bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Better Standard-Uptake-Value Body Habitus Normalizer for Fluorodeoxyglucose in Humans
Authors: Beattie Bradley Jay , Akhurst Tim J , Augensen Finn , Humm John L 
Published: July 2021

Abstract
Purpose

To devise a new body-habitus normalizer to be used in the calculation of a standardized uptake value (SUV) that is specific to the PET tracer 18F-FDG.
Methods

After exclusions for type and extent of cancer and timing of the scan, a cohort of 481 patients was selected for analysis of 18F-FDG uptake into “normal” tissues (presumed to be unaffected by their disease). Among these, 65 patients had only brain concentrations measured and the remaining 416 were randomly divided into an 86-patient test set and a 330-patient training set. Within the test set, normal liver, spleen and blood measures were made. In the training set, only normal liver concentrations were measured. Using data from the training set, a simple polynomial function of height and weight was selected (following a subjective procedure) to predict each patient’s mean liver percent injected dose per milliliter. This function, when used to normalize measured %ID/ml concentrations, defines a new SUV metric (SUVfdg) which we compared to SUV metrics normalized by body weight (SUVbw), lean-body mass (SUVlbm) and body surface-area (SUVbsa) in a five-fold cross-validation. SUVfdg was also tested on the independent holdout sets utilizing the measurements of normal liver, blood, spleen and brain.
Results

For patients of all sizes including pediatric patients, the normal range of liver 18F-FDG uptake concentration at 60 minutes post injection in units of SUVfdg is 1.0 ± 0.16. Liver, blood and spleen SUVfdg in all comparisons had lower coefficients of variation (CoV) compared to SUVbw SUVlbm and SUVbsa. Blood had a mean SUVfdg value of 0.8 ± 0.11 and showed no correlation with age, height or weight. Brain SUVfdg measures were significantly higher (P < 0.01) in pediatric patients (4.7 ± 0.9) compared to adults (3.1 ± 0.6).
Conclusion

A new SUV metric, SUVfdg, is proposed. It is hoped that SUVfdg will prove to be better at classifying tumor lesions and other tissues compared to SUV metrics in current use and may be useful in predicting patient specific radiation dose. Other tracers may benefit from similarly tracer-specific body habitus normalizers.
Prognostic Model of Head and Neck Squamous Cell Carcinoma Based on 12 Ferroptosis-related Genes
Authors: Li Sijia , Zhang Hongyang , Li Wei 
Published: July 2021

Abstract
Background: The purpose of our study is establishing a model based on ferroptosis-related genes predicting the prognosis of patients with head and neck squamous cell carcinoma (HNSCC).Methods: In our study, transcriptome and clinical data of HNSCC patients were from The Cancer Genome Atlas, ferroptosis-related genes and pathways were from Ferroptosis Signatures Database. Differentially expressed genes (DEGs) were screened by comparing tumor and adjacent normal tissues. Functional enrichment analysis of DEGs, protein-protein interaction network and gene mutation examination were applied. Univariate Cox regression analysis and least absolute shrinkage and selection operator (LASSO) regression were used to identified DEGs. The model was constructed by multivariate Cox regression analysis and verified by Kaplan-Meier analysis. The relationship between risk scores and other clinical features was also analyzed. Univariate and multivariate Cox analysis was used to verified the independence of our model. The model was evaluated by receiver operating characteristic analysis and calculation of the area under the curve (AUC). A nomogram model based on risk score, age, gender and TNM stages was constructed. Our model was also validated in the Gene Expression Omnibus (GEO) verification set. Results: We analyzed data including 500 tumor tissues and 44 adjacent normal tissues and 259 ferroptosis-related genes, then obtained 73 DEGs. Univariate Cox regression analysis screened out 16 genes related to overall survival, and LASSO analysis fingered out 12 of them with prognostic value. A risk score model based on these 12 genes was constructed by multivariate Cox regression analysis. According to the median risk score, patients were divided into high-risk group and low-risk group. The survival rate of high-risk group was significantly lower than that of low-risk group in Kaplan-Meier curve. Risk scores were related to T and grade. Univariate and multivariate Cox analysis showed our model was an independent prognostic factor. The AUC was 0.669. Those all could prove our model had great predictive ability of HNSCC prognosis and it could be validated in GEO dataset. The nomogram showed high accuracy predicting the prognosis of HNSCC patients.Conclusion: Our model based on 12 ferroptosis-related genes performed excellently in predicting the prognosis of HNSCC patients. Ferroptosis-related genes may be promising biomarkers for HNSCC treatment and prognosis.
Remote Meetings in Problem-Based Learning: A Tool for Selection Research in Times of Pandemic
Authors: Cortes Paloma Freire Neves Leal , Bet Camila Delinski , Junior José Francisco dos Santos Silveira , Junior Edivaldo Rosas dos Santos , Cereda Marney Pascoli 
Published: July 2021

Abstract
Active methodologies have been widely used in education to provide greater involvement in the teaching-learning process. In the face of the current pandemic scenario, remote activities are strategies to spread knowledge but require adaptations of face-to-face education. However, no records were found of its use to support research groups, which traditionally are based on personal contacts. The article reports the experience of selecting participants in the development of research in the area of starch prospecting, with an adaptation of the Problem Based Learning (PBL) technique. The proposed problem was the characterization and evaluation of cassava starch for food industries application, using a sample limited to one gram. The PBL technique used research with a qualitative approach, applied nature, descriptive objective, and action research procedures. The five members that constituted the discussion group were from different professional areas and were selected among those who made up a larger group, with starch as the central theme. The PBL technique was adapted to be completed in three videoconference meetings, with intervals of 15 days. Based on the suggestions proposed and improved during the event, it was possible to outline the solution right at the first meeting. An analytical methodology can also be established within the specified limit, capable of prospecting its food industries application. Therefore, PBL as a strategic tool to develop research topics proved effective and flexible, and suitable for remote activities. It is recommended that it be better explored as a team leader and scientific research growth.
The viral accelerated NF-κB pathway drives COVID-19-associated coagulopathy via excessive transcription of tissue factor and plasminogen activator inhibitor 1 – case report
Authors: Leitzke Marco , Schönknecht Peter Oskar Dieter 
Published: July 2021

Abstract
Background The current COVID-19 pandemic creates new clinical challenges almost daily, especially in terms of individual prognoses, diagnostics involving newly discovered pathogenic mechanisms, and the appearance of SARS-CoV-2 mutations. In terms of the thromboembolic complications frequently occurring in COVID-19 patients, there is new evidence that pathognomonic COVID-19-associated coagulopathy (CAC) differs considerably from the coagulant malfunction of common disseminated intravascular coagulation. Thus, bleeding is a rare complication in the initial stages of the disease, whereas thrombotic formations can be seen autopticly in the vasculature of several organs. Therefore, it is speculated that most thromboembolic complications are thrombotic rather than embolic, and CAC is more likely to be a pro-coagulant form of coagulopathy. The reasons for these key differences have remained unknown until very recently. The relationship between SARS-CoV-2 infection and the virus-related acceleration of the transcriptional nuclear factor kappa B (NF-κB)-pathway, with the accompanied excessive downstream release of NF-κB-dependent proteins, is undisputed. Therefore, the roles of the NF-κB-transcribed anti-fibrinolytic plasminogen activator inhibitor (PAI 1) and NF-κB-dependent tissue factor (TF) have become worthy of attention. Inappropriate TF action results in enhanced fibrin clot formation, whereas overexpression of PAI 1 prevents appropriate fibrinolytic reactions. CAC is interpreted as critically contributing to overall COVID-19 pathology and is most likely an independent risk factor for mortality.Case report A 49-year-old male patient was admitted for initially non-specific signs of a previously detected SARS-CoV-2 infection. Despite antibiotic and anti-inflammatory, anticoagulant such as respiratory-supporting therapy, respiratory and inflammatory parameters deteriorated continuously. The COVID-19 specific procoagulant hemostatic disarrangement deteriorated concordantly with the inflammatory parameters. Finally, a pulmonary arterial obstruction was detected, and an ultima ratio veno-pulmonary arterial extracorporeal membrane oxygenation (ECMO) was carried out, which required additional anticoagulatory management. The next day, multiple intracerebral bleeding led to the death of the patient.Conclusions The usual anticoagulatory management is unlikely to avoid intravascular clot formation without developing severe bleeding complications. The ventilation-related acceleration of NF-κB pathway should be limited, as should procoagulatory blood flow interventions. In order to limit the excessive transcription of NF-κB-dependent procoagulant/anti-fibrinolytic proteins vagus nerve stimulation should be considered as a therapeutic tool.
The Effects of Botulinum Toxin-A Injection on Lateral Pterygoid Muscle in Patients with Painful Temporomandibular Joint Click: A Randomized Clinical Trial Study
Authors: Rezazadeh Fahimeh , Esnaashari Negin , Azad Azita , Emad Sara 
Published: July 2021

Abstract
Background: The aim of this study was to investigate the effect of Botulinum toxin-A (BTX-A) injection in lateral pterygoid (LP) muscle and analyze the efficacy of this treatment modality in reducing Temporomandibular disorder (TMD) symptoms. TMD is the main cause of nondental pain in the orofacial area. The most common symptoms of temporomandibular disorder are joints pain and sound and limitation of jaw function. Botulinum toxin (BTX) injection in LP temporarily paralysesis the muscle. BTX injection is considered as a potential treatment for TMD, due to its pain relieving characteristic and its ability to reduce muscle activity. However, these evidences are mostly case series and more studies are required to prove its efficacy. Methods: Thirty-eight patients (19 women and 19 men, mean age: 26.53 years) with painful unilateral temporomandibular joint click and LP muscle tenderness entered the study. They were divided into two groups; one received extraoral Botax injection in LP muscle, and the other was injected by placebo. Pain severity, jaw’s range of movement, click severity and Helkimo-Index, were taken recorded at first and also in follow upin first visit and in one week, one month and three months after intervention. Data were analyzed using Repeated measures ANOVA and t-test.Results: The result showed that click severity was not significantly different between BTX and placebo groups (p=0.07). Pain and Helkimo index were decreased significantly in BTX group (p=0.00 and P=0.006 respectively); however, there was no significant difference when compared between the two groups (P=0.22 and p=1 respectively). There was a significant difference in lateral movements between the groups (p=0.00) but not in protrusion movement (p=0.095).Conclusions: It can be concluded that although some studies state that BTX injection can make the click sound disappear, in this study we did not find a significant difference between two groups. Furthermore, our results showed that click and pain severity were decreased, but the difference was not statistically significant. Therefore, further studies with more dosage of BTX and higher participants seem to be necessary.Trial registration: The local Ethics Committee of Shiraz University of Medical Science approved this research under Ethics code: IR.SUMS.REC. 2018/10/01 and IRCT number: IRCT20130521013406N3.
Clinical Significance of Pancreatic Calcifications: A 15-Year Single Center Observational Study
Authors: Wang Wei , Chai Li , Zhu Naiyi , Wang Qingrou , Chai Weimin , Shen Baiyong 
Published: July 2021

Abstract
Objective

Pancreatic calcifications (PC) are considered specific for chronic pancreatitis (CP), but PC may also be present in non-CP diseases. The aims are to understand the pattern of calcifications in different diseases and to determine they were related to malignant diseases.
Methods

A retrospective study was performed including patients with PC or CP undergoing surgery in the Department of General Surgery of Ruijin Hospital from January 2003 to June 2018.
Results

PC were observed in 168 (4.5%) of the 3755 patients with pancreatic diseases. The majority of patients with PC had three kinds of CP (73.2%) while 26.8% had other five kinds of non-CP diseases. The incidences of PC in the pancreatic diseases were lower than these in previous studies. In patients with non-CP diseases, the incidence of PC in malignant intraductal papillary mucinous neoplasm (IPMN) was significantly higher than benign IPMN (8.3% vs. 0.7%, p = 0.004). In 204 patients with CP, pancreatic calcification (OR = 3.7), advanced age (> 55 years), high BMI (> 24 kg/m2), parenchymal atrophy and pancreatic mass were independent predictors for malignancy. In patients of CP wih pancreatic mass (n = 81), the ability of PC (OR = 28.6) to predict malignancy increased nearly sevenfold.
Conclusion

The disease spectrum with PC was very diverse but the incidences of PC in the pancreatic diseases were low. PC may be related to malignant IPMN in non-CP diseases and is related to malignancy in the patients with CP, including the cases without pancreatic mass.
Brush swab as a noninvasive surrogate for tissue biopsies in oral cancer patients to develop clinically translatable epigenetic biomarkers
Authors: Viet Chi Tonglien , Zhang Xinyu , Xu Ke , Yu Gary , Asam Kesava , Thomas Carissa M. , Callahan Nicholas F. , Doan Coleen , Walker Paul C. , Nguyen Khanh , Kidd Stephanie C. , Lee Steve C. , Grandhi Anupama , Allen Clint T. , Young Simon , Melville James C. , Shum Jonathan W. , Viet Dan T. , Herford Alan S. , Roden Dylan F. , Gonzalez Manuel Lora , Aouizerat Bradley E. 
Published: July 2021

Abstract
Background

Oral squamous cell carcinoma (OSCC) has poor survival rates. There is a pressing need to develop more precise risk assessment methods to tailor clinical treatment. Epigenome-wide association studies in OSCC have not produced a viable biomarker. These studies have relied on methylation array platforms, which are limited in their ability to profile the methylome. In this study, we use MethylCap-Seq (MC-Seq), a comprehensive methylation quantification technique, and brush swab samples, to develop a noninvasive, readily translatable approach to profile the methylome in OSCC patients.
Methods

Three OSCC patients underwent collection of cancer and contralateral normal tissue and brush swab biopsies, totaling 4 samples for each patient. Epigenome-wide DNA methylation quantification was performed using the SureSelectXT Methyl-Seq platform. DNA quality and methylation site resolution were compared between brush swab and tissue samples. Correlation and methylation value difference were determined for brush swabs vs. tissues for each respective patient and site (i.e., cancer or normal). Correlations were calculated between cancer and normal tissues and brush swab samples for each patient to determine the robustness of DNA methylation marks using brush swabs in clinical biomarker studies.
Results

There were no significant differences in DNA yield between tissue and brush swab samples. Mapping efficiency exceeded 90% across all samples, with no differences between tissue and brush swabs. The average number of CpG sites with at least 10x depth of coverage was 2,716,674 for brush swabs and 2,903,261 for tissues. Matched tissue and brush swabs had excellent correlation (r = 0.913 for cancer samples and r = 0.951 for normal samples). The methylation profile of the top 1,000 CpGs was significantly different between cancer and normal samples (mean p-value = 0.00021) but not different between tissues and brush swabs (mean p-value = 0.11).
Conclusions

Our results demonstrate that MC-Seq is an efficient platform for epigenome profiling in cancer biomarker studies, with broader methylome coverage than array-based platforms. Brush swab biopsy provides adequate DNA yield for MC-Seq, and taken together, our findings set the stage for development of a non-invasive methylome quantification technique for oral cancer with high translational potential.
Osteoblasts-derived Exosomes as Novel Communicators in Particle Induced Periprosthetic Osteolysis
Authors: de Souza Wanderson , Piperni Sara G. , Ruivo Carolina F. , Bastos Nuno , Cardoso Patrícia , Oliveira Maria J. , Rocha Luís A. , Granjeiro José M. , Fernandes Maria H. , Melo Sonia A. , Ribeiro Ana R. 
Published: July 2021

Abstract
BackgroundThe inflammatory response to titanium implant-derived wear particles is considered as the hallmark of periprosthetic osteolysis, an event that cause pain, reduce patient motility, ultimately leading to the need of a revision surgery. Although macrophages are major cell players, other cell types such as bone cells can indirectly contribute to periprosthetic osteolysis, however the mechanisms are not fully understood. Exosomes (Exos) has been related with several bone pathologies, with growing body of literature recognizing them as actively shuttle molecules through the body, with their cargo being completely dependent of external stimuli (e.g. chemicals and metals ions and particles). Till the moment, the role of wear debris on osteoblasts exosomes biogenesis is absent and the possible contribution of Exos to osteoimmune communication and periprosthetic osteolysis is still in its infancy. Taking that in consideration, in this work we investigate the effect of wear debris on Exo biogenesis, where two bone cell models were exposed to titanium dioxide nanoparticles (TiO2 NPs) similar in size and composition to wear debris associated with prosthetic implants. The contribution of Exos to periprosthetic osteolysis was evaluated performing functional tests stimulating primary human macrophages with bone-derived Exos.ResultsFor the first time, we report that TiO2 NPs enter in multivesicular bodies, the nascent of Exos and altered osteoblasts derived exosomes secretion and cargo. No significant differences were observed in Exos morphology and size, however mass spectrometry analysis identified urokinase-type plasminogen activator (uPA), specifically enriched in Exos derived from bone cells pre-incubated with TiO2 NPs. Functional tests confirmed the activation of human macrophages towards a mixed phenotype with consequent secretion of pro and anti-inflammatory cytokines. ConclusionsThe external stimuli of osteoblasts to TiO2 NPs induced a dose dependent secretion of Exos, suggesting alterations in their biogenesis as well as in their cargo. Functional tests reveal that enriched uPA exosomal cargo is stimulating macrophages towards a mixed M1 and M2 phenotype inducing the release of pro-and anti-inflammatory signals that are characteristic of periprosthetic osteolysis. Interestingly, uPA may be proposed, in the future, as a possible candidate biomarker to early diagnose particle induced periprosthetic osteolysis, since uPA was also detected in the pseudocapsular interface around implants of patients with loosening of total hip prosthesis and joint replacement surgery, suggesting their active role in disease progression.
Impacts of Storm Surges on a Changing Climate: a Global Bibliometric Analysis of the Coastal Zone
Authors: Leal Karine Bastos , Robaina Luís Eduardo de Souza , De Lima André de Souza 
Published: July 2021

Abstract
An increase in the global mean sea is predicted during the 21st century as a consequence of global average temperature projections. In addition, changes in the strength of atmospheric cyclonic storms may alter the development of storm surges, exacerbating the risks to coastal communities. Based on the fact that the interest and range of papers are growing on this topic, this study aims to present the global scientific production status of studies that have correlated climate change and the impact of storm surges on the coastal zone leading to erosion and flooding (inundation) via a bibliometric analysis. We analyzed 429 papers published in journals between 1991 and February 2021 from the Scopus database. Through the VOSviewer and Bibliometrix R package, we describe the most relevant countries, affiliations, journals, authors, and keywords. Our results demonstrate that there has been an exponential growth in the research topic, and that authors from the United States and the United Kingdom are the most prolific. Among the 1454 authors found, 10 researchers published at least 5 papers on the topic and obtained at least 453 citations in the period. The most represented journals were the Journal of Coastal Research, Climatic Change, and Natural Hazards. We also found, and discuss, the lack of standardization in the choice of keywords, of which climate change, storm surge, and sea level rise are the most frequent. Finally, we have written a guide to facilitate the authors' bibliographic review.
Impact of natural selection on global patterns of genetic variation, and association with clinical phenotypes, at genes involved in SARS-CoV-2 infection.
Authors: Zhang Chao , Verma Anurag , Feng Yuanqing , Melo Marcelo Cardoso dos Reis , McQuillan Michael , Hansen Matthew , Lucas Anastasia , Park Joseph , Ranciaro Alessia , Thompson Simon , Rubel Meghan , Campbell Michael , Beggs William , Hirbo Jibril , Mpoloka Sununguko Wata , Mokone Gaonyadiwe George , Jones Marcus , Nyambo Thomas , Meskel Dawit Wolde , Belay Gurja , Fokunang Charles , Njamnshi Alfred , Omar Sabah , Williams Scott , Rader Daniel , Ritchie Marylyn , Fuente Cesar de la , Sirugo Giorgio , Tishkoff Sarah 
Published: July 2021

Abstract
We investigated global patterns of genetic variation and signatures of natural selection at host genes relevant to SARS-CoV-2 infection (ACE2, TMPRSS2, DPP4, and LY6E). We analyzed novel data from 2,012 ethnically diverse Africans and 15,997 individuals of European and African ancestry with electronic health records, and integrated with global data from the 1000GP. At ACE2, we identified 41 non-synonymous variants that were rare in most populations, several of which impact protein function. However, three non-synonymous variants were common among Central African hunter-gatherers from Cameroon and are on haplotypes that exhibit signatures of positive selection. We identify strong signatures of selection impacting variation at regulatory regions influencing ACE2 expression in multiple African populations. At TMPRSS2, we identified 13 amino acid changes that are adaptive and specific to the human lineage. Genetic variants that are targets of natural selection are associated with clinical phenotypes common in patients with COVID-19.