bluuebunny/crossref_metadata_2025_split huggingface dataset:
The WAVE3/β-Catenin oncogenic signaling regulates chemoresistance in triple negative breast cancer
Authors: Wang Wei , Rana Priyanka S. , Markovic Vesna , Sossey-Alaoui Khalid 
Published: September 2022

Abstract
Background Metastatic breast cancer is responsible for the death of the majority of breast cancer patients. In fact, metastatic BC is the 2nd leading cause of cancer-related deaths in women in the United States and worldwide. Triple negative breast cancer (TNBC), which lack expression of hormone receptors (ER-α and PR) and ErbB2/HER2, are especially lethal due to their highly metastatic behavior, propensity to recur rapidly, and for their resistance to standard of care therapies, through mechanisms that remain incompletely understood. WAVE3 has been established as a promoter of TNBC development and metastatic progression. In this study, we investigated molecular mechanisms whereby WAVE3 promotes therapy-resistance and cancer stemness in TNBC.
Methods The Cancer Genome Atlas (TCGA) dataset was used to study the expression of WAVE3 and β[1]Catenin in breast cancer tumors. Kaplan-Meir Plotter analysis was used to correlate expression of WAVE3 and β-Catenin with breast cancer patients’ survival probability. MTT assay was used to quantify cell survival. CRIPR/Cas9-mediated gene editing, 2D and 3D tumorsphere growth and invasion assays, Immunofluorescence, Western blotting, Semi-quantitative and real-time quantitative PCR analyses were applied to study the WAVE3/β-Catenin oncogenic signaling in TNB. Tumor xenograft assays were used to study the role of WAVE3 in mediating chemotherapy resistance of TNBC tumors.
Results Genetic inactivation of WAVE3 in combination of chemotherapy resulted in inhibition of 2D growth and 3D tumorsphere formation and invasion of TNBC cells in vitro, as well as tumor 3 growth and metastasis in vivo. In addition, while re-expression of phospho-active WAVE3 in the WAVE3-deficient TNBC cells restored the oncogenic activity of WAVE3, re-expression of phospho-mutant WAVE3 did not. Further studies revealed that dual blocking of WAVE3 expression or phosphorylation in combination with chemotherapy treatment inhibited the activity and expression of β-Catenin. Most importantly, the combination of WAVE3-deficiency and chemotherapy suppressed the oncogenic behavior of chemoresistant TNBC cells, both in vitro and in vivo.
Conclusion We identified a novel WAVE3/β-Catenin oncogenic signaling axis that modulate chemoresistance of TNBC. This study suggests that a targeted therapeutic strategy against WAVE3 could be effective for the treatment of chemoresistant TNBC tumors.
New Insights into COL26A1 in Thyroid Carcinoma: Prognostic Prediction, Functional Characterization, Immunological Drug Target and ceRNA Network
Authors: Luo Yulou , Chen Lan , Qu Ximing , Yi Na , Ran Jihua , Chen Yan 
Published: September 2022

Abstract
Backgrounds: Collagen is the main component in extracellular matrix. More and more researches have determined the oncogenic effect of collagen in cancer progression, which is intriguing to be further explored. Collagen type ⅩⅩⅥ alpha 1 chain (COL26A1) is a newly discovered collagen subtype, functions of which still remain poorly demonstrated. No studies have reported the roles of COL26A1 in human cancers ever before. Thus we tried to initially explore the potential associations between COL26A1 and thyroid carcinoma (THCA), in an attempt to enrich the relevant literature, serving as basis for further elucidation and experimental validation.
Results: We processed a series of bioinformatic analysis for exploration, which mainly distributed to 4 aspects: Prognostic/diagnostic prediction, functional characterization, immunological target and ceRNA network. We found that high expression level of COL26A1 infers poor prognosis for patients with THCA. The aberrant expression of COL26A1 could be applied as diagnostic and prognostic biomarker with a certain degree of accuracy. Besides, a novel nomogram containing several independent prognostic factors was established to predict the survival probability of patients with THCA. Functional characterizations implied that COL26A1 is tightly associated with immunological processes, as well as several oncogenic signaling pathways. Subsequently, we determined that high COL26A1 expression is accompanied by higher infiltration levels of multiple immune cells and higher stromal/immune score. Also, the significantly positive correlations of COL26A1 expression with infiltration levels of multiple immune cells and stromal/immune score were determined. In addition, we identified that COL26A1 is significantly positively co-expressed with most immune checkpoints, including PD1, PD-L1, TIGIT, LAG3 and CTLA4. The drugs that can decrease the expression level of COL26A1 were also identified. The predicted lncRNA-miRNA-COL26A1 regulatory axes were displayed.
Conclusions: Our work has primarily appraised COL26A1 as a promising biomarker for diagnosis/prognosis and target for immunotherapy in THCA.
Tumor Cell Integrin β4 and Tumor Stroma E-/P-Selectin Cooperatively Regulate Tumor Growth in vivo
Authors: Genduso Sandra , Freytag Vera , Schetler Daniela , Kirchner Lennart , Schiecke Alina , Maar Hanna , Wicklein Daniel , Gebauer Florian , Bröker Katharina , Stürken Christine , Milde-Langosch Karin , Oliveira-Ferrer Leticia , Ricklefs Franz L. , Ewald Florian , Wolters-Eisfeld Gerrit , Riecken Kristoffer , Unrau Ludmilla , Krause Linda , Bohnenberger Hanibal , Offermann Anne , Perner Sven , Sebens Susanne , Lamszus Katrin , Diehl Linda , Linder Stefan , Jücker Manfred , Schumacher Udo , Lange Tobias 
Published: September 2022

Abstract
Background: The immunological composition of the tumor microenvironment has a decisive influence on the biological course of cancer and is therefore of profound clinical relevance. In this study, we analyzed the cooperative effects of integrin β4 (ITGB4) on tumor cells and E-/ P-selectin on endothelial cells within the tumor stroma for regulating tumor growth by shaping the local and systemic immune environment.
Methods: We used several preclinical mouse models for different solid human cancer types (xenograft and syngeneic) to explore the role of ITGB4 (shRNA-mediated knockdown in tumor cells) and E-/P-selectins (knockout in mice) for tumor growth; effects on apoptosis, proliferation and intratumoral signaling pathways were determined by histological and biochemical methods and 3D in vitro experiments; changes in the intratumoral and systemic innate immune cell composition was determined by flow cytometry; chemokine levels and their attracting potential were measured by ELISA and 3D invasion assays, respectively.
Results: We observed a very robust synergism between ITGB4 and E-/P-selectin for the regulation of tumor growth, accompanied by an increased recruitment of CD11b+ Gr-1Hi cells with low granularity (i.e. myeloid-derived suppressor cells, MDSCs) specifically into ITGB4-depleted tumors. ITGB4-depleted tumors undergo apoptosis and actively attract MDSCs, well-known to promote tumor growth in several cancers, via increased secretion of different chemokines. MDSC trafficking into tumors crucially depends on E-/P-selectin expression. Analyses of clinical samples confirmed an inverse relationship between ITGB4 expression in tumors and number of tumor-infiltrating leukocytes.
Conclusions: These findings suggest a distinct vulnerability of ITGB4Lo tumors for MDSC-directed immunotherapies.
The spatial distribution and source apportionment of heavy metals in soil of Shizuishan, China
Authors: Bai Yiru , Zhang Yuhan , Liu Xu , Wang Youqi 
Published: September 2022

Abstract
Environmental pollution of heavy metals in a typical coal industrial city should be paid more attentions nowadays. The spatial distribution and source apportionment of 8 heavy metals (i.e., Cd, Cr, Co, Zn, Ni, Cu, Pb and Mn) from topsoil (158) of Shizuishan city in Ningxia Hui Autonomous Region of China were investigated using principal component analysis/absolute principal component scores (PCA/APCS) receptor model and the geostatistics analysis. These results showed that the mean concentrations of Cd, Cr, Co, Zn, Ni, Cu and Pb were higher than their soil background values in Ningxia. 99.36% of soil was heavily polluted according to analysis of integrated Nemerow pollution index (PN), whereas 81.65% of soil exhibited the highly strong potential ecological risk by ERI (the comprehensive of potential ecological risk index) values. The source apportionment results showed that 8 heavy metals in soil were mainly from natural(32.39%), industrial (26.56%), traffic emission/coal consumption(20.18%) and atmospheric deposition source(12.73%). Typically, Zn, Mn and Ni were derived from natural source, whereas Cr and Co mainly derived from industrial sources. Cu was from the multiple sources, whereas Pb and Cd was weighted primarily from traffic emission/coal consumption source and atmospheric deposition source, respectively. These findings are crucial for the prevention and control of heavy metal pollution in Shizuishan city.
Sea ice and oxygen
Authors: Hambler Clive 
Published: September 2022

Abstract
1) Atmospheric oxygen cycles on a seasonal basis, as does carbon dioxide.
2) Photosynthesis is likely contributing to these cycles, but the dominant spatial regions are unknown and the contribution of marine plankton has been assumed to be small.
3) Since the cyclic rate of change of carbon dioxide is very highly correlated with that of sea ice, I predict the cyclic rate of change of oxygen will also be, at least at high latitudes.
4) I test and confirm the prediction that seasonal sea ice and oxygen rates are highly coherent at high latitudes, with peak oxygen emission near peak rates of sea ice loss.
5) Determining causality requires far more observations and experimentation.
6) These results provide further evidence that polar phenomena have been neglected in studies of the oxygen and carbon cycles, and are consistent with a proposed major role of high latitudes in carbon dioxide cycles.
A Bone Age Assessment based on a hybrid Knowledge Distillation Paradigm using single ROI
Authors: Mardanpour Malihe , Sepahvand Majid , Abdali-Mohammadi Fardin , Sarabi Homeyra 
Published: September 2022

Abstract
Bone age assessment (BAA) has been widely used in clinical area from pediatric endocrine diagnosis to estimating height of children for adulthood. Advancements in technology has accelerated the evolution of BAA methodologies, one of which is deep learning algorithms, which overcome the drawbacks of conventional approaches. In spite of excellent effectiveness of deep neural networks in detection of the correct class for bone age, they have a significant degree of complexity due to the numerous parameters they employ for each ROI. Therefore, they are not suitable for implementation in edge devices with limited resources. In this paper, we propose a BAA method using a hybrid knowledge distillation (KD) paradigm in order to conquer this difficulty by mapping different ROIs into a single ROI. In this regard, the student receives knowledge from a teacher network that has been pre-trained on six ROIs including bones of five fingers and the wrist, transfers the knowledge of its final response layer and internal layers to the student. Then, six student models each of which is constructed based on just one of these ROIs, while receiving the information of the teacher model by matching the feature maps of intermediate layers and last output of teacher with those of student in distillation modules. Empirical results on Digital Hand Atlas (DHA) report that our student model trained on one ROI obtains 95% accuracy on 19 classes of bone age makes it appropriate for medical IoT deployment. Also, it has competitive performance compared to the other state-of-the-art BAA studies, and performance analysis of our KD with three base KD models indicates superiority of our introduced method.
EMOCATNET: An Efficient CNN-Based Deep Neural Architecture with Effective Channel Attention Mechanism for Emotion Recognition Using EEG Signal
Authors: Mahmud Md. Sultan , Saha Oishy , Fattah Shaikh Anowarul 
Published: September 2022

Abstract
In the arena of human-computer interaction (HCI), emotion recognition using the electroencephalogram (EEG) has obtained a wide range of popularity owing to the significant variations in neural activities in response to different types of emotions. In this paper, an efficient CNN-based end-to-end deep neural network scheme with a channel grouping approach is proposed for automatic emotion recognition. Furthermore, a channel-wise attention mechanism is introduced to distribute the significance of EEG channels according to the relative contribution to the elicitation of different emotions. Unlike conventional methods, an additional stage for extracting features from the input EEG data is avoided which offers a reduction in computational burden. In order to incorporate the inter-channel relationship among different EEG channels, a spatial informative feature extraction block, namely the inter-channel relation (ICR) block is considered in the proposed CNN-based EMOCATNET network. Extensive experimentation is carried out on a publicly available EEG emotion (DEAP) dataset and very satisfactory classification performance is obtained for valence and arousal types of emotions in the 2-class scenario and mixed subject analysis. The average accuracies in the 2-class problem for valence and arousal are found 94.74% and 95.17%, respectively. For the mixed subject analysis, the average accuracies for valence and arousal are 90.91% and 90.71% respectively.
Monkeypox in an immunocompromised patient with underlying human immunodeficiency virus and syphilis infections in Southern Florida of the United States: A Case Report
Authors: Jang Wooyoung , Kandimalla Likhita , Rajan Sivagami , Abreu Rafael , Campos Jamie Enrique 
Published: September 2022

Abstract
Background: The monkeypox virus causes the rare disease monkeypox, and underlying immune deficiencies might lead to worse outcomes. In this report, we described a rare case of monkeypox with an underlying immune deficiency that was combined with human immunodeficiency virus and syphilis infection and discussed differences in initial clinical presentation and clinical course compared to typical monkeypox cases.
Case presentation: We report the case of a 32-year-old male with human immunodeficiency virus infection who was admitted to a hospital in Southern Florida. The patient presented to the emergency department with shortness of breath associated with fever, cough and left sided chest wall pain. Upon arrival, he was found to have left sided pneumothorax and minimal atelectasis in left mid lung with a small pleural effusion at left lung base in chest radiograph. A pustular skin rash consisting of generalized exanthema with small white and red papules was also noticed. The patient was found to be in a state of sepsis with lactic acidosis. An infectious disease specialist raised the possibility of monkeypox, and the sample of the lesion was finally positive for monkeypox deoxyribonucleic acid. In this case, possible diagnosis of skin lesions varied because the patient was positive for syphilis and human immunodeficiency virus, and the differential diagnosis of monkeypox infection was prolonged due to the initial atypical clinical features.
Conclusions: Monkeypox with immunocompromised patient who has human immunodeficiency virus and syphilis infections can present with atypical clinical features and delay a proper diagnosis, which can increase the risk of spreading monkeypox in the hospital. Thus, patients with rash and risky sexual behavior should be screened with monkeypox, and an easily available, rapid, and accurate test is required to stop the transmission of monkeypox in the hospital.
Interpreting Epidemiological Data of Coronavirus Disease 2019 in Indonesia and Its Implication for Travel Advice: a lesson learned
Authors: Kusumaratna Rina , Pakasi Levina S. , Pakasi Trevino A. 
Published: September 2022

Abstract

Background
Descriptive data on major epidemiological parameters of the coronavirus disease 2019 (COVID-19) is reported daily in Indonesia. However, raw data are not sufficient to provide accurate travel advice. The study objective is to conduct analytical statistics of publicly available epidemiology data, focusing on the dynamics of test positivity rate (TPR) and case fatality rate (CFR) to better understand the COVID-19 pandemic in Indonesia.
Methods
This was a cross-sectional study, using electronic data provided by the Ministry of Health of the Republic of Indonesia, between July 2020 to February 2021. Test positivity rate was the number of positive cases divided by the total people tested, multiplied by 100%. Case Fatality Rate was the number of death divided by the total number of died and recovered cases, multiplied by 100%. Monthly comparisons were tested using one-way analysis of variance (ANOVA) and post-hoc analysis with Bonferroni’s method. Correlation between numerical variables was tested using Pearson’s correlation test.
Results
There were 274 daily reports retrieved for analysis. The number of specimens and people tested, and confirmed new cases tended to increase from July 2020 to peak in January 2021. The overall mean TPR was 17.9%, with an increasing trend since December 2020. The number of deaths was increasing since November 2020, but the overall mean CFR was 3.3% with a decreasing trend in 2021.
Conclusions
High transmission implies that travel should be restricted. The case fatality rate is stable with a decreasing trend, reflecting adequate clinical care in Indonesia.
BBB-on-a-chip with Integrated micro-TEER for permeability evaluation of multi-functionalized gold nanorods against Alzheimer’s disease
Authors: Palma-Florez Sujey , López-Canosa Adrián , Moralez-Zavala Francisco , Castaño Oscar , Kogan M. J. , Samitier Josep , Lagunas Anna , Mir Mònica 
Published: September 2022

AbstractBackground The lack of predictive models that mimic the blood-brain barrier (BBB) hinders the development of effective drugs for neurodegenerative diseases. Animal models behave differently from humans, are expensive and have ethical constraints. Organ-on-a-chip (OoC) platforms offer several advantages to resembling physiological and pathological conditions in a versatile, reproducible, and animal-free manner. In addition, OoC give us the possibility to incorporate sensors to determine cell culture features such as trans-endothelial electrical resistance (TEER). Here, we developed a BBB-on-a-chip (BBB-oC) platform with a TEER measurement system in close distance to the barrier used for the first time for the evaluation of the permeability performance of targeted gold nanorods for theranostics of Alzheimer's disease. GNR-PEG-Ang2/D1 is a therapeutic nanosystem previously developed by us consisting of gold nanorods (GNR) functionalized with polyethylene glycol (PEG), angiopep-2 peptide (Ang2) to overcome the BBB and the D1 peptide as beta amyloid fibrillation inhibitor, finally obtaining GNR-PEG-Ang2/D1 which showed to be useful for disaggregation of the amyloid inin vitroandin vivomodels. In this work, we evaluated its cytotoxicity, permeability, and some indications of its impact on the brain endothelium by employing an animal-free device based on neurovascular human cells. Results In this work, we fabricated a BBB-oC with human astrocytes, pericytes and endothelial cells and a TEER measuring system (TEER-BBB-oC) integrated at a micrometric distance of the endothelial barrier. The characterization displayed a neurovascular network and the expression of tight junctions in the endothelium. We produced GNR-PEG-Ang2/D1 and determined its non-cytotoxic range (0.05–0.4 nM) for plated cells included in the BBB-oC and confirmed its harmless effect at the highest concentration (0.4 nM) in the microfluidic device. The permeability assays revealed that GNR-PEG-Ang2/D1 cross the BBB and this entry is facilitated by Ang2 peptide. Parallel to the permeability analysis of GNR-PEG-Ang2/D1, an interesting behavior of the TJs expression was observed after its administration probably related to the ligands on the nanoparticle surface. Conclusion BBB-oC with a novel TEER integrated setup which allow a correct read-out and cell imaging monitoring was proven as a functional and throughput platform to evaluate the brain permeability performance of nanotherapeutics in a physiological environment with human cells, putting forward a viable alternative to animal experimentation.
Predictors of COVID-19 Mortality in Intensive Care Unit Patients
Authors: Gopaul Chavin D. , Ventour Dale , Thomas Davlin 
Published: September 2022

Abstract
Introduction.
Understanding the factors that predict the likelihood of death among intensive care unit (ICU) patients with COVID-19 is important in reducing mortality. This study sought to determine the indicators of mortality risk among ICU patients with COVID-19.
Methods
A retrospective chart review was conducted among 289 files of patients managed at the ICU of two COVID-19 hospitals in Trinidad and Tobago from March 2021 to December 2021. Included patients belonged to either the ICU survivors cohort (n = 82) or the ICU non-survivors cohort (n = 207). Variables collected included CBC and biochemistry reports, and vital signs upon ICU admission and discharge, comorbidities, age, sex, vaccination status, and mortality status up until discharge from the COVID-19 facility. Data was analysed using logistic regressions and Cox proportional hazards models.
Results
The median age of ICU non-survivors was higher (57.0, IQR = 19 years) compared to those who survived (51.50, IQR = 21 years). The univariate analysis indicated that vaccination status has a significant effect on whether ICU patients with COVID-19 survive in hospital (p = 0.041). The interaction between age and sex has a significant effect on whether ICU patients with COVID-19 survive in hospital (p = 0.047). However, the vitals and the CBC parameters are not reliable predictors of survival among ICU patients with COVID-19, but chronic kidney disease and sickle cell disease are significant predictors of survival.
Conclusion
To enhance survival, there is a need a need to pay attention to vaccination status, age and sex of the ICU patients with COVID-19.
STAR Voting, Equality of Voice, and Voter Satisfaction: Design considerations for a novel voting method
Authors: Wolk Sara , Quinn Jameson , Ogren Marcus 
Published: September 2022

Abstract
We introduce STAR Voting as a single-winner voting method which should be considered to replace Plurality Voting for governmental elections. The five star ballot offers an expressive and user-friendly interface which, as we demonstrate, treats political factions equally regardless of how many candidates they field or their position in the political spectrum. We discuss a number of criteria for voting methods relating to strategic voting and vote-splitting. We assess how well these voting methods incentivize and empower voters to voice their honest opinions, and how well these methods allow voters to gain equitable representation. Using a realistic clustered spatial model for voter ideologies, we present the metrics of Voter Satisfaction Efficiency (VSE) and Average Strategic Regret (ASR) to evaluate voting methods with a high degree of granularity. We find that STAR Voting and Smith/Minimax are among the best methods as measured by VSE, markedly outperforming Plurality, Top-Two Runoff, and Instant Runoff. We find that STAR Voting, and especially Smith/Minimax, substantially reduce the need for voters to consider candidate electability as they cast their ballots. We conclude that STAR Voting offers a viable and compelling proposal for more equitable and more representative elections, both for individual voters and for the electorate as a whole.