bluuebunny/crossref_metadata_2025 huggingface dataset:
Patient Safety Comparison of Frameless and Frame-Based Stereotactic Navigation for Brain Biopsy—A Single Center Cohort Study
Authors: Vychopen Martin , Wach Johannes , Borger Valeri , Schneider Matthias , Eichhorn Lars , Maciaczyk Jaroslaw , Bara Gregor , Vatter Hartmut , Banat Mohammed , Hamed Motaz
Published: September 2022

Leksell stereotactic system-based aspiration biopsy is a common procedure in the neurosurgical treatment of deep-seated or multiple brain lesions. This study aimed to evaluate the benefit of frameless biopsy using VarioGuide compared to frame-based biopsy using the Leksell stereotactic system (LSS). We analyzed all brain biopsies using VarioGuide or LSS at our neurooncological Department of Neurosurgery in the University Hospital of Bonn between January 2018 and August 2020. We analyzed demographic data, duration of surgery, size of lesion, localization, and early complications. Uni-variable analyses were carried out on data from both groups. In total, 109 biopsies were compared (40 VarioGuide vs. 69 LSS). Patients with VarioGuide were significant older (74 (62–80) years vs. 67 (57–76) years; p = 0.03) and had a shorter duration of general anesthesia (163 (138–194) min vs. 193 (167–215) min, p < 0.001). We found no significant differences in surgery duration (VarioGuide median 28 min (IQR 20–38); LSS: median 30 min (IQR 25–39); p = 0.1352) or in early complication rates (5% vs. 7%; p = 0.644). A slightly higher false negative biopsy rate was registered in the LSS group (3 vs. 1; p = 0.1347). The size of the lesions also did not differ significantly between the two groups (18.31 ± 26.35 cm3 vs. 12.63 ± 14.62; p = 0.15). Our data showed that biopsies performed using VarioGuide took significantly less time than LSS biopsies and did not differ in complication rates. Both systems offered a high degree of patient safety.
Functional Source Separation-Identified Epileptic Network: Analysis Pipeline
Authors: Olejarczyk Elzbieta , Zappasodi Filippo , Ricci Lorenzo , Pascarella Annalisa , Pellegrino Giovanni , Paulon Luca , Assenza Giovanni , Tecchio Franca
Published: September 2022

This proof-of-concept (PoC) study presents a pipeline made by two blocks: 1. the identification of the network that generates interictal epileptic activity; and 2. the study of the time course of the electrical activity that it generates, called neurodynamics, and the study of its functional connectivity to the other parts of the brain. Network identification is achieved with the Functional Source Separation (FSS) algorithm applied to electroencephalographic (EEG) recordings, the neurodynamics quantified through signal complexity with the Higuchi Fractal Dimension (HFD), and functional connectivity with the Directed Transfer Function (DTF). This PoC is enhanced by the data collected before and after neuromodulation via transcranial Direct Current Stimulation (tDCS, both Real and Sham) in a single drug-resistant epileptic person. We observed that the signal complexity of the epileptogenic network, reduced in the pre-Real, pre-Sham, and post-Sham, reached the level of the rest of the brain post-Real tDCS. DTF changes post-Real tDCS were maintained after one month. The proposed approach can represent a valuable tool to enhance understanding of the relationship between brain neurodynamics characteristics, the effects of non-invasive brain stimulation, and epileptic symptoms.
The Model Sketch for Enhancing Lie Detection and Eliciting Information
Authors: Deeb Haneen , Vrij Aldert , Leal Sharon , Mann Samantha , Burkhardt Jennifer
Published: September 2022

Background: Sketching while narrating is an effective interview technique for eliciting information and cues to deceit. The current research examined the effects of introducing a Model Sketch in investigative interviews andis pre-registered on https://osf.io/kz9mc (accessed on 18 January 2022). Methods: Participants (N = 163) completed a mock mission and were asked to tell the truth or to lie about it in an interview. In Phase 1 of the interview, participants provided either a free recall (control condition), sketched and narrated with exposure to a Model Sketch (Model Sketch-present condition), or sketched and narrated without exposure to a Model Sketch (Model Sketch-absent condition). In Phase 2, all participants provided a free recall without sketching. Results: Truth tellers reported significantly more information than lie tellers. The Model Sketch elicited more location details than a Free recall in Phase 1 and more veracity differences than the other Modality conditions in Phase 2. Conclusion: The Model Sketch seems to enhance the elicitation of information and to have carryover veracity effects in a follow-up free recall.
Non-Linear Analysis and Retrofitting by Steelwork of a Precast RC Warehouse
Authors: Formisano Antonio , Davino Antonio
Published: September 2022

Seismic upgrading and retrofitting of existing constructions is a pressing need for designers and researchers. The necessity of efficient seismic upgrading/retrofitting techniques is, therefore, required in seismic-prone countries, such as Italy. In this framework, steelwork has clearly shown many advantageous applications in the last century. Nonetheless, if compared to other different technologies, steelwork is still limited for consolidation purposes. Moreover, the wide damage provoked by earthquakes to industrial buildings have induced scientific research to investigate the seismic vulnerability of such constructions much more. In the current study, the attention has been, therefore, focused on the use of steelwork systems as anti-seismic intervention techniques from a precast RC industrial warehouse hit by the 2012 Northern Italy earthquakes. Besides the usefulness of steelwork in implementing reliable techniques against earthquakes, the paper has the aim of discussing the different seismic behaviour of the building deriving from dissimilar beam-to-column joint types obtained using steelwork interventions. Other than the widely diffused static scheme with hinges, other types of joints (semi-rigid and rigid), along with the presence of a rigid roof, have been investigated, and the different seismic risk indicators derived from these static schemes have been achieved, highlighting the case of the best seismic behaviour of the warehouse. Finally, the effectiveness of local steel interventions in improving the efficient global response of the building has also been highlighted.
Investigation of Seismic Performance for Low-Rise RC Buildings with Different Patterns of Infill Walls
Authors: Saengyuan Saharat , Latcharote Panon
Published: September 2022

Evaluating the structural performance of low-rise RC buildings with infill walls is an essential issue in Thailand, as most infill walls were not designed for lateral load resistance. The purpose of this study was to predict the structural behavior and illustrate the effects of infill walls. Residential, commercial, and educational buildings were selected as representative buildings with different patterns of infill walls. Based on the results, infill walls contributed to considerable strength and stiffness. Most of the infill walls that affected the low-rise buildings were at the ground floor level. The behavior of the buildings that had a contribution of infill walls was found to be brittle until the infill walls collapsed, and then the buildings became ductile. Some patterns in which infill walls were placed improperly led to a torsional effect, resulting in columns in the affected areas reaching failure criteria more than those without this effect. Considering the NLRHA procedure, only infill walls on the ground floor contributed to the building being subjected to a ground motion. The fully infilled frame tended to reach the infill crack before the other patterns. For the UMRHA procedure, only the first vibration mode was adequate to predict seismic responses, such as roof displacement and top-story drift.
A Methodological Framework to Optimize Data Management Costs and the Hand-Over Phase in Cultural Heritage Projects
Authors: Pinti Lidia , Bonelli Serena
Published: September 2022

This paper illustrates a methodological approach to optimize the data management process and to reduce costs related to information loss, from the preliminary phases to the Facility Management (FM) one. The growing concern about sustainability issues has steadily increased attention to cultural heritage’s key role. Concurrently, Europe promotes the application of digital methods for managing interventions both for new and existing buildings. The data issue, especially in heritage projects, represents a crucial aspect; data-recovering activities or shortages of information contribute to relevant expenses and discourage stakeholders. The research focuses on how procedures involving digitalization, applied to heritage projects, can improve the information workflow, supporting the hand-over stage. Although the application of digital techniques has recognized advantages, enhancements for optimizing time and cost savings are required. The research result is a methodological framework to obtain complete heritage as-built deliverables for the management phase. The defined structure is applied through a case study approach to the restoration of a historical lyric theater. Thus, the as-built model represents a database for controlling costs and maintenance procedures. In the end, the work provides a tangible contribution to the Heritage BIM (HBIM) delivery and can be a starting point for future improvements.
Comprehensive Treatment Algorithms of the Swiss Peritoneal Cancer Group for Peritoneal Cancer of Gastrointestinal Origin
Authors: Adamina Michel , Warlaumont Maxime , Berger Martin D. , Däster Silvio , Delaloye Raphaël , Digklia Antonia , Gloor Beat , Fritsch Ralph , Koeberle Dieter , Koessler Thibaud , Lehmann Kuno , Müller Phaedra , Peterli Ralph , Ris Frédéric , Steffen Thomas , Weisshaupt Christian Stefan , Hübner Martin
Published: September 2022

Peritoneal cancer (PC) is a dire finding, yet in selected patients, long-term survival is possible. Complete cytoreductive surgery (CRS) together with combination immunochemotherapy is essential to achieve cure. Hyperthermic intraperitoneal chemotherapy (HIPEC) and pressurized intraperitoneal aerosol chemotherapy (PIPAC) are increasingly added to the multimodal treatment. The Swiss Peritoneal Cancer Group (SPCG) is an interdisciplinary group of expert clinicians. It has developed comprehensive treatment algorithms for patients with PC from pseudomyxoma peritonei, peritoneal mesothelioma, gastric, and colorectal origin. They include multimodal neoadjuvant treatment, surgical resection, and palliative care. The indication for and results of CRS HIPEC and PIPAC are discussed in light of the current literature. Institutional volume and clinical expertise required to achieve best outcomes are underlined, while inclusion of patients considered for CRS HIPEC and PIPAC in a clinical registry is strongly advised. The present recommendations are in line with current international guidelines and provide the first comprehensive treatment proposal for patients with PC including intraperitoneal chemotherapy. The SPCG comprehensive treatment algorithms provide evidence-based guidance for the multimodal care of patients with PC of gastrointestinal origin that were endorsed by all Swiss clinicians routinely involved in the multimodal care of these challenging patients.
A Treatment Paradigm Shift: Targeted Radionuclide Therapies for Metastatic Castrate Resistant Prostate Cancer
Authors: Parent Ephraim E. , Kase Adam M.
Published: September 2022

The recent approval of 177Lu PSMA-617 (Pluvicto®) by the United States Food and Drug Administration (FDA) is the culmination of decades of work in advancing the field of targeted radionuclide therapy for metastatic prostate cancer. 177Lu PSMA-617, along with the bone specific radiotherapeutic agent, 223RaCl2 (Xofigo®), are now commonly used in routine clinical care as a tertiary line of therapy for men with metastatic castrate resistant prostate cancer and for osseus metastatic disease respectively. While these radiopharmaceuticals are changing how metastatic prostate cancer is classified and treated, there is relatively little guidance to the practitioner and patient as to how best utilize these therapies, especially in conjunction with other more well-established regimens including hormonal, immunologic, and chemotherapeutic agents. This review article will go into detail about the mechanism and effectiveness of these radiopharmaceuticals and less well-known classes of targeted radionuclide radiopharmaceuticals including alpha emitting prostate specific membrane antigen (PSMA)-, gastrin-releasing peptide receptor (GRPR)-, and somatostatin targeted radionuclide therapeutics. Additionally, a thorough discussion of the clinical approach of these agents is included and required futures studies.
Liquid Biopsy, an Everchanging Balance between Clinical Utility and Emerging Technologies
Authors: Cucciniello Linda , Gerratana Lorenzo , Puglisi Fabio
Published: September 2022

To date, tissue biopsy still represents the mainstay for tumor diagnosis and molecular characterization [...]
Targeting Cellular Components of the Tumor Microenvironment in Solid Malignancies
Authors: Belli Carmen , Antonarelli Gabriele , Repetto Matteo , Boscolo Bielo Luca , Crimini Edoardo , Curigliano Giuseppe
Published: September 2022

Cancers are composed of transformed cells, characterized by aberrant growth and invasiveness, in close relationship with non-transformed healthy cells and stromal tissue. The latter two comprise the so-called tumor microenvironment (TME), which plays a key role in tumorigenesis, cancer progression, metastatic seeding, and therapy resistance. In these regards, cancer-TME interactions are complex and dynamic, with malignant cells actively imposing an immune-suppressive and tumor-promoting state on surrounding, non-transformed, cells. Immune cells (both lymphoid and myeloid) can be recruited from the circulation and/or bone marrow by means of chemotactic signals, and their functionality is hijacked upon arrival at tumor sites. Molecular characterization of tumor-TME interactions led to the introduction of novel anti-cancer therapies targeting specific components of the TME, such as immune checkpoint blockers (ICB) (i.e., anti-programmed death 1, anti-PD1; anti-Cytotoxic T-Lymphocyte Antigen 4, anti-CTLA4). However, ICB resistance often develops and, despite the introduction of newer technologies able to study the TME at the single-cell level, a detailed understanding of all tumor-TME connections is still largely lacking. In this work, we highlight the main cellular and extracellular components of the TME, discuss their dynamics and functionality, and provide an outlook on the most relevant clinical data obtained with novel TME-targeting agents, with a focus on T lymphocytes, macrophages, and cancer-associated fibroblasts.
Phase II Study Combining Pembrolizumab with Aromatase Inhibitor in Patients with Metastatic Hormone Receptor Positive Breast Cancer
Authors: Ge Xuan , Yost Susan E. , Lee Jin Sun , Frankel Paul H. , Ruel Christopher , Cui Yujie , Murga Mireya , Tang Aileen , Martinez Norma , Chung Samuel , Yeon Christina , Stewart Daphne , Li Daneng , Rajurkar Swapnil , Somlo George , Mortimer Joanne , Waisman James , Yuan Yuan
Published: September 2022

This study investigated the safety and antitumor activity of aromatase inhibitors (AI) with immune checkpoint inhibitor (ICI) pembrolizumab in patients with hormone receptor positive (HR+) human epidermal growth factor receptor 2-negative (HER2−) metastatic breast cancer (MBC) in a phase II study with a safety lead-in (NCT 02648477). Patients received pembrolizumab plus AI up to 2 years or until confirmed progression or unacceptable toxicity. Key eligibility criteria were HR+ HER2− MBC; RECIST v1.1 measurable disease; adequate organ function; and ECOG 0-1. Primary endpoints were safety and overall response rate. A 3-at-risk design was used for the safety lead-in with a targeted accrual of 20 patients. Grade 2 adverse events (AEs) included 35% fatigue, 20% rash, and 10% hot flashes. Grade 3 immune-related AEs (irAEs) related to pembrolizumab included 5% elevated AST/ALT, 5% rash, and 5% lymphopenia. Two (10%) patients had partial responses, three (15%) had stable disease, and 15 (75%) had progression of disease. Median progression-free survival was 1.8 months (95% CI 1.6, 2.6), median overall survival was 17.2 months (95% CI 9.4, NA), and median follow-up time was 40.1 months (range 31.3–46.8 months). The combination was well tolerated, but clinical activity was comparable to AI alone.
Challenges for Triple Negative Breast Cancer Treatment: Defeating Heterogeneity and Cancer Stemness
Authors: Mahmoud Rinad , Ordóñez-Morán Paloma , Allegrucci Cinzia
Published: September 2022

The Triple Negative Breast Cancer (TNBC) subtype is known to have a more aggressive clinical course compared to other breast cancer subtypes. Targeted therapies for this type of breast cancer are limited and patients are mostly treated with conventional chemo- and radio-therapies which are not specific and do not target resistant cells. Therefore, one of the major clinical challenges is to find compounds that target the drug-resistant cell populations which are responsible for reforming secondary tumours. The molecular profiling of the different TNBC subtypes holds a promise for better defining these resistant cells specific to each tumour. To this end, a better understanding of TNBC heterogeneity and cancer stemness is required, and extensive genomic analysis can help to understand the disease complexity and distinguish new molecular drivers that can be targeted in the clinics. The use of persister cancer cell-targeting therapies combined with other therapies may provide a big advance to improve TNBC patients’ survival.
Prevalence of ARID1A Mutations in Cell-Free Circulating Tumor DNA in a Cohort of 71,301 Patients and Association with Driver Co-Alterations
Authors: Kurzrock Razelle , Aggarwal Charu , Weipert Caroline , Kiedrowski Lesli , Riess Jonathan , Lenz Heinz-Josef , Gandara David
Published: September 2022

ARID1A abnormalities disturb transcriptional processes regulated by chromatin remodeling and correlate with immunotherapy responsiveness. We report the first blood-based cell-free DNA (cfDNA) next-generation sequencing (NGS) ARID1A analysis. From November 2016 through August 2019, 71,301 patients with advanced solid tumors underwent clinical blood-derived cfDNA testing. Of these patients, 62,851 (88%) had ≥1 cfDNA alteration, and 3137 (of the 62,851) (5%) had ≥1 deleterious ARID1A alteration (a frequency similar to the ~6% generally reported in tissue NGS), suggesting this non-invasive test’s value in interrogating ARID1A. ARID1A cfDNA alterations were most frequent in endometrial cancer, 21.3% of patients; bladder cancer, 12.9%; gastric cancer, 11%; cholangiocarcinoma, 10.9%; and hepatocellular carcinoma, 10.6%. Blood samples with a functional ARID1A abnormality had more alterations/sample (median, 6 versus 4; p < 0.0001) and more frequent co-alterations in ≥1 gene in key oncogenic pathways: signal transduction, RAS/RAF/MAPK, PI3K/Akt/mTor, and the cell cycle. Taken together, our data suggest that liquid (blood) biopsies identify ARID1A alterations at a frequency similar to that found in primary tumor material. Furthermore, co-alterations in key pathways, some of which are pharmacologically tractable, occurred more frequently in samples with functional (deleterious) ARID1A alterations than in those without such aberrations, which may inform therapeutic strategies.
Comment on Russo et al. Does Tumor Volume Have a Prognostic Role in Oropharyngeal Squamous Cell Carcinoma? A Systematic Review and Meta-Analysis. Cancers 2022, 14, 2465
Authors: Adrian Gabriel
Published: September 2022

I read the article by Russo et al. [...]
Association between Adverse Events and Prognosis in Patients with Hepatocellular Carcinoma Treated with Atezolizumab Plus Bevacizumab: A Multicenter Retrospective Study
Authors: Shimose Shigeo , Iwamoto Hideki , Tanaka Masatoshi , Niizeki Takashi , Kajiwara Masahiko , Itano Satoshi , Moriyama Etsuko , Shirono Tomotake , Noda Yu , Kamachi Naoki , Nakano Masahito , Kuromatsu Ryoko , Koga Hironori , Kawaguchi Takumi
Published: September 2022

This study aimed to evaluate the correlation between adverse events (AEs) and overall survival (OS) in patients with unresectable hepatocellular carcinoma treated with atezolizumab plus bevacizumab (atezo/beva). This was a multicenter study in which 130 patients were enrolled. Hypertension and skin disorders had a significant correlation with longer survival (median survival time (MST): not reached vs. 14.3 months and not reached vs. 14.8 months, p = 0.001 and p = 0.047, respectively). In contrast, liver injuries were significantly correlated with shorter survival (MST: 14.7 months vs. not reached, p = 0.036), and the median development time was 21 days. In a logistic regression analysis, fatigue ≥ grade 2, liver injury ≥ grade 3, and modified albumin–bilirubin grade 2b were identified as independent factors for discontinuation due to AEs. The OS in the no discontinuation due to AE group was significantly longer than that in the discontinuation due to AEs group (MST not reached vs. 11.2 months, p = 0.001). We concluded that the development of liver injury was a negative factor for OS and that we should be vigilant in monitoring AE during atezo/beva treatments.
Prognostic Capability of TNBC 3-Gene Score among Triple-Negative Breast Cancer Subtypes
Authors: Araujo Jhajaira M. , De la Cruz-Ku Gabriel , Cornejo Melanie , Doimi Franco , Dyer Richard , Gomez Henry L. , Pinto Joseph A.
Published: September 2022

Background: Triple-negative breast cancer (TNBC) is a complex and molecularly heterogeneous entity, with the poorest outcome compared with other breast cancer subtypes. Previously, we developed a TNBC 3-gene score with a significant prognostic capability. This study aims to test the 3-gene score in the different TNBC subtypes. Methods: Data from 204 TNBC patients treated with neoadjuvant chemotherapy were retrieved from public datasets and pooled (GSE25066, GSE58812, and GSE16446). After removing batch effects, cases were classified into Lehman’s TNBC subtypes and then the TNBC 3-gene score was used to evaluate the risk of distant recurrence in each subgroup. In addition, the association with tumor-infiltrating lymphocyte (TILs) levels was evaluated in a retrospective group of 72 TNBC cases. Results: The TNBC 3-gene score was able to discriminate patients with different risks within the pooled cohort (HR = 2.41 for high vs. low risk; 95%CI: 1.50–3.86). The score showed predictive capability in the immunomodulatory subtype (HR = 4.16; 95%CI: 1.63–10.60) and in the mesenchymal stem-like subtype (HR = 18.76; 95%CI: 1.68–208.97). In the basal-like 1, basal-like-2, and mesenchymal subtypes, the observed differential risk patterns showed no statistical significance. The score had poor predictive capability in the luminal androgen receptor subtype (p = 0.765). In addition, a low TNBC 3-gene score was related to a high level of TIL infiltration (p < 0.001). Conclusions: The TNBC 3-gene score is able to predict the risk of distant recurrence in TNBC patients, specifically in the immunomodulatory and mesenchymal stem-like subtype. Despite a small sample size in each subgroup, an improved prognostic capability was seen in TNBC subtypes with tumor-infiltrating components.
Determining the Potential of DNA Damage Response (DDR) Inhibitors in Cervical Cancer Therapy
Authors: Saha Santu , Rundle Stuart , Kotsopoulos Ioannis C. , Begbie Jacob , Howarth Rachel , Pappworth Isabel Y. , Mukhopadhyay Asima , Kucukmetin Ali , Marchbank Kevin J. , Curtin Nicola
Published: September 2022

Cisplatin-based chemo-radiotherapy (CRT) is the standard treatment for advanced cervical cancer (CC) but the response rate is poor (46–72%) and cisplatin is nephrotoxic. Therefore, better treatment of CC is urgently needed. We have directly compared, for the first time, the cytotoxicity of four DDR inhibitors (rucaparib/PARPi, VE-821/ATRi, PF-477736/CHK1i and MK-1775/WEE1i) as single agents, and in combination with cisplatin and radiotherapy (RT) in a panel of CC cells. All inhibitors alone caused concentration-dependent cytotoxicity. Low ATM and DNA-PKcs levels were associated with greater VE-821 cytotoxicity. Cisplatin induced ATR, CHK1 and WEE1 activity in all of the cell lines. Cisplatin only activated PARP in S-phase cells, but RT activated PARP in the entire population. Rucaparib was the most potent radiosensitiser and VE-821 was the most potent chemosensitiser. VE-821, PF-47736 and MK-1775 attenuated cisplatin-induced S-phase arrest but tended to increase G2 phase accumulation. In mice, cisplatin-induced acute kidney injury was associated with oxidative stress and PARP activation and was prevented by rucaparib. Therefore, while all inhibitors investigated may increase the efficacy of CRT, the greatest clinical potential of rucaparib may be in limiting kidney damage, which is dose-limiting.
A Subset of Secreted Proteins in Ascites Can Predict Platinum-Free Interval in Ovarian Cancer
Authors: Carroll Molly J. , Kaipio Katja , Hynninen Johanna , Carpen Olli , Hautaniemi Sampsa , Page David , Kreeger Pamela K.
Published: September 2022

The time between the last cycle of chemotherapy and recurrence, the platinum-free interval (PFI), predicts overall survival in high-grade serous ovarian cancer (HGSOC). To identify secreted proteins associated with a shorter PFI, we utilized machine learning to predict the PFI from ascites composition. Ascites from stage III/IV HGSOC patients treated with neoadjuvant chemotherapy (NACT) or primary debulking surgery (PDS) were screened for secreted proteins and Lasso regression models were built to predict the PFI. Through regularization techniques, the number of analytes used in each model was reduced; to minimize overfitting, we utilized an analysis of model robustness. This resulted in models with 26 analytes and a root-mean-square error (RMSE) of 19 days for the NACT cohort and 16 analytes and an RMSE of 7 days for the PDS cohort. High concentrations of MMP-2 and EMMPRIN correlated with a shorter PFI in the NACT patients, whereas high concentrations of uPA Urokinase and MMP-3 correlated with a shorter PFI in PDS patients. Our results suggest that the analysis of ascites may be useful for outcome prediction and identified factors in the tumor microenvironment that may lead to worse outcomes. Our approach to tuning for model stability, rather than only model accuracy, may be applicable to other biomarker discovery tasks.
Intelligent Identification of Early Esophageal Cancer by Band-Selective Hyperspectral Imaging
Authors: Tsai Tsung-Jung , Mukundan Arvind , Chi Yu-Sheng , Tsao Yu-Ming , Wang Yao-Kuang , Chen Tsung-Hsien , Wu I-Chen , Huang Chien-Wei , Wang Hsiang-Chen
Published: September 2022

In this study, the combination of hyperspectral imaging (HSI) technology and band selection was coupled with color reproduction. The white-light images (WLIs) were simulated as narrow-band endoscopic images (NBIs). As a result, the blood vessel features in the endoscopic image became more noticeable, and the prediction performance was improved. In addition, a single-shot multi-box detector model for predicting the stage and location of esophageal cancer was developed to evaluate the results. A total of 1780 esophageal cancer images, including 845 WLIs and 935 NBIs, were used in this study. The images were divided into three stages based on the pathological features of esophageal cancer: normal, dysplasia, and squamous cell carcinoma. The results showed that the mean average precision (mAP) reached 80% in WLIs, 85% in NBIs, and 84% in HSI images. This study′s results showed that HSI has more spectral features than white-light imagery, and it improves accuracy by about 5% and matches the results of NBI predictions.
Role of Lipids and Lipid Metabolism in Prostate Cancer Progression and the Tumor’s Immune Environment
Authors: Siltari Aino , Syvälä Heimo , Lou Yan-Ru , Gao Yuan , Murtola Teemu J.
Published: September 2022

Modulation of lipid metabolism during cancer development and progression is one of the hallmarks of cancer in solid tumors; its importance in prostate cancer (PCa) has been demonstrated in numerous studies. Lipid metabolism is known to interact with androgen receptor signaling, an established driver of PCa progression and castration resistance. Similarly, immune cell infiltration into prostate tissue has been linked with the development and progression of PCa as well as with disturbances in lipid metabolism. Immuno-oncological drugs inhibit immune checkpoints to activate immune cells’ abilities to recognize and destroy cancer cells. These drugs have proved to be successful in treating some solid tumors, but in PCa their efficacy has been poor, with only a small minority of patients demonstrating a treatment response. In this review, we first describe the importance of lipid metabolism in PCa. Second, we collate current information on how modulation of lipid metabolism of cancer cells and the surrounding immune cells may impact the tumor’s immune responses which, in part, may explain the unimpressive results of immune-oncological treatments in PCa.
MRD Monitoring by Multiparametric Flow Cytometry in AML: Is It Time to Incorporate Immune Parameters?
Authors: Pessach Ilias , Spyropoulos Theodoros , Lamprianidou Eleftheria , Kotsianidis Ioannis
Published: September 2022

Acute myeloid leukemia (AML) is a heterogeneous group of clonal myeloid disorders characterized by intrinsic molecular variability. Pretreatment cytogenetic and mutational profiles only partially inform prognosis in AML, whereas relapse is driven by residual leukemic clones and mere morphological evaluation is insensitive for relapse prediction. Measurable residual disease (MRD), an independent post-diagnostic prognosticator, has recently been introduced by the European Leukemia Net as a new outcome definition. However, MRD techniques are not yet standardized, thus precluding its use as a surrogate endpoint for survival in clinical trials and MRD-guided strategies in real-life clinical practice. AML resistance and relapse involve a complex interplay between clonal and immune cells, which facilitates the evasion of the leukemic clone and which is not taken into account when merely quantifying the residual leukemia. Multiparameter flow cytometry (MFC) offers the possibility of capturing an overall picture of the above interactions at the single cell level and can simultaneously assess the competence of anticancer immune response and the levels of residual clonal cells. In this review, we focus on the current status of MFC-based MRD in diverse AML treatment settings and introduce a novel perspective of combined immune and leukemia cell profiling for MRD assessment in AML.
The Role of Programmed Necrosis in Colorectal Cancer
Authors: Yu Yu-Qiang , Gamez-Belmonte Reyes , Patankar Jay V. , Liebing Eva , Becker Christoph
Published: September 2022

For quite a long time, necrosis was considered a chaotic and unorganized form of cell death. However, studies conducted during the past few decades unveiled multiple types of programmed necrosis, such as necroptosis, pyroptosis and ferroptosis. These types of programmed necrosis have been shown to play crucial roles in mediating pathological processes, including tumorigenesis. Almost all key mediators, such as RIPK3 and MLKL in necroptosis, GSDMD and caspase 1/11 in pyroptosis and GPX4 in ferroptosis, are highly expressed in intestinal epithelial cells (IECs). An aberrant increase or decrease in programmed necrosis in IECs has been connected to intestinal disorders. Here, we review the pathways of programmed necrosis and the specific consequences of regulated necrosis in colorectal cancer (CRC) development. Translational aspects of programmed necrosis induction as a novel therapeutic alternative against CRC are also discussed.
Are Wellness Visits a Possible and Effective Cure for the Increasing Cancer Burden in Poland? Example of Women’s Preventive Services in the U.S.
Authors: Koczkodaj Paweł , Camacho Fabian , Batten George P. , Anderson Roger T.
Published: September 2022

Background: Cancer is one of the leading causes of death among Polish women in general, and first in women aged 25–64. Contributing to this cancer burden are modifiable behavioral risk factors, including low utilization of cancer screenings. Poland has an urgent need for new systemic solutions that will decrease cancer burden in the female Polish population. This study examined the United States’ implementation of preventive wellness visits as a viable solution for implementation in Poland. Methods: Health insurance claims data for nearly three million women in five states of the U.S. were examined to identify use of mammograms, colorectal cancer screening, and lung cancer screening. Three subgroups of the cohort were assessed for the probability of receipt of screening associated with type of healthcare visit history (women with wellness visits—W; with wellness visits and related preventive services and screenings—W+P; and control group—C). All multiple comparisons were significant (alpha = 0.05) at p < 0.0001, except comparison between subgroups (W vs. P+W) for lung cancer screening. Results: Breast and colorectal cancer screenings had substantially higher participation after W and W+P in comparison with C; moreover, a slight increase after W or P+W was seen for lung cancer as well. Conclusions: Results indicate that wellness visits are an effective tool for increasing cancer screening among women in the U.S. Introduction of a similar solution in Poland could potentially help produce higher screening rates, address cancer prevention needs (not only for secondary cancer prevention), and lower cancer burden.
Impact of Tumour Epstein–Barr Virus Status on Clinical Outcome in Patients with Classical Hodgkin Lymphoma (cHL): A Review of the Literature and Analysis of a Clinical Trial Cohort of Children with cHL
Authors: Nohtani Mahdi , Vrzalikova Katerina , Ibrahim Maha , Powell Judith E. , Fennell Éanna , Morgan Susan , Grundy Richard , McCarthy Keith , Dewberry Sarah , Bouchal Jan , Bouchalova Katerina , Kearns Pamela , Murray Paul G.
Published: September 2022

In this study, we have re-evaluated how EBV status influences clinical outcome. To accomplish this, we performed a literature review of all studies that have reported the effect of EBV status on patient outcome and also explored the effect of EBV positivity on outcome in a clinical trial of children with cHL from the UK. Our literature review revealed that almost all studies of older adults/elderly patients have reported an adverse effect of an EBV-positive status on outcome. In younger adults with cHL, EBV-positive status was either associated with a moderate beneficial effect or no effect, and the results in children and adolescents were conflicting. Our own analysis of a series of 166 children with cHL revealed no difference in overall survival between EBV-positive and EBV-negative groups (p = 0.942, log rank test). However, EBV-positive subjects had significantly longer event-free survival (p = 0.0026). Positive latent membrane protein 1 (LMP1) status was associated with a significantly lower risk of treatment failure in a Cox regression model (HR = 0.21, p = 0.005). In models that controlled for age, gender, and stage, EBV status had a similar effect size and statistical significance. This study highlights the age-related impact of EBV status on outcome in cHL patients and suggests different pathogenic effects of EBV at different stages of life.
Intratumoral Niches of B Cells and Follicular Helper T Cells, and the Absence of Regulatory T Cells, Associate with Longer Survival in Early-Stage Oral Tongue Cancer Patients
Authors: Phanthunane Chumut , Wijers Rebecca , De Herdt Maria , Koljenović Senada , Sleijfer Stefan , Baatenburg de Jong Robert , Hardillo José , Debets Reno , Balcioglu Hayri
Published: September 2022

In early oral squamous cell carcinoma (OSCC), the occurrence of clusters between CD20 B cells and CD4 T cells in the invasive margin (IM) can be captured by using the CD20 cluster score, and is positively associated with patient survival. However, the exact contribution of different CD4 T cell subsets, as well as B cell subsets toward patient prognosis is largely unknown. To this end, we studied regulatory T cells ((Treg cells) FOXP3 and CD4), T helper-type 1 cells ((Th1 cells) Tbet and CD4), follicular helper T cells ((Tfh cells) Bcl6 and CD4), B cells (CD20), germinal center B cells ((GC B cells) BCL6 and CD20), and follicular dendritic cells ((fDCs) CD21) for their density, location, and interspacing using multiplex in situ immunofluorescence of 75 treatment-naïve, primary OSCC patients. We observed that Treg, Th1-, Tfh-, and GC B cells, but not fDCs, were abundantly present in the stroma as compared with the tumor, and in the IM as compared with in the center of the tumor. Patients with high CD20 cluster scores had a high density of all three CD4 T cell subsets and GC B cells in the stromal IM as compared with patients with low CD20 cluster scores. Notably, enriched abundance of Tfh cells (HR 0.20, p = 0.04), and diminished abundance of Treg cells (HR 0.10, p = 0.03), together with an overall short distance between Tfh and B cells (HR:0.08, p < 0.01), but not between Treg and B cells (HR 0.43, p = 0.28), were significantly associated with overall survival of patients with OSCC. Our study identified the prognostic value of clusters between CD20 B cells and Tfh cells in the stromal IM of OSCC patients, and enabled an improved understanding of the clinical value of a high CD20 cluster score, which requires validation in larger clinical cohorts.
Anti-Cancer Activity of Cannabis sativa Phytocannabinoids: Molecular Mechanisms and Potential in the Fight against Ovarian Cancer and Stem Cells
Authors: Koltai Hinanit , Shalev Nurit
Published: September 2022

Ovarian cancer (OC) is the most lethal gynecological malignancy, with about 70% of cases diagnosed only at an advanced stage. Cannabis sativa, which produces more than 150 phytocannabinoids, is used worldwide to alleviate numerous symptoms associated with various medical conditions. Recently, studies across a range of cancer types have demonstrated that the phytocannabinoids Δ9-trans-tetrahydrocannabinol (THC) and cannabidiol (CBD) have anti-cancer activity in vitro and in vivo, but also the potential to increase other drugs’ adverse effects. THC and CBD act via several different biological and signaling pathways, including receptor-dependent and receptor-independent pathways. However, very few studies have examined the effectiveness of cannabis compounds against OC. Moreover, little is known about the effectiveness of cannabis compounds against cancer stem cells (CSCs) in general and OC stem cells (OCSCs) in particular. CSCs have been implicated in tumor initiation, progression, and invasion, as well as tumor recurrence, metastasis, and drug resistance. Several hallmarks and concepts describe CSCs. OCSCs, too, are characterized by several markers and specific drug-resistance mechanisms. While there is no peer-reviewed information regarding the effect of cannabis and cannabis compounds on OCSC viability or development, cannabis compounds have been shown to affect genetic pathways and biological processes related to CSCs and OCSCs. Based on evidence from other cancer-type studies, the use of phytocannabinoid-based treatments to disrupt CSC homeostasis is suggested as a potential intervention to prevent chemotherapy resistance. The potential benefits of the combination of chemotherapy with phytocannabinoid treatment should be examined in ovarian cancer patients.
Surgical Outcomes of VRAM vs. Gracilis Flaps in Vulvo-Perineal Reconstruction Following Oncologic Resection: A Proportional Meta-Analysis
Authors: Eseme Ebai A. , Scampa Matteo , Viscardi Juan A. , Ebai Myriam , Kalbermatten Daniel F. , Oranges Carlo M.
Published: September 2022

Pelvic exenteration and abdominoperineal resection are radical techniques commonly used for locally advanced or recurrent pelvic malignancy with high morbidity due to large pelvic defects. Flaps can help provide healthy, well-vascularized, non-irradiated tissues to fill pelvic dead space. We conducted a proportional meta-analysis to compare surgical outcomes of vertical rectus abdominus myocutaneous flap (VRAM) vs. gracilis flap for vulvo-perineal reconstruction following oncologic resection. A comprehensive literature search was conducted in the MEDLINE, PubMed, Embase, Google Scholar, and Cochrane Library databases. Proportional meta-analysis was performed to compare the surgical outcomes of using VRAM or gracilis flaps. Our review yielded 16 eligible studies. The pooled resolution rate of overall donor site complications for VRAM flap (pooled proportion = 0.576 [95% CI 0.387, 0.754]) was significantly higher than the pooled rate of overall donor site complications of gracilis flap (pooled proportion = 0.160 [95% CI 0.058, 0.295]). Partial and total flap necrosis were similar in both groups. There was no statistically significant difference between minor and major complications for both flaps. Both flaps can be used safely for vulvo-perineal reconstruction following oncologic resection with similar recipient site outcomes, although the VRAM flap will have more donor site complications than the gracilis flap.
Visualizing Hydrophobic and Hydrophilic Enzyme Interactions during Immobilization by Means of Infrared Microscopy
Authors: Pauli Oliver , Ecker Achim , Cruz-Izquierdo Alvaro , Basso Alessandra , Serban Simona
Published: September 2022

A novel Fourier transform infrared (FT-IR) microscopy method was developed and used to analyze the diffusion of lipase CalB in two different resins during immobilization. The method consisted of a streamlined sample preparation process and an automated transmission FT-IR microscopic measurement using a commercial benchtop device. The immobilization of CalB was performed on a hydrophobic resin containing aromatic groups (ECR1030M based on divinylbenzene) and on a hydrophilic resin containing ester groups and thus oxygen (ECR8204M based on methacrylate) and FT-IR revealed that the kinetic of immobilization and the distribution of the enzyme on the two resins were completely different. Furthermore, the technique revealed that CalB was immobilized on the external surface only in the case of the hydrophobic ECR1030M in a layer of about 50–70 µm, whereas when immobilized on the hydrophilic carrier ECR8204M the interaction of the enzyme with the carrier was uniform over the full diameter of the polymer bead. The enzyme activity however was higher on the hydrophobic support ECR1030M.
Evidence for the Neuronal Expression and Secretion of Adiponectin
Authors: Abgrall Azénor , Poizat Ghislaine , Prevost Marianne , Riffault Laure , De La Barrera Laura , Hanine Rita , Djordjevic Katarina , Benomar Yacir , Taouis Mohammed
Published: September 2022

Peripheral adiponectin acts on the hypothalamus to inhibit energy expenditure and increase food intake through its receptors AdipoR1 and adipoR2. The hypothalamic expression of adiponectin is poorly documented. We hypothesize that whether hypothalamic adiponectin is confirmed, its expression and secretion could be regulated as peripheral adiponectin. Thus, in the present work, we aim to determine whether adiponectin is expressed in the hypothalamus and in two neuronal cell lines and investigate the potential mechanisms regulating its neuronal expression. Using immunohistochemistry, we show that adiponectin is expressed in the mediobasal hypothalamic neurons of mice. Adiponectin expression is also evidenced in two neuronal cell lines mHypo POMC (an adult mouse hypothalamic cell line) and SH-SY5Y (human neuroblastoma). The neuronal expression of adiponectin is increased in response to rosiglitazone treatment (a PPARγ agonist) and FGF21 and is decreased in insulin-resistant neurons. Furthermore, we show that adiponectin expressed by mHypo POMC neurons is secreted in a culture medium. Adiponectin also diminished the resistin-induced IL6 expression in SIMA9 cells, a microglia cell line. In conclusion, we evidenced the hypothalamic expression of adiponectin and its regulation at the neuronal level.
Molecular Mechanisms of Ferroptosis and Relevance to Cardiovascular Disease
Authors: Xie Lai-Hua , Fefelova Nadezhda , Pamarthi Sri Harika , Gwathmey Judith K.
Published: September 2022

Ferroptosis has recently been demonstrated to be a novel regulated non-apoptotic cell death characterized by iron-dependence and the accumulation of lipid peroxidation that results in membrane damage. Excessive iron induces ferroptosis by promoting the generation of both soluble and lipid ROS via an iron-dependent Fenton reaction and lipoxygenase (LOX) enzyme activity. Cytosolic glutathione peroxidase 4 (cGPX4) pairing with ferroptosis suppressor protein 1 (FSP1) and mitochondrial glutathione peroxidase 4 (mGPX4) pairing with dihydroorotate dehydrogenase (DHODH) serve as two separate defense systems to detoxify lipid peroxidation in the cytoplasmic as well as the mitochondrial membrane, thereby defending against ferroptosis in cells under normal conditions. However, disruption of these defense systems may cause ferroptosis. Emerging evidence has revealed that ferroptosis plays an essential role in the development of diverse cardiovascular diseases (CVDs), such as hemochromatosis-associated cardiomyopathy, doxorubicin-induced cardiotoxicity, ischemia/reperfusion (I/R) injury, heart failure (HF), atherosclerosis, and COVID-19–related arrhythmias. Iron chelators, antioxidants, ferroptosis inhibitors, and genetic manipulations may alleviate the aforementioned CVDs by blocking ferroptosis pathways. In conclusion, ferroptosis plays a critical role in the pathogenesis of various CVDs and suppression of cardiac ferroptosis is expected to become a potential therapeutic option. Here, we provide a comprehensive review on the molecular mechanisms involved in ferroptosis and its implications in cardiovascular disease.
A Novel lncRNA Mediates the Delayed Tooth Eruption of Cleidocranial Dysplasia
Authors: Xin Yuejiao , Liu Yang , Li Jie , Liu Dandan , Zhang Chenying , Wang Yixiang , Zheng Shuguo
Published: September 2022

Delayed eruption of permanent teeth is a common symptom of cleidocranial dysplasia (CCD). Previous studies have focused on the anomaly of osteogenesis resulting from mutations in the Runt-related transcription factor-2 gene (RUNX2). However, deficiencies in osteoclastogenesis and bone resorption, and the epigenetic regulation mediated by long non-coding (lnc)RNAs in CCD remain to be elucidated. Here, a novel osteoclast-specific lncRNA (OC-lncRNA) was identified during the osteoclast differentiation of RAW 264.7 cells transfected with a RUNX2 mutation expression cassette. We further confirmed that OC-lncRNA positively regulated osteoclastogenesis and bone resorption. The OC-lncRNA promoted the expression of CXC chemokine receptor type 3 (CXCR3) by competitively binding to microRNA (miR)-221-5p. The CXCR3–CXC-motif chemokine ligand 10 (CXCL10) interaction and nuclear factor-κB constituted a positive feedback that positively regulated osteoclastogenesis and bone resorption. These results demonstrate that OC-lncRNA-mediated osteoclast dysfunction via the OC-lncRNA–miR-221-5p–CXCR3 axis, which is involved in the process of delayed tooth eruption of CCD.