bluuebunny/crossref_metadata_2025 huggingface dataset:
Technical and Clinical Outcomes of Laparoscopic–Laparotomic Hepatocellular Carcinoma Thermal Ablation with Microwave Technology: Case Series and Review of Literature
Authors: Muglia Riccardo , Marra Paolo , Pinelli Domenico , Dulcetta Ludovico , Carbone Francesco Saverio , Barbaro Alessandro , Celestino Antonio , Colledan Michele , Sironi Sandro
Published: December 2023

Purpose: To evaluate technical and clinical outcomes of intraoperative (laparoscopic/laparotomic) microwave ablation on HCC. Materials and Methods: This is a retrospective single-center study evaluating consecutive patients treated for very early/early-stage HCC with intraoperative microwave ablation from 1 July 2017 to 30 June 2023. In these patients, a percutaneous US-guided approach was excluded due to the nodule’s suboptimal visibility or harmful location and liver resection for a deep position or adherences. Data about the clinical stage, surgical approach, liver pathology and nodules characteristics, technical success, complications, and follow-up were collected. Technical success was intended as the absence of locoregional persistence at follow-up CT/MRI controls. Results: A total of 36 cirrhotic patients (M:F = 30:6, median age 67 years) were enrolled; 18/36 (50%) had a single nodule, 13/36 (36%) had two, 4/36 had three (11%), and 1/36 had four (3%). Among the patients, 24 (67%) were treated with laparoscopy, and 12/36 (33%) with a laparotomic approach. Sixty HCCs of 16.5 mm (6–50 mm) were treated for 7 min (2–30 min) with 100 W of power. A total of 55 nodules (92%) were treated successfully and showed no residual enhancement at the first postoperative follow-up; the other 5/60 (8%) underwent chemo/radioembolization. There was one complication (3%): a biliary fistula treated with percutaneous drainage and glue embolization. The average hospital stay was 3.5 days (1–51 days), and patients were followed up on average for 238 days (13–1792 days). During follow-up, 5/36 patients (14%) underwent liver transplantation, 1/36 (2%) died during hospitalization and 1 after discharge. Conclusions: Laparoscopic/laparotomic intraoperative HCC MW ablation is feasible in patients unsuitable for percutaneous approach or hepatic resection, with rare complications and with good technical and clinical outcomes.
Validation of Inflammatory Prognostic Biomarkers in Pleural Mesothelioma
Authors: Iser Stephanie , Hintermair Sarah , Varga Alexander , Çelik Ali , Sayan Muhammet , Kankoç Aykut , Akyürek Nalan , Öğüt Betül , Bertoglio Pietro , Capozzi Enrico , Solli Piergiorgio , Ventura Luigi , Waller David , Weber Michael , Stubenberger Elisabeth , Ghanim Bahil
Published: December 2023

Evoked from asbestos-induced inflammation, pleural mesothelioma represents a fatal diagnosis. Therapy ranges from nihilism to aggressive multimodality regimens. However, it is still unclear who ultimately benefits from which treatment. We aimed to re-challenge inflammatory-related biomarkers’ prognostic value in times of modern immune-oncology and lung-sparing surgery. The biomarkers (leukocytes, hemoglobin, platelets, neutrophils, lymphocytes, monocytes, neutrophil–lymphocyte ratio (NLR), lymphocyte–monocyte ratio (LMR), platelet–lymphocyte ratio (PLR), C-reactive protein (CRP)) and clinical characteristics (age, sex, histology, therapy) of 98 PM patients were correlated to overall survival (OS). The median OS was 19.4 months. Significant OS advantages (Log-Rank) were observed in multimodal treatment vs. others (26.1 vs. 7.2 months, p < 0.001), surgery (pleurectomy/decortication) vs. no surgery (25.5 vs. 3.8 months, p < 0.001), a high hemoglobin level (cut-off 12 g/dL, 15 vs. 24.2 months, p = 0.021), a low platelet count (cut-off 280 G/L, 26.1 vs. 11.7 months, p < 0.001), and a low PLR (cut-off 194.5, 25.5 vs. 12.3 months, p = 0.023). Histology (epithelioid vs. non-epithelioid, p = 0.002), surgery (p = 0.004), CRP (cut-off 1 mg/dL, p = 0.039), and platelets (p = 0.025) were identified as independent prognostic variables for this cohort in multivariate analysis (Cox regression, covariates: age, sex, histology, stage, CRP, platelets). Our data verified the previously shown prognostic role of systemic inflammatory parameters in patients treated with lung-sparing surgery within multimodality therapy.
Expression of 3q Oncogene SEC62 Predicts Survival in Head and Neck Squamous Cell Carcinoma Patients Treated with Primary Chemoradiation
Authors: Linxweiler Maximilian , Schneider Matthias , Körner Sandrina , Knebel Moritz , Brust Lukas Alexander , Braun Felix Leon , Wemmert Silke , Wagner Mathias , Hecht Markus , Schick Bernhard , Kühn Jan Philipp
Published: December 2023

Primary chemoradiotherapy (CRT) is an established treatment option for locally advanced head and neck squamous cell carcinomas (HNSCC) usually combining intensity modified radiotherapy with concurrent platinum-based chemotherapy. Though the majority of patients can be cured with this regimen, treatment response is highly heterogeneous and can hardly be predicted. SEC62 represents a metastasis stimulating oncogene that is frequently overexpressed in various cancer entities and is associated with poor outcome. Its role in HNSCC patients undergoing CRT has not been investigated so far. A total of 127 HNSCC patients treated with primary CRT were included in this study. The median follow-up was 5.4 years. Pretherapeutic tissue samples of the primary tumors were used for immunohistochemistry targeting SEC62. SEC62 expression, clinical and histopathological parameters, as well as patient outcome, were correlated in univariate and multivariate survival analyses. High SEC62 expression correlated with a significantly shorter overall survival (p = 0.015) and advanced lymph node metastases (p = 0.024). Further significant predictors of poor overall and progression-free survival included response to therapy (RECIST1.1), nodal status, distant metastases, tobacco consumption, recurrence of disease, and UICC stage. In a multivariate Cox hazard proportional regression analysis, only SEC62 expression (p = 0.046) and response to therapy (p < 0.0001) maintained statistical significance as independent predictors of the patients’ overall survival. This study identified SEC62 as an independent prognostic biomarker in HNSCC patients treated with primary CRT. The role of SEC62 as a potential therapeutic target and its interaction with radiation-induced molecular alterations in head and neck cancer cells should further be investigated.
Antitumoral Agent-Induced Constipation: A Systematic Review
Authors: Calsina-Berna Agnès , González-Barboteo Jesús , Llorens-Torromé Silvia , Julià-Torras Joaquim
Published: December 2023

Background: Constipation is a common symptom in patients receiving antitumoral treatment. The mechanisms underlying antitumoral agent-induced constipation (ATAIC) are poorly defined. This systematic review aimed to analyze and synthesize the available information related to the prevalence, etiology, and treatment of ATAIC. Methods: A systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines was conducted. The review included human studies written in English, French, or Spanish involving patients with cancer and containing information about the prevalence, etiology, and treatment of ATAIC. Results: A total of 73 articles were included. The reported prevalence ranged from 0.8% to 86.6%. Six studies reported an ATAIC prevalence of over 50%. The prevalence rates of constipation of grades 3 and 4 ranged between 0 and 11%. The importance of enteric neuronal integrity in gastrointestinal function was reported. The articles with the highest levels of evidence in relation to ATAIC treatment obtained in this systematic review studied treatments with acupuncture, sweet potato, osteopath, probiotics, and moxibustion. Conclusions: The prevalence of constipation in patients undergoing antitumoral treatment is very diverse. Studies specifically designed to report the prevalence of antineoplastic treatment-induced constipation are needed. The importance of enteric neuronal integrity in gastrointestinal function was described. Thus, neuroprotection could be an area of research for the treatment of chemotherapy-induced gastrointestinal disorders.
Prophylactic Interventions for Hereditary Breast and Ovarian Cancer Risks and Mortality in BRCA1/2 Carriers
Authors: Liu Taoran , Yu Jing , Gao Yangyang , Ma Xinyang , Jiang Shan , Gu Yuanyuan , Ming Wai-kit
Published: December 2023

Background: Hereditary breast and ovarian cancers (HBOCs) pose significant health risks worldwide and are mitigated by prophylactic interventions. However, a meta-analysis of their efficacy and the impact of different genetic variants on their effectiveness is lacking. Methods: A systematic review and meta-analysis were conducted, adhering to Cochrane guidelines. The review encompassed studies that involved prophylactic interventions for healthy women with BRCA variants, focusing on cancer incidence and mortality outcomes. The Newcastle–Ottawa Scale was used for risk of bias assessment. We pooled the extracted outcomes using random effects models and conducted subgroup analyses stratified by intervention, variant, and cancer types. Results: A total of 21 studies met the inclusion criteria. The meta-analysis revealed that prophylactic interventions significantly reduced cancer risk and mortality. The subgroup analysis showed a greater protective effect for BRCA2 than BRCA1 variant carriers. Risk-reducing surgeries (RRS) were more effective than chemoprevention, with RRS notably reducing cancer risk by 56% compared to 39% for chemoprevention. Prophylactic oophorectomy significantly reduced HBOC risks, while the effect of prophylactic mastectomy and chemoprevention on mortality was less conclusive. Conclusions: Prophylactic interventions significantly reduce the risk of HBOC and associated mortality. This comprehensive analysis provides insights for future economic evaluations and clinical decision-making in HBOC interventions.
Commensal Fecal Microbiota Profiles Associated with Initial Stages of Intestinal Mucosa Damage: A Pilot Study
Authors: Ruiz-Saavedra Sergio , Arboleya Silvia , Nogacka Alicja M. , González del Rey Carmen , Suárez Adolfo , Diaz Ylenia , Gueimonde Miguel , Salazar Nuria , González Sonia , de los Reyes-Gavilán Clara G.
Published: December 2023

Progressive intestinal mucosal damage occurs over years prior to colorectal cancer (CRC) development. The endoscopic screening of polyps and histopathological examination are used clinically to determine the risk and progression of mucosal lesions. We analyzed fecal microbiota compositions using 16S rRNA gene-based metataxonomic analyses and the levels of short-chain fatty acids (SCFAs) using gas chromatography in volunteers undergoing colonoscopy and histopathological analyses to determine the microbiota shifts occurring at the early stages of intestinal mucosa alterations. The results were compared between diagnosis groups (nonpathological controls and polyps), between samples from individuals with hyperplastic polyps or conventional adenomas, and between grades of dysplasia in conventional adenomas. Some microbial taxa from the Bacillota and Euryarchaeota phyla were the most affected when comparing the diagnosis and histopathological groups. Deeper microbiota alterations were found in the conventional adenomas than in the hyperplastic polyps. The Ruminococcus torques group was enriched in both the hyperplastic polyps and conventional adenomas, whereas the family Eggerthellaceae was enriched only in the hyperplastic polyps. The abundance of Prevotellaceae, Oscillospiraceae, Methanobacteriaceae, Streptococcaceae, Christensenellaceae, Erysipelotrichaceae, and Clostridiaceae shifted in conventional adenomas depending on the grade of dysplasia, without affecting the major SCFAs. Our results suggest a reorganization of microbial consortia involved in gut fermentative processes.
Improving HCC Prognostic Models after Liver Resection by AI-Extracted Tissue Fiber Framework Analytics
Authors: Stulpinas Rokas , Morkunas Mindaugas , Rasmusson Allan , Drachneris Julius , Augulis Renaldas , Gulla Aiste , Strupas Kestutis , Laurinavicius Arvydas
Published: December 2023

Despite advances in diagnostic and treatment technologies, predicting outcomes of patients with hepatocellular carcinoma (HCC) remains a challenge. Prognostic models are further obscured by the variable impact of the tumor properties and the remaining liver parenchyma, often affected by cirrhosis or non-alcoholic fatty liver disease that tend to precede HCC. This study investigated the prognostic value of reticulin and collagen microarchitecture in liver resection samples. We analyzed 105 scanned tissue sections that were stained using a Gordon and Sweet’s silver impregnation protocol combined with Picric Acid–Sirius Red. A convolutional neural network was utilized to segment the red-staining collagen and black linear reticulin strands, generating a detailed map of the fiber structure within the HCC and adjacent liver tissue. Subsequent hexagonal grid subsampling coupled with automated epithelial edge detection and computational fiber morphometry provided the foundation for region-specific tissue analysis. Two penalized Cox regression models using LASSO achieved a concordance index (C-index) greater than 0.7. These models incorporated variables such as patient age, tumor multifocality, and fiber-derived features from the epithelial edge in both the tumor and liver compartments. The prognostic value at the tumor edge was derived from the reticulin structure, while collagen characteristics were significant at the epithelial edge of peritumoral liver. The prognostic performance of these models was superior to models solely reliant on conventional clinicopathologic parameters, highlighting the utility of AI-extracted microarchitectural features for the management of HCC.
Synergistic Sensitization of High-Grade Serous Ovarian Cancer Cells Lacking Caspase-8 Expression to Chemotherapeutics Using Combinations of Small-Molecule BRD4 and CDK9 Inhibitors
Authors: Gasimli Khayal , Raab Monika , Mandal Ranadip , Krämer Andrea , Peña-Llopis Samuel , Tahmasbi Rad Morva , Becker Sven , Strebhardt Klaus , Sanhaji Mourad
Published: December 2023

Ovarian cancer is one of the most lethal gynecological cancers worldwide, with approximately 70% of cases diagnosed in advanced stages. This late diagnosis results from the absence of early warning symptoms and is associated with an unfavorable prognosis. A standard treatment entails a combination of primary chemotherapy with platinum and taxane agents. Tumor recurrence following first-line chemotherapy with Carboplatin and Paclitaxel is detected in 80% of advanced ovarian cancer patients, with disease relapse occurring within 2 years of initial treatment. Platinum-resistant ovarian cancer is one of the biggest challenges in treating patients. Second-line treatments involve PARP or VEGF inhibitors. Identifying novel biomarkers and resistance mechanisms is critical to overcoming resistance, developing newer treatment strategies, and improving patient survival. In this study, we have determined that low Caspase-8 expression in ovarian cancer patients leads to poor prognosis. High-Grade Serous Ovarian Cancer (HGSOC) cells lacking Caspase-8 expression showed an altered composition of the RNA Polymerase II-containing transcriptional elongation complex leading to increased transcriptional activity. Caspase-8 knockout cells display increased BRD4 expression and CDK9 activity and reduced sensitivities to Carboplatin and Paclitaxel. Based on our work, we are proposing three potential therapeutic approaches to treat advanced ovarian cancer patients who exhibit low Caspase-8 expression and resistance to Carboplatin and/or Paclitaxel—combinations of (1) Carboplatin with small-molecule BRD4 inhibitors; (2) Paclitaxel with small-molecule BRD4 inhibitors, and (3) small-molecule BRD4 and CDK9 inhibitors. In addition, we are also proposing two predictive markers of chemoresistance—BRD4 and pCDK9.
Adequacy of Pain Management in Patients Referred for Radiation Therapy: A Subanalysis of the Multicenter ARISE-1 Study
Authors: Donati Costanza , Maggiore Chiara , Maltoni Marco , Rossi Romina , Nardi Elena , Zamagni Alice , Siepe Giambattista , Mammini Filippo , Cellini Francesco , Di Rito Alessia , Portaluri Maurizio , De Tommaso Cristina , Santacaterina Anna , Tamburella Consuelo , Di Franco Rossella , Parisi Salvatore , Cossa Sabrina , Fusco Vincenzo , Bianculli Antonella , Ziccarelli Pierpaolo , Ziccarelli Luigi , Genovesi Domenico , Caravatta Luciana , Deodato Francesco , Macchia Gabriella , Fiorica Francesco , Napoli Giuseppe , Buwenge Milly , Morganti Alessio
Published: December 2023

Background: Pain is a prevalent symptom among cancer patients, and its management is crucial for improving their quality of life. However, pain management in cancer patients referred to radiotherapy (RT) departments is often inadequate, and limited research has been conducted on this specific population. This study aimed to assess the adequacy and effectiveness of pain management when patients are referred for RT. Moreover, we explored potential predictors of adequate pain management. Methods: This observational, prospective, multicenter cohort study included cancer patients aged 18 years or older who were referred to RT departments. A pain management assessment was conducted using the Pain Management Index (PMI), calculated by subtracting the pain score from the analgesic score (PMI < 0 indicated inadequate pain management). Univariate and multivariate analyses were performed to identify predictors of adequate pain management. Results: A total of 1042 cancer outpatients were included in the study. The analysis revealed that 42.9% of patients with pain did not receive adequate pain management based on PMI values. Among patients with pain or taking analgesics and referred to palliative or curative RT, 72% and 75% had inadequate or ineffective analgesic therapy, respectively. The odds of receiving adequate pain management (PMI ≥ 0) were higher in patients undergoing palliative RT (OR 2.52; p < 0.001), with worse ECOG-PS scores of 2, 3 and 4 (OR 1.63, 2.23, 5.31, respectively; p: 0.017, 0.002, 0.009, respectively) compared to a score of 1 for those with cancer-related pain (OR 0.38; p < 0.001), and treated in northern Italy compared to central and southern of Italy (OR 0.25, 0.42, respectively; p < 0.001). Conclusions: In this study, a substantial proportion of cancer patients referred to RT departments did not receive adequate pain management. Educational and organizational strategies are necessary to address the inadequate pain management observed in this population. Moreover, increasing the attention paid to non-cancer pain and an earlier referral of patients for palliative RT in the course of the disease may improve pain response and treatment outcomes.
Multimodal Intraoperative Neurophysiological Monitoring in Intramedullary Spinal Cord Tumors: A 10-Year Single Center Experience
Authors: Tropeano Maria Pia , Rossini Zefferino , Franzini Andrea , Capo Gabriele , Olei Simone , De Robertis Mario , Milani Daniela , Fornari Maurizio , Pessina Federico
Published: December 2023

Objective: The study aimed at evaluating the efficacy and the ability of D-wave monitoring combined with somatosensory evoked potentials (SSEPs) and motor evoked potentials (MEPs) to predict functional outcomes in intramedullary spinal cord tumor (IMSCT) surgery. Methods: Between December 2011 and December 2020, all patients harboring IMSCT who underwent surgery at our institution were prospectively collected in a surgical spinal registry and retrospectively analyzed. Patient charts and surgical and histological reports were analyzed. The multimodal IONM included SSEPs, MEPs, and—whenever possible—D-waves. All patients were evaluated using the modified McCormick and Frankel grade at admission and 3, 6, and 12 months of follow-up. Results: Sixty-four patients were enrolled in the study. SSEP and MEP monitoring was performed in all patients. The D-wave was not recordable in seven patients (11%). Significant IONM changes (at least one evoked potential modality) were registered in 26 (41%) of the 64 patients. In five cases (8%) where the SSEPs and MEPs lost and the D-wave permanently dropped by about 50%, patients experienced a permanent deterioration of their neurological status. Multimodal IONM (SSEP, MEP, and D-wave neuromonitoring) significantly predicted postoperative deficits (p = 0.0001), with a sensitivity of 100.00% and a specificity of 95.65%. However, D-waves demonstrated significantly higher sensitivity (100%) than MEPs (62.5%) and SSEPs (71.42%) alone. These tests’ specificities were 85.10%, 13.89%, and 17.39%, respectively. Comparing the area under ROC curves (AUCs) of these evoked potentials in 53 patients (where all three modalities of IONM were registered) using the pairwise t-test, D-wave monitoring appeared to have higher accuracy and ability to predict postoperative deficits with strong statistical significance compared with MEP and SSEP alone (0.992 vs. 0.798 vs. 0.542; p = 0.018 and p < 0.001). Conclusion: The use of multimodal IONM showed a statistically significant greater ability to predict postoperative deficits compared with SSEP, MEP, and D-wave monitoring alone. D-wave recording significantly increased the accuracy and clinical value of neurophysiological monitoring in IMSCT tumor resection.
The Impact of BRAF V600E Mutation Allele Frequency on the Histopathological Characteristics of Thyroid Cancer
Authors: Abdulhaleem Mawaddah , Bandargal Saruchi , Pusztaszeri Marc Philippe , Rajab Mohannad , Greenspoon Hannah , Krasner Joshua Ross , Da Silva Sabrina Daniela , Forest Véronique-Isabelle , Payne Richard J.
Published: December 2023

Background: A BRAF V600E mutation in papillary thyroid cancer (PTC) has been shown to be associated with aggressive behavior. Nevertheless, not all BRAF V600E PTCs behave aggressively. Allele frequency (AF) is the number of mutated molecules divided by the total number of wild-type molecules at a specific location in the genome. The relationship between BRAF V600E AF and the histopathological features of thyroid malignancies is not well understood. We hypothesized that the BRAF V600E AF will correlate directly with aggressive histopathological behavior. The aim of this study was to examine this relationship. Methods: A retrospective chart review was performed for patients treated for BRAF V600E thyroid malignancies from 2019 to 2022 at McGill University tertiary care hospitals (n = 317). Patients with BRAF V600E-positive malignancies that included information on AF were included (n = 44). The correlation between AF and tumor histopathological features was analyzed. Results: Out of the 44 nodules with a BRAF V600E mutation, those with aggressive features of PTC had a mean AF of 25.8%, which was significantly higher than the non-aggressive group with a mean AF of 10.25% (p = 0.020). Additionally, there was a statistically significant difference in mean AF between patients with a positive sentinel LN (29%) and those with a negative sentinel LN (17.8%) (p = 0.021). Classical PTC was present in 29.5% (13/44) of nodules, with a mean AF of 15.6%. The tall cell subtype was found in 64% (28/44) of nodules, with a mean AF of 23%. Solid and hobnail subtypes were less common in this study, and there was no statistically significant relationship between AF and histopathological subtypes (p = 0.107). Nodules smaller than 1cm had a mean AF of 13.3%, while nodules ranging from 1 2cm had a mean AF of 20.6%, and those larger than 2cm had a mean AF of 27.7%. However, no statistical difference was observed between AF and nodule size (p = 0.160). Conclusion: In this study, BRAF V600E mutations in conjunction with AF help to determine whether thyroid malignancies will display aggressive behavior. This pre-operative finding can help thyroid specialists to determine the extent of thyroidectomy and whether lymph node dissection is required.
Microtissue Culture Provides Clarity on the Relative Chondrogenic and Hypertrophic Response of Bone-Marrow-Derived Stromal Cells to TGF-β1, BMP-2, and GDF-5
Authors: Franco Rose Ann G. , McKenna Eamonn , Shajib Md. Shafiullah , Guillesser Bianca , Robey Pamela G. , Crawford Ross W. , Doran Michael R. , Futrega Kathryn
Published: December 2023

Chondrogenic induction of bone-marrow-derived stromal cells (BMSCs) is typically accomplished with medium supplemented with growth factors (GF) from the transforming growth factor-beta (TGF-β)/bone morphogenetic factor (BMP) superfamily. In a previous study, we demonstrated that brief (1–3 days) stimulation with TGF-β1 was sufficient to drive chondrogenesis and hypertrophy using small-diameter microtissues generated from 5000 BMSC each. This biology is obfuscated in typical large-diameter pellet cultures, which suffer radial heterogeneity. Here, we investigated if brief stimulation (2 days) of BMSC microtissues with BMP-2 (100 ng/mL) or growth/differentiation factor (GDF-5, 100 ng/mL) was also sufficient to induce chondrogenic differentiation, in a manner comparable to TGF-β1 (10 ng/mL). Like TGF-β1, BMP-2 and GDF-5 are reported to stimulate chondrogenic differentiation of BMSCs, but the effects of transient or brief use in culture have not been explored. Hypertrophy is an unwanted outcome in BMSC chondrogenic differentiation that renders engineered tissues unsuitable for use in clinical cartilage repair. Using three BMSC donors, we observed that all GFs facilitated chondrogenesis, although the efficiency and the necessary duration of stimulation differed. Microtissues treated with 2 days or 14 days of TGF-β1 were both superior at producing extracellular matrix and expression of chondrogenic gene markers compared to BMP-2 and GDF-5 with the same exposure times. Hypertrophic markers increased proportionally with chondrogenic differentiation, suggesting that these processes are intertwined for all three GFs. The rapid action, or “temporal potency”, of these GFs to induce BMSC chondrogenesis was found to be as follows: TGF-β1 > BMP-2 > GDF-5. Whether briefly or continuously supplied in culture, TGF-β1 was the most potent GF for inducing chondrogenesis in BMSCs.
Dose-Dependent Effects of Radiation on Mitochondrial Morphology and Clonogenic Cell Survival in Human Microvascular Endothelial Cells
Authors: Wang Li , Rivas Rafael , Wilson Angelo , Park Yu Min , Walls Shannon , Yu Tianzheng , Miller Alexandra C.
Published: December 2023

To better understand radiation-induced organ dysfunction at both high and low doses, it is critical to understand how endothelial cells (ECs) respond to radiation. The impact of irradiation (IR) on ECs varies depending on the dose administered. High doses can directly damage ECs, leading to EC impairment. In contrast, the effects of low doses on ECs are subtle but more complex. Low doses in this study refer to radiation exposure levels that are below those that cause immediate and necrotic damage. Mitochondria are the primary cellular components affected by IR, and this study explored their role in determining the effect of radiation on microvascular endothelial cells. Human dermal microvascular ECs (HMEC-1) were exposed to varying IR doses ranging from 0.1 Gy to 8 Gy (~0.4 Gy/min) in the AFRRI 60-Cobalt facility. Results indicated that high doses led to a dose-dependent reduction in cell survival, which can be attributed to factors such as DNA damage, oxidative stress, cell senescence, and mitochondrial dysfunction. However, low doses induced a small but significant increase in cell survival, and this was achieved without detectable DNA damage, oxidative stress, cell senescence, or mitochondrial dysfunction in HMEC-1. Moreover, the mitochondrial morphology was assessed, revealing that all doses increased the percentage of elongated mitochondria, with low doses (0.25 Gy and 0.5 Gy) having a greater effect than high doses. However, only high doses caused an increase in mitochondrial fragmentation/swelling. The study further revealed that low doses induced mitochondrial elongation, likely via an increase in mitochondrial fusion protein 1 (Mfn1), while high doses caused mitochondrial fragmentation via a decrease in optic atrophy protein 1 (Opa1). In conclusion, the study suggests, for the first time, that changes in mitochondrial morphology are likely involved in the mechanism for the radiation dose-dependent effect on the survival of microvascular endothelial cells. This research, by delineating the specific mechanisms through which radiation affects endothelial cells, offers invaluable insights into the potential impact of radiation exposure on cardiovascular health.
Complex Spatio-Temporal Interplay of Distinct Immune and Bone Cell Subsets during Bone Fracture Healing
Authors: Schlundt Claudia , Saß Radost A. , Bucher Christian H. , Bartosch Sabine , Hauser Anja E. , Volk Hans-Dieter , Duda Georg N. , Schmidt-Bleek Katharina
Published: December 2023

Background: The healing of a bone injury is a highly complex process involving a multitude of different tissue and cell types, including immune cells, which play a major role in the initiation and progression of bone regeneration. Methods: We histologically analyzed the spatio-temporal occurrence of cells of the innate immune system (macrophages), the adaptive immune system (B and T lymphocytes), and bone cells (osteoblasts and osteoclasts) in the fracture area of a femoral osteotomy over the healing time. This study was performed in a bone osteotomy gap mouse model. We also investigated two key challenges of successful bone regeneration: hypoxia and revascularization. Results: Macrophages were present in and around the fracture gap throughout the entire healing period. The switch from initially pro-inflammatory M1 macrophages to the anti-inflammatory M2 phenotype coincided with the revascularization as well as the appearance of osteoblasts in the fracture area. This indicates that M2 macrophages are necessary for the restoration of vessels and that they also play an orchestrating role in osteoblastogenesis during bone healing. The presence of adaptive immune cells throughout the healing process emphasizes their essential role for regenerative processes that exceeds a mere pathogen defense. B and T cells co-localize consistently with bone cells throughout the healing process, consolidating their crucial role in guiding bone formation. These histological data provide, for the first time, comprehensive information about the complex interrelationships of the cellular network during the entire bone healing process in one standardized set up. With this, an overall picture of the spatio-temporal interplay of cellular key players in a bone healing scenario has been created. Conclusions: A spatio-temporal distribution of immune cells, bone cells, and factors driving bone healing at time points that are decisive for this process—especially during the initial steps of inflammation and revascularization, as well as the soft and hard callus phases—has been visualized. The results show that the bone healing cascade does not consist of five distinct, consecutive phases but is a rather complex interrelated and continuous process of events, especially at the onset of healing.
Derivation and Characterization of Novel Cytocompatible Decellularized Tissue Scaffold for Myoblast Growth and Differentiation
Authors: Singh Anshuman , Singh Suraj Kumar , Kumar Vinod , Gupta Jalaj , Kumar Manoj , Sarma Devojit Kumar , Singh Samradhi , Kumawat Manoj , Verma Vinod
Published: December 2023

The selection of an appropriate scaffold is imperative for the successful development of alternative animal protein in the form of cultured meat or lab-grown meat. Decellularized tissues have been suggested as a potential scaffold for cultured meat production owing to their capacity to support an optimal environment and niche conducive to cell proliferation and growth. This approach facilitates the systematic development of 3D tissues in the laboratory. Decellularized scaffold biomaterials have characteristics of high biocompatibility, biodegradation, and various bioactivities, which could potentially address the limitations associated with synthetic bio-scaffold materials. The present study involved the derivation and characterization of a decellularized scaffold from mushroom tissue following subsequent assessment of the scaffold’s capacity to support myogenic differentiation. Mushroom sections were soaked in nuclease and detergent solution for 4 days. Furthermore, decellularization was confirmed by histology and DAPI staining, which showed the removal of cellular components and nuclei. Myoblast cells were seeded onto decellularized tissue, which exhibited excellent cytocompatibility and promoted myogenic growth and differentiation. The study’s findings can serve as a foreground for the generation of an edible and natural scaffold for producing a safe and disease-free source of alternative animal protein, potentially reducing the burden on the health sector caused by conventional animal protein production and consumption.
The Role of Apoptosis and Oxidative Stress in a Cell Spheroid Model of Calcific Aortic Valve Disease
Authors: Coutts Colin W. , Baldwin Ashley M. , Jebeli Mahvash , Jolin Grace E. , Mungai Rozanne W. , Billiar Kristen L.
Published: December 2023

Calcific aortic valve disease (CAVD) is the most common heart valve disease among aging populations. There are two reported pathways of CAVD: osteogenic and dystrophic, the latter being more prevalent. Current two-dimensional (2D) in vitro CAVD models have shed light on the disease but lack three-dimensional (3D) cell–ECM interactions, and current 3D models require osteogenic media to induce calcification. The goal of this work is to develop a 3D dystrophic calcification model. We hypothesize that, as with 2D cell-based CAVD models, programmed cell death (apoptosis) is integral to calcification. We model the cell aggregation observed in CAVD by creating porcine valvular interstitial cell spheroids in agarose microwells. Upon culture in complete growth media (DMEM with serum), calcium nodules form in the spheroids within a few days. Inhibiting apoptosis with Z-VAD significantly reduced calcification, indicating that the calcification observed in this model is dystrophic rather than osteogenic. To determine the relative roles of oxidative stress and extracellular matrix (ECM) production in the induction of apoptosis and subsequent calcification, the media was supplemented with antioxidants with differing effects on ECM formation (ascorbic acid (AA), Trolox, or Methionine). All three antioxidants significantly reduced calcification as measured by Von Kossa staining, with the percentages of calcification per area of AA, Trolox, Methionine, and the non-antioxidant-treated control on day 7 equaling 0.17%, 2.5%, 6.0%, and 7.7%, respectively. As ZVAD and AA almost entirely inhibit calcification, apoptosis does not appear to be caused by a lack of diffusion of oxygen and metabolites within the small spheroids. Further, the observation that AA treatment reduces calcification significantly more than the other antioxidants indicates that the ECM stimulatory effect of AA plays a role inhibiting apoptosis and calcification in the spheroids. We conclude that, in this 3D in vitro model, both oxidative stress and ECM production play crucial roles in dystrophic calcification and may be viable therapeutic targets for preventing CAVD.
Clinical Characteristics of Infants with Symptomatic Congenital and Postnatal Cytomegalovirus Infection—An 11-Year Multicenter Cohort Study in Taiwan
Authors: Chen Yu-Ning , Hsu Kai-Hsiang , Huang Chung-Guei , Chiang Ming-Chou , Chu Shih-Ming , Chen Chyi-Liang , Hsu Jen-Fu , Chueh Ho-Yen
Published: December 2023

(1) Background: Cytomegalovirus (CMV) infection is a prevalent viral disease among infants. The prevalence typically ranges from 0.2% to 2.4% among all newborns. There are limited data regarding the demographic characteristics of infants with symptomatic CMV infections. (2) Methods: In this retrospective cohort study using the Chang Gung Memorial Hospital multicenter database, infants with CMV infection determined by a positive urine culture, positive blood polymerase chain reaction assay or positive immunoglobulin M result for CMV from 2011 through 2021 were included. Clinical characteristics at initial diagnosis, management and outcomes were investigated. Congenital CMV (cCMV) infection is diagnosed within three weeks after birth; postnatal CMV (pCMV) is diagnosed when CMV is detected after the first 3 weeks of life. (3) Results: Among the 505 CMV-infected infants identified, 272 were included in the analysis. According to the age at initial presentation, 21 infants had cCMV infection and 251 had pCMV infection. Higher incidences of prematurity and being small for gestational age and a lower Z score for weight at diagnosis were observed in the cCMV group. While thrombocytopenia (61.9%) was the leading presentation in the cCMV group, hepatitis (59.8%) and prolonged jaundice (21.9%) were more common in the pCMV group. (4) Conclusions: Utilizing an 11-year multicenter database, we demonstrated the characteristics of infants with CMV infection in Taiwan and highlighted the demographic disparities and differing symptoms between the cCMV and pCMV groups. These findings emphasize the necessity for future research to refine screening policies, explore treatment options, and establish follow-up protocols for affected infants.
Patient and Technical Factors Associated with Difficult Arterial Access and Ultrasound Use in the Operating Room
Authors: Yanko Frank M. , Rivera Adovich , Cheon Eric C. , Mitchell John D. , Ballard Heather A.
Published: December 2023

Arterial catheterization enables continuous hemodynamic monitoring but has been shown to cause severe complications, especially when multiple attempts are required. The aim of this study was to explore what factors were associated with multiple attempts and ultrasound use in the operating room. We performed a retrospective analysis of patients who had arterial catheters inserted at a tertiary care children’s hospital from January 2018 to March 2022, identifying clinical factors that were associated with both outcomes. A total of 3946 successful arterial catheter insertions were included. Multivariable analysis showed multiple attempts were associated with noncardiac surgery: pediatric (OR: 1.79, 95% CI: 1.30–2.51), neurologic (OR: 2.63, 95% CI: 1.89–3.57), orthopedic (OR: 3.23, 95% CI: 2.27–4.55), and non-radial artery placement (OR: 5.00, 95% CI: 3.33–7.14) (all p < 0.001). Multivariable analysis showed ultrasound use was associated with neonates (OR: 9.6, 95% CI: 4.1–22.5), infants (OR: 6.98, 95% CI: 4.67–10.42), toddlers (OR: 6.10, 95% CI: 3.8–9.8), and children (OR: 2.0, 95% CI: 1.7–2.5) compared to teenagers, with cardiac surgery being relative to other specialties—pediatric (OR: 0.48, 95% CI: 0.3–0.7), neurologic (OR: 0.27, 95% CI: 0.18–0.40), and orthopedic (OR: 0.38, 95% CI: 0.25–0.58) (all p < 0.001). In our exploratory analysis, increased odds of first-attempt arterial catheter insertion success were associated with cardiac surgery, palpation technique, and radial artery placement. Younger patient age category, ASA III and IV status, cardiac surgery, and anesthesiologist placement were associated with increased odds of ultrasound use.
The Relationship of the PROMIS® Pediatric Physical Activity Measure with Cardiorespiratory Fitness
Authors: Tucker Carole A. , Lawrence Hannah S. , Hooke Mary C.
Published: December 2023

A The PROMIS® Pediatric Physical Activity (PA) measure is a new instrument with established validity that measures a child self-report on short bouts of moderate to rigorous physical activity. The purpose of this study was to explore the relationship of the PROMIS® Pediatric PA item bank with cardiorespiratory fitness and self-efficacy. The study was conducted at the Minnesota State Fair. Youth ages 8 to 18 years completed the PROMIS® Pediatric PA and the Self-Efficacy for PA measures on an iPad. Participants performed 3-min step test with heart rates measured 1 min posttest. Participants (N = 182) were 53% female. The PROMIS® Pediatric PA had a weak, significant negative correlation with the step test measurement (r = −0.23, p = 0.001) and a weak, significant positive correlation with self-efficacy (r = 0.27, p < 0.001). Measurements did not differ between groups by sex or age group (school-age and adolescent). Youth who were obese had significantly higher heart rates post step test (p = 0.004); BMI percentile groups did not differ in other measures. Self-report of PA and the physiologic measure of heart rate are from two related but different physical fitness domains which supports their significant but weak relationship.
Prevalence and Quantification of the Effects of Sexual Harassment Victimization of School-Aged Adolescents
Authors: Marcos Verónica , Seijo Dolores , Montes Álvaro , Arce Ramón
Published: December 2023

Background/aim: Sexual harassment has become a serious social and public health problem in adolescents, causing adverse effects on mental health. Nevertheless, some behaviours arise that, due to their characteristics, might be misinterpreted as sexual harassment. A field study using a survey with non-probabilistic accidental sampling was designed in order to estimate the prevalence of sexual harassment victimization in the Spanish adolescent population as well as to quantify the harms. Method: A total of 1028 Spanish adolescents, 54.3% females and 45.7% males aged 13–17 years (M = 15.21, SD = 1.03), responded to a diagnostic measure of sexual harassment victimization and an inventory measure of internalizing and externalizing mental health problems (MHPs). Results: The results showed a significant prevalence of diagnosed sexual harassment victimization of school-aged adolescents, 24.1%, 95% CI [0.215, 0.267], with adverse effects on internalizing and externalizing MHPs. As for the internalizing MHPs, the results exhibited moderate adverse effects on depression, anxiety, somatic burns, posttraumatic symptoms, and obsessive–compulsive symptoms, as well as mild adverse effects on social anxiety. Regarding externalizing MHPs, the results revealed moderate adverse effects on hyperactivity–impulsivity, anger control, and antisocial behaviour, as well as mild adverse effects on attention problems, aggression, and defiant behaviour. In addition, it was confirmed that sexual harassment victimization affects adolescent females to a greater extent, with the effect being significantly greater in internalizing than in externalizing MHPs. Conclusions: The results obtained are discussed and future lines of research and intervention are proposed to promote the implementation of prevention and intervention programs that address this phenomenon and, in turn, improve the physical, psychological, and social well-being of adolescents.
Analysis of Climate Variability and Its Implications on Rangelands in the Limpopo Province
Authors: Maluleke Phumzile , Moeletsi Mokhele E. , Tsubo Mitsuru
Published: December 2023

In recent decades, southern Africa has experienced a shift towards hotter and drier climate conditions, affecting vital sectors like agriculture, health, water, and energy. Scientific research has shown that the combination of high temperatures and unreliable rainfall can have detrimental effects on agricultural production. Thus, this study focused on assessing climate variability, with implications on rangelands in the Limpopo Province of South Africa over 38 years. Historical climate data from 15 stations, including rainfall and minimum and maximum temperatures from 1980 to 2018, were analysed. To achieve the main objective, various statistics including mean, standard deviation, and coefficient of variation (CV) were computed for all variables across four seasons. The results highlighted significant variability in rainfall, with Musina (71.2%) and Tshiombo (88.3%) stations displaying the highest variability during the September-to-April season. Both minimum and maximum temperatures displayed low variability. The Mann–Kendall test revealed both increasing and decreasing trends in minimum temperatures and rainfall across different stations. Notably, there was a significant increase in maximum temperatures. This study provides valuable climate information for decision makers, aiding in the planning and management of agricultural activities, particularly in understanding how climate variations affect forage availability in rangelands.
Evaluation of the Cyclic Fatigue Resistance of Tia Tornado Blue and Tia Tornado Gold in Curved Canals: In Vitro Study
Authors: Allahem Ziyad , Bendahmash Mohammad , Almeaither Reem , Alfawaz Hussam , Alqedairi Abdullah
Published: December 2023

(1) Background: The aim of this study was to investigate the cyclic fatigue behavior of the newly introduced endodontic instrument systems Tia Tornado Blue and Tia Tornado Gold. (2) Methods: The tested rotary instruments were divided according to their type into four groups as follows: Tia Tornado Blue (TTB), Tia Tornado Gold (TTG), Protaper Gold (PTG), and Vortex Blue (VB). The cyclic fatigue resistance of fifteen instruments of each group, totaling 60, was tested. Each instrument was rotated under continuous motion inside an artificial canal at simulated body temperature at the speed recommended by the manufacturer until fracture. The time to fracture was recorded, and the number of cycles to fracture (NCF) was calculated for each instrument. Additionally, the fractured segment length was calculated, and scanning electron microscopic (SEM) images were captured of the fractured surfaces. (3) Results: Statistical analysis revealed that the VB significantly had the highest NCF followed by the PTG, TTG, and TTB (p < 0.05). The lengths of the fractured segments were found to be similar among the tested instrument, which ranged from 4.42 to 4.86 mm (p > 0.05). SEM images exhibited the typical features of cyclic fatigue. (4) Conclusions: The newly introduced instruments, TTG and TTB, exhibited a significantly lower resistance to cyclic fatigue compared to the PTG and VB rotary instruments.
The Use of Natural Zeolites in Cement-Based Construction Materials—A State of the Art Review
Authors: Alexa-Stratulat Sergiu-Mihai , Olteanu Ioana , Toma Ana-Maria , Pastia Cristian , Banu Oana-Mihaela , Corbu Ofelia-Cornelia , Toma Ionut-Ovidiu
Published: December 2023

Natural zeolite is a honeycomb-structured aluminosilicate mineral with an open crystalline structure which makes it suitable for a variety of applications. Given the beneficial effects of zeolites on the properties of cementitious materials, the present paper aims to summarize the recent findings reported in the scientific literature on the use of zeolites in cement-based construction materials. This paper limits the analysis to natural zeolites. The influence of natural zeolites on the workability and setting time of cement-based construction materials revealed that increasing the zeolite content led to a reduction in workability compared to the control mixes. At the same time, the initial and final setting times of cement pastes showed a decreasing trend with an increase in the replacement percentage. The slow pozzolanic reaction of clinoptilolite zeolite results in lower flexural strength and compressive strength values of mortars at the age of 28 days. Blending zeolites with other supplementary cementitious materials resulted in improved values of the mechanical properties of mortar and concrete. The findings regarding the impact of zeolite on the durability of concrete suggest that zeolite shows promise as a viable alternative to cement, with positive effects on various aspects of durability. The majority of the durability factors are interconnected. The presence of conflicting findings is particularly significant in this context, highlighting the need for a comprehensive approach to address these challenges in the future.