bluuebunny/crossref_metadata_2025 huggingface dataset:
Endocannabinoid System and Exogenous Cannabinoids in Depression and Anxiety: A Review
Authors: Hasbi Ahmed , Madras Bertha K. , George Susan R.
Published: February 2023

Background: There is a growing liberalization of cannabis-based preparations for medical and recreational use. In multiple instances, anxiety and depression are cited as either a primary or a secondary reason for the use of cannabinoids. Aim: The purpose of this review is to explore the association between depression or anxiety and the dysregulation of the endogenous endocannabinoid system (ECS), as well as the use of phytocannabinoids and synthetic cannabinoids in the remediation of depression/anxiety symptoms. After a brief description of the constituents of cannabis, cannabinoid receptors and the endocannabinoid system, the most important evidence is presented for the involvement of cannabinoids in depression and anxiety both in human and from animal models of depression and anxiety. Finally, evidence is presented for the clinical use of cannabinoids to treat depression and anxiety. Conclusions: Although the common belief that cannabinoids, including cannabis, its main studied components—tetrahydrocannabinol (THC) and cannabidiol (CBD)—or other synthetic derivatives have been suggested to have a therapeutic role for certain mental health conditions, all recent systematic reviews that we report have concluded that the evidence that cannabinoids improve depressive and anxiety disorders is weak, of very-low-quality, and offers no guidance on the use of cannabinoids for mental health conditions within a regulatory framework. There is an urgent need for high-quality studies examining the effects of cannabinoids on mental disorders in general and depression/anxiety in particular, as well as the consequences of long-term use of these preparations due to possible risks such as addiction and even reversal of improvement.
Usefulness and Reliability of the Bispectral Index during Balanced Anesthesia for Neurovascular Surgery in New Zealand White Rabbits
Authors: Petrucci Mariafrancesca , Spadavecchia Claudia , Wanderer Stefan , Boillat Gwendoline , Marbacher Serge , García Casalta Luisana Gisela , Casoni Daniela
Published: February 2023

Few data about the electroencephalogram and its calculated indices, such as the bispectral index (BIS), have been reported in rabbits. We aimed to evaluate whether a clinically stable anesthesia was mirrored by consistent and stable BIS values and to investigate the effects of modified cerebral blood supply, due to bilateral carotid clamping and re-opening, on BIS values. We also investigated the effects of fentanyl, as an antinociceptive drug, on the BIS. Sixty-eight rabbits undergoing general anesthesia for surgical creation of carotid bifurcation aneurysms were enrolled. The BIS values were recorded at nine selected time points (TPs) during each procedure and before and after fentanyl administration. The BIS values over time were compared with two-way repeated-measures analysis of variance followed by Tukey test, while the Wilcoxon signed rank test was performed to compare values at clamping and re-opening of the carotids as well as before and after fentanyl administration. The BIS values were significantly lower during anesthesia than at the end of anesthesia and at tracheal extubation; no significant differences were found among other TPs. Adequate depth of anesthesia was mirrored by consistent BIS values among rabbits, and alteration of cerebral blood supply did not modify BIS values, except once. Following fentanyl, BIS values did not change in a clinically relevant way.
Revisiting Multifactor Models of Dyslexia: Do They Fit Empirical Data and What Are Their Implications for Intervention?
Authors: Lorusso Maria Luisa , Toraldo Alessio
Published: February 2023

Developmental dyslexia can be viewed as the result of the effects of single deficits or multiple deficits. This study presents a test of the applicability of a multifactor-interactive model (MFi-M) with a preliminary set of five variables corresponding to different neuropsychological functions involved in the reading process. The model has been tested on a sample of 55 school-age children with developmental dyslexia. The results show that the data fit a model in which each variable contributes to the reading ability in a non-additive but rather interactive way. These findings constitute a preliminary validation of the plausibility of the MFi-M, and encourage further research to add relevant factors and specify their relative weights. It is further discussed how subtype-based intervention approaches can be a suitable and advantageous framework for clinical intervention in a MFi-M perspective.
Current Opinions about the Use of Duloxetine: Results from a Survey Aimed at Psychiatrists
Authors: Alvarez-Mon M. A. , García-Montero Cielo , Fraile-Martinez Oscar , Quintero Javier , Fernandez-Rojo Sonia , Mora Fernando , Gutiérrez-Rojas Luis , Molina-Ruiz Rosa M. , Lahera Guillermo , Álvarez-Mon Melchor , Ortega Miguel A.
Published: February 2023

Major depressive disorder (MDD) is a complex psychiatric disorder that, presented alone or with other comorbidities, requires different adjustments of antidepressant treatments. Some investigations have demonstrated that psychoactive drugs, such as serotonin and norepinephrine reuptake inhibitors (SNRIs), can exert more effective and faster antidepressant effects than other common medications used, such as serotonin selective reuptake inhibitors (SSRIs), although these differences are still controversial. During the last five years, the SNRI duloxetine has shown favorable results in clinical practice for the treatment of MDD, anxiety, and fibromyalgia. Through an online self-completed survey, in the present article, we collected information from 163 psychiatrists regarding the use of duloxetine and its comparison with other psychiatric drugs, concerning psychiatrists’ knowledge and experience, as well as patients’ preferences, symptoms, and well-being. We discussed and contrasted physicians’ reports and the scientific literature, finding satisfactory concordances, and finally concluded that there is agreement regarding the use of duloxetine, not only due to its tolerability and effectiveness but also due to the wide variety of situations in which it can be used (e.g., somatic symptoms in fibromyalgia, diabetes) as it relieves neuropathic pain as well.
Traumatised Children’s Perspectives on Their Lived Experience: A Review
Authors: Chien Wai Tong , Lau Chi Tung
Published: February 2023

Introduction: Most children have exposure of traumatic events during their life, such as natural disasters, accidents, and abuses. A review of traumatised children’s perspective on traumatic events plays an important role in enhancing our understanding and promoting appropriate tailor-made intervention and support to these children. Methods: Four main health-related electronic databases were searched for all English full-text qualitative research articles over the past 11 years to uncover the recent best available perspective/evidence from traumatised children. The PRISMA checklist was adopted to guide the review process. Results: Five themes about children’s experiences and perspectives towards the traumatic events encountered were summarised and integrated from 19 qualitative studies identified. They included daily life problems related to trauma, negative responses to trauma, perceived health needs, coping strategies related to trauma and stress, and growth from traumatic experience. Conclusions: This systematic review provides evidence about responses/impacts and perceived health needs of traumatised children and informs the direction caregivers’ training can take, helping these children by early identification and timely intervention. More research is needed to examine/compare traumatised children’s responses and coping between diverse traumatic experiences, time from exposure, and the sociodemographic characteristics of these children.
Intention to Purchase Eco-Friendly Handcrafted Fashion Products for Gifting and Personal Use: A Comparison of National and Foreign Consumers
Authors: Saepudin Dindin , Shojaei Alireza Shabani , Barbosa Belem , Pedrosa Isabel
Published: February 2023

This study aims to examine consumer intention to purchase eco-friendly, handcrafted fashion products made from upcycled clothing and traditional Indonesian batik fabric. Data were collected via an online questionnaire with 289 participants, including both Indonesian and non-Indonesian consumers. The hypotheses were tested using structural equation modeling in SmartPLS 3. The results showed that fashion motivation and perceived value positively impacted the intention to purchase this type of product for personal use and for gifting. The perceived price had a positive effect on purchase intention for gifting. Altruistic motivations affected attitudes but not purchase intentions. Differences were identified between national and foreign consumers regarding the impact of price perception on attitudes and personal purchase intentions. The study provides practical implications for small businesses, artisan crafts, and entrepreneurs.
An Exploratory Study of Verbal and Non-Verbal Communication in Saudi Arabian Families
Authors: Abed Lowai G. , Abed Mohaned G. , Shackelford Todd K.
Published: February 2023

This exploratory study investigated whether factors such as gender, age, level of education, monthly income, and the number of family members are associated with verbal and non-verbal communication in Saudi Arabian families. A convenience sampling procedure was used to recruit 182 Saudi Arabian adults who responded to a self-report survey. Verbal and non-verbal communication was categorized into positive and negative communication. Descriptive and ordinal regression analyses were conducted to assess the relationships of familial variables with communication. Female gender status had a small negative association with positive communication, whereas the number of family members, level of education, monthly income, and age did not correlate with positive communication or negative communication. The Discussion section addresses the limitations of the current study and identifies several directions for future research, with special attention to the Saudi Arabian family context.
Negative Life Events and Procrastination among Adolescents: The Roles of Negative Emotions and Rumination, as Well as the Potential Gender Differences
Authors: Liu Lizhong , Zhang Tianyi , Xie Xiaochun
Published: February 2023

Procrastination (the intentional delay of action despite knowing that one will be worse off due to the delay) is a widespread phenomenon with various negative consequences, especially among adolescents. Based on relevant evidence, this study examined the relation between negative life events and adolescents’ procrastination, as well as the underlying mechanisms—specifically, the effects of negative emotions and rumination, as well as the potential gender differences. A total of 780 adolescents (Mage = 12.92 years old; 52.2% females) were recruited to complete a set of questionnaires assessing negative life events, procrastination, depression-anxiety-stress symptoms and rumination. Results showed that negative life events were positively associated with procrastination, and negative emotions significantly mediated the relation; rumination played a moderating role in this mediation model, specifically, both the direct and indirect effects in this mediation model were stronger for adolescents with higher rumination. Besides this, gender differences in this moderated mediation model were also found—the indirect effect of negative emotions was stronger for girls, and this mediating effect could be moderated by rumination only for boys. These results expanded our understanding of how negative life events influence procrastination and when (or for whom) negative life events influence procrastination the most. The findings also have significant implications for the prevention and intervention of adolescents’ procrastination.
Predicting Diverse Behaviors of Occupants When Turning Air Conditioners on/off in Residential Buildings: An Extreme Gradient Boosting Approach
Authors: Lyu Jiajun , Hagishima Aya
Published: February 2023

Occupant behavior (OB) has a significant impact on household air-conditioner (AC) energy use. In recent years, bottom-up simulation coupled with stochastic OB modeling has been intensively developed for estimating residential AC consumption. However, a comprehensive analysis of the diverse behavioral preference patterns of occupants regarding AC use is hampered by the limited availability of large-scale residential energy demand data. Therefore, this study aimed to develop a prediction model for the residential household’s AC usage considering various OB-related diversity patterns based on monitoring data of appliance-level electricity use in a residential community of 586 households in Osaka, Japan. First, individual operation schedules and thermal preferences were identified and quantitatively extracted as the two main factors for the diverse behaviors across the whole community. Then, a clustering analysis classified the target households, finding four typical patterns for schedule preferences and three typical patterns for thermal preferences. These results were used, with time and meteorological data in the summer seasons of 2013 and 2014, as inputs for the proposed prediction model using Extreme Gradient Boosting (XGBoost). The optimized XGBoost model showed a satisfactory prediction performance for the on/off state in the testing dataset, with an F1 score of 0.80 and an Area under the Receiver Operating Characteristic (ROC) Curve (AUC) of 0.845.
Effect of the MHS on Earthquake Response of Space Truss Structures under Horizontal Earthquake Motion
Authors: Liu Renjie , Cheng Tianchen , Wen Pan , Wang Chao , Wang Guangyong
Published: February 2023

Space truss structures are commonly used in long-span roof structures. Recently, middle-hung scoreboards (MHS), a kind of large-scale display device flexibly suspended in the center of the roof, have been widely used in gymnasiums. However, the effect of the MHS on dynamic characteristics and earthquake response of space truss structures needs to be investigated. In this paper, the effect on the MHS under horizontal earthquake motion is studied. The simplified model, where the MHS is simplified to four fixed masses on a structure, and the flexibly suspended model are established with Abaqus software, and the earthquake response is analyzed by the time-history method with the dynamic explicit method. The influence laws of the wire extent and the MHS weight are discussed. Compared with the simplified model, the nodal acceleration and the axial force rise up to 2.123 times and 1.575 times, respectively, in the flexibly suspended model, indicating that the amplification effect of the MHS acts significantly under horizontal earthquake motion. It turns out that the earthquake response of a space truss structure could be underestimated if a simplified model is used. The crest acceleration of both top chord nodes and bottom chords nodes are greatly influenced by the MHS weight but little affected by the wire extent. The influence laws of the MHS weight and the wire extent on crest axial forces of structural members are very complicated. The central regions of both the top chords and the bottom chords are the most affected regions, and the boundary regions parallel to the direction of the earthquake motion are the least affected regions. It is suggested that the envelope value under the conditions of different wire extent and MHS weight are used for structural design.
Study of Application of Fiber Reinforced Concrete in Anchorage Zone
Authors: Vavrus Martin , Kralovanec Jakub
Published: February 2023

In the case of post-tensioned or geotechnical structures, the anchorage zone is considered a critical part of the design and construction process. Generally, the failure of the anchorage zone is one of the most common problems. High-bearing stresses create significant transverse tension. For these reasons, conventional reinforcement, usually in the form of closed stirrups, must be designed. The presented analysis is focused on the possible increase of load-carrying capacity of the anchorage zone with steel fiber-reinforced concrete. Three types of specimens were analyzed. The first type of specimen represented the anchorage zone made from standard reinforced concrete. The second and third series of specimens were designed from fiber-reinforced concrete with two different volumes of steel fibers added into the anchorage zone. The parameters used in the numerical analysis of the anchorage zone were experimentally determined on a set of beam specimens. In the analysis, the anchorage zone was loaded by a node force applied on a steel load distribution plate placed on the top edge of the bloc. The performed numerical study suggests that the load-bearing capacity can be increased by adding fiber-reinforced concrete with a higher volume of fiber (Dramix 3D 55/30, volume of fiber of 110 kg/m3) into the vicinity of the anchorage plate.
Integrating Stakeholders’ Priorities into Level of Development Supplemental Guidelines for HBIM Implementation
Authors: Liu Junshan , Foreman Graham , Sattineni Anoop , Li Botao
Published: February 2023

Heritage Building Information Modeling (HBIM) is increasingly utilized to develop accurate and semantic-rich databases for the representation, preservation, and renovation of cultural heritage. A critical factor in successful HBIM delivery is the intended uses of the model, which need to be established by stakeholders at the onset of the program. Despite the greater application of Building Information Modeling (BIM) technologies to HBIM workflows, the discipline continues to lack clarity regarding information requirements from a tenant perspective. The first stage of this research was a review of 26 published HBIM case studies to extract information including HBIM workflows, level of development (LOD) models in the field, and the stakeholders’ participation in the HBIM program. The findings from the case studies conclude that most HBIM methodologies did not seek to understand the needs of assumptive stakeholders and lacked a clearly defined objective. Ten interviews with proprietors of ten different historic courthouses in the southeastern United States were also included in the study, which were used to identify the priorities of HBIM programs from a built heritage stakeholder’s standpoint. These priorities were used in conjunction with reviewed field standards to develop LOD supplement guidelines applicable for HBIM, which were then validated through a case study. The findings of this research conclude that the creation of LOD guidelines for HBIM application is both achievable and advisable, as they allow stakeholders to identify their priorities for HBIM projects. Such guidelines would assist in standardizing the HBIM discipline and disseminating its usefulness to historic building managers. This research also provides standards that allow cultural heritage stakeholders to make informed decisions about potential HBIM programs and maximize the use of resources to implement such programs. Moreover, the methodology implemented in this research offers a valuable example for future studies on HBIM guidelines and regulations.
Comparison of Wood Moisture Meters Operating on Different Principles of Measurement
Authors: Běťák Adam , Zach Jiří , Misák Petr , Vaněrek Jan
Published: February 2023

This experiment compared commercially available moisture meters (three capacitive metersand one resistance meter) and tested their predictive ability at different moisture conditions on selected beech (Fagus sylvatica) and spruce (Picea abies (L.) Karst.) wood samples. The measurements were carried out on the samples at specified moisture intervals ranging from 5% to 30% moisture content (MC). The resistance meter showed a close correlation to gravimetric MC values; the influence of the measuring direction for MC below 17% was found when higher MCs in the transverse direction for both species were archieved. The difference was 4.6 times higher for softwood and 1.6 times higher for hardwood. Differences between radial and tangential transverse measuring were not observed. The close correlation coefficient of MC measurements was also found for capacitive methods. The effect of the direction was found for all the tested meters when higher MC values in the longitudinal measurements were found. This effect was especially significant at an MC of wood higher than 20 wt.%. For two capacitive methods, the effect of annual ring deflection only in the spruce samples was found where higher MC values in the tangential direction were observed.
Recycling Textile Waste to Enhance Building Thermal Insulation and Reduce Carbon Emissions: Experimentation and Model-Based Dynamic Assessment
Authors: Ayed Rabeb , Bouadila Salwa , Skouri Safa , Boquera Laura , Cabeza Luisa F. , Lazaar Mariem
Published: February 2023

By enhancing the thermal properties of cement-based building materials, energy consumption and carbon dioxide (CO2) emissions related to space conditioning in buildings can be alleviated. This study aims to present cement-based composites reinforced by textile fibers for application in building and construction. Several lightweight coating mortars were produced by partially replacing the sand in the mix with different percentages of textile waste. Mechanical and thermal characterizations of the reinforced cementitious composites were performed. The results showed that the thermal conductivity of cementitious compounds decreased as the proportion of reinforcing material in the mixture increased. In terms of mechanical properties, the textile slightly reduced the compressive strength of cementitious mortar, while it improved the flexural strength. A numerical study was then performed to derive the actual impact of these reinforced materials on the thermal behavior of a building element using COMSOL Multiphysics. Numerous configurations of walls coated with different mortar mixtures were studied. The results showed that coating both sides of a building wall with 20 mm of textile-reinforced mortar reduced the internal temperature by 1.5 °C. Thus, the application of these thermally improved mortars as coating mortars appears to be a relevant solution to enhance the thermal performance of buildings.
CD8+ Cell Density Gradient across the Tumor Epithelium–Stromal Interface of Non-Muscle Invasive Papillary Urothelial Carcinoma Predicts Recurrence-Free Survival after BCG Immunotherapy
Authors: Drachneris Julius , Rasmusson Allan , Morkunas Mindaugas , Fabijonavicius Mantas , Cekauskas Albertas , Jankevicius Feliksas , Laurinavicius Arvydas
Published: February 2023

Background: Bacille Calmette–Guerin (BCG) immunotherapy is the first-line treatment in patients with high-risk non-muscle invasive papillary urothelial carcinoma (NMIPUC), the most common type of bladder cancer. The therapy outcomes are variable and may depend on the immune response within the tumor microenvironment. In our study, we explored the prognostic value of CD8+ cell density gradient indicators across the tumor epithelium–stroma interface of NMIPUC. Methods: Clinical and pathologic data were retrospectively collected from 157 NMIPUC patients treated with BCG immunotherapy after transurethral resection. Whole-slide digital image analysis of CD8 immunohistochemistry slides was used for tissue segmentation, CD8+ cell quantification, and the assessment of CD8+ cell densities within the epithelium–stroma interface. Subsequently, the gradient indicators (center of mass and immunodrop) were computed to represent the density gradient across the interface. Results: By univariable analysis of the clinicopathologic factors, including the history of previous NMIPUC, poor tumor differentiation, and pT1 stage, were associated with shorter RFS (p < 0.05). In CD8+ analyses, only the gradient indicators but not the absolute CD8+ densities were predictive for RFS (p < 0.05). The best-performing cross-validated model included previous episodes of NMIPUC (HR = 4.4492, p = 0.0063), poor differentiation (HR = 2.3672, p = 0.0457), and immunodrop (HR = 5.5072, p = 0.0455). Conclusions: We found that gradient indicators of CD8+ cell densities across the tumor epithelium–stroma interface, along with routine clinical and pathology data, improve the prediction of RFS in NMIPUC.
How Much Stress Does a Surgeon Endure? The Effects of the Robotic Approach on the Autonomic Nervous System of a Surgeon in the Modern Era of Thoracic Surgery
Authors: Mazzella Antonio , Casiraghi Monica , Galetta Domenico , Cara Andrea , Maisonneuve Patrick , Petrella Francesco , Lo Iacono Giorgio , Brivio Eleonora , Guiddi Paolo , Pravettoni Gabriella , Spaggiari Lorenzo
Published: February 2023

(1) Objective: the purpose of this study was to evaluate and quantify the stress to which a surgeon is subjected during his/her surgical activity; we compared the individual clinical and psychological responses to stress of two surgeons during their surgical activities via robotic and open approaches. (2) Materials and methods: This was a prospective observational study in which we progressively collected data concerning the surgical performances of two different thoracic surgeons (October 2021–June 2022). We evaluated 20 lung resections performed via robot-assisted surgery and 20 lung resections performed via an open approach by each surgeon; in particular, we evaluated a panel of pre-, peri-, and postoperative data concerning the interventions, the patients, and other outcomes concerning the autonomic nervous system (ANS) and psychological responses to stress of the surgeons during their surgical activities. (3) Results: When analyzing data concerning the ANS activity of two surgeons, during robotic activity we found lower maximum, minimum, and mean heart rates; lower mean respiratory frequencies; lower body temperatures; and lower mean desaturations compared to the open approach activity for both surgeons. The psychological monitoring showed that the open approach created more physical fatigue and frustration but higher levels of satisfaction and performance evaluation. The robot-assisted surgeries showed higher levels of anxiety. (4) Conclusions: for different reasons, the robotic approach stimulated the ANS to a lesser degree, causing less stress for surgeons and ensuring greater comfort.
Metabolic Reprogramming of Breast Tumor-Educated Macrophages Revealed by NMR Metabolomics
Authors: Dias Ana S. , Almeida Catarina R. , Helguero Luisa A. , Duarte Iola F.
Published: February 2023

The metabolic crosstalk between tumor cells and tumor-associated macrophages (TAMs) has emerged as a critical contributor to tumor development and progression. In breast cancer (BC), the abundance of immune-suppressive TAMs positively correlates with poor prognosis. However, little is known about how TAMs reprogram their metabolism in the BC microenvironment. In this work, we have assessed the metabolic and phenotypic impact of incubating THP-1-derived macrophages in conditioned media (CM) from two BC cell lines cultured in normoxia/hypoxia: MDA-MB-231 cells (highly metastatic, triple-negative BC), and MCF-7 cells (less aggressive, luminal BC). The resulting tumor-educated macrophages (TEM) displayed prominent differences in their metabolic activity and composition, compared to control cells (M0), as assessed by exo- and endometabolomics. In particular, TEM turned to the utilization of extracellular pyruvate, alanine, and branched chain keto acids (BCKA), while exhibiting alterations in metabolites associated with several intracellular pathways, including polyamines catabolism (MDA-TEM), collagen degradation (mainly MCF-TEM), adenosine accumulation (mainly MDA-TEM) and lipid metabolism. Interestingly, following a second-stage incubation in fresh RPMI medium, TEM still displayed several metabolic differences compared to M0, indicating persistent reprogramming. Overall, this work provided new insights into the metabolic plasticity of TEM, revealing potentially important nutritional exchanges and immunoregulatory metabolites in the BC TME.
Neurofibromatosis Type 1: Pediatric Aspects and Review of Genotype–Phenotype Correlations
Authors: Peduto Cristina , Zanobio Mariateresa , Nigro Vincenzo , Perrotta Silverio , Piluso Giulio , Santoro Claudia
Published: February 2023

Neurofibromatosis type 1 (NF1) is an autosomal dominant condition, with a birth incidence of approximately 1:2000–3000, caused by germline pathogenic variants in NF1, a tumor suppressor gene encoding neurofibromin, a negative regulator of the RAS/MAPK pathway. This explains why NF1 is included in the group of RASopathies and shares several clinical features with Noonan syndrome. Here, we describe the main clinical characteristics and complications associated with NF1, particularly those occurring in pediatric age. NF1 has complete penetrance and shows wide inter- and intrafamilial phenotypic variability and age-dependent appearance of manifestations. Clinical presentation and history of NF1 are multisystemic and highly unpredictable, especially in the first years of life when penetrance is still incomplete. In this scenario of extreme phenotypic variability, some genotype–phenotype associations need to be taken into consideration, as they strongly impact on genetic counseling and prognostication of the disease. We provide a synthetic review, based on the most recent literature data, of all known genotype–phenotype correlations from a genetic and clinical perspective. Molecular diagnosis is fundamental for the confirmation of doubtful clinical diagnoses, especially in the light of recently revised diagnostic criteria, and for the early identification of genotypes, albeit few, that correlate with specific phenotypes.
Clinical Scores, Biomarkers and IT Tools in Lung Cancer Screening—Can an Integrated Approach Overcome Current Challenges?
Authors: Voigt Wieland , Prosch Helmut , Silva Mario
Published: February 2023

As most lung cancer (LC) cases are still detected at advanced and incurable stages, there are increasing efforts to foster detection at earlier stages by low dose computed tomography (LDCT) based LC screening. In this scoping review, we describe current advances in candidate selection for screening (selection phase), technical aspects (screening), and probability evaluation of malignancy of CT-detected pulmonary nodules (PN management). Literature was non-systematically assessed and reviewed for suitability by the authors. For the selection phase, we describe current eligibility criteria for screening, along with their limitations and potential refinements through advanced clinical scores and biomarker assessments. For LC screening, we discuss how the accuracy of computerized tomography (CT) scan reading might be augmented by IT tools, helping radiologists to cope with increasing workloads. For PN management, we evaluate the precision of follow-up scans by semi-automatic volume measurements of CT-detected PN. Moreover, we present an integrative approach to evaluate the probability of PN malignancy to enable safe decisions on further management. As a clear limitation, additional validation studies are required for most innovative diagnostic approaches presented in this article, but the integration of clinical risk models, current imaging techniques, and advancing biomarker research has the potential to improve the LC screening performance generally.
Nanoscale Prognosis of Colorectal Cancer Metastasis from AFM Image Processing of Histological Sections
Authors: Gavriil Vassilios , Ferraro Angelo , Cefalas Alkiviadis-Constantinos , Kollia Zoe , Pepe Francesco , Malapelle Umberto , De Luca Caterina , Troncone Giancarlo , Sarantopoulou Evangelia
Published: February 2023

Early ascertainment of metastatic tumour phases is crucial to improve cancer survival, formulate an accurate prognostic report of disease advancement, and, most importantly, quantify the metastatic progression and malignancy state of primary cancer cells with a universal numerical indexing system. This work proposes an early improvement to metastatic cancer detection with 97.7 nm spatial resolution by indexing the metastatic cancer phases from the analysis of atomic force microscopy images of human colorectal cancer histological sections. The procedure applies variograms of residuals of Gaussian filtering and theta statistics of colorectal cancer tissue image settings. This methodology elucidates the early metastatic progression at the nanoscale level by setting metastatic indexes and critical thresholds based on relatively large histological sections and categorising the malignancy state of a few suspicious cells not identified with optical image analysis. In addition, we sought to detect early tiny morphological differentiations indicating potential cell transition from epithelial cell phenotypes of low metastatic potential to those of high metastatic potential. This metastatic differentiation, which is also identified in higher moments of variograms, sets different hierarchical levels for metastatic progression dynamics.
Endogenous Extracellular Matrix Regulates the Response of Osteosarcoma 3D Spheroids to Doxorubicin
Authors: Cortini Margherita , Macchi Francesca , Reggiani Francesca , Vitale Emanuele , Lipreri Maria Veronica , Perut Francesca , Ciarrocchi Alessia , Baldini Nicola , Avnet Sofia
Published: February 2023

The extracellular matrix (ECM) modulates cell behavior, shape, and viability as well as mechanical properties. In recent years, ECM disregulation and aberrant remodeling has gained considerable attention in cancer targeting and prevention since it may stimulate tumorigenesis and metastasis. Here, we developed an in vitro model that aims at mimicking the in vivo tumor microenvironment by recapitulating the interactions between osteosarcoma (OS) cells and ECM with respect to cancer progression. We long-term cultured 3D OS spheroids made of metastatic or non-metastatic OS cells mixed with mesenchymal stromal cells (MSCs); confirmed the deposition of ECM proteins such as Type I collagen, Type III collagen, and fibronectin by the stromal component at the interface between tumor cells and MSCs; and found that ECM secretion is inhibited by a neutralizing anti-IL-6 antibody, suggesting a new role of this cytokine in OS ECM deposition. Most importantly, we showed that the cytotoxic effect of doxorubicin is reduced by the presence of Type I collagen. We thus conclude that ECM protein deposition is crucial for modelling and studying drug response. Our results also suggest that targeting ECM proteins might improve the outcome of a subset of chemoresistant tumors.
Stationary Trend in Elevated Serum Alpha-Fetoprotein Level in Hepatocellular Carcinoma Patients
Authors: Yen Yi-Hao , Kee Kwong-Ming , Li Wei-Feng , Liu Yueh-Wei , Wang Chih-Chi , Hu Tsung-Hui , Tsai Ming-Chao , Lin Chih-Yun
Published: February 2023

A recent study from the US showed a decreasing trend in the elevated serum alpha-fetoprotein (AFP) level (i.e., ≥20 ng/mL) in hepatocellular carcinoma (HCC) patients at the time of diagnosis. Furthermore, advanced tumor stage and severe underlying liver disease were associated with elevated AFP levels. We aimed to evaluate this issue in an area endemic for hepatitis B virus (HBV). Between 2011 and 2020, 4031 patients were newly diagnosed with HCC at our institution. After excluding 54 patients with unknown AFP data, the remaining 3977 patients were enrolled in this study. Elevated AFP level was defined as ≥20 ng/mL. Overall, 51.2% of HCC patients had elevated AFP levels; this proportion remained stationary between 2011 and 2020 (51.8% vs. 51.1%). Multivariate analysis showed that female gender (odds ratio (OR) = 1.462; p < 0.001), tumor size per 10 mm increase (OR = 1.155; p < 0.001), multiple tumors (OR = 1.406; p < 0.001), Barcelona Clinic Liver Cancer stages B–D (OR = 1.247; p = 0.019), cirrhosis (OR = 1.288; p = 0.02), total bilirubin > 1.4 mg/dL (OR = 1.218; p = 0.030), and HBV- or hepatitis C virus (HCV)-positive status (OR = 1.720; p < 0.001) were associated with elevated AFP levels. In conclusion, a stationary trend in elevated serum AFP level in HCC patients has been noted in the past 10 years. Advanced tumor stage, severe underlying liver disease, viral etiology, and female gender are associated with elevated AFP levels in HCC patients.
In Situ Imaging of O-Linked β-N-Acetylglucosamine Using On-Tissue Hydrolysis and MALDI Mass Spectrometry
Authors: Escobar Edwin E. , Seeley Erin H. , Serrano-Negrón Jesús E. , Vocadlo David J. , Brodbelt Jennifer S.
Published: February 2023

Post-translational O-glycosylation of proteins via the addition of N-acetylglucosamine (O-GlcNAc) is a regulator of many aspects of cellular physiology. Processes driven by perturbed dynamics of O-GlcNAcylation modification have been implicated in cancer development. Variability in O-GlcNAcylation is emerging as a metabolic biomarker of many cancers. Here, we evaluate the use of MALDI-mass spectrometry imaging (MSI) to visualize the location of O-GlcNAcylated proteins in tissue sections by mapping GlcNAc that has been released by the enzymatic hydrolysis of glycoproteins using an O-GlcNAc hydrolase. We use this strategy to monitor O-GlcNAc within hepatic VX2 tumor tissue. We show that increased O-GlcNAc is found within both viable tumor and tumor margin regions, implicating GlcNAc in tumor progression.
Metastatic Progression of Human Melanoma
Authors: Tímár József , Ladányi Andrea
Published: February 2023

This Topical Collection, comprising 13 papers (10 original articles and 3 reviews), addresses various aspects of the field of melanoma progression: genomic and proteomic approaches, experimental studies, the questions of sentinel lymph node dissection, and metastasis formation of uveal and conjunctival melanomas is also discussed [...]
Single-Stage versus Multi-Stage Intramedullary Nailing for Multiple Synchronous Long Bone Impending and Pathologic Fractures in Metastatic Bone Disease and Multiple Myeloma
Authors: Maheshwari Aditya V. , Kobryn Andriy , Alam Juhayer S. , Tretiakov Mikhail
Published: February 2023

Purpose: Determine whether perioperative outcomes differ between patients who have undergone single or multi-stage IMN procedures for impending or completed pathologic fractures. Methods: Patients were classified into single-stage single-bone (SSSB), single-stage multiple-bone (SSMB), and multi-stage multiple-bone (MSMB) based on procedure timing and number of bones involved. Outcome variables compared included length of stay (LOS), in-hospital mortality and survival, initiation of rehabilitation and adjuvant therapy, and perioperative complications. Results: There were 272 IMNs placed in 181 patients (100 males, 81 females, 55.2% and 44.8%, respectively) with a mean age of 66.3 ± 12.1 years. MSMB had significantly longer LOS (24.3 ± 14.2 days) and rehabilitation initiation (3.4 ± 2.5 days) compared to SSSB (8.5 ± 7.7 and 1.8 ± 1.6 days) and SSMB (11.5 ± 7.6 and 2.0 ± 1.6 days) subjects, respectively (both; p < 0.01). Although total perioperative complication rates in SSMB and MSMB were comparable (33.3% vs. 36.0%), they were significantly higher than SSSB (18%) (p = 0.038). MSMB had significantly more (20%) cardiopulmonary complications than SSMB (11.1%) and SSSB (4.5%) (p = 0.027). All groups exhibited comparative survivorship (8.1 ± 8.6, 7.1 ± 7.2, and 11.4 ± 11.8 months) and in-hospital mortality (4.5%, 8.9%, and 4.0%) (all; p > 0.05). Conclusion: In comparison to MSMB, SSMB intramedullary nailing did not result in higher perioperative complication or in-hospital mortality rates in select patients with synchronous long-bone metastases but led to earlier postoperative discharge and initiation of rehabilitation.
Hypoxia, a Targetable Culprit to Counter Pancreatic Cancer Resistance to Therapy
Authors: Abou Khouzam Raefa , Lehn Jean-Marie , Mayr Hemma , Clavien Pierre-Alain , Wallace Michael Bradley , Ducreux Michel , Limani Perparim , Chouaib Salem
Published: February 2023

Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer, and it is a disease of dismal prognosis. While immunotherapy has revolutionized the treatment of various solid tumors, it has achieved little success in PDAC. Hypoxia within the stroma-rich tumor microenvironment is associated with resistance to therapies and promotes angiogenesis, giving rise to a chaotic and leaky vasculature that is inefficient at shuttling oxygen and nutrients. Hypoxia and its downstream effectors have been implicated in immune resistance and could be contributing to the lack of response to immunotherapy experienced by patients with PDAC. Paradoxically, increasing evidence has shown hypoxia to augment genomic instability and mutagenesis in cancer, suggesting that hypoxic tumor cells could have increased production of neoantigens that can potentially enable their clearance by cytotoxic immune cells. Strategies aimed at relieving this condition have been on the rise, and one such approach opts for normalizing the tumor vasculature to reverse hypoxia and its downstream support of tumor pathogenesis. An important consideration for the successful implementation of such strategies in the clinic is that not all PDACs are equally hypoxic, therefore hypoxia-detection approaches should be integrated to enable optimal patient selection for achieving improved patient outcomes.
Histopathological Aspects of the Prognostic Factors for Salivary Gland Cancers
Authors: Nishida Haruto , Kusaba Takahiro , Kawamura Kazuhiro , Oyama Yuzo , Daa Tsutomu
Published: February 2023

Salivary gland cancers (SGCs) are diagnosed using histopathological examination, which significantly contributes to their progression, including lymph node/distant metastasis or local recurrence. In the current World Health Organization (WHO) Classification of Head and Neck Tumors: Salivary Glands (5th edition), malignant and benign epithelial tumors are classified into 21 and 15 tumor types, respectively. All malignant tumors have the potential for lymph node/distant metastasis or local recurrence. In particular, mucoepidermoid carcinoma (MEC), adenoid cystic carcinoma (AdCC), salivary duct carcinoma, salivary carcinoma, not otherwise specified (NOS, formerly known as adenocarcinoma, NOS), myoepithelial carcinoma, epithelial–myoepithelial carcinoma, and carcinoma ex pleomorphic adenoma (PA) are relatively prevalent. High-grade transformation is an important aspect of tumor progression in SGCs. MEC, AdCC, salivary carcinoma, and NOS have a distinct grading system; however, a universal histological grading system for SGCs has not yet been recommended. Conversely, PA is considered benign; nonetheless, it should be cautiously treated to avoid the development of metastasizing/recurrent PA. The aim of this review is to describe the current histopathological aspects of the prognostic factors for SGCs and discuss the genes or molecules used as diagnostic tools that might have treatment target potential in the future.
Targeting Ubiquitin-like Protein, ISG15, as a Novel Tumor Associated Antigen in Colorectal Cancer
Authors: Nguyen Hong-My , Gaikwad Shreyas , Oladejo Mariam , Paulishak Wyatt , Wood Laurence M.
Published: February 2023

Colorectal cancer (CRC) is the third leading cause of cancer-related deaths in both men and women in the United States. While immune checkpoint inhibitor (ICI) therapy is demonstrating remarkable clinical responses, the resistance and immune-related toxicities associated with ICIs demonstrate the need to develop additional immunotherapy options for CRC patients. Cancer vaccines represent a safe and promising treatment approach for CRC. As previously developed tumor-associated antigen (TAA)-based cancer vaccines for CRC are not demonstrating promising results, we propose that interferon-stimulated gene 15 (ISG15) is a novel TAA and therapeutic target for CRC. Our work demonstrates the anti-tumor efficacy of a Listeria-based vaccine targeting ISG15, designated Lm-LLO-ISG15, in an immunocompetent CRC murine model. The Lm-LLO-ISG15-mediated anti-tumor response is associated with an increased influx of functional T cells, higher production of multiple intracellular cytokines response, a lower number of regulatory T cells, and a greater ratio of effector to regulatory T cells (Teff/Treg) in the tumor microenvironment.
Adjuvant Vaccination with Allogenic Dendritic Cells Significantly Prolongs Overall Survival in High-Grade Gliomas: Results of a Phase II Trial
Authors: Lepski Guilherme , Bergami-Santos Patricia C. , Pinho Mariana P. , Chauca-Torres Nadia E. , Evangelista Gabriela C. M. , Teixeira Sarah F. , Flatow Elizabeth , de Oliveira Jaqueline V. , Fogolin Carla , Peres Nataly , Arévalo Analía , Alves Venâncio A. F. , Barbuto José A. M.
Published: February 2023

Immunotherapy for cancer treatment has gained increased attention in recent years. Recently, our group reported the case of a patient with glioblastoma who underwent vaccination based on dendritic cells and experienced a strong Th1 immune response together with near-complete tumor remission. Here we report the results of a phase I/II prospective, non-controlled clinical trial with 37 patients harboring glioblastoma or grade 4 astrocytomas. At the time of first recurrence after surgery, patients began receiving monthly intradermal injections of allogenic DC-autologous tumor cell hybridomas. Overall survival, quality of life, and immunological profiles were assessed prospectively. Compared with patients in the Genomic Data Commons data bank, overall survival for vaccinated patients with glioblastoma was 27.6 ± 2.4 months (vs. 16.3 ± 0.7, log-rank p < 0.001, hazard ratio 0.53, 95%CI 0.36–0.78, p < 0.01), and it was 59.5 ± 15.9 for vaccinated astrocytoma grade 4 patients (vs. 19.8 ± 2.5, log-rank p < 0.05, hazard ratio 0.18, 95%CI 0.05–0.62, p < 0.01). Furthermore, seven vaccinated patients (two IDH-1-mutated and five wild type) remain alive at the time of this report (overall survival 47.9 months, SD 21.1, range: 25.4–78.6 months since diagnosis; and 34.2 months since recurrence, range: 17.8 to 40.7, SD 21.3). We believe that the data reported here can foster the improvement of treatment protocols for high-grade gliomas based on cellular immunotherapy.
Hydrothermal Synthesis of Bimetallic (Zn, Co) Co-Doped Tungstate Nanocomposite with Direct Z-Scheme for Enhanced Photodegradation of Xylenol Orange
Authors: Alharthi Fahad A. , Al-Nafaei Wedyan Saud , Alshayiqi Alanoud Abdullah , Alanazi Hamdah S. , Hasan Imran
Published: February 2023

In the present study, pristine ZnWO4, CoWO4, and mixed metal Zn0.5Co0.5WO4 were synthesized through the hydrothermal process using a Teflon-lined autoclave at 180 ℃. The synthesized nanomaterials were characterized by various spectroscopic techniques, such as TEM, FTIR, UV–vis, XRD, and SEM-EDX-mapping to confirm the formation of nanocomposite material. The synthesized materials were explored as photocatalysts for the degradation of xylenol orange (XO) under a visible light source and a comparative study was explored to check the efficiency of the bimetallic co-doped nanocomposite to the pristine metal tungstate NPs. XRD analysis proved that reinforcement of Co2+ in ZnWO4 lattice results in a reduction in interplanar distance from 0.203 nm to 0.185 nm, which is reflected in its crystallite size, which reduced from 32 nm to 24 nm. Contraction in crystallite size reflects on the optical properties as the energy bandgap of ZnWO4 reduced from 3.49 eV to 3.33 eV in Zn0.5Co0.5WO4, which is due to the formation of a Z-scheme for charge transfer and enhancement in photocatalytic efficiency. The experimental results suggested that ZnWO4, CoWO4, and Zn0.5Co0.5WO4 NPs achieved a photocatalytic efficiency of 97.89%, 98.10%, and 98.77% towards XO in 120 min of visible solar light irradiation. The kinetics of photodegradation was best explained by pseudo-first-order kinetics and the values of apparent rate const (kapp) also supported the enhanced photocatalytic efficiency of mixed metal Zn0.5Co0.5WO4 NPs towards XO degradation.