bluuebunny/crossref_metadata_2025 huggingface dataset:
Panoramic tongue imaging and deep convolutional machine learning model for diabetes diagnosis in humans
Authors: Balasubramaniyan Saritha , Jeyakumar Vijay , Nachimuthu Deepa Subramaniam
Published: January 2022

Diabetes is a serious metabolic disorder with high rate of prevalence worldwide; the disease has the characteristics of improper secretion of insulin in pancreas that results in high glucose level in blood. The disease is also associated with other complications such as cardiovascular disease, retinopathy, neuropathy and nephropathy. The development of computer aided decision support system is inevitable field of research for disease diagnosis that will assist clinicians for the early prognosis of diabetes and to facilitate necessary treatment at the earliest. In this research study, a Traditional Chinese Medicine based diabetes diagnosis is presented based on analyzing the extracted features of panoramic tongue images such as color, texture, shape, tooth markings and fur. The feature extraction is done by Convolutional Neural Network (CNN)—ResNet 50 architecture, and the classification is performed by the proposed Deep Radial Basis Function Neural Network (RBFNN) algorithm based on auto encoder learning mechanism. The proposed model is simulated in MATLAB environment and evaluated with performance metrics—accuracy, precision, sensitivity, specificity, F1 score, error rate, and receiver operating characteristics (ROC). On comparing with existing models, the proposed CNN based Deep RBFNN machine learning classifier model outperformed with better classification performance and proving its effectiveness.
Gut dysbiosis is associated with acceleration of lupus nephritis
Authors: Valiente Giancarlo R. , Munir Armin , Hart Marcia L. , Blough Perry , Wada Takuma T. , Dalan Emma E. , Willis William L. , Wu Lai-Chu , Freud Aharon G. , Jarjour Wael N.
Published: January 2022

The gut microbiota (GM) exerts a strong influence over the host immune system and dysbiosis of this microbial community can affect the clinical phenotype in chronic inflammatory conditions. To explore the role of the GM in lupus nephritis, we colonized NZM2410 mice with Segmented Filamentous Bacteria (SFB). Gut colonization with SFB was associated with worsening glomerulonephritis, glomerular and tubular immune complex deposition and interstitial inflammation compared to NZM2410 mice free of SFB. With SFB colonization mice experienced an increase in small intestinal lamina propria Th17 cells and group 3 innate lymphoid cells (ILC3s). However, although serum IL-17A expression was elevated in these mice, Th17 cells and ILC3s were not detected in the inflammatory infiltrate in the kidney. In contrast, serum and kidney tissue expression of the macrophage chemoattractants MCP-1 and CXCL1 were significantly elevated in SFB colonized mice. Furthermore, kidney infiltrating F4/80+CD206+M2-like macrophages were significantly increased in these mice. Evidence of increased gut permeability or “leakiness” was also detected in SFB colonized mice. Finally, the intestinal microbiome of SFB colonized mice at 15 and 30 weeks of age exhibited dysbiosis when compared to uncolonized mice at the same time points. Both microbial relative abundance as well as biodiversity of colonized mice was found to be altered. Collectively, SFB gut colonization in the NZM2410 mouse exacerbates kidney disease, promotes kidney M2-like macrophage infiltration and overall intestinal microbiota dysbiosis.
Bedside detection of intracranial midline shift using portable magnetic resonance imaging
Authors: Sheth Kevin N. , Yuen Matthew M. , Mazurek Mercy H. , Cahn Bradley A. , Prabhat Anjali M. , Salehi Sadegh , Shah Jill T. , By Samantha , Welch E. Brian , Sofka Michal , Sacolick Laura I. , Kim Jennifer A. , Payabvash Seyedmehdi , Falcone Guido J. , Gilmore Emily J. , Hwang David Y. , Matouk Charles , Gordon-Kundu Barbara , RN Adrienne Ward , Petersen Nils , Schindler Joseph , Gobeske Kevin T. , Sansing Lauren H. , Sze Gordon , Rosen Matthew S. , Kimberly W. Taylor , Kundu Prantik
Published: January 2022

Neuroimaging is crucial for assessing mass effect in brain-injured patients. Transport to an imaging suite, however, is challenging for critically ill patients. We evaluated the use of a low magnetic field, portable MRI (pMRI) for assessing midline shift (MLS). In this observational study, 0.064 T pMRI exams were performed on stroke patients admitted to the neuroscience intensive care unit at Yale New Haven Hospital. Dichotomous (present or absent) and continuous MLS measurements were obtained on pMRI exams and locally available and accessible standard-of-care imaging exams (CT or MRI). We evaluated the agreement between pMRI and standard-of-care measurements. Additionally, we assessed the relationship between pMRI-based MLS and functional outcome (modified Rankin Scale). A total of 102 patients were included in the final study (48 ischemic stroke; 54 intracranial hemorrhage). There was significant concordance between pMRI and standard-of-care measurements (dichotomous, κ = 0.87; continuous, ICC = 0.94). Low-field pMRI identified MLS with a sensitivity of 0.93 and specificity of 0.96. Moreover, pMRI MLS assessments predicted poor clinical outcome at discharge (dichotomous: adjusted OR 7.98, 95% CI 2.07–40.04, p = 0.005; continuous: adjusted OR 1.59, 95% CI 1.11–2.49, p = 0.021). Low-field pMRI may serve as a valuable bedside tool for detecting mass effect.
Computational identification of 4-carboxyglutamate sites to supplement physiological studies using deep learning
Authors: Naseer Sheraz , Ali Rao Faizan , Fati Suliman Mohamed , Muneer Amgad
Published: January 2022

In biological systems, Glutamic acid is a crucial amino acid which is used in protein biosynthesis. Carboxylation of glutamic acid is a significant post-translational modification which plays important role in blood coagulation by activating prothrombin to thrombin. Contrariwise, 4-carboxy-glutamate is also found to be involved in diseases including plaque atherosclerosis, osteoporosis, mineralized heart valves, bone resorption and serves as biomarker for onset of these diseases. Owing to the pathophysiological significance of 4-carboxyglutamate, its identification is important to better understand pathophysiological systems. The wet lab identification of prospective 4-carboxyglutamate sites is costly, laborious and time consuming due to inherent difficulties of in-vivo, ex-vivo and in vitro experiments. To supplement these experiments, we proposed, implemented, and evaluated a different approach to develop 4-carboxyglutamate site predictors using pseudo amino acid compositions (PseAAC) and deep neural networks (DNNs). Our approach does not require any feature extraction and employs deep neural networks to learn feature representation of peptide sequences and performing classification thereof. Proposed approach is validated using standard performance evaluation metrics. Among different deep neural networks, convolutional neural network-based predictor achieved best scores on independent dataset with accuracy of 94.7%, AuC score of 0.91 and F1-score of 0.874 which shows the promise of proposed approach. The iCarboxE-Deep server is deployed at https://share.streamlit.io/sheraz-n/carboxyglutamate/app.py.
Rubicon-regulated beta-1 adrenergic receptor recycling protects the heart from pressure overload
Authors: Akazawa Yasuhiro , Taneike Manabu , Ueda Hiromichi , Kitazume-Taneike Rika , Murakawa Tomokazu , Sugihara Ryuta , Yorifuji Hiroki , Nishida Hiroki , Mine Kentaro , Hioki Ayana , Omiya Shigemiki , Nakayama Hiroyuki , Yamaguchi Osamu , Yoshimori Tamotsu , Sakata Yasushi , Otsu Kinya
Published: January 2022

Heart failure has high morbidity and mortality in the developed countries. Autophagy is important for the quality control of proteins and organelles in the heart. Rubicon (Run domain Beclin-1-interacting and cysteine-rich domain-containing protein) has been identified as a potent negative regulator of autophagy and endolysosomal trafficking. The aim of this study was to investigate the in vivo role of Rubicon-mediated autophagy and endosomal trafficking in the heart. We generated cardiomyocyte-specific Rubicon-deficient mice and subjected the mice to pressure overload by means of transverse aortic constriction. Rubicon-deficient mice showed heart failure with left ventricular dilatation, systolic dysfunction and lung congestion one week after pressure overload. While autophagic activity was unchanged, the protein amount of beta-1 adrenergic receptor was decreased in the pressure-overloaded Rubicon-deficient hearts. The increases in heart rate and systolic function by beta-1 adrenergic stimulation were significantly attenuated in pressure-overloaded Rubicon-deficient hearts. In isolated rat neonatal cardiomyocytes, the downregulation of the receptor by beta-1 adrenergic agonist was accelerated by knockdown of Rubicon through the inhibition of recycling of the receptor. Taken together, Rubicon protects the heart from pressure overload. Rubicon maintains the intracellular recycling of beta-1 adrenergic receptor, which might contribute to its cardioprotective effect.
Synthesis of zeolitic imidazolate framework-8 and gold nanoparticles in a sustained out-of-equilibrium state
Authors: Dúzs Brigitta , Holló Gábor , Schuszter Gábor , Horváth Dezső , Tóth Ágota , Szalai István , Lagzi István
Published: January 2022

The design and synthesis of crystalline materials are challenging due to the proper control over the size and polydispersity of the samples, which determine their physical and chemical properties and thus applicability. Metal − organic frameworks (MOFs) are promising materials in many applications due to their unique structure. MOFs have been predominantly synthesized by bulk methods, where the concentration of the reagents gradually decreased, which affected the further nucleation and crystal growth. Here we show an out-of-equilibrium method for the generation of zeolitic imidazolate framework-8 (ZIF-8) crystals, where the non-equilibrium crystal growth is maintained by a continuous two-side feed of the reagents in a hydrogel matrix. The size and the polydispersity of the crystals are controlled by the fixed and antagonistic constant mass fluxes of the reagents and by the reaction time. We also present that our approach can be extended to synthesize gold nanoparticles in a redox process.
Expanding structural diversity in a library of disulfide macrocycles through in-situ imide hydrolysis
Authors: Konopka Marcin , Stefankiewicz Artur R.
Published: January 2022

We describe here an unorthodox approach to dynamic covalent chemistry in which the initially-unexpected in-situ hydrolysis of a bis-imide is employed to control the composition of a library of structurally diverse macrocycles. A single building block is used to generate a library of numerous disulfide-based architectures in a one-pot single-step process. The dual-stimuli method is based on simultaneous changes in pH and DMSO concentration to expand the structural diversity of the macrocyclic products. Mechanistic details of this complex process are investigated by the kinetics analysis. We delivered a facile strategy for the synthesis of water-soluble, multicomponent and dynamic macrocycles equipped with number of different functional groups, thus giving a prospect of their application in guest-driven phase transfer.
Geographic and temporal variation in racial and ethnic disparities in SARS-CoV-2 positivity between February 2020 and August 2021 in the United States
Authors: Ferguson Jacqueline M. , Justice Amy C. , Osborne Thomas F. , Magid Hoda S. Abdel , Purnell Amanda L. , Rentsch Christopher T.
Published: January 2022

The coronavirus pandemic has disproportionally impacted racial and ethnic minority communities in the United States. Patterns of these disparities may be changing over time as outbreaks occur in different communities. Utilizing electronic health record data from the US Department of Veterans Affairs (VA), we estimated odds ratios, stratified by time period and region, for testing positive among 1,313,402 individuals tested for SARS-CoV-2 between February 12, 2020 and August 16, 2021 at VA medical facilities. We adjusted for personal characteristics (sex, age, rural/urban residence, VA facility) and a wide range of clinical characteristics that have been evaluated in prior SARS-CoV-2 reports and could potentially explain racial/ethnic disparities in SARS-CoV-2. Our study found racial and ethnic disparities for testing positive were most pronounced at the beginning of the pandemic and decreased over time. A key finding was that the disparity among Hispanic individuals attenuated but remained elevated, while disparities among Asian individuals reversed by March 1, 2021. The variation in racial and ethnic disparities in SARS-CoV-2 positivity by time and region, independent of underlying health status and other demographic characteristics in a nationwide cohort, provides important insight for strategies to prevent further outbreaks.
Automated food intake tracking requires depth-refined semantic segmentation to rectify visual-volume discordance in long-term care homes
Authors: Pfisterer Kaylen J. , Amelard Robert , Chung Audrey G. , Syrnyk Braeden , MacLean Alexander , Keller Heather H. , Wong Alexander
Published: January 2022

Malnutrition is a multidomain problem affecting 54% of older adults in long-term care (LTC). Monitoring nutritional intake in LTC is laborious and subjective, limiting clinical inference capabilities. Recent advances in automatic image-based food estimation have not yet been evaluated in LTC settings. Here, we describe a fully automatic imaging system for quantifying food intake. We propose a novel deep convolutional encoder-decoder food network with depth-refinement (EDFN-D) using an RGB-D camera for quantifying a plate’s remaining food volume relative to reference portions in whole and modified texture foods. We trained and validated the network on the pre-labelled UNIMIB2016 food dataset and tested on our two novel LTC-inspired plate datasets (689 plate images, 36 unique foods). EDFN-D performed comparably to depth-refined graph cut on IOU (0.879 vs. 0.887), with intake errors well below typical 50% (mean percent intake error: $$-4.2$$

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4.2

%). We identify how standard segmentation metrics are insufficient due to visual-volume discordance, and include volume disparity analysis to facilitate system trust. This system provides improved transparency, approximates human assessors with enhanced objectivity, accuracy, and precision while avoiding hefty semi-automatic method time requirements. This may help address short-comings currently limiting utility of automated early malnutrition detection in resource-constrained LTC and hospital settings.
Quantifying the cell morphology and predicting biological behavior of signet ring cell carcinoma using deep learning
Authors: Da Qian , Deng Shijie , Li Jiahui , Yi Hongmei , Huang Xiaodi , Yang Xiaoqun , Yu Teng , Wang Xuan , Liu Jiangshu , Duan Qi , Metaxas Dimitris , Wang Chaofu
Published: January 2022

Signet ring cell carcinoma (SRCC) is a malignant tumor of the digestive system. This tumor has long been considered to be poorly differentiated and highly invasive because it has a higher rate of metastasis than well-differentiated adenocarcinoma. But some studies in recent years have shown that the prognosis of some SRCC is more favorable than other poorly differentiated adenocarcinomas, which suggests that SRCC has different degrees of biological behavior. Therefore, we need to find a histological stratification that can predict the biological behavior of SRCC. Some studies indicate that the morphological status of cells can be linked to the invasiveness potential of cells, however, the traditional histopathological examination can not objectively define and evaluate them. Recent improvements in biomedical image analysis using deep learning (DL) based neural networks could be exploited to identify and analyze SRCC. In this study, we used DL to identify each cancer cell of SRCC in whole slide images (WSIs) and quantify their morphological characteristics and atypia. Our results show that the biological behavior of SRCC can be predicted by quantifying the morphology of cancer cells by DL. This technique could be used to predict the biological behavior and may change the stratified treatment of SRCC.
In silico construction of a multiepitope Zika virus vaccine using immunoinformatics tools
Authors: Antonelli Ana Clara Barbosa , Almeida Vinnycius Pereira , de Castro Fernanda Oliveira Feitosa , Silva Jacyelle Medeiros , Pfrimer Irmtraut Araci Hoffmann , Cunha-Neto Edecio , Maranhão Andréa Queiroz , Brígido Marcelo Macedo , Resende Renato Oliveira , Bocca Anamélia Lorenzetti , Fonseca Simone Gonçalves
Published: January 2022

Zika virus (ZIKV) is an arbovirus from the Flaviviridae family and Flavivirus genus. Neurological events have been associated with ZIKV-infected individuals, such as Guillain-Barré syndrome, an autoimmune acute neuropathy that causes nerve demyelination and can induce paralysis. With the increase of ZIKV infection incidence in 2015, malformation and microcephaly cases in newborns have grown considerably, which suggested congenital transmission. Therefore, the development of an effective vaccine against ZIKV became an urgent need. Live attenuated vaccines present some theoretical risks for administration in pregnant women. Thus, we developed an in silico multiepitope vaccine against ZIKV. All structural and non-structural proteins were investigated using immunoinformatics tools designed for the prediction of CD4 + and CD8 + T cell epitopes. We selected 13 CD8 + and 12 CD4 + T cell epitopes considering parameters such as binding affinity to HLA class I and II molecules, promiscuity based on the number of different HLA alleles that bind to the epitopes, and immunogenicity. ZIKV Envelope protein domain III (EDIII) was added to the vaccine construct, creating a hybrid protein domain-multiepitope vaccine. Three high scoring continuous and two discontinuous B cell epitopes were found in EDIII. Aiming to increase the candidate vaccine antigenicity even further, we tested secondary and tertiary structures and physicochemical parameters of the vaccine conjugated to four different protein adjuvants: flagellin, 50S ribosomal protein L7/L12, heparin-binding hemagglutinin, or RS09 synthetic peptide. The addition of the flagellin adjuvant increased the vaccine's predicted antigenicity. In silico predictions revealed that the protein is a probable antigen, non-allergenic and predicted to be stable. The vaccine’s average population coverage is estimated to be 87.86%, which indicates it can be administered worldwide. Peripheral Blood Mononuclear Cells (PBMC) of individuals with previous ZIKV infection were tested for cytokine production in response to the pool of CD4 and CD8 ZIKV peptide selected. CD4 + and CD8 + T cells showed significant production of IFN-γ upon stimulation and IL-2 production was also detected by CD8 + T cells, which indicated the potential of our peptides to be recognized by specific T cells and induce immune response. In conclusion, we developed an in silico universal vaccine predicted to induce broad and high-coverage cellular and humoral immune responses against ZIKV, which can be a good candidate for posterior in vivo validation.
Factors associated with injury and re-injury occurrence in female pole dancers
Authors: Szopa Andrzej , Domagalska-Szopa Małgorzata , Urbańska Aleksandra , Grygorowicz Monika
Published: January 2022

The aim of the study was to recognise what participant-, training- and post-injury-related factors are associated with an injury and re-injury occurrence in female pole dancers (PDs). 320 female PDs fulfilled a custom survey. 1050 injuries were reported by 276 PDs, 59% of injuries were related to lower extremity, 39% to upper extremity and 10% to spine and trunk. 156 PDs reported sustaining a re-injury, and overall, 628 re-injuries were reported. The median weekly pole-specific training session volume was 90 min and 240 min in the low and high qualified group, respectively. The total training volume was 180 min in the low qualified PDs and 240 min in the high qualified group. PDs with higher height and spending more time on pole-specific training in studio and on other forms of training have higher odds of sustaining an injury. PDs with lower level of experience in training, who sustained an injury, and who had a shorter pause between the moment of injury and the return to performance, and thus who did not fully recover, have higher odds of sustaining a re-injury. Sport-specific injury prevention strategies should be developed and implemented in this cohort, since over 85% of pole dancers reported sustaining some kind of injury.
A scoring system combining clinical, radiological, and histopathological examinations for differential diagnosis between lipoma and atypical lipomatous tumor/well-differentiated liposarcoma
Authors: Asano Yohei , Miwa Shinji , Yamamoto Norio , Hayashi Katsuhiro , Takeuchi Akihiko , Igarashi Kentaro , Yonezawa Hirotaka , Araki Yoshihiro , Morinaga Sei , Nojima Takayuki , Ikeda Hiroko , Tsuchiya Hiroyuki
Published: January 2022

This study evaluated the diagnostic accuracy of clinical, radiological, and histopathological examinations for differential diagnosis between atypical lipomatous tumor (ALT)/well-differentiated liposarcoma (WDLS) and lipoma, and aimed to develop a new combined scoring system for the preoperative diagnosis of ALT/WDLS. Eighty-nine lipomas and 56 ALT/WDLS were included and their clinical characteristics, magnetic resonance imaging (MRI) findings, histological findings by hematoxylin and eosin (HE) staining were investigated. Then, univariate and multivariate logistic regression analyses were performed for the findings, and a combined scoring system consisted of predictive factors of ALT/WDLS was developed. The univariate and multivariate logistic regression analyses revealed that tumor location (lower extremity), deep site, size (> 11 cm), thick septa (> 2 mm), enhancement of septa or nodular lesions, and lipoblasts were significantly different for the diagnosis of ALT/WDLS. We developed a combined scoring system based on the six predictive factors (total 0–16 points, the cutoff was 9 points). The area under the curve was 0.945, and sensitivity was 87.6% and specificity was 91.1% by the receiver operating characteristics curve. This combined scoring system does not require special equipment and reagents such as fluorescence in situ hybridization (FISH), and anyone can use it easily in many medical institutions with high diagnostic accuracy.
Recombinant inbred lines and next-generation sequencing enable rapid identification of candidate genes involved in morphological and agronomic traits in foxtail millet
Authors: Fukunaga Kenji , Abe Akira , Mukainari Yohei , Komori Kaho , Tanaka Keisuke , Fujihara Akari , Yaegashi Hiroki , Kobayashi Michie , Ito Kazue , Ohsako Takanori , Kawase Makoto
Published: January 2022

We constructed recombinant inbred lines (RILs) between a Japanese and a Taiwanese landrace of foxtail millet and employed next-generation sequencing, such as flexible ddRAD-seq and Nanopore sequencing to identify the candidate genes involved in the crop evolution of foxtail millet. We successfully constructed a linkage map using flexible ddRAD-seq with parents and RILs and detected major QTLs for each of three traits: leaf sheath colors, spikelet-tipped bristles (stb), and days to heading (DTH). (1) For leaf sheath colors, we identified the C gene on chromosome IV. (2) We identified a homeobox (HOX14) gene for stb on chromosome II, which shows homology with HvVrs1 in barley. (3) Finally, we identified a QTL with a large effect on DTH on chromosome II. A parent of the RILs from Taiwan and Yugu1 had a Harbinger-like TE in intron 3 of this gene. We also investigated the geographical distribution of the TE insertion type of this gene and found that the insertion type is distributed in the northern part of East Asia and intensively in South and Southeast Asia, suggesting that loss/reduction of function of this gene plays an important role in spreading into the northern part of East Asia and subtropical and tropical zones.
Novel ratio-metric features enable the identification of new driver genes across cancer types
Authors: Sudhakar Malvika , Rengaswamy Raghunathan , Raman Karthik
Published: January 2022

An emergent area of cancer genomics is the identification of driver genes. Driver genes confer a selective growth advantage to the cell. While several driver genes have been discovered, many remain undiscovered, especially those mutated at a low frequency across samples. This study defines new features and builds a pan-cancer model, cTaG, to identify new driver genes. The features capture the functional impact of the mutations as well as their recurrence across samples, which helps build a model unbiased to genes with low frequency. The model classifies genes into the functional categories of driver genes, tumour suppressor genes (TSGs) and oncogenes (OGs), having distinct mutation type profiles. We overcome overfitting and show that certain mutation types, such as nonsense mutations, are more important for classification. Further, cTaG was employed to identify tissue-specific driver genes. Some known cancer driver genes predicted by cTaG as TSGs with high probability are ARID1A, TP53, and RB1. In addition to these known genes, potential driver genes predicted are CD36, ZNF750 and ARHGAP35 as TSGs and TAB3 as an oncogene. Overall, our approach surmounts the issue of low recall and bias towards genes with high mutation rates and predicts potential new driver genes for further experimental screening. cTaG is available athttps://github.com/RamanLab/cTaG.
Activity of vehicles in the bus rapid transit system Metrobús in Mexico City
Authors: Martínez-González Jaspe U. , Riascos Alejandro P.
Published: January 2022

In this paper, we analyze a massive dataset with registers of the movement of vehicles in the bus rapid transit system Metrobús in Mexico City from February 2020 to April 2021. With these records and a division of the system into 214 geographical regions (segments), we characterize the vehicles’ activity through the statistical analysis of speeds in each zone. We use the Kullback–Leibler distance to compare the movement of vehicles in each segment and its evolution. The results for the dynamics in different zones are represented as a network where nodes define segments of the system Metrobús and edges describe similarity in the activity of vehicles. Community detection algorithms in this network allow the identification of patterns considering different levels of similarity in the distribution of speeds providing a framework for unsupervised classification of the movement of vehicles. The methods developed in this research are general and can be implemented to describe the activity of different transportation systems with detailed records of the movement of users or vehicles.
BIRC2–BIRC3 amplification: a potentially druggable feature of a subset of head and neck cancers in patients with Fanconi anemia
Authors: Roohollahi Khashayar , de Jong Yvonne , Pai Govind , Zaini Mohamad Amr , de Lint Klaas , Sie Daoud , Rooimans Martin A. , Rockx Davy , Hoskins Elizabeth E. , Ameziane Najim , Wolthuis Rob , Joenje Hans , Wells Susanne I. , Dorsman Josephine
Published: January 2022

Head-and-neck squamous cell carcinomas (HNSCCs) are relatively common in patients with Fanconi anemia (FA), a hereditary chromosomal instability disorder. Standard chemo-radiation therapy is not tolerated in FA due to an overall somatic hypersensitivity to such treatment. The question is how to find a suitable alternative treatment. We used whole-exome and whole genome mRNA sequencing to identify major genomic and transcriptomic events associated with FA-HNSCC. CRISPR-engineered FA-knockout models were used to validate a number of top hits that were likely to be druggable. We identified deletion of 18q21.2 and amplification of 11q22.2 as prevailing copy-number alterations in FA HNSCCs, the latter of which was associated with strong overexpression of the cancer-related genes YAP1, BIRC2, BIRC3 (at 11q22.1-2). We then found the drug AZD5582, a known small molecule inhibitor of BIRC2-3, to selectively kill FA tumor cells that overexpressed BIRC2-3. This occurred at drug concentrations that did not affect the viability of untransformed FA cells. Our data indicate that 11q22.2 amplifications are relatively common oncogenic events in FA-HNSCCs, as holds for non FA-HNSCC. Therefore, chemotherapeutic inhibition of overexpressed BIRC2-3 may provide the basis for an approach to develop a clinically realistic treatment of FA-HNSCCs that carry 11q22.2 amplifications.
Objective to identify and verify the regulatory mechanism of DTNBP1 as a prognostic marker for hepatocellular carcinoma
Authors: Cheng Xianyi , Li Dezhi , Qi Tiangyang , Sun Jia , Zhou Tao , Zheng Wei V.
Published: January 2022

Although the overall survival of hepatocellular carcinoma (HCC) patients has been significantly improved, prognostic clinical evaluation remains a substantial problem owing to the heterogeneity and complexity of tumor. A reliable and accurate predictive biomarker may assist physicians in better monitoring of patient treatment outcomes and follow the overall survival of patients. Accumulating evidence has revealed that DTNBP1 plays functional roles in cancer prognosis. Therefore, the expression and function of DTNBP1in HCC was systematically investigated in our study. The expression and prognostic value of DTNBP1 were investigated using the data from Cancer Genome Atlas (TCGA) database, Gene Expression Omnibus (GEO) cohorts and clinical samples. A series of cellular function assays were performed to elucidate the effect of DTNBP1 on cellular proliferation, apoptosis and metastasis. Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment and Protein–protein interaction (PPI) network construction were performed to screen the genes with highest interaction scores with DTNBP1. Finally, the underlying mechanism was also analyzed using Gene Set Enrichment Analysis (GSEA) and confirmed using RT-qPCR and western blotting. DTNBP1 was upregulated in many types of cancers, especially in HCC. The DTNBP1 expression levels is associated with clinicopathologic variables and patient survival status. The differential expression of DTNBP1 could be used to determine the risk stratification of patients with HCC. DTNBP1 deficiency inhibited cell proliferation and metastasis, but promoted cell apoptosis. Mechanistically, DTNBP1 regulated the cell cycle progression through affecting the expression of cell cycle-related genes such as CDC25A, CCNE1, CDK2, CDC20, CDC25B, CCNB1, and CDK1. DTNBP1, which regulates the cell cycle progression, may be used as a prognostic marker for HCC.
Insights into opium poppy (Papaver spp.) genetic diversity from genotyping-by-sequencing analysis
Authors: Hong Uyen Vu Thuy , Tamiru-Oli Muluneh , Hurgobin Bhavna , Okey Christopher R. , Abreu Artur R. , Lewsey Mathew G.
Published: January 2022

Opium poppy (Papaver somniferum) is one of the world’s oldest medicinal plants and a versatile model system to study secondary metabolism. However, our knowledge of its genetic diversity is limited, restricting utilization of the available germplasm for research and crop improvement. We used genotyping-by-sequencing to investigate the extent of genetic diversity and population structure in a collection of poppy germplasm consisting of 91 accessions originating in 30 countries of Europe, North Africa, America, and Asia. We identified five genetically distinct subpopulations using discriminate analysis of principal components and STRUCTURE analysis. Most accessions obtained from the same country were grouped together within subpopulations, likely a consequence of the restriction on movement of poppy germplasm. Alkaloid profiles of accessions were highly diverse, with morphine being dominant. Phylogenetic analysis identified genetic groups that were largely consistent with the subpopulations detected and that could be differentiated broadly based on traits such as number of branches and seed weight. These accessions and the associated genotypic data are valuable resources for further genetic diversity analysis, which could include definition of poppy core sets to facilitate genebank management and use of the diversity for genetic improvement of this valuable crop.
Atypical dependence of excited exciton energy levels and electron-hole correlation on emission energy in pyramidal InP-based quantum dots
Authors: Gawełczyk Michał
Published: January 2022

We calculate the spectrum of excited exciton states in application-relevant self-assembled pyramidal quantum dots grown in InAs/InP and InAs/AlGaInAs material systems. These types of dots have been recently shown to combine the emission in the third optical fiber window with low surface density and a reasonable level of in-plane symmetry of emitters, which predestines them for studies on single- and entangled-photon emission and for corresponding applications. The spectrum of optically active excited states is crucial for successful resonant and quasi-resonant excitation of emitters, allowing for conservation of angular momentum and addressing individual selected quantum states. Here, we show that in both types of studied dots, due to their specific morphology of truncated pyramid, the density of excited-state ladder, especially the s–p shell splitting may follow an unconventional dependence on emission energy, opposite to the one typically met in regular quantum dots. We obtain this result via modeling based on available morphological data and calculation within the multi-band $${{\varvec{k}} {\cdot } {\varvec{p}}}$$

k

·

p

envelope-function theory combined with the configuration-interaction method used to calculate exciton states. Then, we explain this observation in purely geometric terms, as a result of an increasing effective quantum confinement width in a pyramid that is progressively cut from the top. Additionally, we show that the inverted trend is also manifested in the amount of electron-hole correlation in the exciton ground state, which also shows an anomalous dependence on emission energy and quantum dot volume.
PEA-15 engages in allosteric interactions using a common scaffold in a phosphorylation-dependent manner
Authors: Ikedife Joyce , He Jianlin , Wei Yufeng
Published: January 2022

Phosphoprotein enriched in astrocytes, 15 kDa (PEA-15) is a death-effector domain (DED) containing protein involved in regulating mitogen-activated protein kinase and apoptosis pathways. In this molecular dynamics study, we examined how phosphorylation of the PEA-15 C-terminal tail residues, Ser-104 and Ser-116, allosterically mediates conformational changes of the DED and alters the binding specificity from extracellular-regulated kinase (ERK) to Fas-associated death domain (FADD) protein. We delineated that the binding interfaces between the unphosphorylated PEA-15 and ERK2 and between the doubly phosphorylated PEA-15 and FADD are similarly composed of a scaffold that includes both the DED and the C-terminal tail residues of PEA-15. While the unphosphorylated serine residues do not directly interact with ERK2, the phosphorylated Ser-116 engages in strong electrostatic interactions with arginine residues on FADD DED. Upon PEA-15 binding, FADD repositions its death domain (DD) relative to the DED, an essential conformational change to allow the death-inducing signaling complex (DISC) assembly.
High performance silicon electrode enabled by titanicone coating
Authors: Huertas Zahilia Cabán , Settipani Daniel , Flox Cristina , Morante Joan Ramon , Kallio Tanja , Biendicho Jordi Jacas
Published: January 2022

This paper presents the electrochemical performance and characterization of nano Si electrodes coated with titanicone (TiGL) as an anode for Li ion batteries (LIBs). Atomic layer deposition (ALD) of the metal combined with the molecular layer deposition (MLD) of the organic precursor is used to prepare coated electrodes at different temperatures with improved performance compared to the uncoated Si electrode. Coated electrodes prepared at 150 °C deliver the highest capacity and best current response of 1800 mAh g−1 at 0.1 C and 150 mAh g−1 at 20 C. This represented a substantial improvement compared to the Si baseline which delivers a capacity of 1100 mAh g−1 at 0.1 C but fails to deliver capacity at 20 C. Moreover, the optimized coated electrode shows an outstanding capacity of 1200 mAh g−1 at 1 C for 350 cycles with a capacity retention of 93%. The improved discharge capacity, electrode efficiencies, rate capability and electrochemical stability for the Si-based electrode presented in this manuscript are directly correlated to the optimized TiGL coating layer deposited by the ALD/MLD processes, which enhances lithium kinetics and electronic conductivity as demonstrated by equivalent circuit analysis of low frequency impedance data and conductivity measurements. The coating strategy also stabilizes SEI film formation with better Coulombic efficiencies (CE) and improves long cycling stability by reducing capacity lost.
Clinical significance of controlling nutritional status score (CONUT) in evaluating outcome of postoperative patients with gastric cancer
Authors: Xiao Qi , Li Xiaoqing , Duan Baojun , Li Xiaofan , Liu Sida , Xu Boyu , Shi Shuai , Zhang Jin , Qin Haoyuan , Duan Xianglong , Pu Yansong
Published: January 2022

The stomach is the main digestive organ in humans. Patients with gastric cancer often develop digestive problems, which result in poor nutrition. Nutritional status is closely related to postoperative complications and quality of life (QoL) in patients with gastric cancer. The controlling nutritional status (CONUT) score is a novel tool to evaluate the nutritional status of patients. However, the relationship of the CONUT score with postoperative complications, QoL, and psychological status in patients with gastric cancer has not been investigated. The present follow-up study was conducted in 106 patients who underwent radical gastrectomy in our hospital between 2014 and 2019. The CONUT score, postoperative complications, psychological status, postoperative QoL scores, and overall survival (OS) of patients with gastric cancer were collected, and the relationship between them was analyzed. A significant correlation was observed between the CONUT score and postoperative complications of gastric cancer (P < 0.001), especially anastomotic leakage (P = 0.037). The multivariate regression analysis exhibited that the CONUT score (P = 0.002) is an independent risk factor for postoperative complications. The CONUT score was correlated with the state anxiety questionnaire (S-AI) for evaluating psychological status (P = 0.032). However, further regression analysis exhibited that the CONUT score was not an independent risk factor for psychological status. Additionally, the CONUT score was associated with postoperative QoL. The multivariate regression analysis exhibited that the CONUT score was an independent risk factor for the global QoL (P = 0.048). Moreover, the efficiency of CONUT score, prognostic nutrition index, and serum albumin in evaluating complications, psychological status, and QoL was compared, and CONUT score was found to outperform the other measures (Area Under Curve, AUC = 0.7368). Furthermore, patients with high CONUT scores exhibited shorter OS than patients with low CONUT scores (P = 0.005). Additionally, the postoperative complications (HR 0.43, 95% CI 0.21–0.92, P = 0.028), pathological stage (HR 2.26, 95% CI 1.26–4.06, P = 0.006), and global QoL (HR 15.24, 95% CI 3.22–72.06, P = 0.001) were associated with OS. The CONUT score can be used to assess the nutritional status of patients undergoing gastric cancer surgery and is associated with the incidence of postoperative complications and QoL.
Entropy considerations in improved circuits for a biologically-inspired random pulse computer
Authors: Stipčević Mario , Batelić Mateja
Published: January 2022

We present five novel or modified circuits intended for building a universal computer based on random pulse computing (RPC) paradigm, a biologically-inspired way of computation in which variable is represented by a frequency of a random pulse train (RPT) rather than by a logic state. For the first time we investigate operation of RPC circuits from the point of entropy. In particular, we introduce entropy budget criterion (EBC) to reliably predict whether it is even possible to create a deterministic circuit for a given mathematical operation and show its relevance to numerical precision of calculations. Based on insights gained from the EBC, unlike in the previous art, where randomness is obtained from electronics noise or a pseudorandom shift register while processing circuitry is deterministic, in our approach both variable generation and signal processing rely on the random flip-flop (RFF) whose randomness is derived from a fundamentally random quantum process. This approach offers an advantage in higher precision, better randomness of the output and conceptual simplicity of circuits.
New support roller profile design for railway wheel re-profiling process by under-floor lathes with a single cutting tool
Authors: Corral Eduardo , Meneses Jesús , Gómez García M. J. , Castejón Cristina , García-Prada Juan Carlos
Published: January 2022

The wheel re-profiling is an important part of railway wheelset maintenance. Researchers and railway operators have been very concerned about how to minimize the loss of time during wheel re-profiling without decreasing safety. Avoiding wheelset disassembly means considerable time savings, while reducing wheel damage during operation. Underfloor wheel lathes are the most appropriate tool to achieve this double objective, and therefore the most used nowadays. Multi-cut tool lathes have the disadvantage of being extremely expensive. On the other hand, with single tool lathes, re-profiling is not smooth or safe enough when current convex profile support rollers are used. It is well known by the companies that during reprofiling the wheel suffers impacts/damaged. In this article, a methodology to optimize the profile of the support rollers used in underfloor single tool lathes for railway wheel re-profiling is proposed. This novel profile design will minimize damage and increase the safety of such lathes, since it proposes a greater smoothness in the process. Simulations of re-profiling process have been carried out by the finite element method showing that the designed roller profile reduces drastically the impact/damage during the operation. The impact generated between the re-profiling wheel and the rollers is avoided. Profile-optimized support rollers have been used in a real underfloor wheel lathe, showing good results.
Comparative accuracy of cervical cancer screening strategies in healthy asymptomatic women: a systematic review and network meta-analysis
Authors: Terasawa Teruhiko , Hosono Satoyo , Sasaki Seiju , Hoshi Keika , Hamashima Yuri , Katayama Takafumi , Hamashima Chisato
Published: January 2022

To compare all available accuracy data on screening strategies for identifying cervical intraepithelial neoplasia grade ≥ 2 in healthy asymptomatic women, we performed a systematic review and network meta-analysis. MEDLINE and EMBASE were searched up to October 2020 for paired-design studies of cytology and testing for high-risk genotypes of human papillomavirus (hrHPV). The methods used included a duplicate assessment of eligibility, double extraction of quantitative data, validity assessment, random-effects network meta-analysis of test accuracy, and GRADE rating. Twenty-seven prospective studies (185,269 subjects) were included. The combination of cytology (atypical squamous cells of undetermined significance or higher grades) and hrHPV testing (excepting genotyping for HPV 16 or 18 [HPV16/18]) with the either-positive criterion (OR rule) was the most sensitive/least specific, whereas the same combination with the both-positive criterion (AND rule) was the most specific/least sensitive. Compared with standalone cytology, non-HPV16/18 hrHPV assays were more sensitive/less specific. Two algorithms proposed for primary cytological testing or primary hrHPV testing were ranked in the middle as more sensitive/less specific than standalone cytology and the AND rule combinations but more specific/less sensitive than standalone hrHPV testing and the OR rule combination. Further research is needed to assess these results in population-relevant outcomes at the program level.
Electronic structure and thermal conductance of the MASnI3/Bi2Te3 interface: a first-principles study
Authors: Morimoto Masayuki , Kawano Shoya , Miyamoto Shotaro , Miyazaki Koji , Hayase Shuzi , Iikubo Satoshi
Published: January 2022

To develop high-performance thermoelectric devices that can be created using printing technology, the interface of a composite material composed of MASnI3 and Bi2Te3, which individually show excellent thermoelectric performance, was studied based on first-principles calculations. The structural stability, electronic state, and interfacial thermal conductance of the interface between Bi2Te3 and MASnI3 were evaluated. Among the interface structure models, we found stable interface structures and revealed their specific electronic states. Around the Fermi energy, the interface structures with TeII and Bi terminations exhibited interface levels attributed to the overlapping electron densities for Bi2Te3 and MASnI3 at the interface. Calculation of the interfacial thermal conductance using the diffuse mismatch model suggested that construction of the interface between Bi2Te3 and MASnI3 could reduce the thermal conductivity. The obtained value was similar to the experimental value for the inorganic/organic interface.
Colonoscopic image synthesis with generative adversarial network for enhanced detection of sessile serrated lesions using convolutional neural network
Authors: Yoon Dan , Kong Hyoun-Joong , Kim Byeong Soo , Cho Woo Sang , Lee Jung Chan , Cho Minwoo , Lim Min Hyuk , Yang Sun Young , Lim Seon Hee , Lee Jooyoung , Song Ji Hyun , Chung Goh Eun , Choi Ji Min , Kang Hae Yeon , Bae Jung Ho , Kim Sungwan
Published: January 2022

Computer-aided detection (CADe) systems have been actively researched for polyp detection in colonoscopy. To be an effective system, it is important to detect additional polyps that may be easily missed by endoscopists. Sessile serrated lesions (SSLs) are a precursor to colorectal cancer with a relatively higher miss rate, owing to their flat and subtle morphology. Colonoscopy CADe systems could help endoscopists; however, the current systems exhibit a very low performance for detecting SSLs. We propose a polyp detection system that reflects the morphological characteristics of SSLs to detect unrecognized or easily missed polyps. To develop a well-trained system with imbalanced polyp data, a generative adversarial network (GAN) was used to synthesize high-resolution whole endoscopic images, including SSL. Quantitative and qualitative evaluations on GAN-synthesized images ensure that synthetic images are realistic and include SSL endoscopic features. Moreover, traditional augmentation methods were used to compare the efficacy of the GAN augmentation method. The CADe system augmented with GAN synthesized images showed a 17.5% improvement in sensitivity on SSLs. Consequently, we verified the potential of the GAN to synthesize high-resolution images with endoscopic features and the proposed system was found to be effective in detecting easily missed polyps during a colonoscopy.