bluuebunny/crossref_metadata_2025 huggingface dataset:
Life Cycle Assessment of the Sustainability of Alkali-Activated Binders
Authors: Alhassan Mohammad , Alkhawaldeh Ayah , Betoush Nour , Alkhawaldeh Mohammad , Huseien Ghasan Fahim , Amaireh Layla , Elrefae Ahmad
Published: February 2023

Limiting the consumption of nonrenewable resources and minimizing waste production and associated gas emissions are the main priority of the construction sector to achieve a sustainable future. This study investigates the sustainability performance of newly developed binders known as alkali-activated binders (AABs). These AABs work satisfactorily in creating and enhancing the concept of greenhouse construction in accordance with sustainability standards. These novel binders are founded on the notion of utilizing ashes from mining and quarrying wastes as raw materials for hazardous and radioactive waste treatment. The life cycle assessment, which depicts material life from the extraction of raw materials through the destruction stage of the structure, is one of the most essential sustainability factors. A recent use for AAB has been created, such as the use of hybrid cement, which is made by combining AAB with ordinary Portland cement (OPC). These binders are a successful answer to a green building alternative if the techniques used to make them do not have an unacceptable negative impact on the environment, human health, or resource depletion. The Technique for Order Preference by Similarity to Ideal Solution (TOPSIS) software was employed for choosing the optimal materials’ alternative depending on the available criteria. The results revealed that AAB concrete provided a more ecologically friendly alternative than OPC concrete, higher strength for comparable water/binder ratio, and better performance in terms of embodied energy, resistance to freeze–thaw cycles, high temperature resistance, and mass loss due to acid attack and abrasion.
Industrial Biotechnology Conservation Processes: Similarities with Natural Long-Term Preservation of Biological Organisms
Authors: Laurent Alexis , Scaletta Corinne , Abdel-Sayed Philippe , Raffoul Wassim , Hirt-Burri Nathalie , Applegate Lee Ann
Published: February 2023

Cryopreservation and lyophilization processes are widely used for conservation purposes in the pharmaceutical, biotechnological, and food industries or in medical transplantation. Such processes deal with extremely low temperatures (e.g., −196 °C) and multiple physical states of water, a universal and essential molecule for many biological lifeforms. This study firstly considers the controlled laboratory/industrial artificial conditions used to favor specific water phase transitions during cellular material cryopreservation and lyophilization under the Swiss progenitor cell transplantation program. Both biotechnological tools are successfully used for the long-term storage of biological samples and products, with reversible quasi-arrest of metabolic activities (e.g., cryogenic storage in liquid nitrogen). Secondly, similarities are outlined between such artificial localized environment modifications and some natural ecological niches known to favor metabolic rate modifications (e.g., cryptobiosis) in biological organisms. Specifically, examples of survival to extreme physical parameters by small multi-cellular animals (e.g., tardigrades) are discussed, opening further considerations about the possibility to reversibly slow or temporarily arrest the metabolic activity rates of defined complex organisms in controlled conditions. Key examples of biological organism adaptation capabilities to extreme environmental parameters finally enabled a discussion about the emergence of early primordial biological lifeforms, from natural biotechnology and evolutionary points of view. Overall, the provided examples/similarities confirm the interest in further transposing natural processes and phenomena to controlled laboratory settings with the ultimate goal of gaining better control and modulation capacities over the metabolic activities of complex biological organisms.
Introduction to a New Open Access Journal Published by MDPI: Blockchains
Authors: Gai Keke , Zhu Liehuang
Published: February 2023

Blockchain, one of the representative technologies of Web 3 [...]
Histologic Definition of Enhancing Core and FLAIR Hyperintensity Region of Glioblastoma, IDH-Wild Type: A Clinico-Pathologic Study on a Single-Institution Series
Authors: Broggi Giuseppe , Altieri Roberto , Barresi Valeria , Certo Francesco , Barbagallo Giuseppe Maria Vincenzo , Zanelli Magda , Palicelli Andrea , Magro Gaetano , Caltabiano Rosario
Published: February 2023

The extent of resection beyond the enhancing core (EC) in glioblastoma IDH-wild type (GBM, IDHwt) is one of the most debated topics in neuro-oncology. Indeed, it has been demonstrated that local disease recurrence often arises in peritumoral areas and that radiologically-defined FLAIR hyperintensity areas of GBM IDHwt are often visible beyond the conventional EC. Therefore, the need to extend the surgical resection also to the FLAIR hyperintensity areas is a matter of debate. Since little is known about the histological composition of FLAIR hyperintensity regions, in this study we aimed to provide a comprehensive description of the histological features of EC and FLAIR hyperintensity regions sampled intraoperatively using neuronavigation and 5-aminolevulinic acid (5-ALA) fluorescence, in 33 patients with GBM, IDHwt. Assessing a total 109 histological samples, we found that FLAIR areas consisted in: (i) fragments of white matter focally to diffusely infiltrated by tumor cells in 76% of cases; (ii) a mixture of white matter with reactive astrogliosis and grey matter with perineuronal satellitosis in 15% and (iii) tumor tissue in 9%. A deeper knowledge of the histology of FLAIR hyperintensity areas in GBM, IDH-wt may serve to better guide neurosurgeons on the choice of the most appropriate surgical approach in patients with this neoplasm.
In Vitro and Predictive Computational Toxicology Methods for the Neurotoxic Pesticide Amitraz and Its Metabolites
Authors: Giorgini Marialuce , Taroncher Mercedes , Ruiz María-José , Rodríguez-Carrasco Yelko , Tolosa Josefa
Published: February 2023

The Varroa destructor parasite is responsible for varroasis in honeybees worldwide, the most destructive disease among parasitic diseases. Thus, different insecticides/acaricides have been widely used within beehives to control these parasitic diseases. Namely, amitraz is the most used acaricide due to its high efficacy shown against Varroa destructor. However, pesticides used for beehive treatments could be incorporated into the honey and accumulate in other hive products. Hence, honeybee health and the impairment of the quality of honey caused by pesticides have gained more attention. Amitraz and its main metabolites, N-(2,4-dimethylphenyl) formamide (2,4-DMF) and 2,4-dimethylaniline (2,4-DMA), are known to be potent neurotoxicants. In this research, the cytotoxicity of amitraz and its metabolites has been assessed by MTT and PC assays in HepG2 cells. In addition, possible target receptors by in silico strategies have been surveyed. Results showed that amitraz was more cytotoxic than its metabolites. According to the in silico ADMEt assays, amitraz and its metabolites were predicted to be compounds that are able to pass the blood–brain barrier (BBB) and induce toxicity in the central and peripheral nervous systems. The main target class predicted for amitraz was the family of A G protein-coupled receptors that comprises responses to hormones and neurotransmitters. This affects, among other things, reproduction, development, locomotion, and feeding. Furthermore, amitraz and its metabolites were predicted as active compounds interacting with diverse receptors of the Tox21-nuclear receptor signaling and stress response pathways.
Task Challenge and Employee Performance: A Moderated Mediation Model of Resilience and Digitalization
Authors: Saleem Irfan , Qureshi Tahir Masood , Verma Amitabh
Published: February 2023

Lately, organizations are giving attention to enhancing employee resilience due to turbulent economic times caused by lockdowns in the last couple of years. This explanatory research proposes and tests the mediating role of employee resilience to link task challenge and employee performance during the COVID-19 pandemic in government schools of Oman using the broaden-and-build theory. An explanatory research design was used for this empirical study. An Arabic-translated questionnaire version was designed to collect primary data online during the lockdown using simple random sampling. We used the Preacher and Hayes macro to analyze moderated mediation using cross-sectional data and analyzed 441 responses. The findings confirm the mediation roles of employee resilience and moderating roles of digitalization during unusual circumstances. The study has implications for the school administrators, Omani policymakers and schooling staff of the Middle Eastern educational industry.
Green Tunnel Solutions: An Overview of Sustainability Trends in the Last Decade (2013–2022)
Authors: Lombardi Mara , Berardi Davide , Galuppi Marta , Barbieri Maurizio
Published: February 2023

In the last decade, green solutions for road tunnels have steadily emerged in the field of engineering. The focus has been on using renewable energy sources to conserve energy and address issues of disaster risk management, territorial resilience and vulnerability, especially as these issues relate to critical infrastructures (CIs), such as roads and railways. Focusing on the equilibrium of the infrastructure through integrated system services and their external effects guarantees a better evaluation of both effects as they relate to other systems and energy consumption optimisation. To this end, a systematic literature review has been conducted herein that collects and analyses studies carried out in the last decade that relate to green energy solutions in tunnels. Upon a review of the Scopus database from 2013 to 2022, 46 conceptual and empirical studies were selected. Classifications and discussions were then developed according to the main issues identified (e.g., energy saving in road tunnels, zero-energy tunnels, renewable energy sources, tunnel safety lighting, and sustainable infrastructure). Each contribution constitutes a part of the current literature that combines the problems of tunnel safety (as represented by the energy costs of safety devices, e.g., tunnel lighting systems) with issues of renewable energy sources in tunnels. The results of this systematic review offer ideas for future directions of the ‘green’ vision for tunnel infrastructure. This study represents the state-of-the-art of renewable energy solutions currently present worldwide. Gaps in the literature that have yet to be addressed include how to build a green system as well as how to balance its life costs. The review supports the claim that the integration of renewable energy sources can exploit innovative solutions related to the concept of resilience.
Multi-Agent Simulation on Staff Evacuation Behavior in Elderly Nursing Home Fire Emergencies
Authors: Lim Haewon , Lee Hyunsoo , Hwang Ji-Hyoun
Published: February 2023

Elderly nursing homes in South Korea are vulnerable to evacuation in emergency situations such as fires. There are many elderly residents with reduced self-walking ability, so if a disaster such as a fire occurs, it is very likely to lead to a large number of human injuries. In elderly nursing homes, it is impossible for many elderly people to evacuate voluntarily without the help of staff. Therefore, it is very important to guide the behavior of staff when evacuating. The purpose of this study is to evaluate the effect of evacuation behavior of staff on evacuation time in a fire emergency in an elderly nursing home by adopting an agent-based simulation approach. The effect of staff evacuation behavior on the evacuation time was investigated based on the results of a new agent-based evacuation simulation model. In the simulation model, there are conditions for caregivers to designate and evacuate the elderly, as well as to set the evacuation priority for the elderly. The results of this study show that having the elderly occupants designated by the staff according to their zones and evacuating them together was the most important in reducing the evacuation time. This study contributes to a new agent-based evacuation simulation model by confirming whether the evacuation behavior of employees affects the evacuation time.
Associations between Elderly Residents’ Supermarket Accessibility and Built Environmental Features in Seoul, Korea
Authors: Kim Donghyun , Hwang Jaeseok , Park Jina
Published: February 2023

Scholars have examined the relationship between destination accessibility and various pedestrian-friendly environments in neighborhoods. However, there have been few studies on whether micro-scale environmental features promote access to supermarkets. This study fills these gaps by examining the accessibility of supermarkets and the meso- and micro-scale environmental features. In particular, environmental features that pedestrians can experience at the eye-level were estimated using the Naver pedestrian direction API and semantic segmentation technique. Multivariate regression models were employed to determine whether neighborhoods with high supermarket accessibility ensure walkable environments for the elderly. Our findings have shown that the walkability differs according to different levels of supermarket accessibility. Neighborhoods with high supermarket accessibility had high density and high diversity, and they provided high-quality sidewalk pavement. Conversely, elderly residents in neighborhoods with low accessibility had to pass through more pedestrian crossing facilities and steep slopes to go to do their shopping. These results can provide insight to policymakers and planners about the uneven accessibility of supermarkets and help improve neighborhood walkability for the elderly.
Causal Link of Human Papillomavirus in Barrett Esophagus and Adenocarcinoma: Are We There Yet?
Authors: Rajendra Shanmugarajah , Sharma Prateek
Published: February 2023

Esophageal cancer is a relatively common malignancy worldwide with a high mortality (5-year survival of <15%). Despite screening, surveillance, improved imaging and treatment, the exponential rise in OAC continues. The strongest risk factors for OAC are chronic heartburn and metaplastic transformation of the lower third of the esophagus (Barrett’s esophagus). The risk profile includes Caucasian race, male gender older age, obesity and smoking. Although the tumor risk in BO has been progressively revised downwards, the exponential rise in OAC remains unchecked. This paradox points to an unidentified missing link. Relatively recently, we provided the world’s initial data for a strong association of biologically relevant hr-HPV with BD and OAC. Since then, systematic reviews and meta-analysis have documented HPV DNA prevalence rates in OAC of between 13 to 35%. In this review, we provide some evidence for a probable causal relationship between hr-HPV and OAC. This is challenging given the multifactorial etiology and long latency. Increasingly, high-risk HPV (hr-HPV) is regarded as a risk factor for OAC. This discovery will aid identification of a sub-group of high-risk progressors to esophageal cancer by surveillance and the development of effective preventive strategies including vaccination.
Meta-Analysis of Modulated Electro-Hyperthermia and Tumor Treating Fields in the Treatment of Glioblastomas
Authors: Szasz Attila Marcell , Arrojo Alvarez Elisabeth Estefanía , Fiorentini Giammaria , Herold Magdolna , Herold Zoltan , Sarti Donatella , Dank Magdolna
Published: February 2023

Background: Glioblastoma is one of the most difficult to treat and most aggressive brain tumors, having a poor survival rate. The use of non-invasive modulated electro-hyperthermia (mEHT) and Tumor Treating Fields (TTF) devices has been introduced in the last few decades, both of which having proven anti-tumor effects. Methods: A meta-analysis of randomized and observational studies about mEHT and TTF was conducted. Results: A total of seven and fourteen studies about mEHT and TTF were included, with a total number of 450 and 1309 cases, respectively. A 42% [95% confidence interval (95% CI): 25–59%] 1-year survival rate was found for mEHT, which was raised to 61% (95% CI: 32–89%) if only the studies conducted after 2008 were investigated. In the case of TTF, 1-year survival was 67% (95% CI: 53–81%). Subgroup analyses revealed that newly diagnosed patients might get extra benefits from the early introduction of the devices (mEHT all studies: 73% vs. 37%, p = 0.0021; mEHT studies after 2008: 73% vs. 54%, p = 0.4214; TTF studies: 83% vs. 52%, p = 0.0083), compared with recurrent glioblastoma. Conclusions: Our meta-analysis showed that both mEHT and TTF can improve glioblastoma survival, and the most benefit may be achieved in newly diagnosed cases.
Sodium Fluorescein-Guided Surgery for Resection of Brain Metastases from Lung Cancer: A Consecutive Case Series Study and Literature Review
Authors: Cheng Xing , Chen Jie , Tang Ronghua , Ruan Jian , Mao Deqiang , Yang Haifeng
Published: February 2023

(1) Introduction and objective: Surgical resection plays an important role in the multidisciplinary treatment of lung cancer patients with brain metastases (BMs). Precisely distinguishing the tumor border intraoperatively to improve and maximize the extent of resection (EOR) without causing permanent neurological defects is crucial but still challenging. Therefore, we introduced our experience of utilizing sodium fluorescein (SF) in microneurosurgery of BMs from lung cancer. This study aims to evaluate whether the use of SF-guided surgery has a positive impact on postoperative outcomes. (2) Materials and methods: A retrospective study was performed to collect data on a consecutive case series of patients with BMs from lung cancer who underwent surgical resection from January 2020 to December 2021 at the Department of Neuro-Oncology, Chongqing University Cancer Hospital. A total of 52 patients were enrolled, of which 23 received SF-guided surgery and 29 did not. EOR was assessed pre- and postoperatively on T1 contrast-enhanced MRI. Clinical and epidemiological data as well as follow-up were gathered and analyzed. (3) Results: Compared with the non-SF-guided group, the SF-guided group revealed a significantly better EOR (87.0% vs. 62.1%) and a lower incidence of local recurrence (8.7% vs. 34.5%). Survival benefits were seen in patients with NSCLC, patients who were undergoing SF-guided surgery, and patients receiving postoperative systemic therapy. (4) Conclusions: SF-guiding under the YELLOW 560 nm filter is a safe and feasible tool for improving the EOR in patients with BMs from lung cancer, leading to better local recurrence control and prolonged survival.
Identifying Solitary Granulomatous Nodules from Solid Lung Adenocarcinoma: Exploring Robust Image Features with Cross-Domain Transfer Learning
Authors: Feng Bao , Chen Xiangmeng , Chen Yehang , Yu Tianyou , Duan Xiaobei , Liu Kunfeng , Li Kunwei , Liu Zaiyi , Lin Huan , Li Sheng , Chen Xiaodong , Ke Yuting , Li Zhi , Cui Enming , Long Wansheng , Liu Xueguo
Published: February 2023

Purpose: This study aimed to find suitable source domain data in cross-domain transfer learning to extract robust image features. Then, a model was built to preoperatively distinguish lung granulomatous nodules (LGNs) from lung adenocarcinoma (LAC) in solitary pulmonary solid nodules (SPSNs). Methods: Data from 841 patients with SPSNs from five centres were collected retrospectively. First, adaptive cross-domain transfer learning was used to construct transfer learning signatures (TLS) under different source domain data and conduct a comparative analysis. The Wasserstein distance was used to assess the similarity between the source domain and target domain data in cross-domain transfer learning. Second, a cross-domain transfer learning radiomics model (TLRM) combining the best performing TLS, clinical factors and subjective CT findings was constructed. Finally, the performance of the model was validated through multicentre validation cohorts. Results: Relative to other source domain data, TLS based on lung whole slide images as source domain data (TLS-LW) had the best performance in all validation cohorts (AUC range: 0.8228–0.8984). Meanwhile, the Wasserstein distance of TLS-LW was 1.7108, which was minimal. Finally, TLS-LW, age, spiculated sign and lobulated shape were used to build the TLRM. In all validation cohorts, The AUC ranges were 0.9074–0.9442. Compared with other models, decision curve analysis and integrated discrimination improvement showed that TLRM had better performance. Conclusions: The TLRM could assist physicians in preoperatively differentiating LGN from LAC in SPSNs. Furthermore, compared with other images, cross-domain transfer learning can extract robust image features when using lung whole slide images as source domain data and has a better effect.
Amino Acid-Metabolizing Enzymes in Advanced High-Grade Serous Ovarian Cancer Patients: Value of Ascites as Biomarker Source and Role for IL4I1 and IDO1
Authors: Grobben Yvonne , den Ouden Judith E. , Aguado Cristina , van Altena Anne M. , Kraneveld Aletta D. , Zaman Guido J. R.
Published: February 2023

The molecular mechanisms contributing to immune suppression in ovarian cancer are not well understood, hampering the successful application of immunotherapy. Amino acid-metabolizing enzymes are known to contribute to the immune-hostile environment of various tumors through depletion of amino acids and production of immunosuppressive metabolites. We aimed to collectively evaluate the activity of these enzymes in high-grade serous ovarian cancer patients by performing targeted metabolomics on plasma and ascites samples. Whereas no indication was found for enhanced l-arginine or l-glutamine metabolism by immunosuppressive enzymes in ovarian cancer patients, metabolism of l-tryptophan by indoleamine 2,3-dioxygenase 1 (IDO1) was significantly elevated compared to healthy controls. Moreover, high levels of l-phenylalanine- and l-tyrosine-derived metabolites associated with interleukin 4 induced 1 (IL4I1) activity were found in ovarian cancer ascites samples. While l-tryptophan is a major substrate of both IDO1 and IL4I1, only its enhanced conversion into l-kynurenine by IDO1 could be detected, despite the observed activity of IL4I1 on its other substrates. In ascites of ovarian cancer patients, metabolite levels were higher compared to those in plasma, demonstrating the value of utilizing this fluid for biomarker identification. Finally, elevated metabolism of l-phenylalanine and l-tyrosine by IL4I1 correlated with disease stage, pointing towards a potential role for IL4I1 in ovarian cancer progression.
A Network of MicroRNAs and mRNAs Involved in Melanosome Maturation and Trafficking Defines the Lower Response of Pigmentable Melanoma Cells to Targeted Therapy
Authors: Vitiello Marianna , Mercatanti Alberto , Podda Maurizio Salvatore , Baldanzi Caterina , Prantera Antonella , Sarti Samanta , Rizzo Milena , Salvetti Alessandra , Conte Federica , Fiscon Giulia , Paci Paola , Poliseno Laura
Published: February 2023

Background: The ability to increase their degree of pigmentation is an adaptive response that confers pigmentable melanoma cells higher resistance to BRAF inhibitors (BRAFi) compared to non-pigmentable melanoma cells. Methods: Here, we compared the miRNome and the transcriptome profile of pigmentable 501Mel and SK-Mel-5 melanoma cells vs. non-pigmentable A375 melanoma cells, following treatment with the BRAFi vemurafenib (vem). In depth bioinformatic analyses (clusterProfiler, WGCNA and SWIMmeR) allowed us to identify the miRNAs, mRNAs and biological processes (BPs) that specifically characterize the response of pigmentable melanoma cells to the drug. Such BPs were studied using appropriate assays in vitro and in vivo (xenograft in zebrafish embryos). Results: Upon vem treatment, miR-192-5p, miR-211-5p, miR-374a-5p, miR-486-5p, miR-582-5p, miR-1260a and miR-7977, as well as GPR143, OCA2, RAB27A, RAB32 and TYRP1 mRNAs, are differentially expressed only in pigmentable cells. These miRNAs and mRNAs belong to BPs related to pigmentation, specifically melanosome maturation and trafficking. In fact, an increase in the number of intracellular melanosomes—due to increased maturation and/or trafficking—confers resistance to vem. Conclusion: We demonstrated that the ability of pigmentable cells to increase the number of intracellular melanosomes fully accounts for their higher resistance to vem compared to non-pigmentable cells. In addition, we identified a network of miRNAs and mRNAs that are involved in melanosome maturation and/or trafficking. Finally, we provide the rationale for testing BRAFi in combination with inhibitors of these biological processes, so that pigmentable melanoma cells can be turned into more sensitive non-pigmentable cells.
Intraoperative Imaging Techniques to Improve Surgical Resection Margins of Oropharyngeal Squamous Cell Cancer: A Comprehensive Review of Current Literature
Authors: de Kleijn Bertram J. , Heldens Gijs T. N. , Herruer Jasmijn M. , Sier Cornelis F. M. , Piazza Cesare , de Bree Remco , Guntinas-Lichius Orlando , Kowalski Luiz P. , Vander Poorten Vincent , Rodrigo Juan P. , Zidar Nina , Nathan Cherie-Ann , Tsang Raymond K. , Golusinski Pawel , Shaha Ashok R. , Ferlito Alfio , Takes Robert P.
Published: February 2023

Inadequate resection margins in head and neck squamous cell carcinoma surgery necessitate adjuvant therapies such as re-resection and radiotherapy with or without chemotherapy and imply increasing morbidity and worse prognosis. On the other hand, taking larger margins by extending the resection also leads to avoidable increased morbidity. Oropharyngeal squamous cell carcinomas (OPSCCs) are often difficult to access; resections are limited by anatomy and functionality and thus carry an increased risk for close or positive margins. Therefore, there is a need to improve intraoperative assessment of resection margins. Several intraoperative techniques are available, but these often lead to prolonged operative time and are only suitable for a subgroup of patients. In recent years, new diagnostic tools have been the subject of investigation. This study reviews the available literature on intraoperative techniques to improve resection margins for OPSCCs. A literature search was performed in Embase, PubMed, and Cochrane. Narrow band imaging (NBI), high-resolution microendoscopic imaging, confocal laser endomicroscopy, frozen section analysis (FSA), ultrasound (US), computed tomography scan (CT), (auto) fluorescence imaging (FI), and augmented reality (AR) have all been used for OPSCC. NBI, FSA, and US are most commonly used and increase the rate of negative margins. Other techniques will become available in the future, of which fluorescence imaging has high potential for use with OPSCC.
Combining sCD163 with CA 19-9 Increases the Predictiveness of Pancreatic Ductal Adenocarcinoma
Authors: Stuhr Liva K. , Madsen Kasper , Johansen Astrid Z. , Chen Inna M. , Hansen Carsten P. , Jensen Lars H. , Hansen Torben F. , Kløve-Mogensen Kirstine , Nielsen Kaspar R. , Johansen Julia S.
Published: February 2023

The objective of this study was to evaluate the diagnostic and prognostic potential of soluble CD163 (sCD163) in patients with pancreatic ductal adenocarcinoma (PDAC). Preoperative serum samples from 255 patients with PDAC were analyzed for sCD163 using a commercially available enzyme-linked immunosorbent assay. The diagnostic value of sCD163 was evaluated using receiver operating characteristic (ROC) curves. The prognostic significance of sCD163 was evaluated by Cox regression analysis and Kaplan–Meier survival curves. sCD163 was significantly increased in patients with PDAC, across all stages, compared to healthy subjects (stage 1: p value = 0.033; stage 2–4: p value ≤ 0.0001). ROC curves showed that sCD163 combined with CA 19-9 had the highest diagnostic potential compared to sCD163 and CA 19-9 alone both in patients with local PDAC and patients with advanced PDAC. Univariate and multivariate analysis showed no association between sCD163 and overall survival. This study found elevated levels of circulating sCD163 in patients with PDAC, regardless of stage, compared to healthy subjects. This suggests that sCD163 may have a clinical value as a novel diagnostic biomarker in PDAC.
Exosome-Transmitted tRF-16-K8J7K1B Promotes Tamoxifen Resistance by Reducing Drug-Induced Cell Apoptosis in Breast Cancer
Authors: Sun Chunxiao , Huang Xiang , Li Jun , Fu Ziyi , Hua Yijia , Zeng Tianyu , He Yaozhou , Duan Ningjun , Yang Fan , Liang Yan , Wu Hao , Li Wei , Zhang Yuchen , Yin Yongmei
Published: February 2023

Tamoxifen resistance remains a challenge in hormone receptor-positive (HR+) breast cancer. Recent evidence suggests that transfer ribonucleic acid (tRNA)-derived fragments play pivotal roles in the occurrence and development of various tumors. However, the relationship between tRNA-derived fragments and tamoxifen resistance remains unclear. In this study, we found that the expression of tRF-16-K8J7K1B was upregulated in tamoxifen-resistant cells in comparison with tamoxifen-sensitive cells. Higher levels of tRF-16-K8J7K1B were associated with shorter disease-free survival in HR+ breast cancer. Overexpression of tRF-16-K8J7K1B promotes tamoxifen resistance. Moreover, extracellular tRF-16-K8J7K1B could be packaged into exosomes and could disseminate tamoxifen resistance to recipient cells. Mechanistically, exosomal tRF-16-K8J7K1B downregulates the expression of apoptosis-related proteins, such as caspase 3 and poly (ADP-ribose) polymerase, by targeting tumor necrosis factor-related apoptosis-inducing ligand in receptor cells, thereby reducing drug-induced cell apoptosis. Therapeutically, the inhibition of exosomal tRF-16-K8J7K1B increases the sensitivity of breast cancer cells to tamoxifen in vivo. These data demonstrate that exosomal tRF-16-K8J7K1B may be a novel therapeutic target to overcome tamoxifen resistance in HR+ breast cancer.
The Rochester Modified Magee Algorithm (RoMMa): An Outcomes Based Strategy for Clinical Risk-Assessment and Risk-Stratification in ER Positive, HER2 Negative Breast Cancer Patients Being Considered for Oncotype DX® Testing
Authors: Turner Bradley M. , Finkelman Brian S. , Hicks David G. , Numbereye Numbere , Moisini Ioana , Dhakal Ajay , Skinner Kristin , Sanders Mary Ann G. , Wang Xi , Shayne Michelle , Schiffhauer Linda , Katerji Hani , Zhang Huina
Published: February 2023

Introduction: Multigene genomic profiling has become the standard of care in the clinical risk-assessment and risk-stratification of ER+, HER2− breast cancer (BC) patients, with Oncotype DX® (ODX) emerging as the genomic profile test with the most support from the international community. The current state of the health care economy demands that cost-efficiency and access to testing must be considered when evaluating the clinical utility of multigene profile tests such as ODX. Several studies have suggested that certain lower risk patients can be identified more cost-efficiently than simply reflexing all ER+, HER2− BC patients to ODX testing. The Magee equationsTM use standard histopathologic data in a set of multivariable models to estimate the ODX recurrence score. Our group published the first outcome data in 2019 on the Magee equationsTM, using a modification of the Magee equationsTM combined with an algorithmic approach—the Rochester Modified Magee algorithm (RoMMa). There has since been limited published outcome data on the Magee equationsTM. We present additional outcome data, with considerations of the TAILORx risk-stratification recommendations. Methods: 355 patients with an ODX recurrence score, and at least five years of follow-up or a BC recurrence were included in the study. All patients received either Tamoxifen or an aromatase inhibitor. None of the patients received adjuvant systemic chemotherapy. Results: There was no significant difference in the risk of recurrence in similar risk categories (very low risk, low risk, and high risk) between the average Modified Magee score and ODX recurrence score with the chi-square test of independence (p > 0.05) or log-rank test (p > 0.05). Using the RoMMa, we estimate that at least 17% of individuals can safely avoid ODX testing. Conclusion: Our study further reinforces that BC patients can be confidently stratified into lower and higher-risk recurrence groups using the Magee equationsTM. The RoMMa can be helpful in the initial clinical risk-assessment and risk-stratification of BC patients, providing increased opportunities for cost savings in the health care system, and for clinical risk-assessment and risk-stratification in less-developed geographies where multigene testing might not be available.
Impact of Surgical Care Bundle on Surgical Site Infection after Non-Reconstructive Breast Cancer Surgery: A Single-Centre Retrospective Comparative Cohort Study
Authors: Chin Kian , Wärnberg Fredrik , Kovacs Anikó , Olofsson Bagge Roger
Published: February 2023

Background: Surgical-site infections (SSIs) are the commonest cause of healthcare-related infections. Although a surgical care bundle (SCB), defined as a group of preventative measures, is effective in reducing SSIs, it has not been well documented in breast cancer surgery. We aimed to investigate the impact of SCB on SSI. Methods: A single-centre retrospective comparative cohort study between 2016 and 2020 was carried out. An SCB including eight different measures was implemented in October 2018 at Sahlgrenska University Hospital, Sweden. Patients who underwent non-reconstructive breast cancer surgery were included for analysis. The primary endpoint was SSI within 30 days after surgery. Results: Overall, 10.4% of patients (100/958) developed SSI. After SCB implementation, the overall SSI rate reduced from 11.8% to 8.9% (p = 0.15). The largest SSI rate reduction was seen in the subgroup that underwent breast conservation and sentinel lymph node biopsy (SLNB), from 18.8% to 9.8% (p = 0.01). In this multivariable analysis adjusting for patient and treatment factors, the implementation of SCB resulted in a statistically significant reduction in SSI risk (OR 0.63, 95% CI 0.40–0.99, p = 0.04). Conclusions: The implementation of a SCB could reduce the incidence of SSI in breast cancer surgery.
Integrated Intensified Chemoradiation in the Setting of Total Neoadjuvant Therapy (TNT) in Patients with Locally Advanced Rectal Cancer: A Retrospective Single-Arm Study on Feasibility and Efficacy
Authors: Lo Greco Maria Chiara , La Rocca Madalina , Marano Giorgia , Finocchiaro Irene , Liardo Rocco Luca Emanuele , Milazzotto Roberto , Acquaviva Grazia , Basile Antonello , Palmucci Stefano , Foti Pietro Valerio , Pergolizzi Stefano , Pontoriero Antonio , Parisi Silvana , Spatola Corrado
Published: February 2023

While surgery is considered the main treatment for early-stage rectal cancer, locally advanced rectal cancer needs to be handled with a multidisciplinary approach. Based on literature data suggesting promising advantages of total neoadjuvant therapy (TNT), we performed a retrospective, single-arm, single-center study on 45 patients affected by histologically and radiologically proven locally advanced rectal cancer, with the aim of analyzing the feasibility and short-term efficacy of an integrated intensified treatment in the setting of TNT. Each analyzed patient performed three cycles of FOLFOX4 or De Gramont induction chemotherapy (iCT), followed by concurrent chemoradiotherapy (CRT) with long course radiotherapy (LCRT) plus concomitant boost and continuous 5-FU infusion, followed by three cycles of FOLFOX4 or De Gramont consolidation chemotherapy (conCT) and then surgery with total mesorectal excision. At a median follow-up of 30 months, this strategy has shown to be feasible and effective in terms of pathological complete response (pCR) and short-term disease-free survival (DFS).
Central Nervous System Progression/Relapse in Mature T- and NK-Cell Lymphomas
Authors: Bhansali Rahul S. , Barta Stefan K.
Published: February 2023

Non-Hodgkin lymphomas (NHL) are cancers of mature B-, T-, and NK-cells which display marked biological heterogeneity between different subtypes. Mature T- and NK-cell neoplasms are an often-aggressive subgroup of NHL and make up approximately 15% of all NHL. Long-term follow up studies have demonstrated that patients with relapsed/refractory disease have dismal outcomes; in particular, secondary central nervous system (CNS) involvement is associated with higher mortality, though it remains controversial whether this independently confers worse outcomes or if it simply reflects more aggressive systemic disease. Possible risk factors predictive of CNS involvement, such as an elevated lactate dehydrogenase and more than two sites of extranodal involvement, may suggest the latter, though several studies have suggested that discrete sites of anatomic involvement or tumor histology may be independent risk factors as well. Ultimately, small retrospective case series form the basis of our understanding of this rare but devastating event but have not yet demonstrated a consistent benefit of CNS-directed prophylaxis in preventing this outcome. Nonetheless, ongoing efforts are working to establish the epidemiology of CNS progression/relapse in mature T- and NK-cell lymphomas with the goal of identifying clinicopathologic risk factors, which may potentially help discern which patients may benefit from CNS-directed prophylactic therapy or more aggressive systemic therapy.
Biodiesel Production from Waste Plant Oil over a Novel Nano-Catalyst of Li-TiO2/Feldspar
Authors: Hanif Maryam , Bhatti Ijaz Ahmad , Shahzad Khurram , Hanif Muhammad Asif
Published: February 2023

A novel Li-impregnated TiO2 catalyst loaded on feldspar mineral (Li-TiO2/feldspar) was synthesized via a wet impregnation method and was characterized using X-ray diffraction (XRD), scanning electron microscopy (SEM), and Fourier transform infrared (FTIR) analysis. Using these techniques, it was possible to confirm the catalyst’s structural organization with a high crystallinity. This catalyst was used in the transesterification of five waste plant oils of Citrullus colocynthis (bitter apple), Pongamia pinnata (karanja), Sinapis arvensis (wild mustard), Ricinus communis (castor) and Carthamus oxyacantha (wild safflower). The catalytic tests were performed at temperatures ranging from 40 to 80 °C, employing a variable methanol/ester molar ratio (5:1, 10:1, 15:1, 20:1 and 25:1) and different catalyst concentrations (0.5%, 1%, 1.5%, 2% and 2.5%) relative to the total reactants mass. Conversion of 98.4% of fatty acid methyl esters (FAMEs) was achieved for Pongamia pinnata (karanja). The main fatty acids present in bitter apple, karanja, wild mustard, castor and wild safflower oils were linoleic acid (70.71%), oleic acid (51.92%), erucic acid (41.43%), ricinoleic acid (80.54%) and linoleic acid (75.17%), respectively. Li-TiO2/feldspar produced more than 96% for all the feedstocks. Fuel properties such as iodine value (AV), cetane number (CN), cloud point (CP), iodine value (IV), pour point (PP) and density were within the ranges specified in ASTM D6751.
Molecular Influence of Resiniferatoxin on the Urinary Bladder Wall Based on Differential Gene Expression Profiling
Authors: Lepiarczyk Ewa , Paukszto Łukasz , Wiszpolska Marta , Łopieńska-Biernat Elżbieta , Bossowska Agnieszka , Majewski Mariusz Krzysztof , Majewska Marta
Published: February 2023

Resiniferatoxin (RTX) is a potent capsaicin analog used as a drug for experimental therapy to treat neurogenic disorders associated with enhanced nociceptive transmission, including lower urinary tract symptoms. The present study, for the first time, investigated the transcriptomic profile of control and RTX-treated porcine urinary bladder walls. We applied multistep bioinformatics and discovered 129 differentially expressed genes (DEGs): 54 upregulated and 75 downregulated. Metabolic pathways analysis revealed five significant Kyoto Encyclopedia of Genes and Genomes (KEGG) items (‘folate biosynthesis’, ‘metabolic pathways’, ‘sulfur relay system’, ‘sulfur metabolism’ and ‘serotonergic synapse’) that were altered after RTX intravesical administration. A thorough analysis of the detected DEGs indicated that RTX treatment influenced the signaling pathways regulating nerve growth, myelination, axon specification, and elongation. Many of the revealed DEGs are involved in the nerve degeneration process; however, some of them were implicated in the initiation of neuroprotective mechanisms. Interestingly, RTX intravesical installation was followed by changes in the expression of genes involved in synaptic plasticity and neuromodulation, including 5-HT, H2S, glutamate, and GABA transmission. The obtained results suggest that the toxin may exert a therapeutic, antinociceptive effect not only by acting on TRPV1 receptors.
Lateral Diffusion of NKCC1 Contributes to Chloride Homeostasis in Neurons and Is Rapidly Regulated by the WNK Signaling Pathway
Authors: Côme Etienne , Blachier Simon , Gouhier Juliette , Russeau Marion , Lévi Sabine
Published: February 2023

An upregulation of the Na+-K+-2Cl− cotransporter NKCC1, the main chloride importer in mature neurons, can lead to depolarizing/excitatory responses mediated by GABA type A receptors (GABAARs) and, thus, to hyperactivity. Understanding the regulatory mechanisms of NKCC1 would help prevent intra-neuronal chloride accumulation that occurs in pathologies with defective inhibition. The cell mechanisms regulating NKCC1 are poorly understood. Here, we report in mature hippocampal neurons that GABAergic activity controls the membrane diffusion and clustering of NKCC1 via the chloride-sensitive WNK lysine deficient protein kinase 1 (WNK1) and the downstream Ste20 Pro-line Asparagine Rich Kinase (SPAK) kinase that directly phosphorylates NKCC1 on key threonine residues. At rest, this signaling pathway has little effect on intracellular Cl− concentration, but it participates in the elevation of intraneuronal Cl− concentration in hyperactivity conditions associated with an up-regulation of NKCC1. The fact that the main chloride exporter, the K+-Cl− cotransporter KCC2, is also regulated in mature neurons by the WNK1 pathway indicates that this pathway will be a target of choice in the pathology.
Thalidomide Attenuates Mast Cell Activation by Upregulating SHP-1 Signaling and Interfering with the Action of CRBN
Authors: Chang Hyeun-Wook , Sim Kyeong-Hwa , Lee Youn-Ju
Published: February 2023

Allergy is a chronic inflammatory disease, and its incidence has increased worldwide in recent years. Thalidomide, which was initially used as an anti-emetic drug but was withdrawn due to its teratogenic effects, is now used to treat blood cancers. Although the anti-inflammatory and immunomodulatory properties of thalidomide have been reported, little is known about its influence on the mast cell-mediated allergic reaction. In the present study, we aimed to evaluate the anti-allergic activity of thalidomide and the underlying mechanism using mouse bone marrow-derived mast cells (BMMCs) and passive cutaneous anaphylaxis (PCA) mouse models. Thalidomide markedly decreased the degranulation and release of lipid mediators and cytokines in IgE/Ag-stimulated BMMCs, with concurrent inhibition of FcεRI-mediated positive signaling pathways including Syk and activation of negative signaling pathways including AMP-activated protein kinase (AMPK) and SH2 tyrosine phosphatase-1 (SHP-1). The knockdown of AMPK or SHP-1 with specific siRNA diminished the inhibitory effects of thalidomide on BMMC activation. By contrast, the knockdown of cereblon (CRBN), which is the primary target protein of thalidomide, augmented the effects of thalidomide. Thalidomide reduced the interactions of CRBN with Syk and AMPK promoted by FcεRI crosslinking, thereby relieving the suppression of AMPK signaling and suppressing Syk signaling. Furthermore, oral thalidomide treatment suppressed the PCA reaction in mice. In conclusion, thalidomide suppresses FcεRI-mediated mast cell activation by activating the AMPK and SHP-1 pathways and antagonizing the action of CRBN, indicating that it is a potential anti-allergic agent.
Multifunctional Materials Based on the Solid Solutions of the (Na, K, Cd0.5)NbO3 (KNN-Cd) System Modified with Rare Earth Elements: Crystal Structure, Microstructure, and Macroresponses
Authors: Konstantin Andryushin , Palatnikov Mikhail , Shilkina Lidiya , Nagaenko Alexandr , Shcherbina Olga , Smirnov Maxim , Sidorov Nikolay , Kubrin Stanislav , Rudskaya Anzhela , Rudskiy Daniil , Reznichenko Larisa
Published: February 2023

Ceramic samples of polycomponent solid solutions (SSs) Na0.90K0.05Cd0.05NbO3 (Cd-modified KNN) and [(Na0.90K0.05Cd0.05)0.95REE0.05]NbO3, where REE = La, Pr, Tb, Dy, Ho, were obtained by the uniaxial hot pressing (UHP) method. The crystal lattice structures, morphological features of the microstructure, and dielectric and thermophysical properties of these ceramics have been investigated. For the first time, their strength characteristics (Young’s modulus) and the critical stress intensity factor of the mode I Kic have been estimated. Photoluminescent properties have been compared in SSs [(Na0.90K0.05Cd0.05)0.95REE0.05]NbO3 in the visible wavelength range.
Genome-Wide Identification and Expression Analysis of the bHLH Transcription Factor Family and Its Response to Abiotic Stress in Mongolian Oak (Quercus mongolica)
Authors: Zhan Hao , Liu Hanzhang , Ai Wanfeng , Han Xiaoyi , Wang Yu , Lu Xiujun
Published: February 2023

The basic helix-loop-helix (bHLH) family, one of the largest families of transcription factors in plants, is extensively involved in the growth, development, and stress response of several woody plants. However, no systematic analysis of the bHLH gene family in Quercus mongolica has been reported. We characterize QmbHLH genes and identify the functions of QmbHLH proteins in Q. mongolica. We used bioinformatics approaches, qRT-PCR analysis, and RNA sequencing data to examine chromosomal distributions, gene structures, and conserved patterns, and identified 89 QmbHLH genes, which were divided into 21 subgroups based on the phylogenetic analysis of bHLH genes in Arabidopsis thaliana. Segmental replication played a more prominent role than tandem duplication in the expansion of the QmbHLH gene family. Based on patterns of tissue-specific expression, protein interactions, and cis-element analysis, QmbHLH genes may be extensively involved in the growth and development of Q. mongolica. In leaves, stems, and roots, 12 selected QmbHLH genes exhibited responsiveness to abiotic stresses (salt, cold, weak light, and drought). Our study facilitates follow-up functional investigations of the bHLH gene family in Q. mongolica and provides novel insights into bHLH superfamilies in woody plants.