bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of Model Accuracy in Eyes Open and Closed EEG Data: Effect of Data Pre-Processing and Validation Methods
Authors: Mattiev Jamolbek , Sajovic Jakob , Drevenšek Gorazd , Rogelj Peter
Published: December 2022

Eyes open and eyes closed data is often used to validate novel human brain activity classification methods. The cross-validation of models trained on minimally preprocessed data is frequently utilized, regardless of electroencephalography data comprised of data resulting from muscle activity and environmental noise, affecting classification accuracy. Moreover, electroencephalography data of a single subject is often divided into smaller parts, due to limited availability of large datasets. The most frequently used method for model validation is cross-validation, even though the results may be affected by overfitting to the specifics of brain activity of limited subjects. To test the effects of preprocessing and classifier validation on classification accuracy, we tested fourteen classification algorithms implemented in WEKA and MATLAB, tested on comprehensively and simply preprocessed electroencephalography data. Hold-out and cross-validation were used to compare the classification accuracy of eyes open and closed data. The data of 50 subjects, with four minutes of data with eyes closed and open each was used. The algorithms trained on simply preprocessed data were superior to the ones trained on comprehensively preprocessed data in cross-validation testing. The reverse was true when hold-out accuracy was examined. Significant increases in hold-out accuracy were observed if the data of different subjects was not strictly separated between the test and training datasets, showing the presence of overfitting. The results show that comprehensive data preprocessing can be advantageous for subject invariant classification, while higher subject-specific accuracy can be attained with simple preprocessing. Researchers should thus state the final intended use of their classifier.
Influence of Graphene Nanoplatelets on the Performance of Axial Suspension Plasma-Sprayed Hydroxyapatite Coatings
Authors: Khan Pearlin Amaan , Thoutam Aravind Kumar , Gopal Vasanth , Gurumallesh Aswin , Joshi Shrikant , Palaniappan Arunkumar , Markocsan Nicolaie , Manivasagam Geetha
Published: December 2022

Axial suspension plasma spraying (ASPS) is an alternative technique to atmospheric plasma spraying (APS), which uses a suspension of much finer powders (<5-micron particle size) as the feedstock. It can produce more refined microstructures than APS for biomedical implants. This paper highlights the influence of incorporated graphene nanoplatelets (GNPs) on the behavior of ASPS hydroxyapatite (HAp) coatings. The characterization of the ASPS coatings (HAp + varying GNP contents) was carried out using scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), confocal Raman microscopy (CRM), white light interferometry (WLI), and contact angle measurements. The evaluation of the mechanical properties such as the hardness, roughness, adhesion strength, and porosity was carried out, along with a fretting wear performance. Additionally, the biocompatibility of the Hap + GNP coatings was evaluated using cytotoxicity testing which revealed a decrease in the cell viability from 92.7% to 85.4%, with an increase in the GNP wt.%. The visualization of the cell’s components was carried out using SEM and Laser Scanning Microscopy. Furthermore, the changes in the genetic expression of the various cellular markers were assessed to analyze the epigenetic changes in human mesenchymal stem cells. The gene expression changes suggested that GNPs upregulated the proliferation marker and downregulated the pluripotent markers by a minimum of three folds.
An Optimal Approach for Heart Sound Classification Using Grid Search in Hyperparameter Optimization of Machine Learning
Authors: Fuadah Yunendah Nur , Pramudito Muhammad Adnan , Lim Ki Moo
Published: December 2022

Heart-sound auscultation is one of the most widely used approaches for detecting cardiovascular disorders. Diagnosing abnormalities of heart sound using a stethoscope depends on the physician’s skill and judgment. Several studies have shown promising results in automatically detecting cardiovascular disorders based on heart-sound signals. However, the accuracy performance needs to be enhanced as automated heart-sound classification aids in the early detection and prevention of the dangerous effects of cardiovascular problems. In this study, an optimal heart-sound classification method based on machine learning technologies for cardiovascular disease prediction is performed. It consists of three steps: pre-processing that sets the 5 s duration of the PhysioNet Challenge 2016 and 2022 datasets, feature extraction using Mel frequency cepstrum coefficients (MFCC), and classification using grid search for hyperparameter tuning of several classifier algorithms including k-nearest neighbor (K-NN), random forest (RF), artificial neural network (ANN), and support vector machine (SVM). The five-fold cross-validation was used to evaluate the performance of the proposed method. The best model obtained classification accuracy of 95.78% and 76.31%, which was assessed using PhysioNet Challenge 2016 and 2022, respectively. The findings demonstrate that the suggested approach obtained excellent classification results using PhysioNet Challenge 2016 and showed promising results using PhysioNet Challenge 2022. Therefore, the proposed method has been potentially developed as an additional tool to facilitate the medical practitioner in diagnosing the abnormality of the heart sound.
Automatic Segmentation of Cervical Cells Based on Star-Convex Polygons in Pap Smear Images
Authors: Zhao Yanli , Fu Chong , Zhang Wenchao , Ye Chen , Wang Zhixiao , Ma Hong-feng
Published: December 2022

Cervical cancer is one of the most common cancers that threaten women’s lives, and its early screening is of great significance for the prevention and treatment of cervical diseases. Pathologically, the accurate segmentation of cervical cells plays a crucial role in the diagnosis of cervical cancer. However, the frequent presence of adherent or overlapping cervical cells in Pap smear images makes separating them individually a difficult task. Currently, there are few studies on the segmentation of adherent cervical cells, and the existing methods commonly suffer from low segmentation accuracy and complex design processes. To address the above problems, we propose a novel star-convex polygon-based convolutional neural network with an encoder-decoder structure, called SPCNet. The model accomplishes the segmentation of adherent cells relying on three steps: automatic feature extraction, star-convex polygon detection, and non-maximal suppression (NMS). Concretely, a new residual-based attentional embedding (RAE) block is suggested for image feature extraction. It fuses the deep features from the attention-based convolutional layers with the shallow features from the original image through the residual connection, enhancing the network’s ability to extract the abundant image features. And then, a polygon-based adaptive NMS (PA-NMS) algorithm is adopted to screen the generated polygon proposals and further achieve the accurate detection of adherent cells, thus allowing the network to completely segment the cell instances in Pap smear images. Finally, the effectiveness of our method is evaluated on three independent datasets. Extensive experimental results demonstrate that the method obtains superior segmentation performance compared to other well-established algorithms.
Potential Inhibitors of SARS-CoV-2 Main Protease (Mpro) Identified from the Library of FDA-Approved Drugs Using Molecular Docking Studies
Authors: Verma Dipesh Kumar , Kapoor Srajan , Das Satyajeet , Thakur Krishan Gopal
Published: December 2022

The Corona Virus Infectious Disease-2019 (COVID-19) outbreak originated at Wuhan, China, in December 2019. It has already spread rapidly and caused more than 6.5 million deaths worldwide. Its causal agent is a beta-coronavirus named SARS-CoV-2. Many efforts have already been made to develop new vaccines and drugs against these viruses, but over time, it has changed its molecular nature and evolved into more lethal variants, such as Delta and Omicron. These will lead us to target its more-conserved proteins. The sequences’ BLAST and crystal structure of the main protease Mpro suggest a high sequence and structural conservation. Mpro is responsible for the proteolytic maturation of the polyprotein essential for the viral replication and transcription, which makes it an important drug target. Discovery of new drug molecules may take years before getting to the clinics. So, considering urgency, we performed molecular docking studies using FDA-approved drugs to identify molecules that could potentially bind to the substrate-binding site and inhibit SARS-CoV-2’s main protease (Mpro). We used the Glide module in the Schrödinger software suite to perform molecular docking studies, followed by MM-GBSA-based energy calculations to score the hit molecules. Molecular docking and manual analysis suggest that several drugs may bind and potentially inhibit Mpro. We also performed molecular simulations studies for selected compounds to evaluate protein–drug interactions. Considering bioavailability, lesser toxicity, and route of administration, some of the top-ranked drugs, including lumefantrine (antimalarial), dipyridamole (coronary vasodilator), dihydroergotamine (used for treating migraine), hexoprenaline (anti asthmatic), riboflavin (vitamin B2), and pantethine (vitamin B5) may be taken forward for further in vitro and in vivo experiments to investigate their therapeutic potential.
A Novel TLR4-SYK Interaction Axis Plays an Essential Role in the Innate Immunity Response in Bovine Mammary Epithelial Cells
Authors: Yang Fan , Yuan Lu , Xiang Minghui , Jiang Qiang , Zhang Manling , Chen Fanghui , Tong Jie , Huang Jinming , Cai Yafei
Published: December 2022

Mammary gland epithelium, as the first line of defense for bovine mammary gland immunity, is crucial in the process of mammary glands’ innate immunity, especially that of bovine mammary epithelial cells (bMECs). Our previous studies successfully marked SYK as an important candidate gene for mastitis traits via GWAS and preliminarily confirmed that SYK expression is down-regulated in bMECs with LPS (E. coli) stimulation, but its work mechanism is still unclear. In this study, for the first time, in vivo, TLR4 and SYK were colocalized and had a high correlation in mastitis mammary epithelium; protein–protein interaction results also confirmed that there was a direct interaction between them in mastitis tissue, suggesting that SYK participates in the immune regulation of the TLR4 cascade for bovine mastitis. In vitro, TLR4 also interacts with SYK in LPS (E. coli)-stimulated or GBS (S. agalactiae)-infected bMECs, respectively. Moreover, TLR4 mRNA expression and protein levels were little affected in bMECsSYK- with LPS stimulation or GBS infection, indicating that SYK is an important downstream element of the TLR4 cascade in bMECs. Interestingly, IL-1β, IL-8, NF-κB and NLRP3 expression in LPS-stimulated or GBS-infected bMECsSYK- were significantly higher than in the control group, while AKT1 expression was down-regulated, implying that SYK could inhibit the IL-1β, IL-8, NF-κB and NLRP3 expression and alleviate inflammation in bMECs with LPS and GBS. Taken together, our solid evidence supports that TLR4/SYK/NF-κB signal axis in bMECs regulates the innate immunity response to LPS or GBS.
Biomonitoring Exposure and Early Diagnosis in Silicosis: A Comprehensive Review of the Current Literature
Authors: Căluțu Iulia-Maria , Smărăndescu Raluca-Andreea , Rașcu Agripina
Published: December 2022

Silicosis is a particular form of lung fibrosis attributable to occupational exposure to crystalline silica. The occupational exposure to crystalline silica also increases the risk of chronic obstructive pulmonary disease (COPD), cancer and lung infections, especially pulmonary tuberculosis. Silicosis is currently diagnosed in previously exposed workers by standard chest X-ray, when lesions are visible and irreversible. Therefore, it would be necessary to find specific and non-invasive markers that could detect silicosis in earlier stages, before the occurrence of X-ray opacities. In this narrative review, we present several diagnostic, monitoring and predictive biomarkers with high potential in the management of silicosis, such as: pro- and anti-inflammatory cytokines (TNF (Tumour necrosis factor-α), IL-1 (Interleukin-1), IL-6, IL-10), CC16 (Clara cell 16, an indirect marker of epithelial cell destruction), KL-6 (Krebs von den Lungen 6, an indirect marker of alveolar epithelial damage), neopterin (indicator of cellular immunity) and MUC5B gene (Mucin 5B, a gel-forming mucin in mucus). Studies have shown that all the aforementioned markers have a high potential for early diagnosis or evaluation of progression in silicosis and represent promising alternatives to radiology. We consider that a multicentric study is needed to evaluate these biomarkers in correlation with occupational history, histopathological examination, imaging signs and pulmonary functions tests on large groups of subjects to better evaluate the accuracy of the presented biomarkers.
Dissociating Language and Thought in Human Reasoning
Authors: Coetzee John P. , Johnson Micah A. , Lee Youngzie , Wu Allan D. , Iacoboni Marco , Monti Martin M.
Published: December 2022

What is the relationship between language and complex thought? In the context of deductive reasoning there are two main views. Under the first, which we label here the language-centric view, language is central to the syntax-like combinatorial operations of complex reasoning. Under the second, which we label here the language-independent view, these operations are dissociable from the mechanisms of natural language. We applied continuous theta burst stimulation (cTBS), a form of noninvasive neuromodulation, to healthy adult participants to transiently inhibit a subregion of Broca’s area (left BA44) associated in prior work with parsing the syntactic relations of natural language. We similarly inhibited a subregion of dorsomedial frontal cortex (left medial BA8) which has been associated with core features of logical reasoning. There was a significant interaction between task and stimulation site. Post hoc tests revealed that performance on a linguistic reasoning task, but not deductive reasoning task, was significantly impaired after inhibition of left BA44, and performance on a deductive reasoning task, but not linguistic reasoning task, was decreased after inhibition of left medial BA8 (however not significantly). Subsequent linear contrasts supported this pattern. These novel results suggest that deductive reasoning may be dissociable from linguistic processes in the adult human brain, consistent with the language-independent view.
Subthalamic Nucleus Deep Brain Stimulation Treats Parkinson’s Disease Patients with Cardiovascular Disease Comorbidity: A Retrospective Study of a Single Center Experience
Authors: Zhang Changming , Xu Jiakun , Wu Bin , Ling Yuting , Guo Qianqian , Wang Simin , Liu Lige , Jiang Nan , Chen Ling , Liu Jinlong
Published: December 2022

Background: Subthalamic nucleus (STN) deep brain stimulation (DBS) is an effective method for treating Parkinson’s disease (PD). However, safety of STN-DBS treating PD patients with cardiovascular disease (CVD) comorbidity is rarely focused and reported. The aim of this study is to investigate the efficacy and safety of STN-DBS treating PD patients with CVD comorbidity. Methods: We retrospectively included PD patients with CVD comorbidity who underwent STN-DBS under general anesthesia in our center from January 2019 to January 2021. Patient’s PD symptoms and cardiopulmonary function were evaluated by a multi-disciplinary team (MDT) before surgery. Post-operative clinical outcome and complications were collected until 1-year follow-up. Results: A total of 38 patients (26 men/12 women) of mean body mass index (BMI) 24.36 ± 3.11 kg/m2, with different CVD comorbidity were finally speculated in the study. These CVD include mainly hypertension, coronary artery disease, thoracic aortic aneurysm, heart valve replacement, pacemaker implantation, atrial fibrillation, patent foramen ovale, and so on. The mean systolic blood pressure (SBP) of 38 patients at admission day, pre-operation day, and discharge day timepoint was 135.63 ± 18.08 mmHg, 137.66 ± 12.26 mmHg, and 126.87 ± 13.36 mmHg, respectively. This showed that blood pressure was controlled well under stable and normal state. The indicators of myocardial infarction Troponin T (Tn T-T) levels at pre-operation, 1 day and 7 days after operation timepoint were 0.014 ± 0.011 ng/mL, 0.015 ± 0.011 ng/mL, and 0.014 ± 0.008 ng/mL, showing no significant fluctuation (F = 0.038, p = 0.962). STN-DBS improved PD patients’ UPDRS III scores by 51.38% (t = 12.33, p < 0.0001) at 1-year follow-up compared with pre-operative baseline. A total of 11 adverse events were recorded until 1-year follow-up. No obvious cardiovascular complications such as intracranial hematoma or clot-related events occurred within 1 year after surgery except 1 case of hematuria. Conclusions: STN-DBS under general anesthesia is safe and effective for treating PD patients with CVD comorbidity. Our clinical experience and protocol of the MDT offers comprehensive perioperative evaluation for DBS surgery and mitigates bleeding and cardiovascular-associated events in PD patients with CVD comorbidity.
Subthreshold Oscillating Waves in Neural Tissue Propagate by Volume Conduction and Generate Interference
Authors: Chiang Chia-Chu , Durand Dominique M.
Published: December 2022

Subthreshold neural oscillations have been observed in several brain regions and can influence the timing of neural spikes. However, the spatial extent and function of these spontaneous oscillations remain unclear. To study the mechanisms underlying these oscillations, we use optogenetic stimulation to generate oscillating waves in the longitudinal hippocampal slice expressing optopatch proteins. We found that optogenetic stimulation can generate two types of neural activity: suprathreshold neural spikes and subthreshold oscillating waves. Both waves could propagate bidirectionally at similar speeds and go through a transection of the tissue. The propagating speed is independent of the oscillating frequency but increases with increasing amplitudes of the waves. The endogenous electric fields generated by oscillating waves are about 0.6 mV/mm along the dendrites and about 0.3 mV/mm along the cell layer. We also observed that these oscillating waves could interfere with each other. Optical stimulation applied simultaneously at each slice end generated a larger wave in the middle of the tissue (constructive interference) or destructive interference with laser signals in opposite phase. However, the suprathreshold neural spikes were annihilated when they collided. Finally, the waves were not affected by the NMDA blocker (APV) and still propagated in the presence of tetrodotoxin (TTX) but at a significantly lower amplitude. The role of these subthreshold waves in neural function is unknown, but the results show that at low amplitude, the subthreshold propagating waves lack a refractory period allowing a novel analog form of preprocessing of neural activity by interference independent of synaptic transmission.
Multi-Omics Analyses Identify Signatures in Patients with Liver Cirrhosis and Hepatocellular Carcinoma
Authors: Lai Ming-Wei , Chu Yu-De , Hsu Chao-Wei , Chen Yi-Cheng , Liang Kung-Hao , Yeh Chau-Ting
Published: December 2022

Gut bacterial/viral dysbiosis, changes in circulating metabolites, and plasma cytokines/chemokines have been previously associated with various liver diseases. Here, we analyzed the associations between fecal microbial composition, circulating metabolites, and plasma cytokines/chemokines in patients with liver cirrhosis (LC) and hepatocellular carcinoma (HCC). We recruited 10 HCC patients, 18 LC patients, and 17 healthy individuals. Their stool samples were used for gene sequencing of bacterial 16S rRNA and viral genomes, while plasma samples were utilized for the determination of endotoxin, zonulin, metabolite, and cytokine/chemokine levels. Dysbiosis was observed among gut bacteria and viruses, with significant changes in abundance at the genus and species levels, respectively. However, no differences were found between cohorts in the alpha and beta diversity. Plasma lipopolysaccharides and zonulin, but not trimethylamine N-oxide, were progressively increased in LC and HCC subjects. Profiling plasma metabolites and selected cytokines/chemokines revealed differential changes in the LC and HCC cohorts. Following joint correlation and correlation network analyses, regardless of etiology, common network signatures shared by LC and HCC patients were characterized by the gut virus Stenotrophomonas virus DLP5 and the uncultured Caudovirales phage, plasma metabolites pyruvic acid and acetic acid, and plasma cytokines/chemokines eotaxin and PDGF-AB/BB, respectively. Additionally, LC- and HCC-specific correlation networks were also identified. This study provides novel insights into altered gut microbial/viral composition that may contribute to pre-HCC disorders, metabolic reprogramming, or inflammatory microenvironments for hepatocarcinogenesis.
Radiotherapeutic Strategies to Overcome Resistance of Breast Cancer Brain Metastases by Considering Immunogenic Aspects of Cancer Stem Cells
Authors: Hintelmann Katharina , Petersen Cordula , Borgmann Kerstin
Published: December 2022

Breast cancer is the most diagnosed cancer in women, and symptomatic brain metastases (BCBMs) occur in 15–20% of metastatic breast cancer cases. Despite technological advances in radiation therapy (RT), the prognosis of patients is limited. This has been attributed to radioresistant breast cancer stem cells (BCSCs), among other factors. The aim of this review article is to summarize the evidence of cancer-stem-cell-mediated radioresistance in brain metastases of breast cancer from radiobiologic and radiation oncologic perspectives to allow for the better interpretability of preclinical and clinical evidence and to facilitate its translation into new therapeutic strategies. To this end, the etiology of brain metastasis in breast cancer, its radiotherapeutic treatment options, resistance mechanisms in BCSCs, and effects of molecularly targeted therapies in combination with radiotherapy involving immune checkpoint inhibitors are described and classified. This is considered in the context of the central nervous system (CNS) as a particular metastatic niche involving the blood–brain barrier and the CNS immune system. The compilation of this existing knowledge serves to identify possible synergistic effects between systemic molecularly targeted therapies and ionizing radiation (IR) by considering both BCSCs’ relevant resistance mechanisms and effects on normal tissue of the CNS.
Implementation of Comprehensive Genomic Profiling in Ovarian Cancer Patients: A Retrospective Analysis
Authors: Peleg Hasson Shira , Hershkovitz Dov , Adar Lyri , Brezis Miriam , Shachar Eliya , Aks Rona , Galmor Lee , Raviv Yuval , Ben Neriah Shira , Merimsky Ofer , Sabo Edmond , Wolf Ido , Safra Tamar
Published: December 2022

Comprehensive genomic profiling (CGP) allows for the detection of driver alterations at high resolution, but the limited number of approved targeted therapies and their high costs have contributed to its limited clinical utilization. We retrospectively compared data of 946 women with ovarian cancer (11.4% were referred to CGP, and 88.6% served as control) to examine whether CGP provides a prognosis benefit. Patient baseline parameters were similar between the groups. Cox regression analysis adjusted for age, disease stage at diagnosis, and recurrence status showed statistically significantly longer median overall survival (mOS) in the CGP group versus the control (73.4 versus 54.5 months, p < 0.001). Fifty-four patients (52.9%) had actionable mutations with potential treatments; twenty-six (48.2%) were treated with matched targeted therapy, showing a trend for longer mOS than the eighty-six women in the CGP group who were not given a suggested treatment (105.5 versus 63.6 months, p = 0.066). None of the genomic alterations predicted metastasis location. CCNE1 amplification and KRAS mutations were associated with shorter mOS. Patients with tumor mutation burden ≥4 mutations/megabase had longer mOS. High loss of heterozygosity was associated with longer mOS (99.0 versus 48.2 months, p = 0.004). CGP testing may provide both prognostic and predictive insights for treatment of patients with ovarian cancer. Prospective studies of larger cohorts are warranted.
Controversies in the Front-Line Treatment of Systemic Peripheral T Cell Lymphomas
Authors: Sorigue Marc , Kuittinen Outi
Published: December 2022

Systemic peripheral T cell lymphomas (PTCL) are a rare and clinically and biologically heterogeneous group of disorders with scarce and generally low-quality evidence guiding their management. In this manuscript, we tackle the current controversies in the front-line treatment of systemic PTCL including (1) whether CNS prophylaxis should be administered; (2) whether CHOEP should be preferred over CHOP; (3) what role brentuximab vedotin should have; (4) whether stem cell transplant (SCT) consolidation should be used and whether autologous or allogeneic; (5) how should molecular subtypes (including DUSP22 or TP63-rearranged ALCL or GATA3 or TBX21 PTCL, NOS) impact therapeutic decisions; and (6) whether there is a role for targeted agents beyond brentuximab vedotin.
In-Hospital Mortality and Morbidity in Cancer Patients with COVID-19: A Nationwide Analysis from the United States
Authors: Abuhelwa Ziad , Alsughayer Anas , Abuhelwa Ahmad Y. , Beran Azizullah , Sayeh Wasef , Khokher Waleed , Sajdeya Omar , Khuder Sadik , Assaly Ragheb
Published: December 2022

Background: Coronavirus disease 2019 (COVID-19) caused significant mortality and mortality worldwide. There is limited information describing the outcomes of COVID-19 in cancer patients. Methods: We utilized the Healthcare Cost and Utilization Project Nationwide Inpatient Sample (NIS) 2020 database to collect information on cancer patients hospitalized for COVID-19 in the United States. Using the International Classification of Diseases, 10th revision, Clinical Modification (ICD-10-CM) coding system, adult (≥18 years) patients with COVID-19 were identified. Adjusted analyses were performed to assess for mortality, morbidity, and resource utilization among cancer patients. Results: A total of 1,050,045 patients were included. Of them, 27,760 had underlying cancer. Cancer patients were older and had more comorbidities. The all-cause in-hospital mortality rate in cancer patients was 17.58% vs. 11% in non-cancer. After adjusted logistic regression, cancer patients had a 21% increase in the odds of all-cause in-hospital mortality compared with those without cancer (adjusted odds ratio (aOR) 1.21, 95%CI 1.12–1.31, p-value < 0.001). Additionally, an increased odds in acute respiratory failure rate was found (aOR 1.14, 95%CI 1.06–1.22, p-value < 0.001). However, no significant differences were found in the odds of septic shock, acute respiratory distress syndrome, and mechanical ventilation between the two groups. Additionally, no significant differences in the mean length of hospital stay and the total hospitalization charges between cancer and non-cancer patients. Conclusion: Cancer patients hospitalized for COVID-19 had increased odds of all-cause in hospital mortality and acute respiratory failure compared with non-cancer patients.
Outcome for Pediatric Adreno-Cortical Tumors Is Best Predicted by the COG Stage and Five-Item Microscopic Score—Report from the German MET Studies
Authors: Kuhlen Michaela , Kunstreich Marina , Wudy Stefan A. , Holterhus Paul-Martin , Lessel Lienhard , Schneider Dominik T. , Brecht Ines B. , Schewe Denis M. , Seitz Guido , Roecken Christoph , Vokuhl Christian , Johann Pascal D. , Frühwald Michael C. , Vorwerk Peter , Redlich Antje
Published: December 2022

Background: Adrenocortical tumors (ACTs) encompassing the adrenocortical adenoma (ACA), carcinoma (ACC), and tumors of undetermined malignant potential (ACx) are rare endocrine neoplasms with a poor prognosis. We report on pediatric ACT patients registered with the Malignant Endocrine Tumor studies and explore the EXPeRT recommendations for management. Patients: Data from the ACT patients (<18 years) were analyzed. For the risk prediction, the patients were retrospectively assigned to the COG stages and the five-item score. Results: By December 2021, 161 patients with ACT (ACA n = 51, ACx n = 19, and ACC n = 91) had been reported (the median age at the diagnosis was 4.3 years with a range of 0.1–17.8), with lymph node and distant metastases in 10.7% and 18.9% of the patients with ACC/ACx. The mean follow-up was 4.5 years (with a range of 0–16.7). The three-year overall (OS) and event-free survival (EFS) rates were 65.5% and 50.6%. In the univariate analyses, the OS was impaired for patients aged ≥ 4 years (p = 0.001) with the initial biopsy (p = 0.016), tumor spillage (p = 0.028), incomplete tumor resection (p < 0.001), unfavorable histology (p = 0.047), and COG stages III/IV (p = 0.002). Multivariate analysis revealed COG stages III/IV and an unfavorable five-item score as independent negative prognostic factors for the EFS and OS. Conclusions: Age defines the clinical presentation and prognosis in pediatric ACTs. The outcome is best predicted by the COG stage and five-item score.
Deep Learning-Based Screening of Urothelial Carcinoma in Whole Slide Images of Liquid-Based Cytology Urine Specimens
Authors: Tsuneki Masayuki , Abe Makoto , Kanavati Fahdi
Published: December 2022

Urinary cytology is a useful, essential diagnostic method in routine urological clinical practice. Liquid-based cytology (LBC) for urothelial carcinoma screening is commonly used in the routine clinical cytodiagnosis because of its high cellular yields. Since conventional screening processes by cytoscreeners and cytopathologists using microscopes is limited in terms of human resources, it is important to integrate new deep learning methods that can automatically and rapidly diagnose a large amount of specimens without delay. The goal of this study was to investigate the use of deep learning models for the classification of urine LBC whole-slide images (WSIs) into neoplastic and non-neoplastic (negative). We trained deep learning models using 786 WSIs by transfer learning, fully supervised, and weakly supervised learning approaches. We evaluated the trained models on two test sets, one of which was representative of the clinical distribution of neoplastic cases, with a combined total of 750 WSIs, achieving an area under the curve for diagnosis in the range of 0.984–0.990 by the best model, demonstrating the promising potential use of our model for aiding urine cytodiagnostic processes.
Large Cancer Pedigree Involving Multiple Cancer Genes including Likely Digenic MSH2 and MSH6 Lynch Syndrome (LS) and an Instance of Recombinational Rescue from LS
Authors: Vogelaar Ingrid P. , Greer Stephanie , Wang Fan , Shin GiWon , Lau Billy , Hu Yajing , Haraldsdottir Sigurdis , Alvarez Rocio , Hazelett Dennis , Nguyen Peter , Aguirre Francesca P. , Guindi Maha , Hendifar Andrew , Balcom Jessica , Leininger Anna , Fairbank Beth , Ji Hanlee , Hitchins Megan P.
Published: December 2022

Lynch syndrome (LS), caused by heterozygous pathogenic variants affecting one of the mismatch repair (MMR) genes (MSH2, MLH1, MSH6, PMS2), confers moderate to high risks for colorectal, endometrial, and other cancers. We describe a four-generation, 13-branched pedigree in which multiple LS branches carry the MSH2 pathogenic variant c.2006G>T (p.Gly669Val), one branch has this and an additional novel MSH6 variant c.3936_4001+8dup (intronic), and other non-LS branches carry variants within other cancer-relevant genes (NBN, MC1R, PTPRJ). Both MSH2 c.2006G>T and MSH6 c.3936_4001+8dup caused aberrant RNA splicing in carriers, including out-of-frame exon-skipping, providing functional evidence of their pathogenicity. MSH2 and MSH6 are co-located on Chr2p21, but the two variants segregated independently (mapped in trans) within the digenic branch, with carriers of either or both variants. Thus, MSH2 c.2006G>T and MSH6 c.3936_4001+8dup independently confer LS with differing cancer risks among family members in the same branch. Carriers of both variants have near 100% risk of transmitting either one to offspring. Nevertheless, a female carrier of both variants did not transmit either to one son, due to a germline recombination within the intervening region. Genetic diagnosis, risk stratification, and counseling for cancer and inheritance were highly individualized in this family. The finding of multiple cancer-associated variants in this pedigree illustrates a need to consider offering multicancer gene panel testing, as opposed to targeted cascade testing, as additional cancer variants may be uncovered in relatives.
The Male Mouse Meiotic Cilium Emanates from the Mother Centriole at Zygotene Prior to Centrosome Duplication
Authors: López-Jiménez Pablo , Pérez-Martín Sara , Hidalgo Inés , García-Gonzalo Francesc R. , Page Jesús , Gómez Rocio
Published: December 2022

Cilia are hair-like projections of the plasma membrane with an inner microtubule skeleton known as axoneme. Motile cilia and flagella beat to displace extracellular fluids, playing important roles in the airways and reproductive system. On the contrary, primary cilia function as cell-type-dependent sensory organelles, detecting chemical, mechanical, or optical signals from the extracellular environment. Cilia dysfunction is associated with genetic diseases called ciliopathies and with some types of cancer. Cilia have been recently identified in zebrafish gametogenesis as an important regulator of bouquet conformation and recombination. However, there is little information about the structure and functions of cilia in mammalian meiosis. Here we describe the presence of cilia in male mouse meiotic cells. These solitary cilia formed transiently in 20% of zygotene spermatocytes and reached considerable lengths (up to 15–23 µm). CEP164 and CETN3 localization studies indicated that these cilia emanate from the mother centriole prior to centrosome duplication. In addition, the study of telomeric TFR2 suggested that cilia are not directly related to the bouquet conformation during early male mouse meiosis. Instead, based on TEX14 labeling of intercellular bridges in spermatocyte cysts, we suggest that mouse meiotic cilia may have sensory roles affecting cyst function during prophase I.
Rotational Guided Growth: A Preliminary Study of Its Use in Children
Authors: Paley Dror , Shannon Claire
Published: December 2022

Torsional malalignment of the legs is common in children, and those that do not remodel may benefit from surgical correction. Traditionally, this is corrected with an open osteotomy. Guided growth is the gold standard for minimally invasive angular correction and has been investigated for use in torsional deformities. This study presents our preliminary results of rotationally guided growth in the femur and tibia using a novel technique of peripheral flexible tethers. A total of 8 bones in 5 patients were treated with flexible tethers consisting of separated halves of a hinge plate (Orthopediatrics Pega Medical, Montreal, QC, Canada), which were fixed to the epiphysis and metaphysis at 45° angles to the physis and connected with Fibertape (Arthrex, Naples, FL, USA). The implants are placed medially and laterally in the opposite 45° inclination, determined by the desired direction of rotation. Additionally, the average treatment time was 12 months. All patients corrected the rotational malalignment by clinical evaluation. The average rotational change was 30° in the femurs and 9.5° in the tibias. Further, the average follow-up was 18 months, with no recurrence of the rotational deformity. There was no change in longitudinal growth in the patients who underwent bilateral treatment. Rotational guided growth with flexible tether devices is a novel technique that successfully corrects torsional malalignment without invasive osteotomy surgery.
Patterned Graphene-Based Metamaterials for Terahertz Wave Absorption
Authors: Zhou Siyuan , Bi Kaixi , Li Qiannan , Mei Linyu , Niu Yaokai , Fu Wenxiao , Han Shuqi , Zhang Shuai , Mu Jiliang , Tan Ligang , Geng Wenping , Chou Xiujian
Published: December 2022

Graphene-based metamaterials have been widely applied in optoelectronic devices, optical modulators, and chemical sensors due to the outstanding tunability and optical response in the terahertz (THz) region. Here, tunable THz metamaterial absorbers based on patterned graphene are designed, fabricated, and modulated. The proposed metamaterial absorbers are constructed by the top layer of patterned graphene arrays and the aluminum (Al) film separated by polyimide (PI). The different THz absorption spectra can be acquired by changing the patterns of graphene. In order to verify the simulation results, a series of tests were conducted by THz time-domain spectrometer (THz-TDS) systems. The proposed absorbers are able to be insensitive to the angle of the incident wave. Besides, chemical doping is applied to turn the Fermi level of graphene and the absorption performance is promoted with the increase of the Fermi level. The experimental results have been demonstrated to have associated resonant peaks with the simulation results. The aim of this paper is to exhibit a systematic study on graphene-based THz metamaterial absorbers, including the simulation and experiments. By comparing the simulation and experimental results, it is useful to clarify the relevant theories and manufacturing processes. The work will provide a further step in the development of high-performance terahertz devices, including tunable absorbers, sensors, and electro-optic switches.
Tumor-Bowel Fistula as a Rare Form of Recurrent Ovarian Cancer—Imaging and Treatment: Preliminary Report
Authors: Jankowska-Lombarska Melania , Grabowska-Derlatka Laretta , Derlatka Pawel
Published: December 2022

Background. The aim of this pilot study was to evaluate the value of imaging techniques, including computed tomography (CT) and magnetic resonance imaging (MRI), in the diagnosis of a tumor-bowel fistula as a rare form of epithelial ovarian cancer (EOC) relapse. We also performed an initial assessment of the effectiveness of the treatment of this form of relapse. Methods. The study group consisted of eight patients with suspected platinum-sensitive recurrence in the form of a tumor/bowel fistula. All patients finished their first line of chemotherapy and subsequently showed complete remission for 6 months or more. To qualify patients for further treatment, CT and MRI were performed, which suggested the presence of a fistula between the recurrent tumor and intestine. DESKTOP study criteria were used to qualify patients for secondary cytoreduction. Second-line chemotherapy was given after secondary debulking. Results. In all patients, fistulas formed between the tumor and large bowel. On CT, the fistulas were indirectly visible. In all cases, the fistula was visible on MR images, which showed hypointensity on the T2 and T1 post-contrast sequences but did not show restricted diffusion on the diffusion-weighted imaging (DWI) sequence. Patients who were qualified for the study underwent secondary debulking with bowel resection. In all eight cases, the fistula between the tumor and surrounding organs was confirmed. During surgery, seven intestinal anastomoses and one colostomy were performed. No residual macroscopic tumor remained in seven cases (resection R0-87.5%). The progression-free survival (PFS) was 8.4–22.6 months (median 13.4). In the group with cytoreduction R0, the median PFS was 15.5 months (12–22). Conclusion. In patients with suspected EOC recurrence with clinically suspected fistula, CT scan is not sufficient. In CT, the presence of a fistula is suspected based on indirect symptoms. MRI, as a method with much greater tissue resolution, confirms the diagnosis. In addition, MRI can identify the point of the tumor/bowel junction. This is especially true with a large infiltration covering several intestinal parts. Bowel resection with simultaneous anastomosis is a good and safe solution for these patients. However, appropriate qualification for the procedure is necessary, which will allow for surgery without residual macroscopic disease (R0 surgery). Due to the small number of cases, our results cannot be generalized. We treat them as a hypothesis that can be verified in a larger study.
First Record of Nematode Larvae in the Amphipod Ischyrocerus commensalis Colonizing Red King Crabs in the Barents Sea
Authors: Dvoretsky Alexander G. , Plaksina Mariana P. , Dvoretsky Vladimir G.
Published: December 2022

In this study, nematodes were first reported in the amphipods, Ischyrocerus commensalis, collected from the introduced and commercially important red king crabs, Paralithodes camtschaticus, in the coastal Barents Sea in July 2022. Commensal amphipods were registered on all red king crabs captured (n = 70, prevalence 100%). Further laboratory analysis revealed that 11 out of 467 amphipod individuals (prevalence 2.4%) harbored single third-stage larvae of Hysterothylacium sp. l. (Nematoda: Anisakidae). The nematode larvae ranged from 0.63 to 6.10 mm in body length. Due to the low prevalence of nematodes and lower vulnerability of the host amphipods to fish predators, negative effects on the Barents Sea ecosystem through the range expansion of crab-associated amphipods and their parasites are unlikely.
Obesity and Its Multiple Clinical Implications between Inflammatory States and Gut Microbiotic Alterations
Authors: Milano Walter , Carizzone Francesca , Foia Mariagabriella , Marchese Magda , Milano Mariafrancesca , Saetta Biancamaria , Capasso Anna
Published: December 2022

Obesity is a chronic multifactorial disease that has become a serious health problem and is currently widespread over the world. It is, in fact, strongly associated with many other conditions, including insulin resistance, type 2 diabetes, cardiovascular and neurodegenerative diseases, the onset of different types of malignant tumors and alterations in reproductive function. According to the literature, obesity is characterized by a state of low-grade chronic inflammation, with a substantial increase in immune cells, specifically macrophage infiltrates in the adipose tissue which, in turn, secrete a succession of pro-inflammatory mediators. Furthermore, recent studies on microbiota have postulated new possible mechanisms of interaction between obesity and unbalanced nutrition with inflammation. This intestinal “superorganism” complex seems to influence not only the metabolic balance of the host but also the immune response, favoring a state of systemic inflammation and insulin resistance. This review summarizes the major evidence on the interactions between the gut microbiota, energetic metabolism and host immune system, all leading to a convergence of the fields of immunology, nutrients physiology and microbiota in the context of obesity and its possible clinical complications. Finally, possible therapeutic approaches aiming to rebalance the intestinal microbial ecosystem are evaluated to improve the alteration of inflammatory and metabolic states in obesity and related diseases.
Experimental Connectivity Analysis for Drones in Greenhouses
Authors: Pantos Christos , Hildmann Hanno , Valente João
Published: December 2022

This study aims to explore the communication capabilities for video crucial applications of two commercial drones—the Parrot AR.Drone 2.0 and the Parrot Anafi—in a greenhouse environment. Experiments were conducted on Received Signal Strength (RSS), Round-Trip Time (RTT) and the throughput on 802.11n at the 2.4 GHz network. From the experiments, it was found that none of the UAVs have an isotropic radiation pattern. Indoor measurements close to the roof and the ground were more prone to signal degradation. Even though the RTT of the Parrot Anafi was higher than that of the AR.Drone 2.0, the Anafi in almost all cases managed to achieve higher throughput and lower path loss, proving its superiority for video application. In addition, the maximum distance that the Parrot Anafi could fly in the greenhouse without any video quality loss was 110 m, while the AR.Drone 2.0 was hardly able to reach 30 m. Finally, the effect of the propellers has an insignificant impact on the UAV connection characteristics in all tested scenarios.
Quantum Chaos in the Dynamics of Molecules
Authors: Takatsuka Kazuo
Published: December 2022

Quantum chaos is reviewed from the viewpoint of “what is molecule?”, particularly placing emphasis on their dynamics. Molecules are composed of heavy nuclei and light electrons, and thereby the very basic molecular theory due to Born and Oppenheimer gives a view that quantum electronic states provide potential functions working on nuclei, which in turn are often treated classically or semiclassically. Therefore, the classic study of chaos in molecular science began with those nuclear dynamics particularly about the vibrational energy randomization within a molecule. Statistical laws in probabilities and rates of chemical reactions even for small molecules of several atoms are among the chemical phenomena requiring the notion of chaos. Particularly the dynamics behind unimolecular decomposition are referred to as Intra-molecular Vibrational energy Redistribution (IVR). Semiclassical mechanics is also one of the main research fields of quantum chaos. We herein demonstrate chaos that appears only in semiclassical and full quantum dynamics. A fundamental phenomenon possibly giving birth to quantum chaos is “bifurcation and merging” of quantum wavepackets, rather than “stretching and folding” of the baker’s transformation and the horseshoe map as a geometrical foundation of classical chaos. Such wavepacket bifurcation and merging are indeed experimentally measurable as we showed before in the series of studies on real-time probing of nonadiabatic chemical reactions. After tracking these aspects of molecular chaos, we will explore quantum chaos found in nonadiabatic electron wavepacket dynamics, which emerges in the realm far beyond the Born-Oppenheimer paradigm. In this class of chaos, we propose a notion of Intra-molecular Nonadiabatic Electronic Energy Redistribution (INEER), which is a consequence of the chaotic fluxes of electrons and energy within a molecule.
A Networked Method for Multi-Evidence-Based Information Fusion
Authors: Liang Qian , Liu Zhongxin , Chen Zengqiang
Published: December 2022

Dempster–Shafer evidence theory is an effective way to solve multi-sensor data fusion problems. After developing many improved combination rules, Dempster–Shafer evidence theory can also yield excellent results when fusing highly conflicting evidence. However, these approaches still have deficiencies if the conflicting evidence is due to sensor malfunction. This work presents a combination method by integrating information interaction graph and Dempster–Shafer evidence theory; thus, the multiple evidence fusion process is expressed as a network. In particular, the credibility of each piece of evidence is obtained by measuring the distance between the evidence first. After that, the credibility of the evidence is evaluated, keeping the unreliable evidence out of the information interaction network. With the fusion of connected evidence, the accuracy of the fusion result is improved. Finally, application results show that the presented method is effective.