bluuebunny/crossref_metadata_2025 huggingface dataset:
Educational agents and institutions called into action in suicide prevention, intervention, and postvention
Authors: De Oliveira Janaina Minelli , Dueñas Jorge-Manuel , Morales-Vives Fabia , Gallardo-Nieto Elena
Published: September 2023

Introduction

Suicide is the second leading cause of death in the 15 to 29 age group worldwide, and is a severe public health problem. Adolescent and young adult individuals attend educational institutions which can play an essential role in detecting and preventing suicide. For this reason, the purpose of this research is to identify what educational institutions and agents are called into action in suicide prevention, intervention, and postvention.

Methods

The method of systematic review of the literature based on the PRISMA protocol was used. The review protocol was registered in PROSPERO (PROSPERO 2020 CRD42020189127). The systematic review yielded 66 articles published between 1990 and February 2023.

Results

The results show that a wide variety of educational stakeholders are required to intervene for suicide prevention, interventions and postvention between primary education and college. The study describes the different programs that have been provided, the countries in which they have been implemented and the agents who have been targeted. It also identifies gaps in the research on suicide in the educational field.

Discussion

Overall, educational suicide initiatives report positive effects on participants’ understanding, attitudes, and beliefs regarding suicide and suicide prevention, although some studies have expressed some caution.
Depletion of tet2 results in age-dependent changes in DNA methylation and gene expression in a zebrafish model of myelodysplastic syndrome
Authors: Neelamraju Yaseswini , Gjini Evisa , Chhangawala Sagar , Fan Hao , He Shuning , Jing Chang-Bin , Nguyen Ashley T. , Prajapati Subhash , Sheridan Caroline , Houvras Yariv , Melnick Ari , Look A. Thomas , Garrett-Bakelman Francine E.
Published: September 2023

Introduction

Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal hematopoietic disorders characterized by ineffective hematopoiesis, cytopenias, and dysplasia. The gene encoding ten-eleven translocation 2 (tet2), a dioxygenase enzyme that catalyzes the conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine, is a recurrently mutated tumor suppressor gene in MDS and other myeloid malignancies. Previously, we reported a stable zebrafish line with a loss-of-function mutation in the tet2 gene. The tet2m/m-mutant zebrafish developed a pre-MDS state with kidney marrow dysplasia, but normal circulating blood counts by 11 months of age and accompanying anemia, signifying the onset of MDS, by 24 months of age.

Methods

In the current study, we collected progenitor cells from the kidney marrows of the adult tet2m/m and tet2wt/wt fish at 4 and 15 months of age and conducted enhanced reduced representation of bisulfite sequencing (ERRBS) and bulk RNA-seq to measure changes in DNA methylation and gene expression of hematopoietic stem and progenitor cells (HSPCs).

Results and discussion

A global increase in DNA methylation of gene promoter regions and CpG islands was observed in tet2m/m HSPCs at 4 months of age when compared with the wild type. Furthermore, hypermethylated genes were significantly enriched for targets of SUZ12 and the metal-response-element-binding transcription factor 2 (MTF2)—involved in the polycomb repressive complex 2 (PRC2). However, between 4 and 15 months of age, we observed a paradoxical global decrease in DNA methylation in tet2m/m HSPCs. Gene expression analyses identified upregulation of genes associated with mTORC1 signaling and interferon gamma and alpha responses in tet2m/m HSPCs at 4 months of age when compared with the wild type. Downregulated genes in HSPCs of tet2-mutant fish at 4 months of age were enriched for cell cycle regulation, heme metabolism, and interleukin 2 (IL2)/signal transducer and activator of transcription 5 (STAT5) signaling, possibly related to increased self-renewal and clonal advantage in HSPCs with tet2 loss of function. Finally, there was an overall inverse correlation between overall increased promoter methylation and gene expression.
A pre-eruptív intrakoronális reszorpció előfordulása és jelentősége bölcsességfogak esetében
Authors: Janovics Kata , Soós Balázs , Gurdán Zsuzsanna , Pacheco Ana Esther , Lempel Edina , Bán Ágnes , Szalma József
Published: September 2023

Bevezetés: A pre-eruptív intrakoronális reszorpció (PEIR) a koronális fogszövetek jól körülírható radiolucens léziója.Célunk volt megállapítani a PEIR prevalenciáját az impaktált alsó bölcsességfogak körében, valamint meghatározni azesetleges terápiás döntést befolyásoló szerepét.Vizsgálati anyag és módszer: Retrospektív vizsgálatunkban 6775 betegből 20 beteg 21 PEIR elv áltozást mutatóbölcsességfoga került bevonásra. Demográfiai adatokat gyűjtöttünk, valamint ortopantomogram-elemzést végeztünk.Eredmények: A nemek aránya 0,67 (8 férfi, 12 nő) volt, 31 ± 25 év átlagéletkorral. Alsó bölcsességfogat érintő PEIRa betegek 0,3%-ában (21/6775) volt látható, ami az összes PEIR 30,9%-a (21/68) volt. A léziók 28,6%-a volt előrehaladott(6/21), és ezen fogak 66,7%-ánál láttunk pulpaérintettséget (4/6). Előrehaladott PEIR esetén a betegek szignifikánsanidősebbek voltak (p = 0,0128, Mann-Whitney-teszt). Az esetek 47,6%-ában találtunk ektópiát (10/21), 9 esetben (42,9%)pedig rotációt. A PEIR-ek 19%-a fokozott idegsérülési rizikóval (4/21) párosult, előrehaladott lézió esetént (≥ 7-es osztályzat)66,7%-ban volt felismerhető magas rizikót jósló specifikus panorámaröntgen radiológiai jelkombináció (4/6).Következtetések: A PEIR jelenléte és karakterisztikája módosíthatja és meghatározhatja eseteink követésének ütemezését,vagy befolyással lehet a terápiás döntéseinkre.
US Swine Industry Stakeholder Perceptions of Precision Livestock Farming Technology: A Q-Methodology Study
Authors: Akinyemi Babatope E. , Akaichi Faical , Siegford Janice M. , Turner Simon P.
Published: September 2023

This study used the Q-methodology approach to analyze perceptions of precision livestock farming (PLF) technology held by stakeholders directly or indirectly involved in the US swine industry. To see if stakeholders’ perceptions of PLF changed over time as PLF is a rapidly evolving field, we deliberately followed up with stakeholders we had interviewed 6 months earlier. We identified three distinct points of view: PLF improves farm management, animal welfare, and laborer work conditions; PLF does not solve swine industry problems; PLF has limitations and could lead to data ownership conflict. Stakeholders with in-depth knowledge of PLF technology demonstrated elevated levels of optimism about it, whereas those with a basic understanding were skeptical of PLF claims. Despite holding different PLF views, all stakeholders agreed on the significance of training to enhance PLF usefulness and its eventual adoption. In conclusion, we believe this study’s results hold promise for helping US swine industry stakeholders make better-informed decisions about PLF technology implementation.
Neurophysiological Assessment of An Innovative Maritime Safety System in Terms of Ship Operators’ Mental Workload, Stress, and Attention in the Full Mission Bridge Simulator
Authors: Ronca Vincenzo , Uflaz Esma , Turan Osman , Bantan Hadi , MacKinnon Scott N. , Lommi Andrea , Pozzi Simone , Kurt Rafet Emek , Arslan Ozcan , Kurt Yasin Burak , Erdem Pelin , Akyuz Emre , Vozzi Alessia , Di Flumeri Gianluca , Aricò Pietro , Giorgi Andrea , Capotorto Rossella , Babiloni Fabio , Borghini Gianluca
Published: September 2023

The current industrial environment relies heavily on maritime transportation. Despite the continuous technological advances for the development of innovative safety software and hardware systems, there is a consistent gap in the scientific literature regarding the objective evaluation of the performance of maritime operators. The human factor is profoundly affected by changes in human performance or psychological state. The difficulty lies in the fact that the technology, tools, and protocols for investigating human performance are not fully mature or suitable for experimental investigation. The present research aims to integrate these two concepts by (i) objectively characterizing the psychological state of mariners, i.e., mental workload, stress, and attention, through their electroencephalographic (EEG) signal analysis, and (ii) validating an innovative safety framework countermeasure, defined as Human Risk-Informed Design (HURID), through the aforementioned neurophysiological approach. The proposed study involved 26 mariners within a high-fidelity bridge simulator while encountering collision risk in congested waters with and without the HURID. Subjective, behavioral, and neurophysiological data, i.e., EEG, were collected throughout the experimental activities. The results showed that the participants experienced a statistically significant higher mental workload and stress while performing the maritime activities without the HURID, while their attention level was statistically lower compared to the condition in which they performed the experiments with the HURID (all p < 0.05). Therefore, the presented study confirmed the effectiveness of the HURID during maritime operations in critical scenarios and led the way to extend the neurophysiological evaluation of the HFs of maritime operators during the performance of critical and/or standard shipboard tasks.
Brain Tumor Classification from MRI Using Image Enhancement and Convolutional Neural Network Techniques
Authors: Rasheed Zahid , Ma Yong-Kui , Ullah Inam , Ghadi Yazeed Yasin , Khan Muhammad Zubair , Khan Muhammad Abbas , Abdusalomov Akmalbek , Alqahtani Fayez , Shehata Ahmed M.
Published: September 2023

The independent detection and classification of brain malignancies using magnetic resonance imaging (MRI) can present challenges and the potential for error due to the intricate nature and time-consuming process involved. The complexity of the brain tumor identification process primarily stems from the need for a comprehensive evaluation spanning multiple modules. The advancement of deep learning (DL) has facilitated the emergence of automated medical image processing and diagnostics solutions, thereby offering a potential resolution to this issue. Convolutional neural networks (CNNs) represent a prominent methodology in visual learning and image categorization. The present study introduces a novel methodology integrating image enhancement techniques, specifically, Gaussian-blur-based sharpening and Adaptive Histogram Equalization using CLAHE, with the proposed model. This approach aims to effectively classify different categories of brain tumors, including glioma, meningioma, and pituitary tumor, as well as cases without tumors. The algorithm underwent comprehensive testing using benchmarked data from the published literature, and the results were compared with pre-trained models, including VGG16, ResNet50, VGG19, InceptionV3, and MobileNetV2. The experimental findings of the proposed method demonstrated a noteworthy classification accuracy of 97.84%, a precision success rate of 97.85%, a recall rate of 97.85%, and an F1-score of 97.90%. The results presented in this study showcase the exceptional accuracy of the proposed methodology in accurately classifying the most commonly occurring brain tumor types. The technique exhibited commendable generalization properties, rendering it a valuable asset in medicine for aiding physicians in making precise and proficient brain diagnoses.
Relation of MRI-Visible Perivascular Spaces and Other MRI Markers of Cerebral Small Vessel Disease
Authors: Rodriguez Lara Frances , Toro Arturo Ruben , Pinheiro Adlin , Demissie Serkalem , Ekenze Oluchi , Martinez Oliver , Parva Pedram , Charidimou Andreas , Ghosh Saptaparni , DeCarli Charles , Seshadri Sudha , Habes Mohamad , Maillard Pauline , Romero Jose Rafael
Published: September 2023

Perivascular spaces (PVS) visible on brain MRI signal cerebral small vessel disease (CSVD). The coexistence of PVS with other CSVD manifestations likely increases the risk of adverse neurological outcomes. We related PVS to other CSVD manifestations and brain volumes that are markers of vascular brain injury and neurodegeneration. Framingham Heart Study (FHS) participants with CSVD ratings on brain MRI were included. PVS were rated in the basal ganglia (BG) and centrum semiovale (CSO) into grades I–IV and a category reflecting high burden in single or mixed CSO-BG regions. We related PVS to covert brain infarcts (CBI), white matter hyperintensities (WMH), cerebral microbleeds (CMB), total brain, hippocampal, and cortical gray matter volumes using adjusted multivariable regression analyses. In 2454 participants (mean age 54 ± 12 years), we observed that higher PVS burden in both BG and CSO was related to CMB in lobar and deep brain regions and increased WMH. Greater CSO PVS burden was associated with decreased total cortical gray volumes. PVS are associated with ischemic markers of CSVD and neurodegeneration markers. Further studies should elucidate the causality between PVS and other CSVD manifestations.
Effects of Damage to the Integrity of the Left Dual-Stream Frontotemporal Network Mediated by the Arcuate Fasciculus and Uncinate Fasciculus on Acute/Subacute Post-Stroke Aphasia
Authors: Yu Qiwei , Jiang Yuer , Sun Yan , Ju Xiaowen , Ye Tianfen , Liu Na , Qian Surong , Liu Kefu
Published: September 2023

(1) Background: To investigate the correlation between the integrity of the left dual-stream frontotemporal network mediated by the arcuate fasciculus (AF) and uncinate fasciculus (UF), and acute/subacute post-stroke aphasia (PSA). (2) Methods: Thirty-six patients were recruited and received both a language assessment and a diffusion tensor imaging (DTI) scan. Correlations between diffusion indices in the bilateral LSAF/UF and language performance assessment were analyzed with correlation analyses. Multiple linear regression analysis was also implemented to investigate the effects of the integrity of the left LSAF/UF on language performance. (3) Results: Correlation analyses showed that the diffusion indices, including mean fractional anisotropy (FA) values and the fiber number of the left LSAF rather than the left UF was significantly positively associated with language domain scores (p < 0.05). Multiple linear regression analysis revealed an independent and positive association between the mean FA value of the left LSAF and the percentage score of language subsets. In addition, no interaction effect of the integrity of the left LSAF and UF on language performance was found (p > 0.05). (4) Conclusions: The integrity of the left LSAF, but not the UF, might play important roles in supporting residual language ability in individuals with acute/subacute PSA; simultaneous disruption of the dual-stream frontotemporal network mediated by the left LSAF and UF would not result in more severe aphasia than damage to either pathway alone.
Impact of Steel Fiber Volume Fraction and Morphology on the Strength of Recycled Aggregate Concrete
Authors: You Peibo , Ma Zhili , Zhang Lijuan , Wang Yi , Feng Qi , Li Li
Published: September 2023

Steel-fiber-reinforced recycled coarse aggregate concrete (SFRCAC) has great potential for use in structural members due to environmental and economic reasons. A comparison of SF’s reinforcing effect on the strength of RCAC with natural recycled coarse aggregate concrete (NCAC) was conducted through experiments and analysis. Three types of steel fiber—milling (MF), shear-wave (SWF), and both-end hooked (BF)—were used. The SF volume fraction (Vf) was taken as 0, 0.5%, 1.0%, 1.5%, and 2%. The results show that SF has a similar reinforcing effect on NCAC and RCAC. The reinforcing effect of SF on the strength of RCAC is relevant to the strength of the RCAC matrix. The suitable content range of SF is from 0.5% to 1.5% in terms of the reinforcement effects on the compressive strength (ffcu) and splitting tensile strength (ffts) of RCAC. SF with a higher aspect ratio (AR) has a better reinforcing effect on the splitting tensile strength (ffts) and flexural strength (fftm) of RCAC. The equations of ffts/fts and fftm/ftm with the characteristic parameters of steel fiber (λf) were put forward to accurately determine the dosage of SF.
From Geotechnical Data to GeoBIM Models: Testing Strategies for an Ex-Industrial Site in Turin
Authors: Fonsati Arianna , Cosentini Renato Maria , Tundo Chiara , Osello Anna
Published: September 2023

Over the years, the use of Building Information Modelling (BIM) methods has changed the workflows of various actors, providing better integration across different domains and allowing for new ways of working. This paper outlines the interest towards the integration of BIM with geotechnical/geological modelling (GeoBIM), which still represents a major challenge in several respects. The present study aims to provide a flexible method for assessing various integration strategies and to establish a preferred workflow based on the selected requirements and preference parameters. This integration is designed to provide a final federated model that can also be archived in the as-built documentation. Four alternative processes were selected to analyse the specific types of data and transformations required in the process. Each process was applied on a real case study in order to test the developed assessment framework using the Analytical Hierarchy Process (AHP). Due to technological advances, modelling and integration workflows change rapidly; however, our results show that the proposed evaluation framework is universal and adaptable to any new integration approach. Further research efforts must be undertaken to reduce attribute data losses and enhance the interoperability between systems and professionals.
Indirect Treatment Comparison of First-Line CDK4/6-Inhibitors in Post-Menopausal Patients with HR+/HER2− Metastatic Breast Cancer
Authors: Zhao Joseph J. , Fong Khi Yung , Chan Yiong Huak , Tey Jeremy , Dawood Shaheenah , Lee Soo Chin , Finn Richard S. , Sundar Raghav , Lim Joline S. J.
Published: September 2023

Background: CDK4/6-inhibitors have demonstrated similar efficacy and are considered an effective first-line endocrine treatment of patients with hormone-receptor positive (HR+)/human-epidermal-growth-factor-receptor-2 negative (HER2−) metastatic breast cancer (MBC) in the endpoint of progression-free survival (PFS). Amongst these, palbociclib was first to achieve regulatory approval, followed subsequently by ribociclib and abemaciclib. However, recent updates of overall survival (OS) showed inconsistencies in the OS benefit for palbociclib compared with the other two CDK4/6-inhibitors. With the lack of head-to-head comparison studies, our study sought to compare indirect survival outcomes between CDK4/6-inhibitors in this setting using a novel reconstructive algorithm. Methods: Phase III randomized trials comparing first-line aromatase inhibitor with/without a CDK4/6-inhibitor in post-menopausal patients with HR+/HER2− MBC were identified through systemic review and literature search of online archives of published manuscripts and conference proceedings. A graphical reconstructive algorithm was utilized to retrieve time-to-event data from reported Kaplan-Meier OS and PFS plots to allow for comparison of survival outcomes. Survival analyses were conducted with Cox proportional-hazards model with a shared-frailty term. Results: Three randomized phase III trials—PALOMA-2, MONALEESA-2 and MONARCH-3—comprising 1827 patients were included. Indirect pairwise comparisons of all CDK4/6-inhibitors showed no significant PFS differences (all p > 0.05). Likewise, indirect treatment comparison between ribociclib vs. palbociclib (one-stage: HR = 0.903, 95%-CI: 0.746–1.094, p = 0.297), abemaciclib vs. palbociclib (one-stage: HR = 0.843, 95%-CI: 0.690–1.030, p = 0.094) and abemaciclib vs. ribociclib (one-stage: HR = 0.933, 95%-CI: 0.753–1.157, p = 0.528) failed to demonstrate a significant OS difference. Conclusions: Findings from this indirect treatment comparison suggest no significant PFS or OS differences between CDK4/6-inhibitors in post-menopausal patients with HR+/HER2− MBC.
Pencil Beam Scanning Bragg Peak FLASH Technique for Ultra-High Dose Rate Intensity-Modulated Proton Therapy in Early-Stage Breast Cancer Treatment
Authors: Lattery Grant , Kaulfers Tyler , Cheng Chingyun , Zhao Xingyi , Selvaraj Balaji , Lin Haibo , Simone Charles B. , Choi J. Isabelle , Chang Jenghwa , Kang Minglei
Published: September 2023

Bragg peak FLASH-RT can deliver highly conformal treatment and potentially offer improved normal tissue protection for radiotherapy patients. This study focused on developing ultra-high dose rate (≥40 Gy × RBE/s) intensity-modulated proton therapy (IMPT) for hypofractionated treatment of early-stage breast cancer. A novel tracking technique was developed to enable pencil beaming scanning (PBS) of single-energy protons to adapt the Bragg peak (BP) to the target distally. Standard-of-care PBS treatment plans of consecutively treated early-stage breast cancer patients using multiple energy layers were reoptimized using this technique, and dose metrics were compared between single-energy layer BP FLASH and conventional IMPT plans. FLASH dose rate coverage by volume (V40Gy/s) was also evaluated for the FLASH sparing effect. Distal tracking can precisely stop BP at the target distal edge. All plans (n = 10) achieved conformal IMPT-like dose distributions under clinical machine parameters. No statistically significant differences were observed in any dose metrics for heart, ipsilateral lung, most ipsilateral breast, and CTV metrics (p > 0.05 for all). Conventional plans yielded slightly superior target and skin dose uniformities with 4.5% and 12.9% lower dose maxes, respectively. FLASH-RT plans reached 46.7% and 61.9% average-dose rate FLASH coverage for tissues receiving more than 1 and 5 Gy plan dose total under the 250 minimum MU condition. Bragg peak FLASH-RT techniques achieved comparable plan quality to conventional IMPT while reaching adequate dose rate ratios, demonstrating the feasibility of early-stage breast cancer clinical applications.
Breaching the Fortress of Tumor Microenvironment to Control Cancer Metastasis
Authors: Jaguri Aayami , Ahmad Aamir
Published: September 2023

As the primary cause of death for >90% of cancers, metastasis is the fourth and final stage of cancer during which cells gain the ability to leave their primary site, invade surrounding tissues, and disseminate to distant organs [...]
Current Status of Angiogenesis Inhibitors as Second-Line Treatment for Unresectable Colorectal Cancer
Authors: Otsu Satoshi , Hironaka Shuichi
Published: September 2023

Colorectal cancer is the third most common disease and the second most common cause of death around the world. The drug for second-line treatment depends on the drugs used in first-line treatment and the biomarker status. As biomarkers, the RAS gene, BRAF gene, and dMMR/MSI-H, TMB-H, and HER2 statuses have been established in clinical practice, and the corresponding molecularly targeted therapeutic agents are selected based on the biomarker status. Given the frequency of biomarkers, it is assumed that when patients move on to second-line treatment, an angiogenesis inhibitor is selected in many cases. For second-line treatment, three angiogenesis inhibitors, bevacizumab (BEV), ramucirumab (RAM), and aflibercept (AFL), are available, and one of them is combined with cytotoxic agents. These three angiogenesis inhibitors are known to inhibit angiogenesis through different mechanisms of action. Although no useful biomarkers have been established for the selection of angiogenesis inhibitors, previous biomarker studies have suggested that angiogenesis-related factors such as VEGF-A and VEGF-D might be predictors of the therapeutic efficacy of angiogenesis inhibitors. These biomarkers are measured as protein levels in plasma and are considered to be promising biomarkers. We consider that the rationale for selecting among these three angiogenesis inhibitors should be clarified to benefit patients.
Small Renal Masses: Developing a Robust Radiomic Signature
Authors: Maddalo Michele , Bertolotti Lorenzo , Mazzilli Aldo , Flore Andrea Giovanni Maria , Perotta Rocco , Pagnini Francesco , Ziglioli Francesco , Maestroni Umberto , Martini Chiara , Caruso Damiano , Ghetti Caterina , De Filippo Massimo
Published: September 2023

(1) Background and (2) Methods: In this retrospective, observational, monocentric study, we selected a cohort of eighty-five patients (age range 38–87 years old, 51 men), enrolled between January 2014 and December 2020, with a newly diagnosed renal mass smaller than 4 cm (SRM) that later underwent nephrectomy surgery (partial or total) or tumorectomy with an associated histopatological study of the lesion. The radiomic features (RFs) of eighty-five SRMs were extracted from abdominal CTs bought in the portal venous phase using three different CT scanners. Lesions were manually segmented by an abdominal radiologist. Image analysis was performed with the Pyradiomic library of 3D-Slicer. A total of 108 RFs were included for each volume. A machine learning model based on radiomic features was developed to distinguish between benign and malignant small renal masses. The pipeline included redundant RFs elimination, RFs standardization, dataset balancing, exclusion of non-reproducible RFs, feature selection (FS), model training, model tuning and validation of unseen data. (3) Results: The study population was composed of fifty-one RCCs and thirty-four benign lesions (twenty-five oncocytomas, seven lipid-poor angiomyolipomas and two renal leiomyomas). The final radiomic signature included 10 RFs. The average performance of the model on unseen data was 0.79 ± 0.12 for ROC-AUC, 0.73 ± 0.12 for accuracy, 0.78 ± 0.19 for sensitivity and 0.63 ± 0.15 for specificity. (4) Conclusions: Using a robust pipeline, we found that the developed RFs signature is capable of distinguishing RCCs from benign renal tumors.
Recent Insights into the Biomarkers, Molecular Targets and Mechanisms of Non-Alcoholic Steatohepatitis-Driven Hepatocarcinogenesis
Authors: Kakehashi Anna , Suzuki Shugo , Wanibuchi Hideki
Published: September 2023

Non-alcoholic fatty liver disease (NAFLD) or metabolic dysfunction-associated steatotic liver disease (MASLD) and steatohepatitis (NASH) are chronic hepatic conditions leading to hepatocellular carcinoma (HCC) development. According to the recent “multiple-parallel-hits hypothesis”, NASH could be caused by abnormal metabolism, accumulation of lipids, mitochondrial dysfunction, and oxidative and endoplasmic reticulum stresses and is found in obese and non-obese patients. Recent translational research studies have discovered new proteins and signaling pathways that are involved not only in the development of NAFLD but also in its progression to NASH, cirrhosis, and HCC. Nevertheless, the mechanisms of HCC developing from precancerous lesions have not yet been fully elucidated. Now, it is of particular importance to start research focusing on the discovery of novel molecular pathways that mediate alterations in glucose and lipid metabolism, which leads to the development of liver steatosis. The role of mTOR signaling in NASH progression to HCC has recently attracted attention. The goals of this review are (1) to highlight recent research on novel genetic and protein contributions to NAFLD/NASH; (2) to investigate how recent scientific findings might outline the process that causes NASH-associated HCC; and (3) to explore the reliable biomarkers/targets of NAFLD/NASH-associated hepatocarcinogenesis.
Treatment of Colorectal Cancer in Certified Centers: Results of a Large German Registry Study Focusing on Long-Term Survival
Authors: Völkel Vinzenz , Gerken Michael , Kleihues-van Tol Kees , Schoffer Olaf , Bierbaum Veronika , Bobeth Christoph , Roessler Martin , Reissfelder Christoph , Fürst Alois , Benz Stefan , Rau Bettina M. , Piso Pompiliu , Distler Marius , Günster Christian , Hansinger Judith , Schmitt Jochen , Klinkhammer-Schalke Monika
Published: September 2023

(1) Background: The WiZen study is the largest study so far to analyze the effect of the certification of designated cancer centers on survival in Germany. This certification program is provided by the German Cancer Society (GCS) and represents one of the largest oncologic certification programs worldwide. Currently, about 50% of colorectal cancer patients in Germany are treated in certified centers. (2) Methods: All analyses are based on population-based clinical cancer registry data of 47.440 colorectal cancer (ICD-10-GM C18/C20) patients treated between 2009 and 2017. The primary outcome was 5-year overall survival (OAS) after treatment at certified cancer centers compared to treatment at other hospitals; the secondary endpoint was recurrence-free survival. Statistical methods included Kaplan–Meier analysis and multivariable Cox regression. (3) Results: Treatment at certified hospitals was associated with significant advantages concerning 5-year overall survival (HR 0.92, 95% CI 0.89, 0.96, adjusted for a broad range of confounders) for colon cancer patients. Concentrating on UICC stage I–III patients, for whom curative treatment is possible, the survival benefit was even larger (colon cancer: HR 0.89, 95% CI 0.84, 0.94; rectum cancer: HR 0.91, 95% CI 0.84, 0.97). (4) Conclusions: These results encourage future efforts for further implementation of the certification program. Patients with colorectal cancer should preferably be directed to certified centers.
The Clinical Validation of Modulated Electro-Hyperthermia (mEHT)
Authors: Lee Sun-Young , Lorant Gergo , Grand Laszlo , Szasz Attila Marcell
Published: September 2023

The mEHT method uses tissues’ thermal and bioelectromagnetic heterogeneity for the selective mechanisms. The success of the therapy for advanced, relapsed, and metastatic aggressive tumors can only be demonstrated by measuring survival time and quality of life (QoL). The complication is that mEHT-treated patients cannot be curatively treated any longer with “gold standards”, where the permanent progression of the disease, the refractory, relapsing situation, the organ failure, the worsening of blood counts, etc., block them. Collecting a cohort of these patients is frequently impossible. Only an intent-to-treat (ITT) patient group was available. Due to the above limitations, many studies have single-arm data collection. The Phase III trial of advanced cervix tumors subgrouping of HIV-negative and -positive patients showed the stable efficacy of mEHT in all patients’ subgroups. The single-arm represents lower-level evidence, which can be improved by comparing the survival data of various studies from different institutes. The Kaplan–Meier probability comparison had no significant differences, so pooled data were compared to other methods. Following this approach, we demonstrate the feasibility and superiority of mEHT in the cases of glioblastoma multiform, pancreas carcinomas, lung tumors, and colorectal tumors.
5-Years Analysis of Effectivity and Toxicity of Ultra-Hypofractionated Proton Radiotherapy in the Treatment of Low- and Intermediate-Risk Prostate Cancer—A Retrospective Analysis
Authors: Kubeš Jiri , Sláviková Silvia , Vítek Pavel , Haas Alexandra , Ondrová Barbora , Dedečková Kateřina , Andrlík Michal , Domanský Martin , Jiránková Kateřina , Schlencová Veronika , Harazimová Anh , Turková Barbora , Doležal Tomáš , Al-Hamami Sarah Falah Abass , Vondráček Vladimír
Published: September 2023

Background: We retrospectively analyzed the 5-year biochemical disease-free survival (bDFS) and occurrence of late toxicity in prostate cancer patients treated with pencil beam scanning (PBS) proton radiotherapy. Methodology: In the period from January 2013 to June 2018, 853 patients with prostate cancer were treated with an ultra-hypofractionated schedule (36.25 GyE/five fractions). The mean PSA value was 6.7 (0.7–19.7) µg/L. There were 318 (37.3%), 314 (36.8%), and 221 (25.9%) patients at low (LR), favorable intermediate (F-IR), and unfavorable intermediate risk (U-IR), respectively. Neoadjuvant hormonal therapy was administered to 197 (23.1%) patients, and 7 (0.8%) patients had adjuvant hormonal therapy. The whole group of patients reached median follow-up time at 62.7 months, and their mean age was 64.8 (40.0–85.7) years. The bDFS rates and late toxicity profile were evaluated. Results: Median treatment time was 10 (7–38) days. Estimated 5-year bDFS rates were 96.5%, 93.7%, and 91.2% for low-, favorable intermediate-, and unfavorable intermediate-risk groups, respectively. Cumulative late toxicity (CTCAE v4.0) of G2+ was as follows: gastrointestinal (GI)—G2: 9.1%; G3: 0.5%; genitourinary (GU)—G2: 4.3%, and no G3 toxicity was observed. PSA relapse was observed in 58 (6.8%) patients: 16 local, 22 lymph node, 4 bone recurrences, and 10 combined sites of relapse were detected. Throughout the follow-up period, 40 patients (4.7%) died, though none due to prostate cancer. Conclusion: Ultra-hypofractionated proton beam radiotherapy is an effective treatment for low- and favorable intermediate-risk prostate cancer, with long-term bDFS rates comparable to other techniques. It is promising for unfavorable intermediate-risk prostate cancer and has acceptable long-term GI and favorable GU toxicity.
Immunotherapy and Liver Transplantation: A Narrative Review of Basic and Clinical Data
Authors: Wassmer Charles-Henri , El Hajji Sofia , Papazarkadas Xenofon , Compagnon Philippe , Tabrizian Parissa , Lacotte Stéphanie , Toso Christian
Published: September 2023

Immune checkpoint inhibitors (ICIs) have improved the management of patients with intermediate- and advanced-stage HCC, even making some of them potential candidates for liver transplantation. However, acute rejection has been observed after ICI therapy, challenging its safety in transplant settings. We summarize the key basic impact of immune checkpoints on HCC and liver transplantation. We analyze the available case reports and case series on the use of ICI therapy prior to and after liver transplantation. A three-month washout period is desirable between ICI therapy and liver transplantation to reduce the risk of acute rejection. Whenever possible, ICIs should be avoided after liver transplantation, and especially so early after a transplant. Globally, more robust prospective data in the field are required.
Head and Neck Squamous Cell Carcinoma Biopsies Maintained Ex Vivo on a Perfusion Device Show Gene Changes with Time and Clinically Relevant Doses of Irradiation
Authors: Green Victoria , Baldwin Lydia , England James , Marshall Gayle , Frost Lucy , Moore Craig , Greenman John
Published: September 2023

Advancements in 3-Dimensional (3D) culture models for studying disease have increased significantly over the last two decades, but fully understanding how these models represent in vivo still requires further investigation. The current study investigated differences in gene expression between a baseline sample and that maintained on a tissue-on-chip perfusion device for up to 96 h, with and without clinically-relevant doses of irradiation, to allow differentiation of model and treatment effects. Tumour tissue samples from 7 Head and Neck Squamous Cell Carcinomas (HNSCC) patients were sub-divided and either fixed immediately upon excision or maintained in a tissue-on-chip device for 48 and 96 h, with or without 2 Gray (Gy) or 10 Gy irradiation. Gene expression was measured using an nCounter® PanCancer Progression Panel. Differentially expressed genes between pre- and post-ex vivo culture, and control and irradiated samples were identified using nSolver software (version 4.0). The secretome from the tumour-on-chip was analysed for the presence of cytokines using a Proteome Profiler™ platform. Significant numbers of genes both increased (n = 6 and 64) and decreased (n = 18 and 58) in expression in the tissue maintained on-chip for 48 and 96 h, respectively, compared to fresh tissue; however, the irradiation schedule chosen did not induce significant changes in gene expression or cytokine secretion. Although HNSCC tissue maintained ex vivo shows a decrease in a large proportion of altered genes, 25% and 53% (48 and 96 h) do show increased expression, suggesting that the tissue remains functional. Irradiation of tumour tissue-on-chip needs to be conducted for longer time periods for specific gene changes to be observed, but we have shown, for the first time, the feasibility of using this perfusion platform for studying the genomic response of HNSCC tissue biopsies.
Analysis of Structural Boundary Effects of Copper-Coated Films and Their Application to Space Antennas
Authors: Zhou Xiaotao , Li Huanxiao , Ma Xiaofei
Published: September 2023

Copper-coated films are a solution for flexible electronic devices. One of the applications is a flexible-tension film-deployable antenna, which is a large deployable space antenna with broad application prospects. To analyze the possibility of applying coated films to the antenna, surface accuracy evaluation is required. The finite element method (FEM) was used to analyze the surface accuracy of the copper-coated thin-film structures. Both wrinkling and stretching–bending coupling deformation were considered. Simplified models were applied to study factors influencing the surface accuracy under boundary effects. Different sizes of coated area and different boundary conditions were simulated. The results showed the characteristic boundary effects of copper-coated thin-film structures and the influence curve of film thickness and patch size on boundary effects. These findings will inform the design and analysis of variable-stiffness thin-film antennas. On this basis, the application of a flexible-tension film-deployable antenna is discussed, along with a measure to improve the surface accuracy.
Effect of Interface Curvature on Local Growth Behavior and Stress of Thermal Barrier Coatings
Authors: Wang Lulu , Yu Jun , Zhang Tao , Wang Zhe , Ding Kunying
Published: September 2023

It is well known that coating spalling often occurs between the top ceramic coating (TC) and the metal bonding coating (BC) during the working process where the thermal mismatch stress between the layers plays a key role. Dynamic changes in the thermally grown oxide (TGO) between the facing and bonding layers during thermal cycling increase the thermal mismatch at the interface. The effect of oxide thickening on localized mismatch stresses under thermal cycling with different interfacial curvatures is quantitatively investigated using numerical methods in this paper. A dynamic growth model of the oxide was developed based on the consideration of the composition and morphology of the thermally grown oxide. The results show that TGO growth behavior, local stress evolution, crack initiation location, and crack propagation length are influenced by the interface curvature at the same aspect ratio. The interface between the oxide layer and the bonding layer gradually developed significant tensile to dangerous stresses during thermal cycling. These tensile stresses are predominantly distributed at the crest during the early stages of thermal exposure and gradually transferred to the near-peak (the region near the peak) and ramp regions (the region in between the peak and the valley) as the oxidation process progressed. The crack initiation and propagation phenomenon can be observed at various regions during thermal exposure. Increasing interface curvature leads to an earlier dangerous stress moment in the ramp area due to higher maximum tensile stress. Therefore, the small changes in the interface curvature severely affected the location and time of crack initiation and the crack length.
Integration of Antifouling and Anti-Cavitation Coatings on Propellers: A Review
Authors: Zhang Jingying , Qin Weihua , Chen Wenrui , Feng Zenghui , Wu Dongheng , Liu Lanxuan , Wang Yang
Published: September 2023

The performance of an entire ship is increasingly impacted by propellers, which are the essential components of a ship’s propulsion system that have growing significance in a variety of aspects. Consequently, it has been a hot research topic and a challenge to develop high-performance antifouling and anti-cavitation coatings due to the issue of marine biofouling and cavitation faced by propellers in high-intensity service. While there is an overwhelming number of publications on antifouling and anti-cavitation coatings, a limited number of papers focus on integrated protective coatings on propellers. In this paper, we evaluated the development of antifouling and anti-cavitation coatings for ship propellers in the marine environment as well as their current status of research. These coatings include self-polishing antifouling coatings, fouling-releasing antifouling coatings, and biomimetic antifouling coatings for static seawater anti-biofouling, as well as anti-cavitation organic coatings and anti-cavitation inorganic coatings for dynamic seawater anti-cavitation. This review also focuses both on the domestic and international research progress status of integrated antifouling and anti-cavitation coatings for propellers. It also provides research directions for the future development of integrated antifouling and anti-cavitation coatings on propellers.
A New Zn(II) Azido Complex of L-Arginine: X-ray Crystal Structure, Hirshfeld, and AIM Studies
Authors: Altowyan Mezna Saleh , Yousri Amal , Albering Jörg H. , Fischer Roland C. , Abu-Youssef Morsy A. M. , Ayoup Mohammed Salah , Barakat Assem , Soliman Saied M.
Published: September 2023

The synthesis and X-ray crystal structure analyses of the azido complex [Zn(N3)(Arg)2](N3)·3H2O, where Arg is L-arginine, were presented. The molecular structure of the complex was further studied using FT-IR spectra as well as atoms in molecules (AIM) theory. An analysis of the crystal data indicated monoclinic crystal system and P21 space group with a = 13.0283(5) Å, b = 15.2032(7) Å, c = 13.3633(6) Å, β = 114.3580(10)°, V = 2411.28(18) Å3, and Z = 4. Two of the [Zn(N3)(Arg)2](N3)·3H2O formulae represent the asymmetric unit of this complex where the geometric parameters of both units are slightly different. In [Zn(N3)(Arg)2](N3)·3H2O, the central Zn(II) ion is penta-coordinated with two Arg molecules as a bidentate ligand and one terminally coordinated azide ion. Each of the two Arg molecules are located trans to one another and coordinated with the Zn(II) via the N and O atoms of the amino and carboxylate groups, respectively. Hence, Zn(II) is five-coordinated and has a distorted square pyramidal coordination geometry. The supramolecular structure of the [Zn(N3)(Arg)2](N3)·3H2O complex was inspected using the Hirshfeld analysis. The O···H (26.6–28.4%), H···H (32.3–35.3%), and N···H (30.4–34.0%) contacts are the most significant interactions in the crystal structure of the [Zn(N3)(Arg)2](N3)·3H2O complex. The Zn–N, and Zn–O bonds have slight covalent interactions based on the AIM study.
Something’s Fishy: An Unexpected Intertidal Encounter with the New Zealand Lancelet, Epigonichthys hectori (Benham, 1901), near the Whangarei Heads, NZ
Authors: de Gier Werner , Hubert Jeroen
Published: September 2023

A specimen of the endemic New Zealand lancelet Epigonichthys hectori (Benham, 1901) was found and photographed in the intertidal area of a beach near the Whangarei Heads in New Zealand. This only lancelet species for New Zealand is rarely caught and is known for its specific habitat requirements, demanding clean, coarse sand. The specimen was found in an almost dried-out puddle during low tide on a beach with a lot of human activity. The species is also known to inhabit greater depths, making this observation (together with another recent, unpublished record) a constitution for evidence that it also inhabits tidal areas. Distribution records from the literature are reviewed, plotted on a map, and supplemented by this new observation.
Distribution and Characteristics of Two Species of Stingless Bee Hives (Tetragonula spp.) in the Rural Landscape of Sumedang Regency (Indonesia)
Authors: Withaningsih Susanti , Diaz Fauzan , Rozi Fakhrur , Parikesit Parikesit
Published: September 2023

Tetragonula beekeeping is in high demand, and the activity of hunting wild Tetragonula bees in nature is increasing. The purpose of this study was to determine the type and distribution of wild stingless bee colonies in the Sumedang area of Indonesia, as well as the characteristics of their hives in nature. We used survey methods in this research. Data collection was accomplished by studying and collecting biotic and abiotic data around hives. Two species of Tetragonula bees were found, namely Tetragonula laeviceps Smith at 71 locations in 6 sub-districts and Tetragonula drescheri Schwarz at 9 locations in 5 districts. Tetragonula bees like to occupy building gaps and holes in the stems of tall plants. Differences were found in the length of the hive entrance, the thickness of the hive door, the texture of the hive door, and the direction of the hive door for each species. Environmental factors such as temperature, humidity, and light intensity greatly affect colony activity, whereas wind speed and weather conditions affect the condition of the hive door. The presence of food sources around the hive also affects the survival of the colony and colony activity.
Dynamic Causal Modeling and Online Collaborative Forecasting of Air Quality in Hong Kong and Macao
Authors: He Cheng , Ren Jia , Liu Wenjian
Published: September 2023

The Hong Kong and Macao Special Administrative Regions, situated within China’s Guangdong–Hong Kong–Macao Greater Bay Area, significantly influence and are impacted by their air quality conditions. Rapid urbanization, high population density, and air pollution from diverse factors present challenges, making the health of the atmospheric environment in these regions a research focal point. This study offers three key contributions: (1) It applied an interpretable dynamic Bayesian network (DBN) to construct a dynamic causal model of air quality in Hong Kong and Macao, amidst complex, unstable, multi-dimensional, and uncertain factors over time. (2) It investigated the dynamic interaction between meteorology and air quality sub-networks, and both qualitatively and quantitatively identified, evaluated, and understood the causal relationships between air pollutants and their determinants. (3) It facilitated an online collaborative forecast of air pollutant concentrations, enabling pollution warnings. The findings proposed that a DBN-based dynamic causal model can effectively explain and manage complex atmospheric environmental systems in Hong Kong and Macao. This method offers crucial insights for decision-making and the management of atmospheric environments not only in these regions but also for neighboring cities and regions with similar geographical contexts.
Quasi-Hyperbolically Symmetric γ-Metric
Authors: Herrera Luis , Di Prisco Alicia , Ospino Justo , Carot Jaume
Published: September 2023

We carry out a systematic study on the motion of test particles in the region inner to the naked singularity of a quasi-hyperbolically symmetric γ-metric. The geodesic equations are written and analyzed in detail. The obtained results are contrasted with the corresponding results obtained for the axially symmetric γ-metric and the hyperbolically symmetric black hole. As in this latter case, it is found that test particles experience a repulsive force within the horizon (naked singularity), which prevents them from reaching the center. However, in the present case, this behavior is affected by the parameter γ which measures the departure from the hyperbolical symmetry. These results are obtained for radially moving particles as well as for particles moving in the θ−r subspace. The possible relevance of these results in the explanation of extragalactic jets is revealed.