bluuebunny/crossref_metadata_2025 huggingface dataset:
Using Generalized Regression Neural Network to Retrieve Bare Surface Soil Moisture From Radarsat-2 Backscatter Observations, Regardless of Roughness Effect
Authors: Zeng Ling , Liu Quanming , Jing Linhai , Lan Ling , Feng Jun
Published: April 2021

The combined influence of surface soil moisture and roughness on radar backscatters has been limiting SAR’s application in soil moisture retrieval. In the past research, multi-temporal analysis and artificial neural network (ANN) inversion of physically based forward models were regarded as promising methods to decouple that combined influence. However, the former does not consider soil roughness change over a relatively longer period and the latter makes it hard to thoroughly eliminate the effect of soil roughness. This study proposes to use generalized regression neural network (GRNN) to derive bare surface soil moisture (BSSM) from radar backscatter observations regardless of the effect of soil roughness (GRNN inversion of backscatter observations). This method not only can derive BSSM from radar backscatters, provided soil roughness is unknown in any long period, but also can train models based on small-size sample data so as to reduce the manual error of training data created by simulation of physically based models. The comparison of validations between BSSM-backscatter models and BSSM-roughness-backscatter models both analyzed by GRNN shows that the incorporation of soil roughness cannot raise the prediction accuracy of models and, instead, even reduce it, indicating that the combined influence is thoroughly decoupled when being analyzed by GRNN. Moreover, BSSM-backscatter models by GRNN are recommended due to their good prediction, even compared to those related models in past publications.
Arg-Vasotocin Directly Activates Isotocin Receptors and Induces COX2 Expression in Ovoviviparous Guppies
Authors: Lyu Li Kang , Li Jian Shuang , Wang Xiao Jie , Yao Yi Jia , Li Ji Fang , Li Yun , Wen Hai Shen , Qi Xin
Published: April 2021

Oxytocin (OT) is a crucial regulator of reproductive behaviors, including parturition in mammals. Arg-vasopressin (AVP) is a nonapeptide homologous to Arg-vasotocin (AVT) in teleosts that has comparable affinity for the OT receptor. In the present study, ovoviviparous guppies (Poecilia reticulata) were used to study the effect of AVT on delivery mediated by the activation of prostaglandin (PG) biosynthesis via isotocin (IT) receptors (ITRs). One copy each of it and avt and two copies of itrs were identified in guppies. The results of the affinity assay showed that various concentrations of AVT and IT (10−6, 10−7, and 10−8 mol/L) significantly activated itr1 (P < 0.05). In vitro experiments revealed significant upregulation (P < 0.05) of cyclooxygenase 2 (cox2), which is the rate-limiting enzyme involved in PG biosynthesis, and itr1 by AVT and IT. Furthermore, dual in situ hybridization detected positive signals for itr1 and cox2 at the same site, implying that ITR1 may regulate cox2 gene expression. Measurement of prostaglandin F2a (PGF2a) concentrations showed that AVT induced PGF2a synthesis (P < 0.05) and that the effect of IT was not significant. Finally, intraperitoneal administration of PGF2a significantly induced premature parturition of guppies. This study is the first to identify and characterize AVT and ITRs in guppies. The findings suggest that AVT promotes PG biosynthesis via ITR and that PGF2a induces delivery behavior in ovoviviparous guppies.
Single Hormone Receptor-Positive Metaplastic Breast Cancer: Similar Outcome as Triple-Negative Subtype
Authors: Mao Jinqian , Hu Jin , Zhang Yanting , Shen Jian , Dong Fang , Zhang Ximeng , Ming Jie , Huang Tao , Run Xiaoqin
Published: April 2021

Background

Metaplastic breast cancer (MBC) is a rare and aggressive subtype of the breast. To understand the characteristics and prognosis of single hormone receptor-positive (HR+) MBC (estrogen receptor-positive [ER+]/progesterone receptor-negative [PR-] and ER-/PR+), we compared these tumors to double HR+ tumors as well as HR- tumors.

Patients and Methods

The Surveillance, Epidemiology, and End Results database was used to analyze MBC between 1975 and 2016. The effect of HR status was evaluated using a multivariate Cox regression model.

Results

We included 3369 patients with a median follow-up time of 42 months (range 0-322 months). In this study, 280 (8.3%) cases were double HR+ tumors, 2597 (77.1%) were double HR- tumors, and 492 (14.6%) cases were single HR+ tumors, of which 159 (4.7%) cases were ER-/PR+ tumors and 333 (9.9%) were ER+/PR- tumors. On multivariate Cox analysis, the prognosis was related to age, race/ethnicity, tumor grade, TNM stage, and surgery. HR status remained no impact on breast cancer-specific survival (BCSS). In the Kaplan-Meier curve, HR status was not associated with better BCSS or overall survival (OS). In patients without HER2 overexpression, the BCSS and OS of ER+/PR- and ER-/PR+ tumors were not significantly different from that of ER-/PR- and ER+/PR+ tumors. The difference remains no significant in patients with HER2 overexpression.

Conclusions

In comparison with both ER-/PR- and ER+/PR+ tumors, we have identified clinically and biologically distinct features of single HR+ tumors. In patients with or without HER2 overexpression, the prognosis of single HR+ tumors was similar to ER-/PR- and ER+/PR+ tumors.
Potential Networks Regulated by MSCs in Acute-On-Chronic Liver Failure: Exosomal miRNAs and Intracellular Target Genes
Authors: Zhang Jing , Gao Juan , Lin Dengna , Xiong Jing , Wang Jialei , Chen Junfeng , Lin Bingliang , Gao Zhiliang
Published: April 2021

Acute-on-chronic liver failure (ACLF) is a severe syndrome associated with high mortality. Alterations in the liver microenvironment are one of the vital causes of immune damage and liver dysfunction. Human bone marrow mesenchymal stem cells (hBMSCs) have been reported to alleviate liver injury via exosome-mediated signaling; of note, miRNAs are one of the most important cargoes in exosomes. Importantly, the miRNAs within exosomes in the hepatic microenvironment may mediate the mesenchymal stem cell (MSC)-derived regulation of liver function. This study investigated the hepatocyte exosomal miRNAs which are regulated by MSCs and the target genes which have potential in the treatment of liver failure. Briefly, ACLF was induced in mice using carbon tetrachloride and primary hepatocytes were isolated and co-cultured (or not) with MSCs under serum-free conditions. Exosomes were then collected, and the expression of exosomal miRNAs was assessed using next-generation sequencing; a comparison was performed between liver cells from healthy versus ACLF animals. Additionally, to identify the intracellular targets of exosomal miRNAs in humans, we focused on previously published data, i.e., microarray data and mass spectrometry data in liver samples from ACLF patients. The biological functions and signaling pathways associated with differentially expressed genes were predicted using gene ontology and Kyoto Encyclopedia of Genes and Genomics enrichment analyses; hub genes were also screened based on pathway analysis and the prediction of protein-protein interaction networks. Finally, we constructed the hub gene-miRNA network and performed correlation analysis and qPCR validation. Importantly, our data revealed that MSCs could regulate the miRNA content within exosomes in the hepatic microenvironment. MiR-20a-5p was down-regulated in ACLF hepatocytes and their exosomes, while the levels of chemokine C-X-C Motif Chemokine Ligand 8 (CXCL8; interleukin 8) were increased in hepatocytes. Importantly, co-culture with hBMSCs resulted in up-regulated expression of miR-20a-5p in exosomes and hepatocytes, and down-regulated expression of CXCL8 in hepatocytes. Altogether, our data suggest that the exosomal miR-20a-5p/intracellular CXCL8 axis may play an important role in the reduction of liver inflammation in ACLF in the context of MSC-based therapies and highlights CXCL8 as a potential target for alleviating liver injury.
A Population-Specific Major Allele Reference Genome From The United Arab Emirates Population
Authors: Daw Elbait Gihan , Henschel Andreas , Tay Guan K. , Al Safar Habiba S.
Published: April 2021

The ethnic composition of the population of a country contributes to the uniqueness of each national DNA sequencing project and, ideally, individual reference genomes are required to reduce the confounding nature of ethnic bias. This work represents a representative Whole Genome Sequencing effort of an understudied population. Specifically, high coverage consensus sequences from 120 whole genomes and 33 whole exomes were used to construct the first ever population specific major allele reference genome for the United Arab Emirates (UAE). When this was applied and compared to the archetype hg19 reference, assembly of local Emirati genomes was reduced by ∼19% (i.e., some 1 million fewer calls). In compiling the United Arab Emirates Reference Genome (UAERG), sets of annotated 23,038,090 short (novel: 1,790,171) and 137,713 structural (novel: 8,462) variants; their allele frequencies (AFs) and distribution across the genome were identified. Population-specific genetic characteristics including loss-of-function variants, admixture, and ancestral haplogroup distribution were identified and reported here. We also detect a strong correlation between FST and admixture components in the UAE. This baseline study was conceived to establish a high-quality reference genome and a genetic variations resource to enable the development of regional population specific initiatives and thus inform the application of population studies and precision medicine in the UAE.
Is It Feasible to Use CMV-Specific T-Cell Adoptive Transfer as Treatment Against Infection in SOT Recipients?
Authors: García-Ríos Estéfani , Nuévalos Marcos , Mancebo Francisco J. , Pérez-Romero Pilar
Published: April 2021

During the last decade, many studies have demonstrated the role of CMV specific T-cell immune response on controlling CMV replication and dissemination. In fact, it is well established that transplanted patients lacking CMV-specific T-cell immunity have an increased occurrence of CMV replication episodes and CMV-related complications. In this context, the use of adoptive transfer of CMV-specific T-cells has been widely investigated and applied to Hematopoietic Stem Cell Transplant patients and may be useful as a therapeutic alternative, to reconstitute the CMV specific T-cell response and to control CMV viremia in patients receiving a transplantation. However, only few authors have explored the use of T-cell adoptive transfer in SOT recipients. We propose a novel review in which we provide an overview of the impact of using CMV-specific T-cell adoptive transfer on the control of CMV infection in SOT recipients, the different approaches to stimulate, isolate and expand CMV-specific T-cells developed over the years and a discussion of the possible use of CMV adoptive cellular therapy in this SOT population. Given the timeliness and importance of this topic, we believe that such an analysis will provide important insights into CMV infection and its treatment/prevention.
Regulation and Function of ILC3s in Pulmonary Infections
Authors: Hoffmann Joseph P. , Kolls Jay K. , McCombs Janet E.
Published: April 2021

Lower respiratory infections are among the leading causes of morbidity and mortality worldwide. These potentially deadly infections are further exacerbated due to the growing incidence of antimicrobial resistance. To combat these infections there is a need to better understand immune mechanisms that promote microbial clearance. This need in the context of lung infections has been further heightened with the emergence of SARS-CoV-2. Group 3 innate lymphoid cells (ILC3s) are a recently discovered tissue resident innate immune cell found at mucosal sites that respond rapidly in the event of an infection. ILC3s have clear roles in regulating mucosal immunity and tissue homeostasis in the intestine, though the immunological functions in lungs remain unclear. It has been demonstrated in both viral and bacterial pneumonia that stimulated ILC3s secrete the cytokines IL-17 and IL-22 to promote both microbial clearance as well as tissue repair. In this review, we will evaluate regulation of ILC3s during inflammation and discuss recent studies that examine ILC3 function in the context of both bacterial and viral pulmonary infections.
Rhesus Macaque Activating Killer Immunoglobulin-Like Receptors Associate With Fc Receptor Gamma (FCER1G) and Not With DAP12 Adaptor Proteins Resulting in Stabilized Expression and Enabling Signal Transduction
Authors: Hasan Mohammad Zahidul , Walter Lutz
Published: April 2021

Activating killer cell immunoglobulin-like receptors (KIR) in macaques are thought to be derived by genetic recombination of the region encoding the transmembrane and intracellular part of KIR2DL4 and a KIR3D gene. As a result, all macaque activating KIR possess a positively charged arginine residue in the transmembrane region. As human KIR2DL4 associates with the FCER1G (also called Fc receptor-gamma, FcRγ) adaptor, we hypothesized that in contrast to human and great ape the activating KIRs of macaques associate with FcRγ instead of DAP12. By applying co-immunoprecipitation of transfected as well as primary cells, we demonstrate that rhesus macaque KIR3DS05 indeed associates with FcRγ and not with DAP12. This association with FcRγ results in increased and substantially stabilized surface expression of KIR3DS05. In addition, we demonstrate that binding of specific ligands of KIR3DS05, Mamu-A1*001 and A1*011, resulted in signal transduction in the presence of FcRγ in contrast to DAP12.
Surface Circulation and Vertical Structure of Upper Ocean Variability Around Fernando de Noronha Archipelago and Rocas Atoll During Spring 2015 and Fall 2017
Authors: Costa da Silva Alex , Chaigneau Alexis , Dossa Alina N. , Eldin Gerard , Araujo Moacyr , Bertrand Arnaud
Published: April 2021

Using current, hydrographic and satellite observations collected off Northeast Brazil around the Fernando de Noronha Archipelago and Rocas Atoll during two oceanographic cruises (spring 2015 and fall 2017), we investigated the general oceanic circulation and its modifications induced by the islands. In spring 2015, the area was characterized by lower SST (26.6°C) and deep mixed-layer (∼90 m). At this depth, a strong current shear was observed between the central branch of the eastward flowing near-surface South Equatorial Current and the westward flowing South Equatorial Undercurrent. In contrast, in fall 2017, SST was higher (∼28.8°C) and the mixed-layer shallower (∼50 m). The shear between the central South Equatorial Current and the South Equatorial Undercurrent was weaker during this period. Interestingly, no oxygen-rich water from the south (retroflection of the North Brazil undercurrent) was observed in the region in fall 2017. In contrast, we revealed the presence of an oxygen-rich water entrained by the South Equatorial Undercurrent reaching Rocas Atoll in spring 2015. Beside these global patterns, island wake effects were noted. The presence of islands, in particular Fernando de Noronha, strongly perturbs central South Equatorial Current and South Equatorial Undercurrent features, with an upstream core splitting and a reorganization of single current core structures downstream of the islands. Near islands, flow disturbances impact the thermohaline structure and biogeochemistry, with a negative anomaly in temperature (−1.3°C) and salinity (−0.15) between 200 and 400 m depth in the southeast side of Fernando Noronha (station 5), where the fluorescence peak (>1.0 mg m–3) was shallower than at other stations located around Fernando de Noronha, reinforcing the influence of flow-topography. Satellite maps of sea-surface temperature and chlorophyll-a confirmed the presence of several submesoscale features in the study region. Altimetry data suggested the presence of a cyclonic mesoscale eddy around Rocas Atoll in spring 2015. A cyclonic vortex (radius of 28 km) was actually observed in subsurface (150–350 m depth) southeast of Rocas Atoll. This vortex was associated with topographically induced South Equatorial Undercurrent flow separation. These features are likely key processes providing an enrichment from the subsurface to the euphotic layer near islands, supplying local productivity.
Consolidation of Viscoelastic Soil With Vertical Drains for Continuous Drainage Boundary Conditions Incorporating a Fractional Derivative Model
Authors: Chen Peishuai , Li Jiacheng , Huang Minghua , Li Dejie
Published: April 2021

In geotechnical engineering, vertical drainage is the most economical method for accelerating the consolidation of a large area of soft ground. In this study, we analyze the viscoelasticity of the soil and the actual drainage conditions on the top surface of the soil, and then we introduce continuous drainage boundary conditions and adopt a fractional derivative model to describe the viscoelasticity of the soil. With the use of a viscoelasticity model, the governing partial differential equation for vertical drains under continuous drainage boundary conditions is obtained. With the application of the Crump numerical inversion method, the consolidation solution for vertical drains is also obtained. Further, the rationality of the proposed solution is verified by several examples. Moreover, some examples are provided to discuss the influence of interface drainage parameters on the top surface of soil and the viscoelasticity parameters of soil on the consolidation behavior of vertical drains. The proposed method can be applied in the fields of transport engineering to predict the consolidation settlement of a foundation reinforced by vertical drains.
Control of Streptococcal Infections: Is a Common Vaccine Target Achievable Against Streptococcus agalactiae and Streptococcus pneumoniae
Authors: Bedeley Edmund , Gori Andrea , Yeboah-Manu Dorothy , Diallo Kanny
Published: April 2021

Both Streptococcus agalactiae [group B streptococcus (GBS)] and Streptococcus pneumoniae (pneumococcus) remain significant pathogens as they cause life threatening infections mostly in children and the elderly. The control of diseases caused by these pathogens is dependent on antibiotics use and appropriate vaccination. The introduction of the pneumococcal conjugate vaccines (PCVs) against some serotypes has led to reduction in pneumococcal infections, however, the subsequent serotype switching, and replacement has been a serious challenge. On the other hand, no vaccine is yet licensed for use in the control of GBS diseases. In this review, we provide an overview of the history and global disease burden, disease pathophysiology and management, vaccines update, and the biology of both pathogens. Furthermore, we address recent findings regarding structural similarities that could be explored for vaccine targets across both mucosal pathogens. Finally, we conclude by proposing future genomic sequence comparison using the wealth of available sequences from both species and the possibility of identifying more related structural components that could be exploited for pan-pathogen vaccine development.
Deep Neural Networks for Depression Recognition Based on 2D and 3D Facial Expressions Under Emotional Stimulus Tasks
Authors: Guo Weitong , Yang Hongwu , Liu Zhenyu , Xu Yaping , Hu Bin
Published: April 2021

The proportion of individuals with depression has rapidly increased along with the growth of the global population. Depression has been the currently most prevalent mental health disorder. An effective depression recognition system is especially crucial for the early detection of potential depression risk. A depression-related dataset is also critical while evaluating the system for depression or potential depression risk detection. Due to the sensitive nature of clinical data, availability and scale of such datasets are scarce. To our knowledge, there are few extensively practical depression datasets for the Chinese population. In this study, we first create a large-scale dataset by asking subjects to perform five mood-elicitation tasks. After each task, subjects' audio and video are collected, including 3D information (depth information) of facial expressions via a Kinect. The constructed dataset is from a real environment, i.e., several psychiatric hospitals, and has a specific scale. Then we propose a novel approach for potential depression risk recognition based on two kinds of different deep belief network (DBN) models. One model extracts 2D appearance features from facial images collected by an optical camera, while the other model extracts 3D dynamic features from 3D facial points collected by a Kinect. The final decision result comes from the combination of the two models. Finally, we evaluate all proposed deep models on our built dataset. The experimental results demonstrate that (1) our proposed method is able to identify patients with potential depression risk; (2) the recognition performance of combined 2D and 3D features model outperforms using either 2D or 3D features model only; (3) the performance of depression recognition is higher in the positive and negative emotional stimulus, and females' recognition rate is generally higher than that for males. Meanwhile, we compare the performance with other methods on the same dataset. The experimental results show that our integrated 2D and 3D features DBN is more reasonable and universal than other methods, and the experimental paradigm designed for depression is reasonable and practical.
Inflammation and Insulin Resistance as Risk Factors and Potential Therapeutic Targets for Alzheimer’s Disease
Authors: Vinuesa Angeles , Pomilio Carlos , Gregosa Amal , Bentivegna Melisa , Presa Jessica , Bellotto Melina , Saravia Flavia , Beauquis Juan
Published: April 2021

Overnutrition and modern diets containing high proportions of saturated fat are among the major factors contributing to a low-grade state of inflammation, hyperglycemia and dyslipidemia. In the last decades, the global rise of type 2 diabetes and obesity prevalence has elicited a great interest in understanding how changes in metabolic function lead to an increased risk for premature brain aging and the development of neurodegenerative disorders such as Alzheimer’s disease (AD). Cognitive impairment and decreased neurogenic capacity could be a consequence of metabolic disturbances. In these scenarios, the interplay between inflammation and insulin resistance could represent a potential therapeutic target to prevent or ameliorate neurodegeneration and cognitive impairment. The present review aims to provide an update on the impact of metabolic stress pathways on AD with a focus on inflammation and insulin resistance as risk factors and therapeutic targets.
Influence of High Pass Filter Settings on Motor Evoked Potentials
Authors: Nikolov Petyo , Hassan Shady S. , Schnitzler Alfons , Groiss Stefan J.
Published: April 2021

Objective

Motor evoked potentials (MEP), obtained by transcranial magnetic stimulation (TMS) are a common tool in clinical research and diagnostic. Nevertheless, reports regarding the influence of filter settings on MEP are sparse. Here, we compared MEP amplitudes and signal to noise ratio (SNR) using multiple high pass filter (HPF) and notch filter settings.

Materials and Methods

Twenty healthy subjects were enrolled in the study. Recruitment curves were obtained with HPF settings varied at 10, 20, 50, and 100 Hz. The four HPF settings were tested both with and without 50 Hz active notch filter. Low pass filter was kept constant at 5 kHz.

Results

MEP amplitudes with HPF at 10 and 20 Hz were significantly higher than at 100 Hz, regardless of the notch filter. However, SNR did not differ among HPF settings. An active notch filter significantly improved SNR.

Conclusion

The reduction in MEP amplitudes with HPF above 20 Hz may be due to noise reduction, since the different HPF conditions did not alter SNR. Thus, higher HPF above 50 Hz may be an option to reduce noise, the use of a notch filter may even improve SNR.

Significance

Our findings are relevant for the selection of filter settings and might be of importance to any researcher who utilizes TMS-MEP.
RETRACTED: miRNA-193a-3p Regulates the AKT2 Pathway to Inhibit the Growth and Promote the Apoptosis of Glioma Cells by Targeting ALKBH5
Authors: Cui Yong , Wang Qi , Lin Jing , Zhang Lei , Zhang Chi , Chen Huairui , Qian Jun , Luo Chun
Published: April 2021

Emerging evidence indicates that microRNA (miR)-193a-3p is involved in the tumor progression of various cancers. However, the biological functions and precise molecular mechanisms of miR-193a-3p in gliomas have not been well documented. Accordingly, this study focused on the tumor suppressor role and molecular mechanisms of miR-193a-3p in glioma cells. miR-193a-3p expression was determined by qRT-PCR in glioma tissues and cell lines. U251 and U87 glioma cells were transfected with a miR-193a-3p mimic. The effects of miR-193a-3p on cell growth and apoptosis were investigated using MTT, colony-forming, and flow cytometry assays. Overexpression of miR-193a-3p in U87 cells also significantly suppressed tumorigenicity and induced apoptosis in the xenograft mouse model. Luciferase assays were conducted to determine if ALKBH5 is a direct target of miR-193a-3p in glioma cells. Immunoprecipitation was used to explore the interaction between ALKBH5 and RAC-serine/threonine-protein kinase 2 (AKT2) in glioma cells. miR-193a-3p was downregulated in glioma tissues and cell lines. miR-193a-3p treatment suppressed proliferation and promoted apoptosis in both U251 and U87 cells. Bioinformatics analysis and luciferase reporter assay identified a novel miR-193a-3p target, ALKBH5. Notably, the antitumor effect of miR-193a-3p transfection in glioma cells may be due to the miR-193a-3p–induced inhibition of AKT2 expression caused by the suppression of ALKBH5 expression. Furthermore, immunoprecipitation indicated that ALKBH5 physically interacted with AKT2 through an RNA-independent mechanism in glioma cells. miR-193a-3p directly targets ALKBH5 to inhibit the growth and promote the apoptosis of glioma cells by suppressing the AKT2 pathway both in vitro and in vivo, and the physical interaction between ALKBH5 and AKT2 is essential for suppressing cell apoptosis by upregulating miR-193a-3p in glioma cells. Our study revealed that the antitumor effects of miR-193a-3p on glioma cells is due to ALKBH5 mediation of the AKT2-induced intrinsic apoptosis signaling pathway.
Step-by-Step Cadaver Dissection and Surgical Technique for Compartmental Tongue and Floor of Mouth Resection
Authors: Grammatica Alberto , Piazza Cesare , Ferrari Marco , Verzeletti Vincenzo , Paderno Alberto , Mattavelli Davide , Schreiber Alberto , Lombardi Davide , Fazio Enrico , Gazzini Luca , Giorgetti Giovanni , Buffoli Barbara , Rodella Luigi Fabrizio , Nicolai Piero , Calabrese Luca
Published: April 2021

Background

The aim of oral cancer surgery is tumor removal within clear margins of healthy tissue: the latter definition in the literature, however, may vary between 1 and 2 cm, and should be intended in the three dimensions, which further complicates its precise measurement. Moreover, the biological behavior of tongue and floor of mouth cancer can be unpredictable and often eludes the previously mentioned safe surgical margins concept due to the complexity of tongue anatomy, the intricated arrangements of its intrinsic and extrinsic muscle fibers, and the presence of rich neurovascular and lymphatic networks within it. These structures may act as specific pathways of loco-regional tumor spread, allowing the neoplasm to escape beyond its visible macroscopic boundaries. Based on this concept, in the past two decades, compartmental surgery (CS) for treatment of oral tongue and floor of mouth cancer was proposed as an alternative to more traditional transoral resections.

Methods

The authors performed three anatomical dissections on fresh-frozen cadaver heads that were injected with red and blue-stained silicon. All procedures were documented by photographs taken with a professional reflex digital camera.

Results

One of these step-by-step cadaver dissections is herein reported, detailing the pivotal points of CS with the aim to share this procedure at benefit of the youngest surgeons.

Conclusions

We herein present the CS step-by-step technique to highlight its potential in improving loco-regional control by checking all possible routes of tumor spread. Correct identification of the anatomical space between tumor and nodes (T-N tract), spatial relationships of extrinsic tongue muscles, as well as neurovascular bundles of the floor of mouth, are depicted to improve knowledge of this complex anatomical area.
A Non-Invasive Scoring System to Differential Diagnosis of Clear Cell Renal Cell Carcinoma (ccRCC) From Renal Angiomyolipoma Without Visible Fat (RAML-wvf) Based on CT Features
Authors: Wang Xiao-Jie , Qu Bai-Qiang , Zhou Jia-Ping , Zhou Qiao-Mei , Lu Yuan-Fei , Pan Yao , Xu Jian-Xia , Miu You-You , Wang Hong-Qing , Yu Ri-Sheng
Published: April 2021

Background

Renal angiomyolipoma without visible fat (RAML-wvf) and clear cell renal cell carcinoma (ccRCC) have many overlapping features on imaging, which poses a challenge to radiologists. This study aimed to create a scoring system to distinguish ccRCC from RAML-wvf using computed tomography imaging.

Methods

A total of 202 patients from 2011 to 2019 that were confirmed by pathology with ccRCC (n=123) or RAML (n=79) were retrospectively analyzed by dividing them randomly into a training cohort (n=142) and a validation cohort (n=60). A model was established using logistic regression and weighted to be a scoring system. ROC, AUC, cut-off point, and calibration analyses were performed. The scoring system was divided into three ranges for convenience in clinical evaluations, and the diagnostic probability of ccRCC was calculated.

Results

Four independent risk factors are included in the system: 1) presence of a pseudocapsule, 2) a heterogeneous tumor parenchyma in pre-enhancement scanning, 3) a non-high CT attenuation in pre-enhancement scanning, and 4) a heterogeneous enhancement in CMP. The prediction accuracy had an ROC of 0.978 (95% CI, 0.956–0.999; P=0.011), similar to the primary model (ROC, 0.977; 95% CI, 0.954–1.000; P=0.012). A sensitivity of 91.4% and a specificity of 93.9% were achieved using 4.5 points as the cutoff value. Validation showed a good result (ROC, 0.922; 95% CI, 0.854–0.991, P=0.035). The number of patients with ccRCC in the three ranges (0 to <2 points; 2–4 points; >4 to ≤11 points) significantly increased with increasing scores.

Conclusion

This scoring system is convenient for distinguishing between ccRCC and RAML-wvf using four computed tomography features.
APC Promoter Methylation in Gastrointestinal Cancer
Authors: Zhu Lila , Li Xinyu , Yuan Ying , Dong Caixia , Yang Mengyuan
Published: April 2021

The adenomatous polyposis coli (APC) gene, known as tumor suppressor gene, has the two promoters 1A and 1B. Researches on APC have usually focused on its loss-of-function variants causing familial adenomatous polyposis. Hypermethylation, however, which is one of the key epigenetic alterations of the APC CpG sequence, is also associated with carcinogenesis in various cancers. Accumulating studies have successively explored the role of APC hypermethylation in gastrointestinal (GI) tumors, such as in esophageal, colorectal, gastric, pancreatic, and hepatic cancer. In sporadic colorectal cancer, the hypermethylation of CpG island in APC is even considered as one of the primary causative factors. In this review, we systematically summarized the distribution of APC gene methylation in various GI tumors, and attempted to provide an improved general understanding of DNA methylation in GI tumors. In addition, we included a robust overview of demethylating agents available for both basic and clinical researches. Finally, we elaborated our findings and perspectives on the overall situation of APC gene methylation in GI tumors, aiming to explore the potential research directions and clinical values.
The Heterogeneous Metabolic Patterns of Ganglia in 68Ga-PSMA, 11C-choline, and 18F-FDG PET/CT in Prostate Cancer Patients
Authors: Shi Yiping , Wu Jian Guo , Xu Lian , Zhu Yinjie , Wang Yining , Huang Gan , Liu Jianjun , Chen Ruohua
Published: April 2021

Purpose

Studies have indicated that PSMA-positive ganglia represent a diagnostic pitfall for nuclear medicine physicians. No studies have described choline and FDG uptake in ganglia, which may be a source of misdiagnosis. Herein, we described the percentage and uptake pattern of 68Ga-PSMA, 11C-choline and 18F-FDG PET/CT in ganglia and evaluated the heterogeneous metabolic patterns of ganglia to differentiate from lymph node metastases (LNM).

Methods

Thirty-nine patients who underwent 11C-choline PET/CT and 120 patients who underwent 68Ga-PSMA PET/CT and 18F-FDG PET/CT were retrospectively analyzed. The prevalence of PSMA-positive, choline-positive and FDG-positive ganglia was determined, the SUVmax of ganglia in different locations were measured, and the configuration was described. The SUVmax cutoff of PSMA-PET, choline-PET and FDG-PET was determined by ROC curve analysis to differentiate ganglia from LNM.

Results

329 PSMA-positive ganglia were identified in 120 patients, 95 choline-positive ganglia were identified in 39 patients, and 39 FDG-positive ganglia were identified in 34 patients. PSMA-positive uptake was observed in 98.3%, 95.8%, and 80.0% of cervical, coeliac, and sacral ganglia, respectively. Choline-positive uptake was observed in 84.6%, 97.4%, and 61.5% of cervical, coeliac, and sacral ganglia, respectively. FDG-positive uptake was observed in 16.7%, 13.3%, and 2.5% of cervical, coeliac, and sacral ganglia, respectively. Cervical and coeliac ganglia had a higher rate of PSMA-positive uptake than sacral ganglia. Choline uptake was highest in coeliac ganglia followed by cervical and sacral ganglia. PSMA, choline or FDG uptake in LNM was all significantly higher than ganglia. ROC curve analysis revealed that at a 4.1 SUVmax cutoff of PSMA-PET, the sensitivity, specificity and accuracy of LNM identification was 88.4%, 97.9% and 96.2%, respectively. ROC curve analysis revealed that at a 2.35 SUVmax cutoff for choline-PET, the sensitivity, specificity, and accuracy of LNM identification was 95.0%, 92.6% and 93.0%, respectively. ROC curve analysis revealed that at a 2.55 SUVmax cutoff for FDG-PET, the sensitivity, specificity, and accuracy of LNM identification was 77.3%, 87.2%, and 81.9%, respectively. PSMA-, Choline- and FDG-positive ganglia are mainly band-shaped; most LNMs exhibited nodular and teardrop-shaped configuration.

Conclusion

68Ga-PSMA and 11C-choline uptake in ganglia was common, and FDG-positive ganglia were observed at lower frequency. Using 68Ga-PSMA, 11C-choline and 18F-FDG uptake and anatomic location and configuration, the differentiation of ganglia from adjacent LNM is feasible.
Effectiveness of Trainings of General Practitioners on Antibiotic Stewardship: Methods of a Pragmatic Quasi-Experimental Study in a Controlled Before-After Design in South-East-Lower Saxony, Germany (WASA)
Authors: Gornyk Daniela , Scharlach Martina , Buhr-Riehm Brigitte , Klett-Tammen Carolina Judith , Eberhard Sveja , Stahmeyer Jona Theodor , Großhennig Anika , Smith Andrea , Meinicke Sarah , Bautsch Wilfried , Krause Gérard , Castell Stefanie
Published: April 2021

Introduction: Antibiotic resistance is a serious threat to global public health. It reduces the effectiveness of treatments for serious bacterial infections and thus increases the risk of fatal outcomes. Antibiotic prescriptions are often not in line with clinical evidence-based guidelines. The process of emergence of resistant bacteria can be slowed down by adherence to guidelines. Yet this adherence seems to be lacking in primary health care.

Methods and Analysis: This pragmatic quasi-experimental study using a controlled before-after design was carried out in South-East-Lower Saxony in 2018–2020. The voluntary attendance of interactive trainings with condensed presentation of current guidelines for general practitioners (GP) on antibiotic management for urinary and respiratory tract infections is regarded as intervention. Those GP not attending the trainings constitute the control group. Data were collected via questionnaires; routine health records are provided by a statutory health insurance. The primary outcome is the proportion of (guideline-based) prescriptions in relation to the relevant ICD-10 codes as well as daily defined doses and the difference in proportion of certain prescriptions according to guidelines before and after the intervention as compared to the control group. Further outcomes are among others the subjectively perceived risk of antibiotic resistance and the attitude toward the guidelines. The questionnaires to assess this are based on theory of planned behavior (TPB) and health action process approach (HAPA). Variations over time and effects caused by measures other than WASA (Wirksamkeit von Antibiotika-Schulungen in der niedergelassenen Aerzteschaft-Effectiveness of antibiotic management training in the primary health care sector) training are taken into account by including the control group and applying interrupted time series analysis.

Ethics and Dissemination: The study protocol and the data protection concept respectively were reviewed and approved by the Ethics Committee of the Hannover Medical School and the Federal Commissioner for Data Protection and Freedom of Information.

Trial Registration:https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00013951, identifier DRKS00013951.
Unraveling Gene Fusions for Drug Repositioning in High-Risk Neuroblastoma
Authors: Liu Zhichao , Chen Xi , Roberts Ruth , Huang Ruili , Mikailov Mike , Tong Weida
Published: April 2021

High-risk neuroblastoma (NB) remains a significant therapeutic challenge facing current pediatric oncology patients. Structural variants such as gene fusions have shown an initial promise in enhancing mechanistic understanding of NB and improving survival rates. In this study, we performed a comprehensive in silico investigation on the translational ability of gene fusions for patient stratification and treatment development for high-risk NB patients. Specifically, three state-of-the-art gene fusion detection algorithms, including ChimeraScan, SOAPfuse, and TopHat-Fusion, were employed to identify the fusion transcripts in a RNA-seq data set of 498 neuroblastoma patients. Then, the 176 high-risk patients were further stratified into four different subgroups based on gene fusion profiles. Furthermore, Kaplan-Meier survival analysis was performed, and differentially expressed genes (DEGs) for the redefined high-risk group were extracted and functionally analyzed. Finally, repositioning candidates were enriched in each patient subgroup with drug transcriptomic profiles from the LINCS L1000 Connectivity Map. We found the number of identified gene fusions was increased from clinical the low-risk stage to the high-risk stage. Although the technical concordance of fusion detection algorithms was suboptimal, they have a similar biological relevance concerning perturbed pathways and regulated DEGs. The gene fusion profiles could be utilized to redefine high-risk patient subgroups with significant onset age of NB, which yielded the improved survival curves (Log-rank p value ≤ 0.05). Out of 48 enriched repositioning candidates, 45 (93.8%) have antitumor potency, and 24 (50%) were confirmed with either on-going clinical trials or literature reports. The gene fusion profiles have a discrimination power for redefining patient subgroups in high-risk NB and facilitate precision medicine-based drug repositioning implementation.
Angiotensin II Receptor Blockers but Not Angiotensin-Converting Enzyme Inhibitors Are Associated With a Reduced Risk of Acute Kidney Injury After Major Surgery
Authors: Yang Shao-Yu , Huang Tao-Min , Lai Tai-Shuan , Chou Nai-Kuan , Tsao Chun-Hao , Huang Yi-Ping , Lin Shuei-Liong , Chen Yung-Ming , Wu Vin-Cent , NSARF study group
Published: April 2021

Objective: We investigated the respective effects of preoperative angiotensin-converting-enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) on the incidence of postoperative acute kidney injury (AKI) and mortality.

Methods: In this nested case-control study, we enrolled 20,276 patients who received major surgery. We collected their baseline demographic data, comorbidities and prescribed medication, the outcomes of postoperative AKI and mortality. AKI was defined by the criteria suggested by KDIGO (Kidney disease: Improving Global Outcome). Logistic regression was used to assess the impact of exposure to ACEIs or ARBs.

Results: Compared with patients without ACEI/ARB, patient who received ARBs had a significantly lower risk for postoperative AKI (adjusted odds ratio (OR) 0.82, p = 0.007). However, ACEI users had a higher risk for postoperative AKI than ARB users (OR 1.30, p = 0.027), whereas the risk for postoperative AKI was not significantly different between the ACEI users and patients without ACEI/ARB (OR 1.07, p = 0.49). Compared with patients without ACEI/ARB, both ACEI and ARB users were associated with a reduced risk of long-term all-cause mortality following surgery (OR 0.47, p = 0.002 and 0.60, p < 0.001 in ACEI and ARB users, respectively), without increasing the risk of hyperkalemia during the index hospitalization (p = 0.20). The risk of long-term all-cause mortality following surgery in ACEIs and ARBs users did not differ significantly (OR 0.74, p = 0.27). Furthermore, the higher the defined daily dose of ARB, the better the protection against AKI provided.

Conclusion: Our study revealed that preoperative use of ARBs was associated with reduced postoperative AKI, which is better in high quantity, whereas preoperative use of ACEIs or ARBs were both associated with reduced mortality and did not increase the risk of hyperkalemia.
Direct Optimal Control Approach to Laser-Driven Quantum Particle Dynamics
Authors: Ramos Ramos A. R. , Kühn O.
Published: April 2021

Optimal control theory is usually formulated as an indirect method requiring the solution of a two-point boundary value problem. Practically, the solution is obtained by iterative forward and backward propagation of quantum wavepackets. Here, we propose direct optimal control as a robust and flexible alternative. It is based on a discretization of the dynamical equations resulting in a nonlinear optimization problem. The method is illustrated for the case of laser-driven wavepacket dynamics in a bistable potential. The wavepacket is parameterized in terms of a single Gaussian function and field optimization is performed for a wide range of particle masses and lengths of the control interval. Using the optimized field in a full quantum propagation still yields reasonable control yields for most of the considered cases. Analysis of the deviations leads to conditions which have to be fulfilled to make the semiclassical single Gaussian approximation meaningful for field optimization.
Three-Dimensional Dirac Semimetal/Organic Thin Film Heterojunction Photodetector With Fast Response and High Detectivity
Authors: Liu Qi , Yang Ming , Zhang Jiangwei , Yang Mingliang , Wang Jun , Zheng Huajing , Gou Jun
Published: April 2021

As a typical three-dimensional Dirac semimetal (3D DSM), Cd3As2 possess ultrahigh carrier mobility, high level of full spectral absorption, fast electron transmission speed, and high photocurrent response, which enable wide applications in infrared photodetector. However, the large dark current of the detector based on Cd3As2 thin film limits the application of the small current response. Hence, we demonstrated heterojunction photodetectors based on n-type 3D DSM Cd3As2 (pristine and Zn doped) and p-type organic (PbPc) by depositing PbPc thin film on Cd3As2 (pristine and Zn doped) thin film using thermal deposition method. These photodetectors can detect the radiation wavelength from 405 to 1,550 nm at room temperature. It is remarkable that this thin film heterojunction photodetector exhibits high detectivity (3.95 × 1011 Jones) and fast response time (160 μs) under bias voltage, which is significantly improved vs. that of Cd3As2-based devices. The excellent performances are attributed to the strong built-in electric field at the interface of p-n junction, which is beneficial for efficient photocarriers collection and transportation. These results show that DSM/organic thin film heterojunction has excellent performance in the application of photodetectors. By combining 3D DSM with organic to form heterojunction, it provides a feasible solution for high-performance photodetectors.
Cross-Cultural Adaptation, Reliability, and Validity of a Brazilian of Short Version of the Posttraumatic Diagnostic Scale
Authors: de Faria Cardoso Cláudia , Ohe Natalia Tiemi , Taba Vera Lúcia , Paiva Tamyres Tomaz , Baltatu Ovidiu Constantin , Campos Luciana Aparecida
Published: April 2021

Background: A short version of the Posttraumatic Diagnostic Scale (PDS) comprising only re-experiencing symptom items has been recently validated on Japanese adults. This short-version-PDS had good psychometric properties among Japanese adults with and without posttraumatic stress disorder (PTSD). The aim of this study was to translate and culturally validate the short-version-PDS for the Brazilian sociolinguistic context.

Methods: A translation of the short-version-PDS was performed based on established guidelines. We enrolled 53 patients with PTSD as a potential comorbidity. The translation and cross-cultural adaptation of the short-version-PDS included forward and back-translation by a Japanese Brazilian researcher and a certified translator; synthesis was achieved by consensus, backward translation, pilot test, and finalization. Content validity coefficient (CVC) was used to assess quality of adaptation. Internal consistency was calculated using Cronbach's alpha coefficient. Spearman correlations were between the new short-version-PDS and the Brazilian version of the posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5), and a receiver operating characteristic (ROC) curve was used to determine the best cut-off values for the short-version-PDS.

Results: The short-version-PDS was well accepted by all subjects, none of the questions were experienced as inappropriate, and all questions of the 3 items were judged important. Item 1 presented CVCt = 0.92; item 2 had a CVCt = 0.87 and item 3 had a CVCt = 0.95. The internal consistency of the final version as measured by Cronbach's alpha was 0.78. The short-version-PDS scale correlated positively with the DSM-5 scale with a Spearman rho of 0.64 (95%CI [0.4-0.8], p < 0.001). The receiver operating characteristic (ROC) curve value was 0.97 (95%CI [0.9-1.0], p < 0.001). The cut-off score for a maximum Youden Index of 0.8 to distinguish moderate from severe from slight PTSD was > 31.0 with sensitivity and specificity are 86.4 and 93.5%, respectively.

Conclusions: This Brazilian Portuguese version of the short-version-PDS had good psychometric properties among Brazilian adults with and without PTSD. Transferability and generalizability of the cut-off scores should be further analyzed.