bluuebunny/crossref_metadata_2025 huggingface dataset:
Automatic Cancer Cell Taxonomy Using an Ensemble of Deep Neural Networks
Authors: Choe Se-woon , Yoon Ha-Yeong , Jeong Jae-Yeop , Park Jinhyung , Jeong Jin-Woo
Published: April 2022

Microscopic image-based analysis has been intensively performed for pathological studies and diagnosis of diseases. However, mis-authentication of cell lines due to misjudgments by pathologists has been recognized as a serious problem. To address this problem, we propose a deep-learning-based approach for the automatic taxonomy of cancer cell types. A total of 889 bright-field microscopic images of four cancer cell lines were acquired using a benchtop microscope. Individual cells were further segmented and augmented to increase the image dataset. Afterward, deep transfer learning was adopted to accelerate the classification of cancer types. Experiments revealed that the deep-learning-based methods outperformed traditional machine-learning-based methods. Moreover, the Wilcoxon signed-rank test showed that deep ensemble approaches outperformed individual deep-learning-based models (p < 0.001) and were in effect to achieve the classification accuracy up to 97.735%. Additional investigation with the Wilcoxon signed-rank test was conducted to consider various network design choices, such as the type of optimizer, type of learning rate scheduler, degree of fine-tuning, and use of data augmentation. Finally, it was found that the using data augmentation and updating all the weights of a network during fine-tuning improve the overall performance of individual convolutional neural network models.
Screening for Prognostic Biomarkers in Metastatic Adrenocortical Carcinoma by Tissue Micro Arrays Analysis Identifies P53 as an Independent Prognostic Marker of Overall Survival
Authors: Hescot Segolene , Faron Matthieu , Kordahi Manal , Do Cao Christine , Naman Annabelle , Lamartina Livia , Hadoux Julien , Leboulleux Sophie , Pattou Francois , Aubert Sébastien , Scoazec Jean-Yves , Al Ghuzlan Abir , Baudin Eric
Published: April 2022

Advanced adrenocortical carcinoma (ACC) has poor but heterogeneous prognosis. Apart from Ki67 index, no prognostic or predictive biomarker has been validated in advanced ACC, so far. We aimed at analyzing expression of a large panel of proteins involved in known altered pathways in ACC (cell cycle, Wnt/ß-catenin, methylation) to identify and prioritize potential prognostic or predictive parameters metastatic ACC population. We conducted a retrospective multicentric study. Overall survival (OS) and partial response according to RECIST 1.1 were primary endpoints. TMA was set up and 16 markers were analyzed. Modified ENSAT and GRAS parameters were characterized for prognostic adjustment. Results: We included 66 patients with a mean age at metastatic diagnosis of 48.7 ± 15.5 years. Median survival was 27.8 months. After adjustment to mENSAT-GRAS parameters, p53 and PDxK were prognostic of OS. No potential biomarker has been identified as predictive factor of response. We identified for the first time P53 as an independent prognostic marker of metastatic adrenocortical carcinoma after mENSAT-GRAS parameter adjustment. Prognostic impact of Wnt/ß-catenin alterations was not confirmed in this cohort of metastatic ACC.
Stereotactic Radiation Therapy versus Brachytherapy: Relative Strengths of Two Highly Efficient Options for the Treatment of Localized Prostate Cancer
Authors: Kissel Manon , Créhange Gilles , Graff Pierre
Published: April 2022

Stereotactic body radiation therapy (SBRT) has become a valid option for the treatment of low- and intermediate-risk prostate cancer. In randomized trials, it was found not inferior to conventionally fractionated external beam radiation therapy (EBRT). It also compares favorably to brachytherapy (BT) even if level 1 evidence is lacking. However, BT remains a strong competitor, especially for young patients, as series with 10–15 years of median follow-up have proven its efficacy over time. SBRT will thus have to confirm its effectiveness over the long-term as well. SBRT has the advantage over BT of less acute urinary toxicity and, more hypothetically, less sexual impairment. Data are limited regarding SBRT for high-risk disease while BT, as a boost after EBRT, has demonstrated superiority against EBRT alone in randomized trials. However, patients should be informed of significant urinary toxicity. SBRT is under investigation in strategies of treatment intensification such as combination of EBRT plus SBRT boost or focal dose escalation to the tumor site within the prostate. Our goal was to examine respective levels of evidence of SBRT and BT for the treatment of localized prostate cancer in terms of oncologic outcomes, toxicity and quality of life, and to discuss strategies of treatment intensification.
Analytical Considerations of Large-Scale Aptamer-Based Datasets for Translational Applications
Authors: Jiang Will , Jones Jennifer C. , Shankavaram Uma , Sproull Mary , Camphausen Kevin , Krauze Andra V.
Published: April 2022

The development and advancement of aptamer technology has opened a new realm of possibilities for unlocking the biocomplexity available within proteomics. With ultra-high-throughput and multiplexing, alongside remarkable specificity and sensitivity, aptamers could represent a powerful tool in disease-specific research, such as supporting the discovery and validation of clinically relevant biomarkers. One of the fundamental challenges underlying past and current proteomic technology has been the difficulty of translating proteomic datasets into standards of practice. Aptamers provide the capacity to generate single panels that span over 7000 different proteins from a singular sample. However, as a recent technology, they also present unique challenges, as the field of translational aptamer-based proteomics still lacks a standardizing methodology for analyzing these large datasets and the novel considerations that must be made in response to the differentiation amongst current proteomic platforms and aptamers. We address these analytical considerations with respect to surveying initial data, deploying proper statistical methodologies to identify differential protein expressions, and applying datasets to discover multimarker and pathway-level findings. Additionally, we present aptamer datasets within the multi-omics landscape by exploring the intersectionality of aptamer-based proteomics amongst genomics, transcriptomics, and metabolomics, alongside pre-existing proteomic platforms. Understanding the broader applications of aptamer datasets will substantially enhance current efforts to generate translatable findings for the clinic.
Multivariant Transcriptome Analysis Identifies Modules and Hub Genes Associated with Poor Outcomes in Newly Diagnosed Multiple Myeloma Patients
Authors: Adebayo Olayinka O. , Dammer Eric B. , Dill Courtney D. , Adebayo Adeyinka O. , Oseni Saheed O. , Griffen Ti’ara L. , Ohandjo Adaugo Q. , Yan Fengxia , Jain Sanjay , Barwick Benjamin G. , Singh Rajesh , Boise Lawrence H. , Lillard, Jr. James W.
Published: April 2022

The molecular mechanisms underlying chemoresistance in some newly diagnosed multiple myeloma (MM) patients receiving standard therapies (lenalidomide, bortezomib, and dexamethasone) are poorly understood. Identifying clinically relevant gene networks associated with death due to MM may uncover novel mechanisms, drug targets, and prognostic biomarkers to improve the treatment of the disease. This study used data from the MMRF CoMMpass RNA-seq dataset (N = 270) for weighted gene co-expression network analysis (WGCNA), which identified 21 modules of co-expressed genes. Genes differentially expressed in patients with poor outcomes were assessed using two independent sample t-tests (dead and alive MM patients). The clinical performance of biomarker candidates was evaluated using overall survival via a log-rank Kaplan–Meier and ROC test. Four distinct modules (M10, M13, M15, and M20) were significantly correlated with MM vital status and differentially expressed between the dead (poor outcomes) and the alive MM patients within two years. The biological functions of modules positively correlated with death (M10, M13, and M20) were G-protein coupled receptor protein, cell–cell adhesion, cell cycle regulation genes, and cellular membrane fusion genes. In contrast, a negatively correlated module to MM mortality (M15) was the regulation of B-cell activation and lymphocyte differentiation. MM biomarkers CTAG2, MAGEA6, CCND2, NEK2, and E2F2 were co-expressed in positively correlated modules to MM vital status, which was associated with MM’s lower overall survival.
Worldwide Burden, Risk Factors, and Temporal Trends of Ovarian Cancer: A Global Study
Authors: Huang Junjie , Chan Wing Chung , Ngai Chun Ho , Lok Veeleah , Zhang Lin , Lucero-Prisno Don Eliseo , Xu Wanghong , Zheng Zhi-Jie , Elcarte Edmar , Withers Mellissa , Wong Martin C. S. ,   on behalf of NCD Global Health Research Group of Association of Pacific Rim Universities (APRU)
Published: April 2022

This study aimed to investigate the most updated worldwide incidence and mortality, risk factors, and epidemiologic trend of ovarian cancer in different countries, regions, and age groups. The Global Cancer Observatory database was used for incidence and mortality rates of ovarian cancer in 2020. Data from Cancer Incidence in Five Continents and the WHO mortality database was accessed for trend analysis. Age-standardized rates (ASRs, per 100,000 persons) were calculated for incidence and mortality. The 10-year annual average percent change (AAPC) was estimated by Joinpoint regression analysis. There was an overall decreasing trend of ovarian cancer, yet its burden has been increasing in lower-income countries and among younger females in some countries. Intensive lifestyle modifications are warranted, especially for the populations at high risk for ovarian cancer, including smoking cessation, alcohol use reduction, physical activity, weight control, and treatment of metabolic diseases.
NUT Is a Driver of p300-Mediated Histone Hyperacetylation: From Spermatogenesis to Cancer
Authors: Rousseaux Sophie , Reynoird Nicolas , Khochbin Saadi
Published: April 2022

In maturing sperm cells, a major genome re-organization takes place, which includes a global increase in the acetylation of histones prior to their replacement by protamines, the latter being responsible for the tight packaging of the male genome. Understanding the function of the oncogenic BRD4-NUT fusion protein in NUT carcinoma (NC) cells has proven to be essential in uncovering the mechanisms underlying histone hyperacetylation in spermatogenic cells. Indeed, these studies have revealed the mechanism by which a cooperation between BRD4, a bromodomain factor of the BET family, NUT, a normally testis-specific factor, and the histone acetyltransferase p300, induces the generation of hyperacetylated chromatin domains which are present in NC cells. The generation of Nut ko mice enabled us to demonstrate a genetic interaction between Nut and Brdt, encoding BRDT, a testis-specific BRD4-like factor. Indeed, in spermatogenic cells, NUT and p300 interact, which results in an increased acetylation of histone H4 at both positions K5 and K8. These two positions, when both acetylated, are specifically recognized by the first bromodomain of BRDT, which then mediates the removal of histone and their replacement by protamines. Taken together, these investigations show that the fusion of NUT to BRD4 in NUT Carcinoma cells reconstitutes, in somatic cells, a functional loop, which normally drives histone hyperacetylation and chromatin binding by a BET factor in spermatogenic cells.
Limitations of Nerve Fiber Density as a Prognostic Marker in Predicting Oncological Outcomes in Hepatocellular Carcinoma
Authors: Bednarsch Jan , Tan Xiuxiang , Czigany Zoltan , Wiltberger Georg , Buelow Roman David , Boor Peter , Lang Sven Arke , Ulmer Tom Florian , Neumann Ulf Peter , Heij Lara Rosaline
Published: April 2022

It has been shown that the presence and density of nerve fibers (NFs; NFD) in the tumor microenvironment (TME) may play an important prognostic role in predicting long-term oncological outcomes in various malignancies. However, the role of NFD in the prognosis of hepatocellular carcinoma (HCC) is yet to be explored. To this end, we aimed to investigate the impact of NFs on oncological outcomes in a large European single-center cohort of HCC patients. In total, 153 HCC patients who underwent partial hepatectomy in a curative-intent setting between 2010 and 2021 at our university hospital were included in this study. Group comparisons between patients with and without NFs were conducted and the association of recurrence-free survival (RFS) and overall survival (OS) with the presence of NFs and other clinico-pathological variables were determined by univariate and multivariable Cox regression models. Patients with NFs in the TME presented with a median OS of 66 months (95% CI: 30–102) compared to 42 months (95% CI: 20–63) for patients without NFs (p = 0.804 log-rank). Further, RFS was 26 months (95% CI: 12–40) for patients with NFs compared to 18 months (95% CI: 9–27) for patients without NFs (p = 0.666 log-rank). In a subgroup analysis, patients with NFD ≤ 5 showed a median OS of 54 months (95% CI: 11–97) compared to 48 months (95% CI: 0–106) for the group of patients with NFD > 5 (p = 0.787 log-rank). Correspondingly, the RFS was 26 months (95% CI: 10–42) in patients with NFD ≤ 5 and 29 months (95% CI: 14–44) for the subcohort with NFD > 5 (p = 0.421 log-rank). Further, group comparisons showed no clinico-pathological differences between patients with NFs (n = 76) and without NFs (n = 77) and NFs were not associated with OS (p = 0.806) and RFS (p = 0.322) in our Cox regression models. In contrast to observations in various malignancies, NFs in the TME and NFD are not associated with long-term oncological outcomes in HCC patients undergoing surgery.
Template-Independent Poly(A)-Tail Decay and RNASEL as Potential Cellular Biomarkers for Prostate Cancer Development
Authors: Kocić Gordana , Hadzi-Djokić Jovan , Veljković Andrej , Roumeliotis Stefanos , Janković-Veličković Ljubinka , Šmelcerović Andrija
Published: April 2022

The post-transcriptional messenger RNA (mRNA) decay and turnover rate of the template-independent poly(A) tail, localized at the 3′-untranslated region (3′UTR) of mRNA, have been documented among subtle mechanisms of uncontrolled cancer tissue growth. The activity of Poly(A) deadenylase and the expression pattern of RNASEL have been examined. A total of 138 prostate tissue specimens from 46 PC patients (cancer specimens, corresponding adjacent surgically healthy tissues, and in their normal counterparts, at least 2 cm from carcinoma) were used. For the stratification prediction of healthy tissue transition into malignant phenotype, the enzyme activity of tumor-adjacent tissue was considered in relation to the presence of microfocal carcinoma. More than a four-times increase in specific enzyme activity (U/L g.prot) was registered in PC on account of both the dissociation of its inhibitor and genome reprogramming. The obtained ROC curve and Youden index showed that Poly(A) deadenylase identified PC with a sensitivity of 93.5% and a specificity of 94.6%. The RNASEL expression profile was raised significantly in PC, but the sensitivity was 40.5% and specificity was 86.9%. A significantly negative correlation between PC and control tissue counterparts with a higher expression pattern in lymphocyte-infiltrated samples were reported. In conclusion, significantly upregulated Poly(A) deadenylase activity may be a checkpoint for the transition of precancerous lesion to malignancy, while RNASEL may predict chronic inflammation.
Plasma-Based Measurements of Tumor Heterogeneity Correlate with Clinical Outcomes in Metastatic Colorectal Cancer
Authors: Yaung Stephanie J. , Ju Christine , Gattam Sandeep , Nicholas Alan , Sommer Nicolas , Bendell Johanna C. , Hurwitz Herbert I. , Lee John J. , Casey Fergal , Price Richard , Palma John F.
Published: April 2022

Sequencing circulating tumor DNA (ctDNA) from liquid biopsies may better assess tumor heterogeneity than limited sampling of tumor tissue. Here, we explore ctDNA-based heterogeneity and its correlation with treatment outcome in STEAM, which assessed efficacy and safety of concurrent and sequential FOLFOXIRI-bevacizumab (BEV) vs. FOLFOX-BEV for first-line treatment of metastatic colorectal cancer. We sequenced 146 pre-induction and 89 post-induction patient plasmas with a 198-kilobase capture-based assay, and applied Mutant-Allele Tumor Heterogeneity (MATH), a traditionally tissue-based calculation of allele frequency distribution, on somatic mutations detected in plasma. Higher levels of MATH, particularly in the post-induction sample, were associated with shorter progression-free survival (PFS). Patients with high MATH vs. low MATH in post-induction plasma had shorter PFS (7.2 vs. 11.7 months; hazard ratio, 3.23; 95% confidence interval, 1.85–5.63; log-rank p < 0.0001). These results suggest ctDNA-based tumor heterogeneity may have potential prognostic value in metastatic cancers.
Biomarkers of Response and Resistance to Immunotherapy in Microsatellite Stable Colorectal Cancer: Toward a New Personalized Medicine
Authors: Huyghe Nicolas , Benidovskaya Elena , Stevens Philippe , Van den Eynde Marc
Published: April 2022

Immune Checkpoint Inhibitors (ICIs) are well recognized as a major immune treatment modality for multiple types of solid cancers. However, for colorectal cancer (CRC), ICIs are only approved for the treatment of Mismatch-Repair-Deficient and Microsatellite Instability-High (dMMR/MSI-H) tumors. For the vast majority of CRC, that are not dMMR/MSI-H, ICIs alone provide limited to no clinical benefit. This discrepancy of response between CRC and other solid cancers suggests that CRC may be inherently resistant to ICIs alone. In translational research, efforts are underway to thoroughly characterize the immune microenvironment of CRC to better understand the mechanisms behind this resistance and to find new biomarkers of response. In the clinic, trials are being set up to study biomarkers along with treatments targeting newly discovered immune checkpoint molecules or treatments combining ICIs with other existing therapies to improve response in MSS CRC. In this review, we will focus on the characteristics of response and resistance to ICIs in CRC, and discuss promising biomarkers studied in recent clinical trials combining ICIs with other therapies.
Labile Heme and Heme Oxygenase-1 Maintain Tumor-Permissive Niche for Endometriosis-Associated Ovarian Cancer
Authors: Hecht Jonathan L. , Janikova Monika , Choudhury Reeham , Liu Fong , Canesin Giacomo , Janovicova Lubica , Csizmadia Eva , Jorgensen Elisa M. , Esselen Katharine M. , Celec Peter , Swanson Kenneth D. , Wegiel Barbara
Published: April 2022

Endometriosis, a painful gynecological condition accompanied by inflammation in women of reproductive age, is associated with an increased risk of ovarian cancer. We evaluated the role of peritoneal heme accumulated during menstrual cycling, as well as peritoneal and lesional macrophage phenotype, in promoting an oncogenic microenvironment. We quantified the heme-degrading enzyme, heme oxygenase-1 (HO-1, encoded by Hmox1) in normal peritoneum, endometriotic lesions and endometriosis-associated ovarian cancer (EAOC) of clear cell type (OCCC). HO-1 was expressed primarily in macrophages and increased in endometrioma and OCCC tissues relative to endometriosis and controls. Further, we compared cytokine expression profiles in peritoneal macrophages (PM) and peripheral blood mononuclear cells (PBMC) in women with endometriosis versus controls as a measure of a tumor-promoting environment in the peritoneum. We found elevated levels of HO-1 along with IL-10 and the pro-inflammatory cytokines (IL-1β, IL-16, IFNγ) in PM but not in PBMC from endometriosis patients. Using LysM-Cre:Hmox1flfl conditional knockout mice, we show that a deficiency of HO-1 in macrophages led to the suppression of growth of ID8 ovarian tumors implanted into the peritoneum. The restriction of ID8 ovarian tumor growth was associated with an increased number of Mac3+ macrophage and B cells in LysM-Cre:Hmox1flfl mice compared to controls. Functional experiments in ovarian cancer cell lines show that HO-1 is induced by heme. Low levels of exogenous heme promoted ovarian cancer colony growth in soft agar. Higher doses of heme led to slower cancer cell colony growth in soft agar and the induction of HO-1. These data suggest that perturbation of heme metabolism within the endometriotic niche and in cancer cells themselves may be an important factor that influences tumor initiation and growth.
Catalysis in Advanced Oxidation Technologies (AOTs) for Water, Air and Soil Treatment
Authors: Guillard Chantal , Robert Didier
Published: April 2022

The environment is what supports life on Earth [...]
Factors Regulating or Regulated by Myogenic Regulatory Factors in Skeletal Muscle Stem Cells
Authors: Shirakawa Tomohiko , Toyono Takashi , Inoue Asako , Matsubara Takuma , Kawamoto Tatsuo , Kokabu Shoichiro
Published: April 2022

MyoD, Myf5, myogenin, and MRF4 (also known as Myf6 or herculin) are myogenic regulatory factors (MRFs). MRFs are regarded as master transcription factors that are upregulated during myogenesis and influence stem cells to differentiate into myogenic lineage cells. In this review, we summarize MRFs, their regulatory factors, such as TLE3, NF-κB, and MRF target genes, including non-myogenic genes such as taste receptors. Understanding the function of MRFs and the physiology or pathology of satellite cells will contribute to the development of cell therapy and drug discovery for muscle-related diseases.
Recent Advancements in Antifibrotic Therapies for Regression of Liver Fibrosis
Authors: Jangra Anshika , Kothari Ashish , Sarma Phulen , Medhi Bikash , Omar Balram Ji , Kaushal Karanvir
Published: April 2022

Cirrhosis is a severe form of liver fibrosis that results in the irreversible replacement of liver tissue with scar tissue in the liver. Environmental toxicity, infections, metabolic causes, or other genetic factors including autoimmune hepatitis can lead to chronic liver injury and can result in inflammation and fibrosis. This activates myofibroblasts to secrete ECM proteins, resulting in the formation of fibrous scars on the liver. Fibrosis regression is possible through the removal of pathophysiological causes as well as the elimination of activated myofibroblasts, resulting in the reabsorption of the scar tissue. To date, a wide range of antifibrotic therapies has been tried and tested, with varying degrees of success. These therapies include the use of growth factors, cytokines, miRNAs, monoclonal antibodies, stem-cell-based approaches, and other approaches that target the ECM. The positive results of preclinical and clinical studies raise the prospect of a viable alternative to liver transplantation in the near future. The present review provides a synopsis of recent antifibrotic treatment modalities for the treatment of liver cirrhosis, as well as a brief summary of clinical trials that have been conducted to date.
Perirhinal Cortex LTP Does Not Require Astrocyte BDNF-TrkB Signaling
Authors: Vignoli Beatrice , Canossa Marco
Published: April 2022

Neurons release and respond to brain-derived neurotrophic factor (BDNF) with bursts of brain activity. BDNF action is known to extend to peri-synaptic astrocytes, contributing to synaptic strengthening. This implies that astrocytes have a set of dynamic responses, some of which might be secondary to activation of the tropomyosin tyrosine kinase B (TrkB) receptor. Here, we assessed the contribution of BDNF to long-term synaptic potentiation (LTP), by specifically deleting TrkB in cortical astrocytes. TrkB deletion had no effect on LTP induction, stabilization and maintenance, indicating that TrkB signaling in astrocytes is extraneous to transducing BDNF activity for synaptic strengthening.
Room-Temperature Infrared Photodetectors with Zero-Dimensional and New Two-Dimensional Materials
Authors: Li Taipeng , Tang Xin , Chen Menglu
Published: April 2022

Infrared photodetectors have received much attention for several decades due to their broad applications in the military, science, and daily life. However, for achieving an ideal signal-to-noise ratio and a very fast response, cooling is necessary in those devices, which makes them bulky and costly. Thus, room-temperature infrared photodetectors have emerged as a hot research direction. Novel low-dimensional materials with their easy fabrication and excellent photoelectronic properties provide a possible solution for room-temperature infrared photodetectors. This review aims to summarize the preparation methods and characterization of several low-dimensional materials (PbS, PbSe and HgTe, new two-dimensional materials) with great concern and the room-temperature infrared photodetectors based on them.
Performance Analysis of an Adaptive Rate Scheme for QoE-Assured Mobile VR Video Streaming
Authors: Chu Thi My Chinh , Zepernick Hans-Jürgen
Published: April 2022

The emerging 5G mobile networks are essential enablers for mobile virtual reality (VR) video streaming applications assuring high quality of experience (QoE) at the end-user. In addition, mobile edge computing brings computational resources closer to the user equipment (UE), which allows offloading computationally intensive processing. In this paper, we consider a network architecture for mobile VR video streaming applications consisting of a server that holds the VR video content, a mobile edge virtualization with prefetching (MVP) unit that handles the VR video packets, and a head-mounted display along with a buffer, which together serve as the UE. Several modulation and coding schemes with different rates are provided by the MVP unit to adaptively cope with the varying wireless link conditions to the UE and the state of the UE buffer. The UE buffer caches VR video packets as needed to compensate for the adaptive rates. A performance analysis is conducted in terms of blocking probability, throughput, queueing delay, and average packet error rate. To capture the effect of fading severity, the analytical expressions for these performance metrics are derived for Nakagami-m fading on the wireless link from the MVP unit to the UE. Numerical results show that the proposed system meets the network requirements needed to assure the QoE levels of different mobile VR video streaming applications.
Flexural Edge Waves in a Thick Piezoelectric Film Resting on a Winkler Foundation
Authors: Althobaiti Saad , Hawwa Muhammad A.
Published: April 2022

This paper is concerned with the analysis of bending edge waves travelling in a thick Kirchhoff-type piezoelectric film resting on a Winkler–Fuss foundation. The electromechanical coupling is accounted for in defining flexural rigidities to embrace piezoelectric and dielectric material constants. Dynamics is solved analytically and demonstrated numerically by assuming harmonic wave propagation. It is observed that an increase of the voltage leads to a decrease of the critical velocity, while an increase of the Winkler’s constant leads to an increase of the critical velocity.
Progressing Vulvar Melanoma Caused by Instability in cKIT Juxtamembrane Domain: A Case Report and Review of Literature
Authors: Englert-Golon Monika , Budny Bartłomiej , Lewandowska Małgorzata , Burchardt Bartosz , Smolarek Natalia , Ziemnicka Katarzyna , Jagodziński Paweł Piotr , Ruchała Marek , Grabowska Marlena , Sajdak Stefan
Published: April 2022

In order to identify the molecular pathways governing melanoma and track its progression, the next-generation sequencing (NGS) approach and targeted sequencing of cancer genes were employed. The primary tumor, as well as metastatic tissue, of an 84-year-old patient diagnosed with vulvar melanoma (VM), were investigated. The primary tumor specimen showed multiple somatic mutations in TP53 gene, suggesting its major contribution to melanoma origin. The metastatic sample showed additional alterations, including other melanoma-related genes. Clinical relevancy is postulated to juxtamembrane region instability of KIT gene (c-KIT). We did not identify BRAF or NRAS alterations, which are typical for the most common melanoma pathway–MAPK cascade. However, it should be noted that this is the first report evidencing PDGFRA in melanoma, although its role in triggering VM needs to be further elucidated.
Histologic and Genotypic Characterization of Lung Cancer in the Inuit Population of the Eastern Canadian Arctic
Authors: Goss Glenwood D. , Spaans Johanna N. , Huntsman David , Asmis Timothy , Andrews Wright Natalie M. , Duciaume Marc , Kaurah Pardeep , Miller Ruth R. , Banerji Shantanu , Sekhon Harmanjatinder S. , Gomes Marcio M.
Published: April 2022

Inuit are the Indigenous Arctic peoples and residents of the Canadian territory of Nunavut who have the highest global rate of lung cancer. Given lung cancer’s mortality, histological and genomic characterization was undertaken to better understand the disease biology. We retrospectively studied all Inuit cases from Nunavut’s Qikiqtani (Baffin) region, referred to the Ottawa Hospital Cancer Center between 2001 and 2011. Demographics were compiled from medical records and tumor samples underwent pathologic/histologic confirmation. Tumors were analyzed by next generation sequencing (NGS) with a cancer hotspot mutation panel. Of 98 patients, the median age was 66 years and 61% were male. Tobacco use was reported in 87%, and 69% had a history of lung disease (tuberculosis or other). Histological types were: non-small cell lung carcinoma (NSCLC), 81%; small cell lung carcinoma, 16%. Squamous cell carcinoma (SCC) represented 65% of NSCLC. NGS on 55 samples demonstrated mutation rates similar to public lung cancer datasets. In SCC, the STK11 F354L mutation was observed at higher frequency than previously reported. This is the first study to characterize the histologic/genomic profiles of lung cancer in this population. A high incidence of SCC, and an elevated rate of STK11 mutations distinguishes this group from the North American population.
Wait Times and Survival in Lung Cancer Patients across the Province of Quebec, Canada
Authors: Denault Marie-Hélène , Labbé Catherine , St-Pierre Carolle , Fournier Brigitte , Gagné Andréanne , Morillon Claudia , Joubert Philippe , Simard Serge , Martel Simon
Published: April 2022

Lung cancer is the leading cause of cancer death worldwide, with a five-year survival of 22% in Canada. Guidelines recommend rapid evaluation of patients with suspected lung cancer, but the impact on survival remains unclear. We reviewed medical records of all patients with newly diagnosed lung cancer in four hospital networks across the province of Quebec, Canada, between 1 February and 30 April 2017. Patients were followed for 3 years. Wait times for diagnosis and treatment were collected, and survival analysis using a Cox regression model was conducted. We included 1309 patients, of whom 39% had stage IV non-small cell lung cancer (NSCLC). Median wait times were, in general, significantly shorter in patients with stage III–IV NSCLC or SCLC. Surgery was associated with delays compared to other types of treatments. Median survival was 12.9 (11.1–15.7) months. The multivariate survival model included age, female sex, performance status, histology and stage, treatment, and the time interval between diagnosis and treatment. Longer wait times had a slightly protective to neutral effect on survival, but this was not significant in the stage I–II NSCLC subgroup. Wait times for the diagnosis and treatment of lung cancer were generally within targets. The shorter wait times observed for advanced NSCLC and SCLC might indicate a tendency for clinicians to act quicker on sicker patients. This study did not demonstrate the detrimental effect of longer wait times on survival.
Survival and Genome Diversity of Vibrio parahaemolyticus Isolated from Edible Aquatic Animals
Authors: Xu Dingxiang , Peng Xu , Xie Lu , Chen Lanming
Published: April 2022

Vibrio parahaemolyticus can cause acute gastroenteritis, wound infection, and septicemia in humans. The waterborne bacterium is frequently isolated from aquatic products worldwide. Nevertheless, little information in genome evolution of V. parahaemolyticus isolated from aquatic animals is yet available. Here we overcome this limitation by specifying six V. parahaemolyticus isolates recovered from edible shellfish, fish, and crustacean. Most isolates with multiple resistance phenotypes grew optimally at 3% NaCl and pH 8.5. Draft genome sequences of the six V. parahaemolyticus isolates (4,937,042 bp to 5,067,778 bp) were determined using the Illumina Hiseq × 10 sequencing platform. Comparative genomic analyses revealed 4622 to 4791 predicted protein-encoding genes, of which 1064 to 1107 were of unknown function. Various mobile genetic elements (MGEs) were identified in the V. parahaemolyticus genomes, including genome islands (n = 5 to 9), prophage gene clusters (n = 0 to 2), integrons (n = 1 to 11), and insertion sequences (n = 0 to 3). A number of antibiotic-resistant (n = 17 to 20), virulence-associated (n = 77 to 79), and strain-specific (n = 131 to 287) genes were also identified, indicating possible horizontal gene transfer via the MGEs and considerable genome variation in the V. parahaemolyticus isolates. Altogether, the results of this study fill prior gaps in our knowledge of the genome evolution of V. parahaemolyticus, as isolated from edible aquatic animals.
Fetal and Maternal Diseases in Pregnancy: From Morphology to Function
Authors: Masselli Gabriele
Published: April 2022

Ultrasound (US) is currently the standard approach for the initial evaluation of fetal anatomy and maternal conditions during pregnancy since it facilitates a real-time examination and is widely available and cost-effective [...]
Radiomics Profiling Identifies the Value of CT Features for the Preoperative Evaluation of Lymph Node Metastasis in Papillary Thyroid Carcinoma
Authors: Yang Guoqiang , Yang Fan , Zhang Fengyan , Wang Xiaochun , Tan Yan , Qiao Ying , Zhang Hui
Published: April 2022

Background: The aim of this study was to identify the increased value of integrating computed tomography (CT) radiomics analysis with the radiologists’ diagnosis and clinical factors to preoperatively diagnose cervical lymph node metastasis (LNM) in papillary thyroid carcinoma (PTC) patients. Methods: A total of 178 PTC patients were randomly divided into a training (n = 125) and a test cohort (n = 53) with a 7:3 ratio. A total of 2553 radiomic features were extracted from noncontrast, arterial contrast-enhanced and venous contrast-enhanced CT images of each patient. Principal component analysis (PCA) and Pearson’s correlation coefficient (PCC) were used for feature selection. Logistic regression was employed to build clinical–radiological, radiomics and combined models. A nomogram was developed by combining the radiomics features, CT-reported lymph node status and clinical factors. Results: The radiomics model showed a predictive performance similar to that of the clinical–radiological model, with similar areas under the curve (AUC) and accuracy (ACC). The combined model showed an optimal predictive performance in both the training (AUC, 0.868; ACC, 86.83%) and test cohorts (AUC, 0.878; ACC, 83.02%). Decision curve analysis demonstrated that the combined model has good clinical application value. Conclusions: Embedding CT radiomics into the clinical diagnostic process improved the diagnostic accuracy. The developed nomogram provides a potential noninvasive tool for LNM evaluation in PTC patients.
Application of Coarse-Grained (CG) Models to Explore Conformational Pathway of Large-Scale Protein Machines
Authors: Shi Danfeng , An Ke , Zhang Honghui , Xu Peiyi , Bai Chen
Published: April 2022

Protein machines are clusters of protein assemblies that function in order to control the transfer of matter and energy in cells. For a specific protein machine, its working mechanisms are not only determined by the static crystal structures, but also related to the conformational transition dynamics and the corresponding energy profiles. With the rapid development of crystallographic techniques, the spatial scale of resolved structures is reaching up to thousands of residues, and the concomitant conformational changes become more and more complicated, posing a great challenge for computational biology research. Previously, a coarse-grained (CG) model aiming at conformational free energy evaluation was developed and showed excellent ability to reproduce the energy profiles by accurate electrostatic interaction calculations. In this study, we extended the application of the CG model to a series of large-scale protein machine systems. The spike protein trimer of SARS-CoV-2, ATP citrate lyase (ACLY) tetramer, and P4-ATPases systems were carefully studied and discussed as examples. It is indicated that the CG model is effective to depict the energy profiles of the conformational pathway between two endpoint structures, especially for large-scale systems. Both the energy change and energy barrier between endpoint structures provide reasonable mechanism explanations for the associated biological processes, including the opening of receptor binding domain (RBD) of spike protein, the phospholipid transportation of P4-ATPase, and the loop translocation of ACLY. Taken together, the CG model provides a suitable alternative in mechanistic studies related to conformational change in large-scale protein machines.
A Family of Fitness Landscapes Modeled through Gene Regulatory Networks
Authors: Yang Chia-Hung , Scarpino Samuel V.
Published: April 2022

Fitness landscapes are a powerful metaphor for understanding the evolution of biological systems. These landscapes describe how genotypes are connected to each other through mutation and related through fitness. Empirical studies of fitness landscapes have increasingly revealed conserved topographical features across diverse taxa, e.g., the accessibility of genotypes and “ruggedness”. As a result, theoretical studies are needed to investigate how evolution proceeds on fitness landscapes with such conserved features. Here, we develop and study a model of evolution on fitness landscapes using the lens of Gene Regulatory Networks (GRNs), where the regulatory products are computed from multiple genes and collectively treated as phenotypes. With the assumption that regulation is a binary process, we prove the existence of empirically observed, topographical features such as accessibility and connectivity. We further show that these results hold across arbitrary fitness functions and that a trade-off between accessibility and ruggedness need not exist. Then, using graph theory and a coarse-graining approach, we deduce a mesoscopic structure underlying GRN fitness landscapes where the information necessary to predict a population’s evolutionary trajectory is retained with minimal complexity. Using this coarse-graining, we develop a bottom-up algorithm to construct such mesoscopic backbones, which does not require computing the genotype network and is therefore far more efficient than brute-force approaches. Altogether, this work provides mathematical results of high-dimensional fitness landscapes and a path toward connecting theory to empirical studies.
Three Risky Decades: A Time for Econophysics?
Authors: Kutner Ryszard , Schinckus Christophe , Stanley Harry Eugene
Published: April 2022

The Special Issue comes out in the increasing accumulation of negative global tensions in many areas [...]
Impacts of Yield and Seasonal Prices on the Operation of Lancang Cascaded Reservoirs
Authors: Xie Mengfei , Feng Suzhen , Wang Jinwen , Zhang Maolin , Chen Cheng
Published: April 2022

This work formulates a stochastic dynamic programming (SDP) model that incorporates seasonal electricity prices and can handle a constraint on power yield, which is assumed to be satisfied at any time it is possible, thus allowing for an analysis of their impacts on the operational performances of cascaded reservoirs. The model is applied to the Lancang Cascade, specifically its two largest reservoirs, Xiaowan and Nuozhadu. The results show that increasing the power yield of the cascade will reduce energy production unfavorably but will impact water spillage favorably, with a power yield of 2000 MW and with a 91% reliability suggested as being a satisfactory operational target. The case study also suggests that using seasonal electricity prices makes the power generation very unstable during weeks 12–20, which is a period of time that is critical to transferring from dry to flooding seasons.
Biogenic Methane Accumulation and Production in the Jurassic Low-Rank Coal, Southwestern Ordos Basin
Authors: Zheng Chao , Ma Dongmin , Chen Yue , Xia Yucheng , Gao Zheng , Li Guofu , Li Weibo
Published: April 2022

Geological conditions are the key for coalbed methane (CBM) accumulation and production. However, the geological feature of CBM accumulation and production in the Jurassic of Ordos Basin lacks systematic and detailed evaluation, resulting in poor CBM production in this area. This study has determined the genetic types of gas according to geochemistry characteristics of the gas, the geological factors to control CBM accumulation and production performance were revealed, and a comprehensive method was established to evaluate favorable areas based on 32 sets of CBM well production data from Jurassic Yan’an Formation. The results show the coal macerals are rich in inertinite (41.13~91.12%), and the maximum reflectance of vitrinite (Ro,max) in coal is 0.56~0.65%. According to gas compositions and carbon isotopes analysis, the δ13C(CH4) is less than −55‰, and the content of heavy hydrocarbon is less than 0.05%. The value of C1/(C2 + C3) is 6800~98,000, that is, the CBM is a typical biogenic gas of low-rank coal. The CBM accumulation model is the secondary biogenic on the gentle slope of the basin margin, in which gas content is closely related to buried depth and hydrodynamic environment, i.e., the high gas content areas are mainly located in the groundwater weak runoff zone at the burial depth of 450 m~650 m, especially in the syncline. Meanwhile, gas production mainly depends on the location of the structure. The high gas production areas of vertical wells were distributed on the gentle slope with high gas content between anticline and syncline, and the horizontal wells with good performance were located near the core of the syncline. According to the above analysis combined with the random forest model, the study area was divided into different production favorable areas, which will provide a scientific basis for the CBM production wells.
Using a Vegetation Index-Based Mixture Model to Estimate Fractional Vegetation Cover Products by Jointly Using Multiple Satellite Data: Method and Feasibility Analysis
Authors: Song Wanjuan , Zhao Tian , Mu Xihan , Zhong Bo , Zhao Jing , Yan Guangjian , Wang Li , Niu Zheng
Published: April 2022

Remote sensing fractional vegetation cover (FVC) requires both finer-resolution and high-frequency in climate and ecosystem research. The increasing availability of finer-resolution (≤ 30 m) remote sensing data makes this possible. However, data from different satellites have large differences in spatial resolution, spectral response function, and so on, making joint use difficult. Herein, we showed that the vegetation index (VI)-based mixture model with the appropriate VI values of pure vegetation (Vv) and bare soil (Vs) from the MODIS BRDF product via the multi-angle VI method (MultiVI) was feasible to estimate FVC with multiple satellite data. Analyses of the spatial resolution and spectral response function differences for MODIS and other satellites including Landsat 8, Chinese GF 1, and ZY 3 predicted that (1) the effect of Vv and Vs downscaling on FVC estimation uncertainty varied from satellite to satellite due to the positioning differences, and (2) after spectral normalization, the uncertainty (RMSDs) for FVC estimation decreased by ~2.6% compared with the results without spectral normalization. FVC estimation across multiple satellite data will help to improve the spatiotemporal resolution of FVC products, which is an important development for numerous biophysical applications. Herein, we proved that the VI-based mixture model with Vv and Vs from MultiVI is a strong candidate.
Extracellular Enzyme Stoichiometry Reveals Soil Microbial Carbon and Phosphorus Limitations in the Yimeng Mountain Area, China
Authors: Wang Lu , Li Kun , Guo Jianyao , Liu Xiumei , Gao Jinhui , Ma Liang , Wei Jinhui , Lu Min , Li Chuanrong
Published: April 2022

Soil extracellular enzymes are considered key components in ecosystem carbon and nutrient cycling, and analysing their stoichiometry is an effective way to reveal the resource limitations on soil microbial metabolism. In this study, the soil and litter of Quercus acutissima plots, Pinus thunbergii plots, Quercus acutissima–Pinus thunbergii mixed-plantation plots, herb plots, and shrub plots in the state-owned Dawa Forest Farm in the Yimeng Mountain area were studied. The total carbon (C), nitrogen (N), and phosphorus (P) contents of litter and the physical and chemical properties of soil were analyzed, along with the activities of four extracellular enzymes related to the soil C, N, and P cycle: β-1,4-glucosidase (BG), β-1,4-N-acetylglucosaminidase (NAG), L-leucine aminopeptidase (LAP), and acid phosphatase (AP). The extracellular enzyme stoichiometric model was used to study and compare the metabolic limitations of soil microorganisms in different plots, and the driving factors of microbial metabolic limitations were explored by redundancy and linear regression analyses. The results showed that the values of BG/(NAG + LAP) were all higher than 1, the values of (NAG + LAP)/AP all lower than 1, and the vector angles of the five plots all greater than 45°, which indicated that the soil microorganisms were relatively limited by C and P. Redundancy and linear regression analysis revealed that soil physical properties (e.g., soil moisture) and litter total C make greater contributions to soil extracellular enzymes and stoichiometry than the other investigated soil parameters, whereas soil chemical properties (e.g., soil organic C and available P) predominantly controlled vector properties. Therefore, microbial metabolism limitations are greatly regulated by soil physical and chemical properties and litter total C and N. Compared with the forest plots, the soil microbial C (1.67) and P (61.07°) limitations of herb plots were relatively higher, which means that the soil microbial communities of forest plots are more stable than those of herb plots in the Yimeng Mountain area. Forest plots were more conducive than other plots to the improvement of soil microbial ecology in this area. This study could be important for illuminating soil microbial metabolism and revealing soil nutrient cycling in the Yimeng Mountain area ecosystem of China.