly Bernhard , Kopp Kristen , Daburger Apollonia , Hoppe Uta C.
Published: February 2021

Since its first appearance in December 2019, the novel Coronavirus SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2) has spread throughout the world at rapid pace causing the coronavirus disease 2019 (Covid-19). Originating in the Chinese province Hubei, more than 91.8 million people globally have now been infected with the coronavirus and more than 1.966.000 patients have died thus far from Covid-19 (as of January 13th 2021). The virus spreads primarily by droplet infection as well as via aerosols during close physical contact. Particularly in medical examinations with close physical contact between examiner and patient, like echocardiography, the risk of contracting the virus is increased. Therefore, the use of personal protective equipment is recommended for the protection of patients and medical personnel alike. In this article, the current recommendations of international professional associations on the use of personal protective equipment and their local implementation are presented.
Machine Learning for Localizing Epileptogenic-Zone in the Temporal Lobe: Quantifying the Value of Multimodal Clinical-Semiology and Imaging Concordance
Authors: Alim-Marvasti Ali , Pérez-García Fernando , Dahele Karan , Romagnoli Gloria , Diehl Beate , Sparks Rachel , Ourselin Sebastien , Clarkson Matthew J. , Duncan John S.
Published: February 2021

Background: Epilepsy affects 50 million people worldwide and a third are refractory to medication. If a discrete cerebral focus or network can be identified, neurosurgical resection can be curative. Most excisions are in the temporal-lobe, and are more likely to result in seizure-freedom than extra-temporal resections. However, less than half of patients undergoing surgery become entirely seizure-free. Localizing the epileptogenic-zone and individualized outcome predictions are difficult, requiring detailed evaluations at specialist centers.

Methods: We used bespoke natural language processing to text-mine 3,800 electronic health records, from 309 epilepsy surgery patients, evaluated over a decade, of whom 126 remained entirely seizure-free. We investigated the diagnostic performances of machine learning models using set-of-semiology (SoS) with and without hippocampal sclerosis (HS) on MRI as features, using STARD criteria.

Findings: Support Vector Classifiers (SVC) and Gradient Boosted (GB) decision trees were the best performing algorithms for temporal-lobe epileptogenic zone localization (cross-validated Matthews correlation coefficient (MCC) SVC 0.73 ± 0.25, balanced accuracy 0.81 ± 0.14, AUC 0.95 ± 0.05). Models that only used seizure semiology were not always better than internal benchmarks. The combination of multimodal features, however, enhanced performance metrics including MCC and normalized mutual information (NMI) compared to either alone (p < 0.0001). This combination of semiology and HS on MRI increased both cross-validated MCC and NMI by over 25% (NMI, SVC SoS: 0.35 ± 0.28 vs. SVC SoS+HS: 0.61 ± 0.27).

Interpretation: Machine learning models using only the set of seizure semiology (SoS) cannot unequivocally perform better than benchmarks in temporal epileptogenic-zone localization. However, the combination of SoS with an imaging feature (HS) enhance epileptogenic lobe localization. We quantified this added NMI value to be 25% in absolute terms. Despite good performance in localization, no model was able to predict seizure-freedom better than benchmarks. The methods used are widely applicable, and the performance enhancements by combining other clinical, imaging and neurophysiological features could be similarly quantified. Multicenter studies are required to confirm generalizability.

Funding: Wellcome/EPSRC Center for Interventional and Surgical Sciences (WEISS) (203145Z/16/Z).
The Potential of Research Drawing on Clinical Free Text to Bring Benefits to Patients in the United Kingdom: A Systematic Review of the Literature
Authors: Ford Elizabeth , Curlewis Keegan , Squires Emma , Griffiths Lucy J. , Stewart Robert , Jones Kerina H.
Published: February 2021

Background: The analysis of clinical free text from patient records for research has potential to contribute to the medical evidence base but access to clinical free text is frequently denied by data custodians who perceive that the privacy risks of data-sharing are too high. Engagement activities with patients and regulators, where views on the sharing of clinical free text data for research have been discussed, have identified that stakeholders would like to understand the potential clinical benefits that could be achieved if access to free text for clinical research were improved. We aimed to systematically review all UK research studies which used clinical free text and report direct or potential benefits to patients, synthesizing possible benefits into an easy to communicate taxonomy for public engagement and policy discussions.

Methods: We conducted a systematic search for articles which reported primary research using clinical free text, drawn from UK health record databases, which reported a benefit or potential benefit for patients, actionable in a clinical environment or health service, and not solely methods development or data quality improvement. We screened eligible papers and thematically analyzed information about clinical benefits reported in the paper to create a taxonomy of benefits.

Results: We identified 43 papers and derived five themes of benefits: health-care quality or services improvement, observational risk factor-outcome research, drug prescribing safety, case-finding for clinical trials, and development of clinical decision support. Five papers compared study quality with and without free text and found an improvement of accuracy when free text was included in analytical models.

Conclusions: Findings will help stakeholders weigh the potential benefits of free text research against perceived risks to patient privacy. The taxonomy can be used to aid public and policy discussions, and identified studies could form a public-facing repository which will help the health-care text analysis research community better communicate the impact of their work.
Slip Rate Variation During the Last ∼210 ka on a Slow Fault in a Transpressive Regime: The Carrascoy Fault (Eastern Betic Shear Zone, SE Spain)
Authors: Martín-Banda Raquel , Insua-Arévalo Juan Miguel , García-Mayordomo Julián
Published: February 2021

Fault slip rate variability over time is a crucial aspect for understanding how single faults interact among each other in fault systems. Several studies worldwide evidence the occurrence of high activity periods with clustering of events and synchronization among faults, followed by long periods of low activity (super-cycles). The increasing gathering of evidence of these phenomena is making fault hazard models quickly evolving and challenging seismic hazard assessment. However, in moderately active fault systems, a determination of fault slip rates can present large uncertainties, that have to be carefully considered when slip rate histories are determined. In this work, we estimate the variation of slip rate in the last ∼210 ky of the NE segment of the left-lateral reverse Carrascoy Fault, one of the main faults forming the Eastern Betic Shear Zone in SE Spain. We study two selected field sites where we have been able to measure offsets and date the sediments along with uncertainties. The first site shows a progressive discordance drawn by different calcretes developed on alluvial deposits. The vertical throw is calculated by modeling the growth of the discordance. The vertical slip rates are estimated dating the deformed calcretes by Uranium Series and by comparing them with a complete regional calcrete dates database compiled from the literature. On the second site, we analyze the geomorphology of different Upper Pleistocene alluvial fans, where three incised channels are offset by the fault, providing the net slip for the last ∼124 ky. We discuss the influence of different factors on the estimate of net slip rates using data from different sources. This analysis highlights the importance of determining an accurate fault geometry and how local data can provide misleading deformation rates. Our results suggest the existence of long periods of low activity disturbed by short high activity periods. Such a pattern of activity along time is defined for the first time in the Eastern Betic Shear Zone, with interesting implications in the seismogenic behavior of the rest of the slow faults within the region.
PCA-SBM Model Green Urbanization Performance Assessment in China
Authors: Chen Rui , Lu Haochun
Published: February 2021

China’s urbanization over the past thirty years has been the fastest in history and has led to significant challenges in balancing urbanization and energy use. As a result, this study proposed a comprehensive green urbanization assessment index system considering energy use and environment protection together. To be specific, principal component analysis was applied to eliminate redundant information, and a slacks-based measure model was used to evaluate urbanization efficiencies. Meanwhile, with super efficiency incorporated, the proposed model enabled to distinguish the DMU from DMUs with same efficiency value, further, a projection analysis was conducted to direct the improvement of the identified inefficient decision-making units (DMUs). Finally, the comprehensive green urbanization index system was applied to a western Chinese province (Sichuan Province) to demonstrate the effectiveness of the proposed models, from which it was found that the overall green urbanization efficiency in Sichuan province was 81.54%, due to an input distribution imbalance and low technical efficiency.
From Binary Model Systems to the Human Microbiome: Factors That Drive Strain Specificity in Host-Symbiont Associations
Authors: Ginete Daren R. , Goodrich-Blair Heidi
Published: February 2021

Microbial symbionts are ubiquitous and can have significant impact on hosts. These impacts can vary in the sign (positive or negative) and degree depending on the identity of the interacting partners. Studies on host-symbiont associations indicate that subspecies (strain) genetic variation can influence interaction outcomes, making it necessary to go beyond species-level distinction to understand host-symbiont dynamics. In this review, we discuss examples of strain specificity found in host-symbiont associations, from binary model systems to the human microbiome. Although host and bacterial factors identified as mediators for specificity could be distinct at the molecular level, they generally fall into two broad functional categories: (1) those that contribute a required activity in support of the association and (2) those involved in antagonistic interactions with organisms outside of the association. We argue here based on current literature that factors from these two categories can work in concert to drive strain specificity and that this strain specificity must be considered to fully understand the molecular and ecological dynamics of host-symbiont associations, including the human microbiome.
Geospatial Distribution of Family Planning Services in Kira Municipality, Wakiso District, Uganda
Authors: Tetui Moses , Ssekamatte Tonny , Akilimali Pierre , Sirike Judith , Fonseca-Rodríguez Osvaldo , Atuyambe Lynn , Makumbi Fredrick Edward
Published: February 2021

Introduction: Access to family planning (FP) services remains a challenge, particularly in informal urban settlements. The unmet need for FP in these settings is high, with a correspondingly high prevalence of unintended pregnancies that may lead to unsafe abortions. However, there is a paucity of quality data on the distribution of FP services in such settings in Uganda. This paper described the geospatial distribution of FP services in Kira Municipality, Wakiso District, Uganda.

Methods: This was a cross-sectional study in which we determined the availability and distribution of FP services in Kira Municipality. Community mapping and analysis were conducted using ArcGIS (version 10.1) and ArcGIS Online. Stata version 13.1 was used for data analysis. Chi-square test was used to compare the contraceptive provision and availability among facilities from informal and formal settlements.

Results: Of the 176 healthcare facilities surveyed, only 42% (n = 74) offered contraceptives in informal settlements. The majority of the facilities were privately owned small clinics (95%). At least 80% of the facilities provided three or more modern contraceptive methods, with no difference (p = 0.107) between facilities in informal and formal settlements. Only 30.7% (p = 0.001) of the facilities provided at least one long-acting contraceptive. Similarly, 20 and 12% (p = 0.001) of the facilities had implants and intrauterine devices (IUDs) on the day of the survey. Almost 25% of the facilities did not offer contraceptive services (counseling and commodities) to unmarried adolescents.

Conclusions: Most facilities were small privately-owned clinics, offering at least three modern contraceptive methods. The unavailability of long-acting reversible methods in the informal settings may affect the quality of FP services due to limited choice. The inequity in service provision that disfavors the unmarried adolescent may increase unwanted/unintended pregnancies. We recommend that local governments and partners work toward filling the existing commodities gap and addressing the discrimination against unmarried adolescents in such settings.
HLA-DRB1*04 as a Risk Allele to Systemic Lupus Erythematosus and Lupus Nephritis in the Malay Population of Malaysia
Authors: Selvaraja Malarvili , Chin Voon Kin , Abdullah Maha , Arip Masita , Amin-Nordin Syafinaz
Published: February 2021

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease afflicting multiple organs. Lupus nephritis (LN) is a serious complication of SLE and remains a major cause of mortality and morbidity. Curative therapy remains unavailable as etiology from genetic and environmental factors is still unclear. The present study was conducted to elucidate the link between HLA-DRB1 gene polymorphisms with SLE and LN through clinical and laboratory/biological presentations in a population of Malaysian Malay females with SLE. A total of 100 Malay female SLE patients inclusive of 70 SLE patients without LN and 30 patients with LN were included in this study. HLA-DRB1 allele examination in SLE patients was performed using PCR-SSO, and the alleles' frequencies were compared with 951 publicly available datasets representing Malay healthy controls in Malaysia. Cytokines and free radical levels were detected by ELISA and bead-based multiplexed Luminex assays. The association between HLA-DRB1 alleles with clinical and serological manifestations and immune mediators was analyzed using different statistical approaches whenever applicable. Our study showed that HLA-DRB1*0405, HLA-DRB1*1502, and HLA-DRB1*1602 were associated with the increased risk of SLE while HLA-DRB1*1201 and HLADRB1*1202 alleles were associated with a lower risk of SLE development. Furthermore, HLA-DRB1*04 showed significant association to LN and arthritis while HLA-DRB1*15 was significantly associated with oral ulcer in Malay SLE patients. Association analysis of HLA-DRB1*04 with clinical and biological factors revealed that HLA-DRB1*04 was significantly associated with Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores, anti-nuclear antibody (ANA), C-reactive protein (CRP) in the blood, and total protein in the urine. SLE carriers with the HLA-DRB1*04 allele were significantly correlated to the increased levels of cytokines (IFN-y, GM-CSF, IL-17F, IL-18, IL-21, and VEGF) and were significantly showing negative correlation to IL-5 and free radicals (LPO and catalase enzyme) levels compared to SLE carriers without HLA-DRB1*04 allele. The results suggested that disease severity in SLE may be determined by HLA-DRB1 alleles. The risk of HLA-DRB1*04 allele with LN was supported by the demonstration of an intense inflammatory response in Malay SLE patients in Malaysia. More studies inclusive of a larger and multiple SLE cohorts in the future are warranted to validate these findings.
Bioprospecting of Novel Extremozymes From Prokaryotes—The Advent of Culture-Independent Methods
Authors: Sysoev Maksim , Grötzinger Stefan W. , Renn Dominik , Eppinger Jörg , Rueping Magnus , Karan Ram
Published: February 2021

Extremophiles are remarkable organisms that thrive in the harshest environments on Earth, such as hydrothermal vents, hypersaline lakes and pools, alkaline soda lakes, deserts, cold oceans, and volcanic areas. These organisms have developed several strategies to overcome environmental stress and nutrient limitations. Thus, they are among the best model organisms to study adaptive mechanisms that lead to stress tolerance. Genetic and structural information derived from extremophiles and extremozymes can be used for bioengineering other nontolerant enzymes. Furthermore, extremophiles can be a valuable resource for novel biotechnological and biomedical products due to their biosynthetic properties. However, understanding life under extreme conditions is challenging due to the difficulties ofin vitrocultivation and observation since > 99% of organisms cannot be cultivated. Consequently, only a minor percentage of the potential extremophiles on Earth have been discovered and characterized. Herein, we present a review of culture-independent methods, sequence-based metagenomics (SBM), and single amplified genomes (SAGs) for studying enzymes from extremophiles, with a focus on prokaryotic (archaea and bacteria) microorganisms. Additionally, we provide a comprehensive list of extremozymes discovered via metagenomics and SAGs.
Hydrogen Sulfide Protects Against Uremic Accelerated Atherosclerosis via nPKCδ/Akt Signal Pathway
Authors: Lu Xiangxue , Li Han , Wang Shixiang
Published: February 2021

Background: Cardiovascular disease is the most common complication and leading cause of death in maintenance hemodialysis patients. Previous studies have found that disorders of cystathionine-gamma-lyase/hydrogen sulfide (CSE/H2S) system in maintenance hemodialysis patients are correlated with the risk of cardiovascular disease. Although the role of CSE/H2S system in UAAS has been preliminarily explored, the molecular mechanism of CSE/H2S is still not systematically elaborated, and the molecular mechanism of nPKCδ and its related signaling pathway in UAAS is still not thoroughly studied.

Methods: Forty chronic kidney disease (CHD) patients were studied and the activation of nPKCδ in peripheral blood mononuclear cells (PBMCs) were detected. ApoE−/− mice aged 6 weeks were treated with 5/6 nephrectomy and high-fat diet to make UAAS model. They were divided into Sham group (Sham group), UAAS group (UAAS group), UAAS+L-cysteine group (UAAS+L-cys group), UAAS+sodium hydrosulfide group (UAAS+NaHS group) and UAAS+propargylglycine group (UAAS+PPG group). The UAAS+L-cys group, UAAS+NaHS group and UAAS+PPG group were respectively given L-cys, NaHS and PPG by intraperitoneal injection. The aorta was taken 6 weeks after surgery. Western blot was used to detect the activation of nPKCδ, the phosphorylation of Akt, and the expression of VCAM-1 in the aorta of mice.

Results: The membrane translocation of nPKCδ in CHD patients with plaque was higher than that in CHD patients without plaque. The membrane translocation of nPKCδ and the expression of VCAM-1 in UAAS group was higher than sham group, L-cys or NaHS injection could suppress the membrane translocation of nPKCδ and the expression of VCAM-1, but PPG treatment resulted in more membrane translocation of nPKCδ and the expression of VCAM-1 (P<0.05, n=6 per group). Akt phosphorylation in UAAS group was lower than sham group, and L-cys or NaHS injection could suppress the degradation of Akt phosphorylation, but PPG treatment resulted in more decrease in the Akt phosphorylation (P<0.05, n=6 per group).

Conclusion: Endogenous CSE/H2S system protected against the formation of UAAS via nPKCδ/Akt signal pathway. The imbalance of CSE/H2S system may participate in the formation of UAAS by affecting the expression of downstream molecule VCAM-1, which may be mediated by nPKCδ/Akt signaling pathway.
Molecular Mechanisms Underlying Reciprocal Interactions Between Sleep Disorders and Parkinson’s Disease
Authors: Yang Zhengjie , Zhang Xiaona , Li Chengqian , Chi Song , Xie Anmu
Published: February 2021

Sleep–wake disruptions are among the most prevalent and burdensome non-motor symptoms of Parkinson’s disease (PD). Clinical studies have demonstrated that these disturbances can precede the onset of typical motor symptoms by years, indicating that they may play a primary function in the pathogenesis of PD. Animal studies suggest that sleep facilitates the removal of metabolic wastes through the glymphatic system via convective flow from the periarterial space to the perivenous space, upregulates antioxidative defenses, and promotes the maintenance of neuronal protein homeostasis. Therefore, disruptions to the sleep–wake cycle have been associated with inefficient metabolic clearance and increased oxidative stress in the central nervous system (CNS). This leads to excessive accumulation of alpha-synuclein and the induction of neuronal loss, both of which have been proposed to be contributing factors to the pathogenesis and progression of PD. Additionally, recent studies have suggested that PD-related pathophysiological alterations during the prodromal phase disrupt sleep and circadian rhythms. Taken together, these findings indicate potential mechanistic interactions between sleep–wake disorders and PD progression as proposed in this review. Further research into the hypothetical mechanisms underlying these interactions would be valuable, as positive findings may provide promising insights into novel therapeutic interventions for PD.
Artificial Intelligence Segmented Dynamic Video Images for Continuity Analysis in the Detection of Severe Cardiovascular Disease
Authors: Zhu Xi , Xia Wei , Bao Zhuqing , Zhong Yaohui , Fang Yu , Yang Fei , Gu Xiaohua , Ye Jing , Huang Wennuo
Published: February 2021

In this paper, an artificial intelligence segmented dynamic video image based on the process of intensive cardiovascular and cerebrovascular disease monitoring is deeply investigated, and a sparse automatic coding deep neural network with a four layers stack structure is designed to automatically extract the deep features of the segmented dynamic video image shot, and six categories of normal, atrial premature, ventricular premature, right bundle branch block, left bundle branch block, and pacing are achieved through hierarchical training and optimization. Accurate recognition of heartbeats with an average accuracy of 99.5%. It provides technical assistance for the intelligent prediction of high-risk cardiovascular diseases like ventricular fibrillation. An intelligent prediction algorithm for sudden cardiac death based on the echolocation network was proposed. By designing an echolocation network with a multilayer serial structure, an intelligent distinction between sudden cardiac death signal and non-sudden death signal was realized, and the signal was predicted 5 min before sudden death occurred, with an average prediction accuracy of 94.32%. Using the self-learning capability of stack sparse auto-coding network, a large amount of label-free data is designed to train the stack sparse auto-coding deep neural network to automatically extract deep representations of plaque features. A small amount of labeled data then introduced to micro-train the entire network. Through the automatic analysis of the fiber cap thickness in the plaques, the automatic identification of thin fiber cap-like vulnerable plaques was achieved, and the average overlap of vulnerable regions reached 87%. The overall time for the automatic plaque and vulnerable plaque recognition algorithm was 0.54 s. It provides theoretical support for accurate diagnosis and endogenous analysis of high-risk cardiovascular diseases.
Enolase 1 Correlated With Cancer Progression and Immune-Infiltrating in Multiple Cancer Types: A Pan-Cancer Analysis
Authors: Xu Wenhua , Yang Wenna , Wu Chunfeng , Ma Xiaocong , Li Haoyu , Zheng Jinghui
Published: February 2021

Enolase 1 (ENO1) is an oxidative stress protein expressed in endothelial cells. This study aimed to investigate the correlation of ENO1 with prognosis, tumor stage, and levels of tumor-infiltrating immune cells in multiple cancers. ENO1 expression and its influence on tumor stage and clinical prognosis were analyzed by UCSC Xena browser, Gene Expression Profiling Interactive Analysis (GEPIA), The Cancer Genome Atlas (TCGA), and GTEx Portal. The ENO1 mutation analysis was performed by cBio Portal, and demonstrated ENO1 mutation (1.8%) did not impact on tumor prognosis. The relationship between ENO1 expression and tumor immunity was analyzed by Tumor Immune Estimation Resource (TIMER) and GEPIA. The potential functions of ENO1 in pathways were investigated by Gene Set Enrichment Analysis. ENO1 expression was significantly different in tumor and corresponding normal tissues. ENO1 expression in multiple tumor tissues correlated with prognosis and stage. ENO1 showed correlation with immune infiltrates including B cells, CD8+ and CD4+ T cells, macrophages, neutrophils, and dendritic cells, and tumor purity. ENO1 was proved to be involved in DNA replication, cell cycle, apoptosis, glycolysis process, and other processes. These findings indicate that ENO1 is a potential prognostic biomarker that correlates with cancer progression immune infiltration.
A Urine-Based Liquid Biopsy Method for Detection of Upper Tract Urinary Carcinoma
Authors: Xu Yansheng , Ma Xin , Ai Xing , Gao Jiangping , Liang Yiming , Zhang Qin , Ma Tonghui , Mao Kaisheng , Zheng Qiaosong , Wang Sizhen , Jiao Yuchen , Zhang Xu , Li Hongzhao
Published: February 2021

Background

Conventional clinical detection methods such as CT, urine cytology, and ureteroscopy display low sensitivity and/or are invasive in the diagnosis of upper tract urinary carcinoma (UTUC), a factor precluding their use. Previous studies on urine biopsy have not shown satisfactory sensitivity and specificity in the application of both gene mutation or gene methylation panels. Therefore, these unfavorable factors call for an urgent need for a sensitive and non-invasive method for the diagnosis of UTUC.

Methods

In this study, a total of 161 hematuria patients were enrolled with (n = 69) or without (n = 92) UTUC. High-throughput sequencing of 17 genes and methylation analysis for ONECUT2 CpG sites were combined as a liquid biopsy test panel. Further, a logistic regression prediction model that contained several significant features was used to evaluate the risk of UTUC in these patients.

Results

In total, 86 UTUC− and 64 UTUC+ case samples were enrolled for the analysis. A logistic regression analysis of significant features including age, the mutation status of TERT promoter, and ONECUT2 methylation level resulted in an optimal model with a sensitivity of 94.0%, a specificity of 93.1%, the positive predictive value of 92.2% and a negative predictive value of 94.7%. Notably, the area under the curve (AUC) was 0.957 in the training dataset while internal validation produced an AUC of 0.962. It is worth noting that during follow-up, a patient diagnosed with ureteral inflammation at the time of diagnosis exhibiting both positive mutation and methylation test results was diagnosed with ureteral carcinoma 17 months after his enrollment.

Conclusion

This work utilized the epigenetic biomarker ONECUT2 for the first time in the detection of UTUC and discovered its superior performance. To improve its sensitivity, we combined the biomarker with high-throughput sequencing of 17 genes test. It was found that the selected logistic regression model diagnosed with ureteral cancer can evaluate upper tract urinary carcinoma risk of patients with hematuria and outperform other existing panels in providing clinical recommendations for the diagnosis of UTUC. Moreover, its high negative predictive value is conducive to rule to exclude patients without UTUC.
Distinguishable Prognostic miRNA Signatures of Head and Neck Squamous Cell Cancer With or Without HPV Infection
Authors: Luo Xiao-jie , Zheng Min , Cao Ming-xin , Zhang Wei-long , Huang Mei-chang , Dai Li , Tang Ya-ling , Liang Xin-hua
Published: February 2021

Since their discovery in the 1990’s, microRNAs (miRNA) have opened up new vistas in the field of cancer biology and are found to have fundamental roles in tumorigenesis and progression. As head and neck squamous cell carcinoma (HNSCC) with positive human papillomavirus (HPV+) is significantly distinct from its HPV negative (HPV−) counterpart in terms of both molecular mechanisms and clinical prognosis, the current study aimed to separately develop miRNA signatures for HPV+ and HPV− HNSCC as well as to explore the potential functions. Both signatures were reliable for the prediction of prognosis in their respective groups. Then Enrichment analysis was performed to predict the potential biological functions of the signatures. Importantly, combining previous studies and our results, we speculated that HPV+ HNSCC patients with low signature score had better immunity against the tumors and enhanced the sensitivity of therapies leading to improved prognosis, while HPV− HNSCC patients with high signature score acquired resistance to therapeutic approaches as well as dysregulation of cell metabolism leading to poor prognosis. Hence, we believe that the identified signatures respectively for HPV+ and HPV− HNSCC, are of great significance in accessing patient outcomes as well as uncovering new biomarkers and therapeutic targets, which are worth further investigation through molecular biology experiments.
Linking Microdosimetric Measurements to Biological Effectiveness in Ion Beam Therapy: A Review of Theoretical Aspects of MKM and Other Models
Authors: Bellinzona V. E. , Cordoni F. , Missiaggia M. , Tommasino F. , Scifoni E. , La Tessa C. , Attili A.
Published: February 2021

Different qualities of radiation are known to cause different biological effects at the same absorbed dose. Enhancements of the biological effectiveness are a direct consequence of the energy deposition clustering at the scales of DNA molecule and cell nucleus whilst absorbed dose is a macroscopic averaged quantity which does not take into account heterogeneities at the nanometer and micrometer scales. Microdosimetry aims to measure radiation quality at cellular or sub-cellular levels trying to increase the understanding of radiation damage mechanisms and effects. Existing microdosimeters rely on the well-established gas-based detectors or the more recent solid-state devices. They provide specific energy z spectra and other derived quantities as lineal energy (y) spectra assessed at the micrometer level. The interpretation of the radio-biological experimental data in the framework of different models has raised interest and various investigations have been performed to link in vitro and in vivo radiobiological outcomes with the observed microdosimetric data. A review of the major models based on experimental microdosimetry, with a particular focus on ion beam therapy applications and an emphasis on the microdosimetric kinetic model (MKM), will be presented in this work, enlightening the advantages of each one in terms of accuracy, initial assumptions, and agreement with experimental data. The MKM has been used to predict different kinds of radiobiological quantities such as the relative biological effects for cell inactivation or the oxygen enhancement ratio. Recent developments of the MKM will be also presented, including new non-Poissonian correction approaches for high linear energy transfer radiation, the inclusion of partial repair effects for fractionation studies, and the extension of the model to account for non-targeted effects. We will also explore developments for improving the models by including track structure and the spatial damage correlation information, by using the full fluence spectrum and by better accounting for the energy-deposition fluctuations at the intra- and inter-cellular level.
Theoretical Investigation of the Passive Transmitter Based on Reconfigurable Metasurface
Authors: Yang Shuai , Zhang Kuang , Ding Xumin , Yang Guohui , Wu Qun
Published: February 2021

Wireless communication has become a standard solution to satisfy the ever-increasing demands of information transfer in our daily life. Furthermore, reconfigurable metasurfaces comprised of multiple tunable unitcells have drawn significant attention due to their superior electromagnetic performance, while the desired electromagnetic response can be controlled by computer. We therefore present a prototype of a wireless communication system based reconfigurable metasurface that works in the microwave frequency range. A 2-D periodical array of a reconfigurable metasurface is loaded with a varactor diode to effectively adjust the in-band transmission and reflection coefficients that maintain different far-field electromagnetic characteristics. The reconfigurable metasurface does not radiate electromagnetic waves and only carries information by adjusting its reflection and transmission coefficients. With this reconfigurable metasurface, a passive communication method can be realized.
Nitrogen Use Efficiency in Durum Wheat Under Different Nitrogen and Water Regimes in the Mediterranean Basin
Authors: Lupini Antonio , Preiti Giovanni , Badagliacca Giuseppe , Abenavoli Maria Rosa , Sunseri Francesco , Monti Michele , Bacchi Monica
Published: February 2021

Improving nitrogen use efficiency (NUE) represents one of the main goals to reduce N input in maximizing crop yield for sustainable agriculture. A NUE key strategy is the exploitation of genetic variation in available germplasm together with the understanding of molecular mechanisms governing this complex trait. Thus, NUE, its components, nitrogen uptake efficiency (NUpE) and nitrogen utilization efficiency (NUtE), and NUE-related traits heritability were evaluated in ancient (Cappelli, Capeiti, Russello, and Mazzancoio) and modern (Messapia, Tiziana, Svevo, and Normanno) wheat genotypes for tackling nitrogen (N) and/or water limitation in both growth chamber and field experiments. Our results exhibited a reduction of NUE, NUpE, and NUtE under water and combined (nitrogen + water) stress in all the genotypes, as expected. The contribution of genetic variability on phenotypic variation was significant for NUtE, harvest index, post-anthesis nitrogen uptake (PANU), and biomass production traits. Moreover, the stress tolerance indexes, calculated and bi-plotted for N and water stresses, exhibited two distinct clusters for many traits as then confirmed by principal component analysis. Although modern varieties showed higher crop yield and NUE under conventional N and water regimes, ancient varieties exhibited best performances to cope with both stresses, mainly under water limitation. Finally, the usage index, which takes into account total biomass increase, underlined that old genotypes were less affected by both stresses during crop cycle. In particular, these genotypes showed the best performances for NUE and its components under both stresses at stem elongation and milk ripening as shown also by PANU. In addition, at these stages, nitrate and ammonium transporter gene expressions in the root were performed, showing the highest activity in ancient varieties. In conclusion, the identification of NUE traits during a specific crop cycle stage, under both N and water limitation, will help in the breeding of more resilient varieties in Mediterranean sustainable agriculture by reducing N supply.
Oryza sativa cv. Nipponbare and Oryza barthii as Unexpected Tolerance and Susceptibility Sources Against Schizotetranychus oryzae (Acari: Tetranychidae) Mite Infestation
Authors: Buffon Giseli , Blasi Édina Aparecida dos Reis , Lamb Thainá Inês , Adamski Janete Mariza , Schwambach Joséli , Ricachenevsky Felipe Klein , Bertolazi Amanda , Silveira Vanildo , Lopes Mara Cristina Barbosa , Sperotto Raul Antonio
Published: February 2021

Cultivated rice (Oryza sativa L.) is frequently exposed to multiple stresses, including Schizotetranychus oryzae mite infestation. Rice domestication has narrowed the genetic diversity of the species, leading to a wide susceptibility. This work aimed to analyze the response of two African rice species (Oryza barthii and Oryza glaberrima), weedy rice (O. sativa f. spontanea), and O. sativa cv. Nipponbare to S. oryzae infestation. Surprisingly, leaf damage, histochemistry, and chlorophyll concentration/fluorescence indicated that the African species present a higher level of leaf damage, increased accumulation of H2O2, and lower photosynthetic capacity when compared to O. sativa plants under infested conditions. Infestation decreased tiller number, except in Nipponbare, and caused the death of O. barthii and O. glaberrima plants during the reproductive stage. While infestation did not affect the weight of 1,000 grains in both O. sativa, the number of panicles per plant was affected only in O. sativa f. spontanea, and the percentage of full seeds per panicle and seed length were increased only in Nipponbare. Using proteomic analysis, we identified 195 differentially abundant proteins when comparing susceptible (O. barthii) and tolerant (Nipponbare) plants under control and infested conditions. O. barthii presents a less abundant antioxidant arsenal and is unable to modulate proteins involved in general metabolism and energy production under infested condition. Nipponbare presents high abundance of detoxification-related proteins, general metabolic processes, and energy production, suggesting that the primary metabolism is maintained more active compared to O. barthii under infested condition. Also, under infested conditions, Nipponbare presents higher levels of proline and a greater abundance of defense-related proteins, such as osmotin, ricin B-like lectin, and protease inhibitors (PIs). These differentially abundant proteins can be used as biotechnological tools in breeding programs aiming at increased tolerance to mite infestation.
Exopolysaccharide Characterization of Rhizobium favelukesii LPU83 and Its Role in the Symbiosis With Alfalfa
Authors: Castellani Lucas G. , Luchetti Abril , Nilsson Juliet F. , Pérez-Giménez Julieta , Wegener Caren , Schlüter Andreas , Pühler Alfred , Lagares Antonio , Brom Susana , Pistorio Mariano , Niehaus Karsten , Torres Tejerizo Gonzalo A.
Published: February 2021

One of the greatest inputs of available nitrogen into the biosphere occurs through the biological N2-fixation to ammonium as result of the symbiosis between rhizobia and leguminous plants. These interactions allow increased crop yields on nitrogen-poor soils. Exopolysaccharides (EPS) are key components for the establishment of an effective symbiosis between alfalfa and Ensifer meliloti, as bacteria that lack EPS are unable to infect the host plants. Rhizobium favelukesii LPU83 is an acid-tolerant rhizobia strain capable of nodulating alfalfa but inefficient to fix nitrogen. Aiming to identify the molecular determinants that allow R. favelukesii to infect plants, we studied its EPS biosynthesis. LPU83 produces an EPS I identical to the one present in E. meliloti, but the organization of the genes involved in its synthesis is different. The main gene cluster needed for the synthesis of EPS I in E. meliloti, is split into three different sections in R. favelukesii, which probably arose by a recent event of horizontal gene transfer. A R. favelukesii strain devoided of all the genes needed for the synthesis of EPS I is still able to infect and nodulate alfalfa, suggesting that attention should be directed to other molecules involved in the development of the symbiosis.
Disturbances of Shared Intentionality in Schizophrenia and Autism
Authors: Salice Alessandro , Henriksen Mads Gram
Published: February 2021

Schizophrenia and autism are today considered complex spectrum disorders characterized by difficulties in social behavior. Drawing on recent advances in collective or shared intentionality studies, we present a novel theoretical approach to these social difficulties by exploring them from the angle of shared intentionality. We begin by describing two forms of shared intentionality: joint intentionality and we-intentionality. Joint intentionality crucially relies on the agents' mentalizing abilities such as mind reading and the ability to factor in (or “to be moved” by) their partner's intentions in deliberation and action planning. By contrast, we-intentionality relies on the agents' capacity to understand themselves as group members and to adopt the group's perspective. In schizophrenia spectrum disorders, we propose that joint intentionality remains unaffected, but we-intentionality may be impaired. In severe autism spectrum disorder (i.e., infantile autism), we propose that both forms of shared intentionality are impaired. We suggest that the source of the problems affecting we-intentionality in schizophrenia spectrum disorders lies primarily in trait-like, anomalous self-experiences. In severe autism spectrum disorder, we suggest that problems with mind reading, the ability to “be moved” by others' intentions, and with the capacity for perspective-taking impede both forms of shared intentionality.
Addressing Mood Disorder Diagnosis' Stigma With an Honest, Open, Proud (HOP)-Based Intervention: A Randomized Controlled Trial
Authors: Modelli Arlete , Candal Setti Viviane P. , van de Bilt Martinus Theodorus , Gattaz Wagner Farid , Loch Alexandre Andrade , Rössler Wulf
Published: February 2021

Introduction: The public stigma and self-stigma contribute to the dilemma of disclosing or not one's own mental illness diagnosis. Studies suggest that revealing it diminishes stress, besides helping with self-esteem. Honest, Open, Proud (HOP) is a group program that aids in the process of deciding on it, reducing its impact. Considering the relevance of this issue, the present study aimed to apply a HOP-based intervention in a group of patients diagnosed with mood disorders.

Methods: A randomized controlled clinical trial was used, including 61 patients with mood disorders, of whom 31 were diagnosed with depression and 30 were diagnosed with bipolar disorder. They were randomly placed on the intervention (HOP) or the control group (unstructured psychoeducation). The evaluations occurred before (T0) and after (T1) the sessions. We administered eight scales, from which three presented relevant results: Coming Out with Mental Illness Scale (COMIS), Cognitive Appraisal of Stigma as a Stressor (CogApp), and Authenticity Scale.

Results: The intervention groups (depression and bipolar) did not present a significant change regarding the decision to disclose their diagnostics. However, the depression group showed a decrease on the perception of stigma as a stressor (T0 = 0.50 vs. T1 = −1.45; p = 0.058). Improvements in post-intervention results were seen for both groups (depression and bipolar) on the Authenticity Scale—self-alienation subscale (T0 = 10.40 vs. T1 = 12.37, p = 0.058).

Conclusion: Our HOP-based intervention appeared to be an important program to aid patients in facing stigma stress, showing positive effects, whether helping to diminish stress or to improve self-conscience, both of which have indirect effects on self-stigma. As it is a compact program, it can bring benefits when applying to public health institutions.
COVID-19 Vaccination Acceptance and Its Associated Factors Among a Middle Eastern Population
Authors: Al-Qerem Walid A. , Jarab Anan S.
Published: February 2021

Background: The Coronavirus disease 2019 (COVID-19) pandemic is a major threat to public health and has had a significant impact on all aspects of life. An effective vaccine is the most anticipated resolution. This study aims to evaluate Jordanian intent to be vaccinated.

Methods: This is a cross-sectional web-based study. Sample characteristics were gathered, and the participants were classified according to the degree of COVID-19 risk based on the categories of the Centers for Disease Control and Prevention (CDC). Participants' KAP toward COVID-19 were assessed, and two scores were calculated: knowledge score and practice score. The association between different sample characteristics and these scores was identified using binary logistical regressions. The participants' vaccination intention was evaluated and multinomial logistic regression was applied to identify the predictors of vaccination intention. Finally, the reasons behind the participants' vaccination refusal/hesitation were determined and categorized into different groups.

Results: 1,144 participants were enrolled in the study (females = 66.5%). 30.4% of the participants were at high risk of COVID-19 complications, and 27.5% were at medium risk. Overall, participants' knowledge of COVID-19 symptoms, transmission methods, protective measures, and availability of cure were high (median of knowledge score = 17 out of 21). High protective practices were followed by many participants (median of practice score = 7 out of 10). 3.7% of participants were infected, and 6.4% suspected they were infected with the COVID-19 virus. 36.8% of the participants answered “No” when asked if they would take the vaccine once it becomes available, and 26.4% answered, “Not sure.” The main reasons for the participants' vaccination refusal or hesitancy were concerns regarding the use of vaccines and a lack of trust in them.

Conclusion: Participants reported high refusal/hesitancy. Several barriers were identified, and efforts should be intensified to overcome these barriers.