bluuebunny/crossref_metadata_2025 huggingface dataset:
The Possible Role of Apathy on Conflict Monitoring: Preliminary Findings of a Behavioral Study on Severe Acquired Brain Injury Patients Using Flanker Tasks
Authors: D’Ippolito Mariagrazia , Spinelli Giuseppe , Iosa Marco , Aglioti Salvatore Maria , Formisano Rita
Published: February 2023

The diagnosis of apathy, one of the most common behavioral changes after acquired brain injury (ABI), is important for improving clinical understanding and treatment of persons with ABI. The main aim of this study was to determine the possible role of apathy in conflict monitoring, by using choice reaction time tasks. Methods: We examined behavioral responses of conflict monitoring during three different flanker tasks in 10 severe ABI patients with or without diagnosis of apathy (3 M, mean age = 56.60; 3 M, mean age ± SD = 58.60, respectively), and 15 healthy controls (9 M, mean age = 54.46) Reaction times (RTs), accuracy, and global index of performance (GIP) were analyzed for each task. Results: Only apathetic ABI patients showed a significant difference from healthy subjects (p-value ≤ 0.001), while the performance of patients without apathy was not significantly different from that of healthy controls (p-value = 0.351). Healthy participants had higher accuracy in comparison to both ABI patients with (p < 0.001) and without (p-value = 0.038) apathy, whilst slower RTs were shown by ABI patients without apathy in comparison to both healthy subjects (p-value = 0.045) and apathetic ABI patients (p-value = 0.022). Only patients with apathy exhibited a significantly higher number of missing trials (p-value = 0.001). Conclusions: Our results may suggest a potential link between apathy following severe ABI and conflict monitoring processes, even though further investigations with larger sample size are needed.
Neurocognitive Deficits in First-Episode and Chronic Psychotic Disorders: A Systematic Review from 2009 to 2022
Authors: Tschentscher Nadja , Woll Christian F. J. , Tafelmaier Julia C. , Kriesche Dominik , Bucher Julia C. , Engel Rolf R. , Karch Susanne
Published: February 2023

Cognitive impairment in patients suffering from schizophrenia spectrum disorders has been discussed as a strong predictor for multiple disease outcome variables, such as response to psychotherapy, stable relationships, employment, and longevity. However, the consistency and severity of cognitive deficits across multiple domains in individuals with first-episode and chronic psychotic disorders is still undetermined. We provide a comprehensive overview of primary research from the years 2009 to 2022. Based on a Cochrane risk assessment, a systematic synthesis of 51 out of 3669 original studies was performed. Impairment of cognitive functioning in patients diagnosed with first-episode psychotic disorders compared with healthy controls was predicted to occur in all assessed cognitive domains. Few overall changes were predicted for chronically affected patients relative to those in the first-episode stage, in line with previous longitudinal studies. Our research outcomes support the hypothesis of a global decrease in cognitive functioning in patients diagnosed with psychotic disorders, i.e., the occurrence of cognitive deficits in multiple cognitive domains including executive functioning, memory, working memory, psychomotor speed, and attention. Only mild increases in the frequency of cognitive impairment across studies were observed at the chronically affected stage relative to the first-episode stage. Our results confirm and extend the outcomes from prior reviews and meta-analyses. Recommendations for psychotherapeutic interventions are provided, considering the broad cognitive impairment already observed at the stage of the first episode. Based on the risk of bias assessment, we also make specific suggestions concerning the quality of future original studies.
Altered Spontaneous Brain Activity in Poststroke Aphasia: A Resting-State fMRI Study
Authors: Li Haozheng , Zhang Hui , Xu Shuai , Wang Mengxing , Zhang Jilei , Liu Jianren , Du Xiaoxia , Hu Ruiping
Published: February 2023

Purpose: Brain areas frequently implicated in language recovery after stroke comprise perilesional sites in the left hemisphere and homotopic regions in the right hemisphere. However, the neuronal mechanisms underlying language restoration are still largely unclear. Methods and materials: In the present study, we investigated the brain function in 15 patients with poststroke aphasia and 30 matched control subjects by combining the regional homogeneity (ReHo) and amplitudes of low-frequency fluctuation (ALFF) analysis methods based on resting-state fMRI. Results: Compared to the control subjects, the patients with aphasia exhibited increased ReHo and ALFF values in the ipsilateral perilesional areas and increased ReHo in the contralesional right middle frontal gyrus. Conclusions: The increased spontaneous brain activity in patients with poststroke aphasia during the recovery period, specifically in the ipsilateral perilesional regions and the homologous language regions of the right hemisphere, has potential implications for the treatment of patients with aphasia.
Exploring the Lived Experience on Recovery from Major Depressive Disorder (MDD) among Women Survivors and Five CHIME Concepts: A Qualitative Study
Authors: Idris Afifah , Md Akhir Noremy , Mohamad Mohd Suhaimi , Sarnon Norulhuda
Published: February 2023

Objective: Depression is estimated to be the leading cause of disease by 2030 and is already the leading cause in women worldwide. In Malaysia, nearly 2.3 million people have experienced depression at least once. Yet, this problem has not been thoroughly investigated and addressed. Thus, a study exploring the lived experience of the survivors needs to be carried out. With most Major Depressive Disorder (MDD) patients being women compared to men, this study focused on women MDD survivors to understand their journey to recovery. Survivors or also called ‘People with Lived Experience’ (PWLE) have a range of first-hand experiences with treatment and recovery, making them an expert by experience. Method: A qualitative study was conducted using purposive sampling of four women survivors. This method was able to explore the experience of informants rigorously as it gave flexibility and encouraged discussion between researchers and informants. The data from in-depth interviews conducted were then analyzed using thematic analysis, focusing on the key concepts of CHIME conceptual framework of recovery. Results: This study found four major themes with fifteen subordinate themes: survivor’s efforts, challenges, social support, and hopes. The findings of this study were then integrated with CHIME framework, also known as the guiding philosophy of recovery for mental illness patients. Conclusion: These findings contributed to a better understanding of the recovery process and supports needed for MDD patients to recover. In addition, this study also gives hopes that MDD patients can recover, therefore breaking the social stigma still prevalent in the community. Based on these first-hand experiences shared by the survivors, it is hoped that the present interventions conducted by related organizations and caregivers can yield improvements so that the current patients who are still struggling with MDD can recover faster holistically. Limitations and implications for future research have also been discussed.
Studying Response to Light in Offices: A Literature Review and Pilot Study
Authors: Collier Jessica M. , Wilkerson Andrea , Durmus Dorukalp , Rodriguez-Feo Bermudez Eduardo
Published: February 2023

Researchers have been exploring the influence of light on health in office settings for over two decades; however, a greater understanding of physiological responses and technology advancements are shifting the way researchers study the influence of light in realistic environments. New technologies paired with Ecological Momentary Assessments (EMAs) administered via smartphones provide ways to collect information about individual light exposure and occupant response throughout the day. The study aims to document occupant response to tunable lighting in a real office environment, including potential beneficial or adverse health and well-being effects. Twenty-three office employees agreed to participate in a twelve-week study examining occupant response to two lighting conditions (static vs. dynamic). No significant differences were observed for any of the measures, highlighting the importance and complexity of in-situ studies conducted in realistic environments. While prior office studies have shown a significant influence on daytime sleepiness and sleep quality, research has not shown mood or stress to be significantly impacted by lighting conditions. Correlation analyses regarding lighting satisfaction, environmental satisfaction, and visual comfort demonstrate a significant relationship between certain items that may inform future studies. Further, the high correlation means it is reasonable to assume that many environmental factors in offices can influence occupant behavior and well-being.
Condition Assessment of Grouped Cable Forces of Cable-Stayed Bridge Using Deflection Data
Authors: Liu Xiaoling , Yi Xiyan , Wang Bing , Liu Ying
Published: February 2023

The stress state of the cable group in a cable-stayed bridge directly affects the overall performance. A novel method for assessing grouped cable forces using deflection data is proposed in this article. Firstly, a simplified equation between the variation in cable forces and the girder deflection was built according to the geometric relationship of the deformation. Secondly, the threshold value of cable force change rate for a single cable can be determined by the proposed theoretical equation and the deflection limit in the specification. On this basis, the evaluation standard of single cable force of piecewise linear mode was established. Thirdly, considering the uniform and non-uniform changes in the cable forces, the condition assessment method of grouped cable forces was established based on the variable weight synthesis method and the gray correlation degree theory. Finally, a case study of a real bridge was undertaken. The results show that the case data validate the correctness of the proposed theoretical equation. The threshold of change rate for long cable is 30%. Six-year assessment scores of grouped cables are generally decreasing, which also reflects the development of other component defects from the side.
A Cost–Benefit Analysis Framework for City-Scale Seismic Retrofitting Scheme of Buildings
Authors: Tian Yuan , Ren Jingyi , Xu Zhen , Qi Mingzhu
Published: February 2023

To improve urban seismic resilience, a reasonable seismic retrofitting scheme for buildings is required. Urban cities contain a large number of buildings, making it challenging to precisely assess the seismic retrofitting benefits of each one. This paper proposes a cost–benefit assessment framework that takes into account seismic risk, seismic damage, retrofit costs, economic losses, and cost–benefit analyses for the city-scale seismic retrofitting of buildings. The proposed framework adopts readily available building parameters, including the number of stories, construction year, total height, structural type, floor area, and response spectrum for structural design. It makes use of empirical seismic retrofitting models and a newly developed story-level seismic loss assessment method combining the physical mechanism and empirical loss ratios. For city-scale cost–benefit analysis, the framework can strike a good balance between data accessibility, computational workload, level of result details, and result accuracy. It can adapt nimbly to earthquake-induced indirect losses and budgetary constraints on retrofitting. The analysis of 98,618 buildings in Xi’an city, China, is carried out. The findings indicate that, when potential indirect economic loss ratios of buildings are neglected, the retrofitting benefits of unreinforced masonry and old buildings are the most significant.
Hot Topics and Trends in Zero-Energy Building Research—A Bibliometrical Analysis Based on CiteSpace
Authors: Wei Jia , Li Jiyang , Zhao Jiafan , Wang Xiaoyang
Published: February 2023

With the development of a low-carbon economy, zero-energy structures will become prevalent and take center stage in the construction industry. This paper uses the CiteSpace software to create knowledge maps of authors, institutions and keywords, and then examined and commented on research publications regarding zero-energy buildings in order to understand the research state and development trends of zero-energy buildings. The findings demonstrate that: (1) Since its inception in 2000, research on zero-energy buildings has advanced significantly; (2) A subject analysis approach is used to identify development trends and research emphasis, and the four research areas with the most papers published are energy fuels, construction building technology, civil engineering and green sustainable science technology; (3) China, the United States and Italy are the countries with the most activity in zero-energy building research; (4) Out of the eight most prominent keywords for the study subjects, the design of zero-energy buildings, the estimation of the carbon emissions of zero-energy buildings, the technical challenges of zero-energy buildings and the follow-up energy-saving measures of zero-energy buildings are the four fundamental topics covered in the most cited papers; (5) There are three obstacles to the development of zero-carbon buildings: unclear standards, immature technology and insufficient development momentum. The following three problems should receive more attention in the future: how to develop a widely accepted zero-carbon building standard; how to coordinate national support to achieve technological breakthroughs; and the establishment of an effective incentive mechanism at the international and national levels to promote the development of zero-carbon buildings.
From Policy to Implementation—An Analytic Network Process (ANP)-Based Assessment Tool for Low Carbon Urban and Neighborhood Planning
Authors: Lei Qinghua , Lau Stephen Siu Yu , Fan Yue , Fu Ivan Chin Shing , Chan Joseph Tin Yeung , Tao Yiqi , Zhang Ling , Lai Hongzhan , Miao Yijia , Qi Yi
Published: February 2023

To achieve the goals of carbon peaking, a national policy instrument for carbon peaking in the building and construction sector has been launched by the Chinese MOHURD (30 June 2022). We have developed an actionable framework for implementing these policy objectives. The framework was designed by classifying and prioritizing selected strategic government recommendations in the form of an interactive indicator system and tool for evaluating the quality of low-carbon urban and neighborhood planning actions based on the decarbonation principles of carbon emission reduction and carbon capture. The analytic network process (ANP) was applied for processing the interactions and prioritizing the indicators (23 in total for the two principles applied). A scorecard was designed for assessing low-carbon urban and neighborhood planning strategies and technologies. The practical implementation of the tool was then tested with two real planning cases, one from a fourth-tier Chinese city and another from a high-density city. The applicability of the tool is further discussed by comparing it with well-developed international assessment tools in other contexts. This article contributes to the literature by first initiating research on the use of this evaluative tool for low-carbon planning and secondly by demonstrating how researchers can convert policies into practical implementations.
Hypoxia-Driven TGFβ Modulation of Side Population Cells in Breast Cancer: The Potential Role of ERα
Authors: Mallini Paraskevi , Chen Miaojuan , Mahkamova Kamilla , Lennard Thomas W. J. , Pan Yue , Wei Dan , Stemke-Hale Katherine , Kirby John A. , Lash Gendie E. , Meeson Annette
Published: February 2023

Epithelial-to-mesenchymal transition (EMT) is known to be important in regulating the behaviour of cancer cells enabling them to acquire stem cell characteristics or by enhancing the stem cell characteristics of cancer stem cells, resulting in these cells becoming more migratory and invasive. EMT can be driven by a number of mechanisms, including the TGF-β1 signalling pathway and/or by hypoxia. However, these drivers of EMT differ in their actions in regulating side population (SP) cell behaviour, even within SPs isolated from the same tissue. In this study we examined CoCl2 exposure and TGF-β driven EMT on SP cells of the MDA-MB-231 and MCF7 breast cancer cell lines. Both TGF-β1 and CoCl2 treatment led to the depletion of MDA-MB-231 SP. Whilst TGF-β1 treatment significantly reduced the MCF7 SP cells, CoCl2 exposure led to a significant increase. Single cell analysis revealed that CoCl2 exposure of MCF7 SP leads to increased expression of ABCG2 and HES1, both associated with multi-drug resistance. We also examined the mammosphere forming efficiency in response to CoCl2 exposure in these cell lines, and saw the same effect as seen with the SP cells. We suggest that these contrasting effects are due to ERα expression and the inversely correlated expression of TGFB-RII, which is almost absent in the MCF7 cells. Understanding the EMT-mediated mechanisms of the regulation of SP cells could enable the identification of new therapeutic targets in breast cancer.
Direct Cell Death Induced by CD20 Monoclonal Antibodies on B Cell Lymphoma Cells Revealed by New Protocols of Analysis
Authors: Constantinides Michael , Fayd’herbe De Maudave Alexis , Potier-Cartereau Marie , Campos-Mora Mauricio , Cartron Guillaume , Villalba Martin
Published: February 2023

CD20 monoclonal antibodies (mAbs) eliminate B cells in several clinical contexts. At least two of these Abs, obinutuzumab (OBI) and rituximab (RTX), induce quick elimination of targets and put cancer patients at risk of tumor lysis syndrome (TLS) within 12–24 h of the first dose. The mechanisms of killing can require the recruiting of effector mechanisms from the patient’s immune system, but they can induce direct killing as well. This can be more rapid than recruiting cellular effectors and/or complement. We showed here that OBI and RTX induce quick (<1 h) and high (up to 60% for OBI) killing of two different B cell lines. This was unveiled by using two different techniques that circumvent cell centrifugation steps: a Muse® Cell Analyzer-based approach and a direct examination of the cells’ physical properties by using forward scatter (FS) area and side scatter (SS) area by flow cytometry. These results excluded the presence of aggregates and were also confirmed by developing a normalized survival ratio based on the co-incubation of RTX- and OBI-sensitive cells with MOLM-13, an insensitive cell line. Finally, this normalized survival ratio protocol confirmed the RTX- and OBI-direct killing on primary tumor B cells from B cell chronic lymphocytic leukemia (B-CLL) and Non-Hodgkin’s lymphoma (NHL) patients. Moreover, we unveiled that direct killing is higher than previously expected and absent in patients’ samples at relapse. We also observed that these mAbs, prior to increasing intracellular calcium levels, decrease calcium entry, although manipulating calcium levels did not affect their cytotoxicity. Altogether, our results show that direct killing is a major mechanism to induce cell death by RTX and OBI mAbs.
Are Aspects of Integrative Concepts Helpful to Improve Pancreatic Cancer Therapy?
Authors: Oei Shiao Li , Schad Friedemann
Published: February 2023

Numerous clinical studies have been conducted to improve the outcomes of patients suffering from pancreatic cancer. Different approaches using targeted therapeutic strategies and precision medicine methods have been investigated, and synergies and further therapeutic advances may be achieved through combinations with integrative methods. For pancreatic tumors, a particular challenge is the presence of a microenvironment and a dense stroma, which is both a physical barrier to drug penetration and a complex entity being controlled by the immune system. Therefore, the state of immunological tolerance in the tumor microenvironment must be overcome, which is a considerable challenge. Integrative approaches, such as hyperthermia, percutaneous irreversible electroporation, intra-tumoral injections, phytotherapeutics, or vitamins, in combination with standard-oncological therapies, may potentially contribute to the control of pancreatic cancer. The combined application of standard-oncological and integrative methods is currently being studied in ongoing clinical trials. An actual overview is given here.
The Genetic and Immunologic Landscape Underlying the Risk of Malignant Progression in Laryngeal Dysplasia
Authors: Chu Francesco , Maffini Fausto , Lepanto Daniela , Vacirca Davide , Taormina Sergio Vincenzo , De Berardinis Rita , Gandini Sara , Vignati Silvano , Ranghiero Alberto , Rappa Alessandra , Chiocca Susanna , Barberis Massimo , Tagliabue Marta , Ansarin Mohssen
Published: February 2023

(1) Background: The development of laryngeal cancer is a multistep process involving structural alterations of the epithelial mucosa, from dysplasia (LDy) to invasive carcinoma. In this study, we define new biomarkers, prognostic for malignant transformation, in patients affected by LDy. (2) Methods: We used targeted next-generation sequencing and immunohistochemical analysis to define the mutational and immunological landscape of 15 laryngeal dysplasia progressing to invasive cancer (progressing dysplasia), as well as 31 cases of laryngeal dysplasia that did not progress to carcinoma (non-progressing dysplasia). Two pathologists independently analyzed the presence of tumor-infiltrating lymphocytes in LDy pre-embedded paraffin-fixed specimens. The RNA-based next-generation sequencing panel OIRRA was used to evaluate the expression of 395 genes related to immune system activation. (3) Results: High TILs are significantly correlated with a higher risk of malignant transformation. The non-brisk pattern was significantly associated with an 86% reduced risk of malignant progression (OR = 0.16, 95% CI: 0.03–0.5, p = 0.008). TILs showed a highly positive correlation with CCR6, CD83, HLA-DPB1, MX1 and SNAI1, and they were inversely correlated with CD48, CIITA, CXCR4, FCER1G, IL1B, LST1 and TLR8. (4) Conclusions: TILs have a great potential to identify high-risk progression dysplasia and thus to define surveillance protocols and prevention programs.
NEDD9 Overexpression Causes Hyperproliferation of Luminal Cells and Cooperates with HER2 Oncogene in Tumor Initiation: A Novel Prognostic Marker in Breast Cancer
Authors: Purazo Marc L. , Ice Ryan J. , Shimpi Rahul , Hoenerhoff Mark , Pugacheva Elena N.
Published: February 2023

HER2 overexpression occurs in 10–20% of breast cancer patients. HER2+ tumors are characterized by an increase in Ki67, early relapse, and increased metastasis. Little is known about the factors influencing early stages of HER2- tumorigenesis and diagnostic markers. Previously, it was shown that the deletion of NEDD9 in mouse models of HER2 cancer interferes with tumor growth, but the role of NEDD9 upregulation is currently unexplored. We report that NEDD9 is overexpressed in a significant subset of HER2+ breast cancers and correlates with a limited response to anti-HER2 therapy. To investigate the mechanisms through which NEDD9 influences HER2-dependent tumorigenesis, we generated MMTV-Cre-NEDD9 transgenic mice. The analysis of mammary glands shows extensive ductal epithelium hyperplasia, increased branching, and terminal end bud expansion. The addition of oncogene Erbb2 (neu) leads to the earlier development of early hyperplastic benign lesions (~16 weeks), with a significantly shorter latency than the control mice. Similarly, NEDD9 upregulation in MCF10A-derived acini leads to hyperplasia-like DCIS. This phenotype is associated with activation of ERK1/2 and AURKA kinases, leading to an increased proliferation of luminal cells. These findings indicate that NEDD9 is setting permissive conditions for HER2-induced tumorigenesis, thus identifying this protein as a potential diagnostic marker for early detection.
Impact of Perineural Invasion and Preexisting Type 2 Diabetes on Patients with Esophageal Squamous Cell Carcinoma Receiving Neoadjuvant Chemoradiotherapy
Authors: Su Nai-Wen , Mok Lai-Man , Chan Mei-Lin , Liu Hung-Chang , Chang Wei-Chin , Yun Chun-Ho , Shieh Tze-Yu , Wu Ming-Che , Lin Huan-Chau , Huang Wen-Chien , Chen Yu-Jen
Published: February 2023

Neoadjuvant chemoradiotherapy (neoCRT) followed by surgery is the cornerstone treatment strategy in locally advanced esophageal squamous cell carcinoma (ESCC). Despite this high- intensity multimodality therapy, most patients still experience recurrences and metastases, especially those who do not achieve a pathological complete response (pCR) after neoCRT. Here, we focused on identifying poor prognostic factors. In this retrospective cohort study; we enrolled 140 patients who completed neoCRT plus surgery treatment sequence with no interval metastasis. Overall, 45 of 140 patients (32.1%) achieved a pCR. The overall survival, disease-free survival (DFS), and metastasis-free survival was significantly better in patients with a pCR than in patients with a non-pCR. In the non-pCR subgroup, the presence of perineural invasion (PNI) and preexisting type 2 diabetes (T2DM) were two factors adversely affecting DFS. After adjusting for other factors, multivariate analysis showed that the hazard ratio (HR) was 2.354 (95% confidence interval [CI] 1.240–4.467, p = 0.009) for the presence of PNI and 2.368 (95% CI 1.351–4.150, p = 0.003) for preexisting T2DM. Patients with a combination of both factors had the worst survival. In conclusion, PNI and preexisting T2DM may adversely affect the prognosis of patients with ESCC receiving neoadjuvant chemoradiotherapy.
Evaluation of the EPR Effect in the CAM-Model by Molecular Imaging with MRI and PET Using 89Zr-Labeled HSA
Authors: Hilbrig Colmar , Löffler Jessica , Fischer Gabriel , Scheidhauer Ellen , Solbach Christoph , Huber-Lang Markus , Beer Ambros J. , Rasche Volker , Winter Gordon
Published: February 2023

Mouse models are commonly used to study the biodistribution of novel radioligands, but alternative models corresponding to the 3Rs principles, such as the chorioallantoic membrane (CAM) model, are highly required. While there are promising data from the CAM model regarding target-specific radiolabeled compounds, its utility for assessing macromolecule biodistribution and analyzing the EPR effect remains to demonstrated. Using 89Zr-labeled human serum albumin, the accumulation of nontarget-specific macromolecules in CAM and mouse xenograft models was studied using PET and MRI. Therefore, the radioligand [89Zr]Zr-DFO-HSA was analyzed in both chicken embryos (n = 5) and SCID mice (n = 4), each with TZM-bl and PC-3 tumor entities. Dynamic PET and anatomical MRI, as well as ex vivo biodistribution analyses, were performed to assess ligand distribution over 24 h. Histological staining and autoradiography verified the intratumoral accumulation. The tumors were successfully visualized for CAM and mouse models by PET, and the albumin influx from the blood into the respective tumors did not differ significantly. The accumulation and retention of HSA in tumors due to the EPR effect was demonstrated for both models. These results highlight that the CAM model is a potential alternative to the mouse model for initial studies with novel radiolabeled macromolecules with respect to the 3Rs principles.
In Vivo Detection of Circulating Cancer-Associated Fibroblasts in Breast Tumor Mouse Xenograft: Impact of Tumor Stroma and Chemotherapy
Authors: Lu Tao , Oomens Lisa , Terstappen Leon W. M. M. , Prakash Jai
Published: February 2023

Cancer-associated fibroblasts (CAFs) are important drivers in the tumor microenvironment and facilitate the growth and survival of tumor cells, as well as metastasis formation. They may travel together with tumor cells to support their survival and aid in the formation of a metastatic niche. In this study, we aimed to study circulating CAFs (cCAFs) and circulating tumor cells (CTCs) in a preclinical breast tumor model in mice in order to understand the effect of chemotherapy on cCAFs and CTC formation. Tumors with MDA-MB-231 human breast tumor cells with/without primary human mammary fibroblasts (representing CAFs) were coinjected in SCID mice to develop tumors. We found that the tumors with CAFs grew faster than tumors without CAFs. To study the effect of the stroma on CTCs and cCAFs, we isolated cells using microsieve filtration technology and established ITGA5 as a new cCAF biomarker, which showed good agreement with the CAF markers FAP and α-SMA. We found that ITGA5+ cCAFs shed in the blood of mice bearing stroma-rich coinjection-based tumors, while there was no difference in CTC formation. Although treatment with liposomal doxorubicin reduced tumor growth, it increased the numbers of both cCAFs and CTCs in blood. Moreover, cCAFs and CTCs were found to form clusters in the chemotherapy-treated mice. Altogether, these findings indicate that the tumor stroma supports tumor growth and the formation of cCAFs. Furthermore, chemotherapy may exacerbate the formation of cCAFs and CTCs, which may eventually support the formation of a metastasis niche in breast cancer.
Long-Term Sequential Digital Dermoscopy of Low-Risk Patients May Not Improve Early Diagnosis of Melanoma Compared to Periodical Handheld Dermoscopy
Authors: Borroni Riccardo , Panasiti Vincenzo , Valenti Mario , Gargiulo Luigi , Perrone Giuseppe , Dall’Alba Roberta , Fava Clarissa , Sacrini Francesco , Mancini Luca , Manara Sofia , Morenghi Emanuela , Costanzo Antonio
Published: February 2023

Sequential digital dermoscopy (SDD) enables the diagnosis of a subgroup of slow-growing melanomas that lack suspicious features at baseline examination but exhibit detectable change on follow-up. The combined use of total-body photography and SDD is recommended in high-risk subjects by current guidelines. To establish the usefulness of SDD for low-risk individuals, we conducted a retrospective study using electronic medical records of low-risk patients with a histopathological diagnosis of cutaneous melanoma between 1 January 2016 and 31 December 2019, who had been referred and monitored for long-term follow-up of clinically suspicious melanocytic nevi. We sought to compare the distribution of “early” cutaneous melanoma, defined as melanoma in situ and pT1a melanoma, between SDD and periodical handheld dermoscopy in low-risk patients. A total of 621 melanomas were diagnosed in a four-year timespan; 471 melanomas were diagnosed by handheld dermoscopy and 150 by digital dermoscopy. Breslow tumor thickness was significantly higher for melanomas diagnosed by handheld compared to digital dermoscopy (0.56 ± 1.53 vs. 0.26 ± 0.84, p = 0.030, with a significantly different distribution of pT stages between the two dermoscopic techniques. However, no significant difference was found with respect to the distribution of pT stages, mean Breslow tumor thickness, ulceration, and prevalence of associated melanocytic nevus in tumors diagnosed on periodical handheld dermoscopy compared to SDD. Our results confirm that periodical dermoscopic examination enables the diagnosis of cutaneous melanoma at an earlier stage compared to first-time examination as this was associated in our patients with better prognostic features. However, in our long-term monitoring of low-risk subjects, Breslow tumor thickness and pT stage distribution did not differ between handheld periodical dermoscopy and SDD.
Precautions during Direct Oral Anticoagulant Introduction in Gynecologic Malignancies: A Single-Center Retrospective Cohort Study
Authors: Shimizu Takanori , Iwama Noriyuki , Tokunaga Hideki , Endo Shun , Miyahara Shuko , Toki Asami , Watanabe Zen , Minato Junko , Hashimoto Chiaki , Ishibashi Masumi , Shigeta Shogo , Shimada Muneaki , Yaegashi Nobuo
Published: February 2023

The risk factors for venous thromboembolism (VTE) recurrence/exacerbation or a change from a direct oral anticoagulant (DOAC) to another anticoagulant in patients with gynecologic cancer using DOACs have not been thoroughly elucidated. Here, we aimed to investigate the risk factors for a composite primary outcome, including VTE recurrence/exacerbation, or a change from a DOAC to another anticoagulant, in this population. A total of 63 patients were analyzed. Risk factors for a primary outcome within 2 years after DOAC initiation were investigated using multiple logistic regression analysis. Among the 63 patients, 10 developed a primary outcome. Clear cell carcinoma of the ovary (adjusted odds ratio (aOR), 18.9; 95% confidence interval (CI), 2.25–350.74), pulmonary embolism (PE) or proximal deep vein thrombosis without PE (aOR, 55.6; 95% CI, 3.29–11,774.66), and D-dimer levels in the third tertile (≥7.6 μg/dL) when VTE was first diagnosed (aOR, 6.37; 95% CI, 1.17–66.61) were associated with increased odds of a primary outcome in patients with gynecologic cancer using DOACs. Patients with one or more risk factors for a primary outcome require careful follow-up after DOAC initiation for the early recognition of treatment failure.
Brachytherapy in the Treatment of Soft-Tissue Sarcomas of the Extremities—A Current Concept and Systematic Review of the Literature
Authors: Neugebauer Johannes , Blum Philipp , Keiler Alexander , Süß Markus , Neubauer Markus , Moser Lukas , Dammerer Dietmar
Published: February 2023

Introduction: Evidence on the use of brachytherapy in soft-tissue sarcoma (STS) is sparse. Therapy regimens are determined more by local interdisciplinary tumor conferences than by standardized protocols. Patient-specific factors complicate the standardized application of therapy protocols. The individuality of the treatment makes it difficult to compare results. Materials and Methods: A comprehensive literature search was conducted, whereby the literature from a period of almost 44 years (1977–2021) was graded and included in this systematic review. For this purpose, PubMed was used as the primary database. Search string included “soft-tissue sarcoma”, “brachytherapy”, and “extremity.” Four independent researchers reviewed the literature. Only full-text articles written in English or German were included. Results: Of the 175 identified studies, 70 were eligible for analysis based on the inclusion and exclusion criteria. The key points to compare were local complications, recurrence rate and correlation with margins of resection, and the use of brachytherapy regarding tumor grading. Conclusion: Brachytherapy represents an important subset of radiotherapy techniques used in STSs, whose indications and applications are constantly evolving, and for which a local control rate of 50% to 96% has been reported as monotherapy, depending on risk factors. However, the best benefit is seen in the combination of further resection and brachytherapy, and most authors at many other centers agree with this treatment strategy.
Correlations between [68Ga]Ga-DOTA-TOC Uptake and Absorbed Dose from [177Lu]Lu-DOTA-TATE
Authors: Bruvoll Ragnar , Blakkisrud Johan , Mikalsen Lars Tore , Connelly James , Stokke Caroline
Published: February 2023

Purpose: The aim of this paper was to investigate correlations between pre- therapeutic [68Ga]Ga-DOTA-TOC uptake and absorbed dose to tumours from therapy with [177Lu]Lu-DOTA-TATE. Methods: This retrospective study included 301 tumours from 54 GEP-NET patients. The tumours were segmented on pre-therapeutic [68Ga]Ga-DOTA-TOC PET/CT, and post-therapy [177Lu]Lu-DOTA-TATE SPECT/CT images, using a fixed 40% threshold. The SPECT/CT images were used for absorbed dose calculations by assuming a linear build-up from time zero to day one, and mono-exponential wash-out after that. Both SUVmean and SUVmax were measured from the PET images. A linear absorbed-dose prediction model was formed with SUVmean as the independent variable, and the accuracy was tested with a split 70–30 training-test set. Results: Mean SUVmean and SUVmax from [68Ga]Ga-DOTA-TOC PET was 24.0 (3.6–84.4) and 41.0 (6.7–146.5), and the mean absorbed dose from [177Lu]Lu-DOTA-TATE was 26.9 Gy (2.4–101.9). A linear relationship between SUVmean and [177Lu]Lu-DOTA-TATE activity concentration at 24 h post injection was found (R2 = 0.44, p < 0.05). In the prediction model, a root mean squared error and a mean absolute error of 1.77 and 1.33 Gy/GBq, respectively, were found for the test set. Conclusions: There was a high inter- and intra-patient variability in tumour measurements, both for [68Ga]Ga-DOTA-TOC SUVs and absorbed doses from [177Lu]Lu-DOTA-TATE. Depending on the required accuracy, [68Ga]Ga-DOTA-TOC PET imaging may estimate the [177Lu]Lu-DOTA-TATE uptake. However, there could be a high variance between predicted and actual absorbed doses.
Recent Advances in Cervical Cancer Management: A Review on Novel Prognostic Factors in Primary and Recurrent Tumors
Authors: Santoro Angela , Inzani Frediano , Angelico Giuseppe , Arciuolo Damiano , Bragantini Emma , Travaglino Antonio , Valente Michele , D’Alessandris Nicoletta , Scaglione Giulia , Sfregola Stefania , Piermattei Alessia , Cianfrini Federica , Roberti Paola , Zannoni Gian Franco
Published: February 2023

Background: Several pathological parameters, including tumor size, depth of stromal invasion, lympho-vascular space invasion and lymph node status, have been proposed as prognostic predictors in cervical cancer. However, given the high mortality and recurrence rate of cervical cancer, novel parameters that are able to provide additional prognostic information are needed in order to allow a better prognostic stratification of cervical cancer patients. Methods: A search was conducted on PubMed to identify relevant literature data regarding prognostic factors in cervical cancer. The key words “cervical cancer”, “prognostic factors”, “pathology”, and “outcome” were used. Results: The novel pathological grading system based on tumor budding and cell nest size appeared the most relevant prognostic factor in primary neoplasms. Moreover, other potentially useful prognostic factors were tumor size, depth of stromal invasion, lympho-vascular space invasion, perineural invasion, tumor-free distance and tumor-infiltrating lymphocytes. Prognostic factors related to advanced-stage cervical cancer, including lymph-nodes status, endometrial and cervical involvement as well as distant metastases, were also taken into consideration. Conclusions: According to our findings, tumor budding and cell nest size grading system, depth of stromal invasion, lympho-vascular space invasion, perineural invasion, tumor-free distance and tumor-infiltrating lymphocytes appeared the most relevant factors included in the pathology report.
Endometrial Cancer Arising in Adenomyosis (EC-AIA): A Systematic Review
Authors: Raffone Antonio , Raimondo Diego , Maletta Manuela , Travaglino Antonio , Renzulli Federica , Neola Daniele , De Laurentiis Umberto , De Laurentiis Francesco , Mabrouk Mohamed , Ianieri Manuel Maria , Seracchioli Renato , Casadio Paolo , Mollo Antonio
Published: February 2023

Endometrial cancer arising in adenomyosis (EC-AIA) is a rare uterine disease characterized by the malignant transformation of the ectopic endometrium within the adenomyotic foci. Clinicopathological and survival data are mostly limited to case reports and a few cohort studies. We aimed to assess the clinicopathological features and survival outcomes of women with EC-AIA through a systematic review of the literature. Six electronic databases were searched, from 2002 to 2022, for all peer-reviewed studies that reported EC-AIA cases. Thirty-seven EC-AIA patients from 27 case reports and four case series were included in our study. In our analysis, EC-AIA appeared as a rare disease that mainly occurs in menopausal women, shares symptoms with endometrial cancer, and is challenging to diagnose preoperatively. Differently from EC, it shows a higher prevalence of the non-endometrioid histotype, advanced FIGO stages, and p53-signature, which might be responsible for its worse prognosis. Future studies are necessary, to confirm our findings and further investigate this rare condition.
F,O,S-Codoped Graphitic Carbon Nitride as an Efficient Photocatalyst for the Synthesis of Benzoxazoles and Benzimidazoles
Authors: Santiago-Aliste Alberto , Sánchez-Hernández Eva , Andrés-Juan Celia , Chamorro-Posada Pedro , Antorrena Guillermo , Martín-Gil Jesús , Martín-Ramos Pablo
Published: February 2023

Graphitic carbon nitride (g-C3N4) is a metal-free heterogeneous catalyst that has attracted attention because of its good chemical stability, cost-effectiveness, and environmental friendliness. In the work presented herein, F,O,S-codoped carbon nitride was synthesized by heating a mixture of melamine cyanurate and trifluoromethanesulfonic acid at 550 °C for 50 min. The obtained product was characterized by transmission electron microscopy, infrared spectroscopy, X-ray powder diffraction, CHNS elemental analysis, total combustion-ion chromatography, X-ray photoelectron spectroscopy, scanning electron microscopy coupled with energy-dispersive X-ray spectroscopy, and UV-Vis spectroscopy. Results point to an F,O,S-codoped g-C3N4. The material was applied as a photocatalyst for the formation of benzoxazoles and benzimidazoles by condensation–aromatization of 2-aminophenol or 1,2-phenylenediamine with suitable aldehydes (viz. benzaldehyde, 4-chlorobenzaldehyde, 2-naphthaldehyde, 2-hydroxybenzaldehyde, and 2-methoxybenzaldehyde), obtaining yields of up to 90% in 15 min under visible light irradiation, with good selectivity and reusability. Thus, the reported findings suggest that this F,O,S-codoped g-C3N4 may hold promise as a metal-free photocatalyst for the rapid synthesis of 2-arylbenzoxazoles and 2-arylbenzimidazoles.
Cryopreservation of the Microalgae Scenedesmus sp.
Authors: Prieto-Guevara Martha , Alarcón-Furnieles Jany , Jiménez-Velásquez César , Hernández-Julio Yamid , Espinosa-Araujo José , Atencio-García Víctor
Published: February 2023

Each phytoplankton species presents a different behavior and tolerance to the cryopreservation process. Therefore, in a species-specific protocol, it is essential to ensure both growth and post-thawing cell viability. In this study, we explored the effect of cryopreservation of Scenedesmus sp. with two cryoprotectants, dimethyl sulfoxide (DMSO) and methanol (MET), at 5% and 10% inclusion for each. In the control treatment, the microalgae were not exposed to cryoprotective agents (Control). Three post-thawing cell viability criteria were used: no cell damage (NCD), cell damage (CD), and marked lesions (LM), and mitochondrial and cell membrane damage was evaluated by flow cytometry. The study was a 2 × 2 factorial design, with five replications by treatments, population growth, and cell damage evaluated from the fifth day after thawing. On the fifth day, the highest percentage of NCD was observed when the microalgae were cryopreserved with DMSO 5% (50%); Regarding the control group, it showed 0% NCD. Flow cytometry analysis reveals minor damage at the membrane and mitochondria (9–10.7%) when DMSO is used at both inclusion percentages (5–10%) after thawing. In the exponential phase, the highest growth rates, doubling time, and yield was observed in cryopreserved cells with MET 5%. The results suggest that DMSO 5% is an ideal treatment for cryopreserving microalgae Scenedesmus sp.
Wnt Pathway in Pancreatic Development and Pathophysiology
Authors: Napolitano Tiziana , Silvano Serena , Ayachi Chaïma , Plaisant Magali , Sousa-Da-Veiga Anette , Fofo Hugo , Charles Benjamin , Collombat Patrick
Published: February 2023

The pancreas is an abdominal gland that serves 2 vital purposes: assist food processing by secreting digestive enzymes and regulate blood glucose levels by releasing endocrine hormones. During embryonic development, this gland originates from epithelial buds located on opposite sites of the foregut endoderm. Pancreatic cell specification and maturation are coordinated by a complex interplay of extrinsic and intrinsic signaling events. In the recent years, the canonical Wnt/β-catenin pathway has emerged as an important player of pancreas organogenesis, regulating pancreatic epithelium specification, compartmentalization and expansion. Importantly, it has been suggested to regulate proliferation, survival and function of adult pancreatic cells, including insulin-secreting β-cells. This review summarizes recent work on the role of Wnt/β-catenin signaling in pancreas biology from early development to adulthood, emphasizing on its relevance for the development of new therapies for pancreatic diseases.
High-Performance Polarization Microscopy Reveals Structural Remodeling in Rat Calcaneal Tendons Cultivated In Vitro
Authors: dos Anjos Eli Heber Martins , Mello Maria Luiza Silveira , Vidal Benedicto de Campos
Published: February 2023

Collagenous tissues exhibit anisotropic optical properties such as birefringence and linear dichroism (LD) as a result of their structurally oriented supraorganization from the nanometer level to the collagen bundle scale. Changes in macromolecular order and in aggregational states can be evaluated in tendon collagen bundles using polarization microscopy. Because there are no reports on the status of the macromolecular organization in tendon explants, the objective of this work was to evaluate the birefringence and LD characteristics of collagen bundles in rat calcaneal tendons cultivated in vitro on substrates that differ in their mechanical stiffness (plastic vs. glass) while accompanying the expected occurrence of cell migration from these structures. Tendon explants from adult male Wistar rats were cultivated for 8 and 12 days on borosilicate glass coverslips (n = 3) and on nonpyrogenic polystyrene plastic dishes (n = 4) and were compared with tendons not cultivated in vitro (n = 3). Birefringence was investigated in unstained tendon sections using high-performance polarization microscopy and image analysis. LD was studied under polarized light in tendon sections stained with the dichroic dyes Ponceau SS and toluidine blue at pH 4.0 to evaluate the orientation of proteins and acid glycosaminoglycans (GAG) macromolecules, respectively. Structural remodeling characterized by the reduction in the macromolecular orientation, aggregation and alignment of collagen bundles, based on decreased average gray values concerned with birefringence intensity, LD and morphological changes, was detected especially in the tendon explants cultivated on the plastic substrate. These changes may have facilitated cell migration from the lateral regions of the explants to the substrates, an event that was observed earlier and more intensely upon tissue cultivation on the plastic substrate. The axial alignment of the migrating cells relative to the explant, which occurred with increased cultivation times, may be due to the mechanosensitive nature of the tenocytes. Collagen fibers possibly played a role as a signal source to cells, a hypothesis that requires further investigation, including studies on the dynamics of cell membrane receptors and cytoskeletal organization, and collagen shearing electrical properties.