bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationships between the Physical Activity Intensity and the Medical Expenditure of Middle-Aged and Elderly People: Parsing from the CHARLS Database
Authors: Chen Linhong , Xu Xiaocang
Published: July 2023

There are many studies on the impact of physical activity on health but few studies on the relationship between physical activity and medical expenditure among the elderly. Based on the China Health and Retirement Longitudinal Survey (CHARLS) database and selected 4456 valid samples, this paper used a two-part model to analyze the effects of high, moderate, and low physical activity intensity on medical expenditure. It is found that the intensity of physical activity was negatively correlated with medical expenditure, and the medical expenditure of the high physical activity intensity group was significantly lower than that of the low physical activity intensity group. For example, compared to people with no physical activity, the total medical expenditure decreased by 22.4%, 40.4%, and 62.5% per week in those with low, moderate, and high physical activity intensity. Thus, the government should provide more places for the elderly to exercise, planning special exercise areas for the elderly in community playgrounds, such as a dancing square, which will also help the elderly to increase their amount of exercise per week and develop a daily exercise habit.
Post-Traumatic Stress Disorder and Mental Health in Chinese College Athletes during and after the COVID-19 Pandemic: The Multiple Mediating Effects of Basic Psychological Needs and Generalized Anxiety Disorder
Authors: Zhao Xiuhan , Liu Zongyu , Zhao Liangyu , Wang Qi , Zhang Liguo
Published: July 2023

Psychological issues have a complex and multidimensional impact on a college athlete’s training and performance. As the reserve talent of competitive sports, it is very important to investigate the psychological health of athletes. This study aims to explore the association between generalized anxiety disorder (GAD), post-traumatic stress disorder (PTSD), basic psychological needs (BPN), and mental health (MH) among Chinese college athletes. Chinese college athletes who were willing to participate in the study, had participated in national competitions, and had a Chinese athlete rating certificate were included in this study. Participants completed the Kessler Psychological Distress Scale (K10), the Generalized Anxiety Disorder Scale (GAD-7), the Impact of Event Scale-Revised (IES-R), and the Basic Needs Satisfaction in General Scale (BNSG-S). The study involved 665 college athletes (415 males and 250 females), with an average age of 20.43 years (SD = 1.68). We performed descriptive statistics, correlation analyses, and moderated chain mediation analyses using SPSS 22.0 and Hayes’ PROCESS macro. The results of the final model showed that basic psychological needs were positively correlated with mental health (r = 0.443, p < 0.001), while PTSD (r = −0.346, p < 0.001) and generalized anxiety disorder (r = −0.527, p < 0.001) were negatively correlated with mental health among college athletes. There were significant indirect impacts. According to the bootstrapping results, basic psychological needs and generalized anxiety disorder played a mediating role in 22.54% and 50.29% of the total effects of PTSD on mental health, respectively. Meanwhile, the chain mediating effect of basic psychological needs and generalized anxiety disorder (7.23%) was also significant. The study’s findings advance our understanding of the connections between PTSD and mental health and highlight the significant roles played by basic psychological needs and generalized anxiety disorder in that link among Chinese college athletes.
Beyond Valence and Arousal: The Role of Age of Acquisition in Emotion Word Recognition
Authors: Wu Chenggang , Shi Yiwen , Zhang Juan
Published: July 2023

Although the age of acquisition (AoA) effect has been established in numerous studies, how emotion word processing is modulated by AoA, along with affective factors, such as valence and arousal, is not well understood. Hence, the influence of age of acquisition (AoA), valence, and arousal on Chinese emotion word recognition was investigated through two experiments. Experiment 1 (N = 30) adopted a valence judgment task to explore the roles of valence and AoA in emotion word recognition, whereas Experiment 2 (N = 30) used a lexical decision task to examine AoA and arousal effects. A mixed linear effects model was used to examine the fixed effects of AoA, arousal, and valence and random effects of participants and items. The findings provided confirmation of the effects of AoA, valence, and arousal. Notably, AoA and valence had independent influences on emotion word recognition, as evidenced by longer reaction times for later-acquired words and negative words compared to early-acquired words and positive words (all ps < 0.05). On the other hand, AoA and arousal demonstrated interdependent effects on emotion word recognition. Specifically, a larger AoA effect was observed for low-arousing words (all ps < 0.05), whereas the influence of AoA on high-arousing words was insignificant. These results underscored the significance of AoA in processing emotion words and highlighted the interplay between AoA and arousal. Additionally, it is plausible to suggest that the AoA effect was primarily perceptual rather than semantic in nature.
Microwave Technology, Its Use and Heating of Composite Aerated Concrete Blocks
Authors: Sobotka Jindřich , Jiroušek Zdeněk , Švecová Táňa , Novotný Miloslav
Published: July 2023

This paper aims to test the method of using microwave technology for drying aerated concrete masonry. Furthermore, the propagation of microwave technology through irradiated elements and the effectiveness of eliminating the moisture of the given blocks were examined. There are various discussions about the potential use of this technology in civil engineering. However, they are often based on inaccurate, superficial knowledge. The cause is usually based on a lack of access to accurate professional knowledge. Although the potential use of microwave technology (MWT) has been known for many decades, its use in civil engineering tends to be of marginal interest. The research and tests are mostly carried out by private facilities, which protect the obtained knowledge as their “know how”. For this reason, VUT Brno teamed up with an implementation company and conducted several dozen experiments with repeated measurements of the effect of MWT on various building materials. Moreover, a number of different tests with drying of building materials, as well as the elimination of biotic pests in buildings have been carried out. However, the vast majority were experiments carried out in laboratory conditions, i.e., under precisely given boundary conditions, which were often very far from the conditions in real construction practice. Therefore, the goal of this experiment was to verify the use of microwave technology during the drying and heating of building materials. The experiments on the heating and drying of aerated concrete parts were divided into several phases, in which the dependence of the depth of heating on the time intervals of irradiation was verified. It was clearly concluded that the drying of this material by microwaves is very effective and efficient, particularly from time and financial viewpoints. Therefore, this technology can be successfully used in construction practice, which has started to be often used with reconstructions.
A Comparison of Load Distribution Methods at the Node and Internal Force Analysis of the Lattice Beam Based on the Winkler Foundation Model
Authors: Fan Junwei , Yang Shijiao , Deng Bo , Sun Bing , Liu Taoying
Published: July 2023

As a new type of retaining structure, lattice beams with tie-back anchor cables have been increasingly used in slope reinforcement and have achieved improved prevention effects. However, the simplified load distribution method (SLDM) at the node, which is the theoretical basis of internal force analysis for lattice beams, is not perfect at present. An alternative new load distribution method (NLDM) at the node based on the force method for the lattice beam was therefore introduced in this paper. Taking into account the loads acting on other nodes of the beams in both directions and according to the static equilibrium condition and deformation compatibility condition at the nodes, NLDM assigns the loads acting on the nodes to the cross beams and vertical beams, respectively, by constructing and solving a system of linear equations. In order to verify the superiority of NLDM, a case of slope reinforced by a lattice beam was introduced in this paper, and the load distribution of the nodes under the design condition was carried out based on both methods. Then, the deflections at the nodes of the lattice beam resting on the Winkler foundation, loaded with the known loads, were analyzed by the superposition method. The results of the deformation analysis showed that the deflections at the same nodes of the beams in both directions based on NLDM were almost equal, thus demonstrating the superiority of NLDM in terms of deformation compatibility. In addition, a comparative analysis of the theoretical bending moments of the lattice beam under the design and the actual working conditions based on both methods was also carried out. The results of the bending moment analysis showed that the bending moments of the cross beam differed significantly in the middle third of the beam length, while the bending moments of the vertical beams differed significantly at the beam sections where the maximum bending moments are located, and the theoretical bending moments under the actual working condition were in relatively good agreement with the measured values. Consequently, NLDM for the lattice beam was self-consistent in terms of the deformation compatibility at the node, and therefore the introduction of this new method provides an important theoretical basis for the accurate internal force analysis of lattice beams.
Emotional Reactions to Different Indoor Solutions: The Role of Age
Authors: Rapuano Mariachiara , Sarno Maria , Ruotolo Francesco , Ruggiero Gennaro , Iuliano Sabrina , Masullo Massimiliano , Maffei Luigi , Cioffi Federico , Iachini Tina
Published: July 2023

Longer life expectancy and global population growth result in new environmental demands to meet different material and psychological needs across the lifespan. Since the physical environment is a fundamental factor in the quality of life, here we investigated which different indoor features (i.e., colors, materials/textures) have the most positive impact on individuals in terms of emotional reactions and whether these reactions could vary with age. Four groups of participants (i.e., younger adults, adults, middle-aged, elderly, age range 19–86 years) were presented with pictures of five different rooms: (1) Modern (white and cold colors with good-quality essential coverings); (2) Basic (white and blue colors; plastic and metal furniture); (3) Vivacious (red, blue, and green elements; soft-textured materials); (4) Comfort (different shades of blue and green; velvet coverings); (5) Nature (brown, orange, and green colors; wood furniture and leather coverings). Participants underwent a six-item questionnaire evaluating their positive and negative reactions to each image. The results showed a more positive evaluation of nature and vivacious rooms than all others. In turn, basic and modern rooms evoked more negative emotions than all others. Aged-related emotional reactions emerged, with the elderly appearing to be more inclined to rely on features, such as colors and covering materials, for the affective evaluation of the environment compared to adults and middle-aged adults. These preliminary results support the need for human-centered design approaches to improve well-being across the lifespan.
Stereotactic Body Radiation Therapy in Gynecologic Oligometastases: An Effective but Underutilized Approach
Authors: Sherwani Zohaib , Parikh Shreel , Yegya-Raman Nikhil , McKenna Kelly , Deek Matthew , Jabbour Salma , Hathout Lara
Published: July 2023

Historically, the role of radiation in gynecological metastatic disease involved palliation for pain or bleeding. Stereotactic Body Radiation Therapy (SBRT) has shown survival benefits in oligometastatic disease from varying primary histologies in recent randomized trials. However, gynecologic primary oligometastases have been underrepresented in these trials. Recent studies across gynecological malignancy types have similarly shown favorable outcomes and acceptable toxicities from treating recurrent or oligometastatic gynecologic cancer (ROMGC) patients with definitive radiation therapy. The largest body of literature reported on the use of SBRT in ovarian cancer, which was found to be an effective option, especially in the setting of chemo-resistant disease. Despite the encouraging outcomes using SBRT in oligometastatic gynecologic malignancies, SBRT remains underutilized given the lack of randomized studies studying ROMGC with long term follow-up. While waiting for future prospective trials to establish the role of SBRT as the standard of care in ROMGC patients, this review focuses on reporting the advantages and drawbacks of this technique and examines the current literature to help guide patient centered treatment decisions.
Epidermal Growth Factor Receptor T790M Mutation Testing in Non-Small Cell Lung Cancer: An International Collaborative Study to Assess Molecular EGFR T790M Testing in Liquid Biopsy
Authors: Filipits Martin , Kainz Verena , Sebek Viktor , Zach Herwig ,   on behalf of the Liquid Biopsy Collaborative Study Group
Published: July 2023

Background: The detection of the EGFR T790M (T790M) mutation in non-small cell lung cancer (NSCLC) patients who progressed under treatment with first- or second-generation EGFR-tyrosine kinase inhibitors (TKIs) is important to offer a subsequent therapy with a third-generation EGFR-TKI. Liquid biopsy is a powerful tool to determine the T790M mutation status. Several liquid biopsy platforms with varying degrees of accuracy are available to test for T790M mutations, and sensitivities may differ among these methods. Methods: As no standard exists for the testing of T790M mutation in liquid biopsy, we performed a collaborative study to describe and compare the sensitivity of different in-house liquid biopsy platforms for the detection of the T790M mutation, EGFR exon 19 deletion (del19) and EGFR L858R mutation (L858R) across multiple participating laboratories in seven Central and Eastern European countries. Results: Of the 25 invited laboratories across Central and Eastern Europe, 21 centers participated and received 10 plasma samples spiked with cell-line DNA containing the T790M, del19, or L858R mutation in different concentrations. In-house PCR-based and NGS-based methods were used accordingly, and results were reported as in routine clinical practice. Two laboratories, which used the AmoyDx® EGFR 29 Mutations Detection Kit (AmoyDx) with Cobas® cfDNA Sample Preparation Kit and QX200 Droplet Digital PCR (ddPCR) with the QIAamp Circulating Nucleic Acid Kit identified all ten samples correctly. Cobas® EGFR Mutation Test v2 (Cobas), the NGS methods, and the IdyllaTM detection method used in this study performed within the known sensitivity range of each detection method. Conclusions: If a negative result was obtained from methods with lower sensitivity (e.g., Cobas), repeated liquid biopsy testing and/or tissue biopsy analysis should be performed whenever possible, to identify T790M-positive patients to allow them to receive the optimal second-line treatment with a third-generation EGFR TKI.
Risk Factors, Prevalence, and Outcomes of Invasive Fungal Disease Post Hematopoietic Cell Transplantation and Cellular Therapies: A Retrospective Monocenter Real-Life Analysis
Authors: Gavriilaki Eleni , Dolgyras Panagiotis , Dimou-Mpesikli Sotiria , Poulopoulou Aikaterini , Evangelidis Paschalis , Evangelidis Nikolaos , Demosthenous Christos , Zachrou Evangelia , Siasios Panagiotis , Mallouri Despina , Vardi Anna , Bousiou Zoi , Panteliadou Alkistis , Batsis Ioannis , Masmanidou Marianna , Lalayanni Chrysavgi , Yannaki Evangelia , Sotiropoulos Damianos , Anagnostopoulos Achilles , Vyzantiadis Timoleon-Achilleas , Sakellari Ioanna
Published: July 2023

(1) Background: Autologous, allogeneic hematopoietic cell transplantation (HCT) and other cellular therapies, including CAR T cell and gene therapy, constitute a cornerstone in the management of various benign and malignant hematological disorders. Invasive fungal infections (IFD) remain a significant cause of morbidity and mortality in HCT recipients. Therefore, we investigated the prevalence and risk factors of IFD following HCT and other cellular therapies in an era of novel antifungal prophylaxis. (2) Methods: In this study, we retrospectively enrolled adult HCT recipients who were treated at our JACIE-accredited center according to standard operating procedures over the last decade (2013–2022). (3) Results: 950 patients who received cellular therapies were studied. None of the 19 CAR T cell and neither of the two gene therapy recipients developed IFD whereas 3/456 autologous HCT recipients who suffered from primary refractory/relapsed lymphomas presented with probable IFD. Overall, 11 patients who received allogeneic HCT experienced probable IFD, possible IFD was found in 31/473, and IFD was proven in 10/473. A second IFD episode was present in three patients. Four-year OS was significantly lower in proven compared to probable IFD (p = 0.041) and was independently associated with HCT-CI (p = 0.040) and chronic GVHD (p = 0.045). (4) Conclusions: In this real-world cohort, the prevalence of proven and probable IFD in an era of novel antifungal prophylaxis was found to be relatively low. However, IFDs were associated with poor outcomes for patients who received allogeneic HCT.
B7-H3 Associates with IMPDH2 and Regulates Cancer Cell Survival
Authors: Alhamad Salwa , Elmasry Yassmin , Uwagboe Isabel , Chekmeneva Elena , Sands Caroline , Cooper Benjamin W. , Camuzeaux Stephane , Salam Ash , Parsons Maddy
Published: July 2023

Lung cancer is one of the most common cancers worldwide, and despite improvements in treatment regimens, patient prognosis remains poor. Lung adenocarcinomas develop from the lung epithelia and understanding how specific genetic and environmental factors lead to oncogenic transformation in these cells is of great importance to define the pathways that contribute to tumorigenesis. The recent rise in the use of immunotherapy to treat different cancers has prompted the exploration of immune modulators in tumour cells that may provide new targets to manipulate this process. Of these, the B7 family of cell surface receptors, which includes PD-1, is of particular interest due to its role in modulating immune cell responses within the tumour microenvironment. B7-H3 (CD276) is one family member that is upregulated in many cancer types and suggested to contribute to tumour–immune interactions. However, the function and ligand(s) for this receptor in normal lung epithelia and the mechanisms through which the overexpression of B7-H3 regulate cancer progression in the absence of immune cell interactions remain unclear. Here, we present evidence that B7-H3 is associated with one of the key rate-limiting metabolic enzymes IMPDH2, and the localisation of this complex is altered in human lung cancer cells that express high levels of B7-H3. Mechanistically, the IMPDH2:B7-H3 complex provides a protective role in cancer cells to escape oxidative stress triggered by chemotherapy, thus leading to cell survival. We further demonstrate that the loss of B7-H3 in cancer cells has no effect on growth or migration in 2D but promotes the expansion of 3D spheroids in an IMPDH2-dependent manner. These findings provide new insights into the B7-H3 function in the metabolic homeostasis of normal and transformed lung cancer cells, and whilst this molecule remains an interesting target for immunotherapy, these findings caution against the use of anti-B7-H3 therapies in certain clinical settings.
Divergent Oxidative Stress in Normal Tissues and Inflammatory Cells in Hodgkin and Non-Hodgkin Lymphoma
Authors: Marini Cecilia , Cossu Vanessa , Lanfranchi Francesco , Carta Sonia , Vitale Francesca , D’Amico Francesca , Bauckneht Matteo , Morbelli Silvia , Donegani Maria Isabella , Chiola Silvia , Raffa Stefano , Sofia Luca , Di Raimondo Tania , Ballerini Filippo , Ghiggi Chiara , Durando Paolo , Ravera Silvia , Riondato Mattia , Orengo Anna Maria , Bruno Silvia , Chiesa Sabrina , Sambuceti Gianmario
Published: July 2023

Background: Previous studies reported mitochondrial and endoplasmic reticulum redox stress in peripheral blood mononucleated cells (PBMCs) of treatment-naïve Hodgkin lymphoma (HL) patients. Here, we assessed whether this response also applies to non-HL (NHL) patients, and whether the oxidative damage is a selective feature of PBMCs or, rather, also affects tissues not directly involved in the inflammatory response. Methods: Isolated PBMCs of 28 HL, 9 diffuse large B cell lymphoma, 8 less aggressive-NHL, and 45 controls underwent flow cytometry to evaluate redox stress and uptake of the glucose analogue 2-NBDG. This analysis was complemented with the assay of malondialdehyde (MDA) levels and enzymatic activity of glucose-6P-dehydrogenase and hexose-6P-dehydrogenase (H6PD). In all lymphoma patients, 18F-fluoro-deoxyglucose uptake was estimated in the myocardium and skeletal muscles. Results: Mitochondrial reactive oxygen species generation and MDA levels were increased only in HL patients as well as H6PD activity and 2-NBDG uptake. Similarly, myocardial FDG retention was higher in HL than in other groups as opposed to a similar tracer uptake in the skeletal muscle. Conclusions: Redox stress of PBMCs is more pronounced in HL with respect to both NHL groups. This phenomenon is coherent with an increased activity of H6PD that also extends to the myocardium.
Aberrant Glycosylation as Immune Therapeutic Targets for Solid Tumors
Authors: Matsumoto Yasuyuki , Ju Tongzhong
Published: July 2023

Glycosylation occurs at all major types of biomolecules, including proteins, lipids, and RNAs to form glycoproteins, glycolipids, and glycoRNAs in mammalian cells, respectively. The carbohydrate moiety, known as glycans on glycoproteins and glycolipids, is diverse in their compositions and structures. Normal cells have their unique array of glycans or glycome which play pivotal roles in many biological processes. The glycan structures in cancer cells, however, are often altered, some having unique structures which are termed as tumor-associated carbohydrate antigens (TACAs). TACAs as tumor biomarkers are glycan epitopes themselves, or glycoconjugates. Some of those TACAs serve as tumor glyco-biomarkers in clinical practice, while others are the immune therapeutic targets for treatment of cancers. A monoclonal antibody (mAb) to GD2, an intermediate of sialic-acid containing glycosphingolipids, is an example of FDA-approved immune therapy for neuroblastoma indication in young adults and many others. Strategies for targeting the aberrant glycans are currently under development, and some have proceeded to clinical trials. In this review, we summarize the currently established and most promising aberrant glycosylation as therapeutic targets for solid tumors.
Pediatric Cancers: Insights and Novel Therapeutic Approaches
Authors: Agarwal Saurabh
Published: July 2023

Pediatric cancers cast a dark shadow over the lives of countless children and their families and represent a leading cause of mortality among children worldwide [...]
Image Perceptual Similarity Metrics for the Assessment of Basal Cell Carcinoma
Authors: Spyridonos Panagiota , Gaitanis Georgios , Likas Aristidis , Seretis Konstantinos , Moschovos Vasileios , Feldmeyer Laurence , Heidemeyer Kristine , Zampeta Athanasia , Bassukas Ioannis D.
Published: July 2023

Efficient management of basal cell carcinomas (BCC) requires reliable assessments of both tumors and post-treatment scars. We aimed to estimate image similarity metrics that account for BCC’s perceptual color and texture deviation from perilesional skin. In total, 176 clinical photographs of BCC were assessed by six physicians using a visual deviation scale. Internal consistency and inter-rater agreement were estimated using Cronbach’s α, weighted Gwet’s AC2, and quadratic Cohen’s kappa. The mean visual scores were used to validate a range of similarity metrics employing different color spaces, distances, and image embeddings from a pre-trained VGG16 neural network. The calculated similarities were transformed into discrete values using ordinal logistic regression models. The Bray–Curtis distance in the YIQ color model and rectified embeddings from the ‘fc6’ layer minimized the mean squared error and demonstrated strong performance in representing perceptual similarities. Box plot analysis and the Wilcoxon rank-sum test were used to visualize and compare the levels of agreement, conducted on a random validation round between the two groups: ‘Human–System’ and ‘Human–Human.’ The proposed metrics were comparable in terms of internal consistency and agreement with human raters. The findings suggest that the proposed metrics offer a robust and cost-effective approach to monitoring BCC treatment outcomes in clinical settings.
Decursinol Angelate Inhibits Glutamate Dehydrogenase 1 Activity and Induces Intrinsic Apoptosis in MDR-CRC Cells
Authors: Chang Sukkum Ngullie , Kang Sun Chul
Published: July 2023

Colorectal cancer (CRC) was the second most commonly diagnosed cancer worldwide and the second most common cause of cancer-related deaths in Europe in 2020. After CRC patients’ recovery, in many cases a patient’s tumor returns and develops chemoresistance, which has remained a major challenge worldwide. We previously published our novel findings on the role of DA in inhibiting the activity of GDH1 using in silico and enzymatic assays. No studies have been conducted so far to explain the inhibitory role of DA against glutamate dehydrogenase in MDR-CRC cells. We developed a multidrug-resistant colorectal cancer cell line, HCT-116MDR, after treatment with cisplatin and 5-fluorouracil. We confirmed the MDR phenotype by evaluating the expression of MDR1, ABCB5, extracellular vesicles, polyploidy, DNA damage response markers and GDH1 in comparison with parental HCT-116WT (HCT-116 wild type). Following confirmation, we determined the IC50 and performed clonogenic assay for the efficacy of decursinol angelate (DA) against HCT-116MDR (HCT-116 multidrug resistant). Subsequently, we evaluated the novel interactions of DA with GDH1 and the expression of important markers regulating redox homeostasis and cell death. DA treatment markedly downregulated the expression of GDH1 at 50 and 75 μM after 36 h, which directly correlated with reduced expression of the Krebs cycle metabolites α-ketoglutarate and fumarate. We also observed a systematic dose-dependent downregulation of MDR1, ABCB5, TERT, ERCC1 and γH2AX. Similarly, the expression of important antioxidant markers was also downregulated. The markers for intrinsic apoptosis were notably upregulated in a dose-dependent manner. The results were further validated by flow cytometry and TUNEL assay. Additionally, GDH1 knockdown on both HCT-116WT and HCT-116MDR corresponded to a decreased expression of γH2AX, catalase, SOD1 and Gpx-1, and an eventual increase in apoptosis markers. In conclusion, inhibition of GDH1 increased ROS production, decreased cell proliferation and increased cell death.
Development and Validation of a Nomogram for Preoperative Prediction of Early Recurrence after Upfront Surgery in Pancreatic Ductal Adenocarcinoma by Integrating Deep Learning and Radiological Variables
Authors: Xiang Fei , He Xiang , Liu Xingyu , Li Xinming , Zhang Xuchang , Fan Yingfang , Yan Sheng
Published: July 2023

Around 80% of pancreatic ductal adenocarcinoma (PDAC) patients experience recurrence after curative resection. We aimed to develop a deep-learning model based on preoperative CT images to predict early recurrence (recurrence within 12 months) in PDAC patients. The retrospective study included 435 patients with PDAC from two independent centers. A modified 3D-ResNet18 network was used for a deep learning model construction. A nomogram was constructed by incorporating deep learning model outputs and independent preoperative radiological predictors. The deep learning model provided the area under the receiver operating curve (AUC) values of 0.836, 0.736, and 0.720 in the development, internal, and external validation datasets for early recurrence prediction, respectively. Multivariate logistic analysis revealed that higher deep learning model outputs (odds ratio [OR]: 1.675; 95% CI: 1.467, 1.950; p < 0.001), cN1/2 stage (OR: 1.964; 95% CI: 1.036, 3.774; p = 0.040), and arterial involvement (OR: 2.207; 95% CI: 1.043, 4.873; p = 0.043) were independent risk factors associated with early recurrence and were used to build an integrated nomogram. The nomogram yielded AUC values of 0.855, 0.752, and 0.741 in the development, internal, and external validation datasets. In conclusion, the proposed nomogram may help predict early recurrence in PDAC patients.
Development and External Validation of Partial Proportional Odds Risk Prediction Models for Cancer Stage at Diagnosis among Males and Females in Canada
Authors: Biziaev Timofei , Aktary Michelle L. , Wang Qinggang , Chekouo Thierry , Bhatti Parveen , Shack Lorraine , Robson Paula J. , Kopciuk Karen A.
Published: July 2023

Risk prediction models for cancer stage at diagnosis may identify individuals at higher risk of late-stage cancer diagnoses. Partial proportional odds risk prediction models for cancer stage at diagnosis for males and females were developed using data from Alberta’s Tomorrow Project (ATP). Prediction models were validated on the British Columbia Generations Project (BCGP) cohort using discrimination and calibration measures. Among ATP males, older age at diagnosis was associated with an earlier stage at diagnosis, while full- or part-time employment, prostate-specific antigen testing, and former/current smoking were associated with a later stage at diagnosis. Among ATP females, mammogram and sigmoidoscopy or colonoscopy were associated with an earlier stage at diagnosis, while older age at diagnosis, number of pregnancies, and hysterectomy were associated with a later stage at diagnosis. On external validation, discrimination results were poor for both males and females while calibration results indicated that the models did not over- or under-fit to derivation data or over- or under-predict risk. Multiple factors associated with cancer stage at diagnosis were identified among ATP participants. While the prediction model calibration was acceptable, discrimination was poor when applied to BCGP data. Updating our models with additional predictors may help improve predictive performance.
Venous Thromboembolism and Primary Thromboprophylaxis in Perioperative Pancreatic Cancer Care
Authors: Willems R. A. L. , Michiels N. , Lanting V. R. , Bouwense S. , van den Broek B. L. J. , Graus M. , Klok F. A. , Groot Koerkamp B. , de Laat B. , Roest M. , Wilmink J. W. , van Es N. , Mieog J. S. D. , ten Cate H. , de Vos-Geelen J.
Published: July 2023

Recent studies have shown that patients with pancreatic ductal adenocarcinoma (PDAC) treated with neoadjuvant chemo(radio)therapy followed by surgery have an improved outcome compared to patients treated with upfront surgery. Hence, patients with PDAC are more and more frequently treated with chemotherapy in the neoadjuvant setting. PDAC patients are at a high risk of developing venous thromboembolism (VTE), which is associated with decreased survival rates. As patients with PDAC were historically offered immediate surgical resection, data on VTE incidence and associated preoperative risk factors are scarce. Current guidelines recommend primary prophylactic anticoagulation in selected groups of patients with advanced PDAC. However, recommendations for patients with (borderline) resectable PDAC treated with chemotherapy in the neoadjuvant setting are lacking. Nevertheless, the prevention of complications is crucial to maintain the best possible condition for surgery. This narrative review summarizes current literature on VTE incidence, associated risk factors, risk assessment tools, and primary thromboprophylaxis in PDAC patients treated with neoadjuvant chemo(radio)therapy.
Pseudokinases, Tribbles Proteins and Cancer
Authors: Velasco Guillermo , Link Wolfgang
Published: July 2023

The human kinome comprises 518 protein kinases, of which approximately 10% lack one or more of the conserved amino acids necessary for catalytic activity [...]
Specialist Palliative Care for Patients with Cancer: More Than End-of-Life Care
Authors: Gouldthorpe Craig , Power Jenny , Taylor Amy , Davies Andrew
Published: July 2023

Palliative care has traditionally focused on end-of-life care for patients with advanced cancer. This has since expanded to include symptom management and quality-of-life improvement from the moment of cancer diagnosis. Specialist palliative care teams work across community and inpatient settings and focus on dealing with complex problems whilst supporting healthcare colleagues in providing generalist palliative care. This article will outline the principles of palliative care, models of palliative care delivery, the distinctions between palliative care and supportive care, and the role of specialist palliative care in cancer survivorship.
Machine Learning Integrating 99mTc Sestamibi SPECT/CT and Radiomics Data Achieves Optimal Characterization of Renal Oncocytic Tumors
Authors: Klontzas Michail E. , Koltsakis Emmanouil , Kalarakis Georgios , Trpkov Kiril , Papathomas Thomas , Karantanas Apostolos H. , Tzortzakakis Antonios
Published: July 2023

The increasing evidence of oncocytic renal tumors positive in 99mTc Sestamibi Single Photon Emission Tomography/Computed Tomography (SPECT/CT) examination calls for the development of diagnostic tools to differentiate these tumors from more aggressive forms. This study combined radiomics analysis with the uptake of 99mTc Sestamibi on SPECT/CT to differentiate benign renal oncocytic neoplasms from renal cell carcinoma. A total of 57 renal tumors were prospectively collected. Histopathological analysis and radiomics data extraction were performed. XGBoost classifiers were trained using the radiomics features alone and combined with the results from the visual evaluation of 99mTc Sestamibi SPECT/CT examination. The combined SPECT/radiomics model achieved higher accuracy (95%) with an area under the curve (AUC) of 98.3% (95% CI 93.7–100%) than the radiomics-only model (71.67%) with an AUC of 75% (95% CI 49.7–100%) and visual evaluation of 99mTc Sestamibi SPECT/CT alone (90.8%) with an AUC of 90.8% (95%CI 82.5–99.1%). The positive predictive values of SPECT/radiomics, radiomics-only, and 99mTc Sestamibi SPECT/CT-only models were 100%, 85.71%, and 85%, respectively, whereas the negative predictive values were 85.71%, 55.56%, and 94.6%, respectively. Feature importance analysis revealed that 99mTc Sestamibi uptake was the most influential attribute in the combined model. This study highlights the potential of combining radiomics analysis with 99mTc Sestamibi SPECT/CT to improve the preoperative characterization of benign renal oncocytic neoplasms. The proposed SPECT/radiomics classifier outperformed the visual evaluation of 99mTc Sestamibii SPECT/CT and the radiomics-only model, demonstrating that the integration of 99mTc Sestamibi SPECT/CT and radiomics data provides improved diagnostic performance, with minimal false positive and false negative results.
Gastro-Intestinal Disorders and Micronutrient Deficiencies following Oncologic Esophagectomy and Gastrectomy
Authors: Teixeira Farinha Hugo , Bouriez Damien , Grimaud Thomas , Rotariu Ana-Maria , Collet Denis , Mantziari Styliani , Gronnier Caroline
Published: July 2023

Primary surgical indications for the esophagus and stomach mainly involve cancer surgeries. In recent years, significant progress has been made in the field of esogastric surgery, driven by advancements in surgical techniques and improvements in perioperative care. The rate of resectability has increased, and surgical strategies have evolved to encompass a broader patient population. However, despite a reduction in postoperative mortality and morbidity, malnutrition remains a significant challenge after surgery, leading to weight loss, muscle mass reduction, and deficiencies in essential nutrients due to digestive complications. Malnutrition worsens quality of life and increases the risk of tumor recurrence, significantly affecting prognosis. Nevertheless, the nutritional consequences following surgery are frequently overlooked, mainly due to a lack of awareness regarding their long-term effects on patients who have undergone digestive surgery, extending beyond six months. Micronutrient deficiencies are frequently observed following both partial and total gastrectomy, as anticipated. Surprisingly, these deficiencies appear to be similarly prevalent in patients who have undergone esophagectomy with iron, vitamins A, B1, B12, D, and E deficiencies commonly observed in up to 78.3% of the patients. Recognizing the distinct consequences associated with each type of intervention underscores the importance of implementing preventive measures, early detection, and prompt management.
Optimal First-Line Medico-Surgical Strategy in Ovarian Cancers: Are We There Yet?
Authors: Quesada Stanislas , Thomas Quentin Dominique , Colombo Pierre-Emmanuel , Fiteni Frederic
Published: July 2023

In spite of tremendous advances in advanced ovarian cancer management through the past decade, notably owing to surgical expertise and novel combination molecules (including bevacizumab and PARP inhibitors), the optimal initial sequential strategy remains a major concern. Indeed, following seminal clinical trials, primary cytoreductive surgery (PCS) followed by adjuvant systemic therapy and interval cytoreductive surgery (ICS) following neoadjuvant chemotherapy (NACT) have been positioned as validated alternatives with distinct pros and cons, although a definite response is still unassessed. In clinical practice, decisions between PCS and ICS rely on multilayer parameters: the tumor itself, the patient, and the health structure. In this state-of-the-art review, we will discuss the current evidence based on clinical trials and real-world data and highlight the remaining questions, including the fittest positioning of PCS vs. ICS and the optimal number of NACT cycles; subsequently, we will discuss current axes of research such as dedicated clinical trials and more global perspectives. These ongoing strategies and perspectives could contribute to improving the patient journey through personalized medicine.
Preparation and Photocatalytic CO Oxidation Performance Study of Au/Oxygen-Deficient (Anatase/B-Phase) TiO2 Heterojunction Microspheres
Authors: Hong Ze , Ouyang Jingying , Li Jiaxin , Zheng Han , Liu Ying
Published: July 2023

Multi-heterojunctions are more promising than single heterojunctions in photocatalysis due to the availability of more interfaces between each component. However, photocatalytic activity is highly dependent on the contact mode of individual components. In this work, we assembled gold nanoparticles/oxygen-deficient (anatase/B-phase) TiO2 multi-heterojunction microspheres using spray pyrolysis and focused on their contact mode-governed photocatalytic activity. The results reveal that using oxygen-deficient (anatase/B-phase) TiO2 microspheres as building blocks could significantly enhance the absorption of visible light and the photocatalytic activity of a gold–TiO2 system toward the photocatalytic carbon monoxide oxidation. Furthermore, loading gold nanoparticles onto B-phase TiO2 could facilitate a more prominent enhancement of activity than that of pure B-phase TiO2, benefiting from the two-electron reduction of oxygen at the interface of TiO2/Au. Meanwhile, the high crystallinity of B-phase TiO2 microspheres allows for a gold loading amount of 1 wt% in the gold/(anatase/B-phase) TiO2 system, which is 1.67 times more active than pure B-phase TiO2 microspheres, in the photocatalytic oxidation of carbon monoxide to generate carbon dioxide.
Highly Selective Transformation of CO2 + H2 into Para-Xylene via a Bifunctional Catalyst Composed of Cr2O3 and Twin-Structured ZSM-5 Zeolite
Authors: Lin Shiyuan , He Ruosong , Wang Wenhang , Wang Yang , Gu Yongqiang , Liu Qiang , Wu Mingbo
Published: July 2023

The abundant C1 source CO2 can be utilized to produce value-added chemicals through hydrogenation technology. A bifunctional catalyst consisting of reducible metal oxide Cr2O3 and acidic zeolite ZSM-5 was designed for the direct conversion of CO2 + H2 into valuable aromatics, especially para-xylene (PX), via the methanol-mediated pathway. The twin structure of ZSM-5 (ZSM-5T), with sinusoidal channels that are predominantly exposed to the external surface, enhances the possibility of the transformation of methanol into PX due to the favorable diffusion dynamic of PX in the sinusoidal channels. Via the bifunctional catalyst Cr2O3&ZSM-5T, a PX selectivity of 28.7% and PX space-time yield (STY) of 2.5 gCH2 h−1 kgcat−1 are achieved at a CO2 conversion rate of 16.5%. Furthermore, we rationally modify the ZSM-5T zeolite via Cu species doping and amorphous SiO2 shell coating (Cu-ZSM-5T@SiO2). After combining with the Cr2O3 catalytic component, the CO2 conversion (18.4%) and PX selectivity (33.8%) are increased to some extent, which systematically increases the STY of PX to 3.0 gCH2 h−1 kgcat−1. The physicochemical property of the acidic zeolite and the corresponding structure-function relationship in enhancing the PX productivity are discovered. Our work provides a novel catalyst design idea to boost PX synthesis performance from CO2 hydrogenation.
Progranulin Protects against Hyperglycemia-Induced Neuronal Dysfunction through GSK3β Signaling
Authors: Dedert Cass , Salih Lyuba , Xu Fenglian
Published: July 2023

Type II diabetes affects over 530 million individuals worldwide and contributes to a host of neurological pathologies. Uncontrolled high blood glucose (hyperglycemia) is a major factor in diabetic pathology, and glucose regulation is a common goal for maintenance in patients. We have found that the neuronal growth factor progranulin protects against hyperglycemic stress in neurons, and although its mechanism of action is uncertain, our findings identified Glycogen Synthase Kinase 3β (GSK3β) as being potentially involved in its effects. In this study, we treated mouse primary cortical neurons exposed to high-glucose conditions with progranulin and a selective pharmacological inhibitor of GSK3β before assessing neuronal health and function. Whole-cell and mitochondrial viability were both improved by progranulin under high-glucose stress in a GSK3β—dependent manner. This extended to autophagy flux, indicated by the expressions of autophagosome marker Light Chain 3B (LC3B) and lysosome marker Lysosome-Associated Membrane Protein 2A (LAMP2A), which were affected by progranulin and showed heterogeneous changes from GSK3β inhibition. Lastly, GSK3β inhibition attenuated downstream calcium signaling and neuronal firing effects due to acute progranulin treatment. These data indicate that GSK3β plays an important role in progranulin’s neuroprotective effects under hyperglycemic stress and serves as a jumping-off point to explore progranulin’s protective capabilities in other neurodegenerative models.
Dysregulation of Immature Sertoli Cell Functions by Exposure to Acetaminophen and Genistein in Rodent Cell Models
Authors: Corpuz-Hilsabeck Maia , Mohajer Nicole , Culty Martine
Published: July 2023

Sertoli cells are essential for germ cell development and function. Their disruption by endocrine disrupting chemicals (EDCs) or drugs could jeopardize spermatogenesis, contributing to male infertility. Perinatal exposure to EDCs and acetaminophen (APAP) disrupts male reproductive functions in animals and humans. Infants can be exposed simultaneously to the dietary soy phytoestrogen genistein (GEN) and APAP used for fever or pain relief. Our goal was to determine the effects of 10–100 µM APAP and GEN, alone or mixed, on immature Sertoli cells using mouse TM4 Sertoli cell line and postnatal-day 8 rat Sertoli cells, by measuring cell viability, proliferation, prostaglandins, genes and protein expression, and functional pathways. A value of 50 µM APAP decreased the viability, while 100 µM APAP and GEN decreased the proliferation. Sertoli cell and eicosanoid pathway genes were affected by GEN and mixtures, with downregulation of Sox9, Cox1, Cox2, and genes relevant for Sertoli cell function, while genes involved in inflammation were increased. RNA-seq analysis identified p53 and TNF signaling pathways as common targets of GEN and GEN mixture in both cell types. These results suggest that APAP and GEN dysregulate immature Sertoli cell function and may aid in elucidating novel EDC and drug targets contributing to the etiology of male infertility.
Soluble Collectin 11 (CL-11) Acts as an Immunosuppressive Molecule Potentially Used by Stem Cell-Derived Retinal Epithelial Cells to Modulate T Cell Response
Authors: Fanelli Giorgia , Romano Marco , Lombardi Giovanna , Sacks Steven H.
Published: July 2023

Retinal pigment epithelium (RPE) cell allotransplantation is seen as a possible solution to retinal diseases. However, the RPE-complement system triggered by the binding of collectin-11 (CL-11) is a potential barrier for RPE transplantation as the complement-mediated inflammatory response may promote T cell recognition. To address this, we investigated the role of CL-11 on T cell immuno-response. We confirmed that RPE cells up-regulated MHC class I and expressed MHC class II molecules in an inflammatory setting. Co-cultures of RPE cells with T cells led to the inhibition of T cell proliferation. We found that CL-11 was partially responsible for this effect as T cell binding of CL-11 inhibited T cell proliferation in association with the downregulation of CD28. We also found that the suppressive action of CL-11 was abrogated in the presence of the RGD peptide given to block the T cell binding of CL-11 by its collagen-like domain. Because RPE cells can bind and secrete CL-11 under stress conditions, we postulate that soluble CL-11 contributes to the immunosuppressive properties of RPE cells. The investigation of this dual biological activity of CL-11, namely as a trigger of the complement cascade and a modulator of T cell responses, may provide additional clues about the mechanisms that orchestrate the immunogenic properties of RPE cells.
Genetic Primary Microcephalies: When Centrosome Dysfunction Dictates Brain and Body Size
Authors: Farcy Sarah , Hachour Hassina , Bahi-Buisson Nadia , Passemard Sandrine
Published: July 2023

Primary microcephalies (PMs) are defects in brain growth that are detectable at or before birth and are responsible for neurodevelopmental disorders. Most are caused by biallelic or, more rarely, dominant mutations in one of the likely hundreds of genes encoding PM proteins, i.e., ubiquitous centrosome or microtubule-associated proteins required for the division of neural progenitor cells in the embryonic brain. Here, we provide an overview of the different types of PMs, i.e., isolated PMs with or without malformations of cortical development and PMs associated with short stature (microcephalic dwarfism) or sensorineural disorders. We present an overview of the genetic, developmental, neurological, and cognitive aspects characterizing the most representative PMs. The analysis of phenotypic similarities and differences among patients has led scientists to elucidate the roles of these PM proteins in humans. Phenotypic similarities indicate possible redundant functions of a few of these proteins, such as ASPM and WDR62, which play roles only in determining brain size and structure. However, the protein pericentrin (PCNT) is equally required for determining brain and body size. Other PM proteins perform both functions, albeit to different degrees. Finally, by comparing phenotypes, we considered the interrelationships among these proteins.