bluuebunny/crossref_metadata_2025 huggingface dataset:
Improved Gravity Wave Drag to Enhance Precipitation Simulation: A Case Study of Typhoon In-Fa
Authors: Liu Kun , Yu Fei , Su Yong , Zhang Hongliang , Chen Qiying , Sun Jian
Published: December 2023

Traditional gravity wave drag parameterizations produce wind stresses that are insensitive to changing horizontal resolution in numerical weather prediction (NWP), partly due to the idealized elliptical assumption. This study employs the modified subgrid-scale orography scheme based on the Fourier transform into gravity wave drag scheme of the China Meteorological Administration Global Forecast System (CMA-GFS) to assess its impacts on simulating precipitation during the slow-moving period of Typhoon In-Fa after its landfall in Zhejiang Province, China. The simulation with the updated scheme can effectively reduce the accumulated precipitation bias of the control one and improve the simulation of precipitation distribution and intensity, especially in the hourly precipitation simulation. The improved scheme primarily influences the wind field of the low-level troposphere and also changes the convergence of the integrated water vapor transport and ascending motions related to the reduced precipitation biases. The modified scheme enhances the tendencies of the horizontal winds caused by the varying horizontal resolutions in the model, strengthening the sensitivity of the gravity wave drag across the horizontal scales. Results from medium-range forecasts indicate the modified scheme benefits the statistics scores of precipitation over China and also reduces root-mean-square errors of 2 m temperature and 10 m winds.
A Study of the Influence of Environmental Factors on Water–Heat Exchange Process in Alpine Wetlands
Authors: Xie Yan , Wen Jun , Zhang Yulin , Chen Jinlei , Yang Xianyu
Published: December 2023

Wetlands, which are composed of soil, vegetation and water, have sufficient water supply and are sensitive to climate change. This study analyzes the coupling degree between wetlands and atmosphere and discusses the influence of environmental factors (solar radiation and water vapor pressure deficit) on latent heat flux by using the experimental data from the Maduo Observatory of Climate and Environment of the Northwest Institute of Eco-Environment and Resource, CAS and WRF models. The results showed that, during the vegetation growing season, the average value of Ω (decoupling factor) is 0.38 in alpine wetlands, indicating that the coupling between wetlands and atmosphere is poor. Solar radiation is the main factor influencing the latent heat flux in the results of both observation data analysis and model simulation, and solar radiation and water vapor pressure deficit still have the opposite reaction to latent heat flux; when solar radiation increased by 30%, the average daily amount of latent heat flux increased from 5.57 MJ·m−2 to 7.50 MJ·m−2; when water vapor pressure deficit increased by 30%, the average daily amount of latent heat flux decreased to 5.17 MJ·m−2. This study provides a new research approach for the study of the parameterization of latent heat flux and evapotranspiration in the context of global climate change
Dynamic and Thermodynamic Contributions to Late 21st Century Projected Rainfall Change in the Congo Basin: Impact of a Regional Climate Model’s Formulation
Authors: Tamoffo Alain T. , Dosio Alessandro , Weber Torsten , Vondou Derbetini A.
Published: December 2023

Addressing the impacts of climate change requires, first of all, understanding the mechanisms driving changes, especially at the regional scale. In particular, policymakers and other stakeholders need physically robust climate change information to drive societal responses to a changing climate. This study analyses late 21st-century (2071–2100) precipitation projections for the Congo Basin under representative concentration pathway (RCP) 8.5, using the Rossby Centre Regional Climate Model (RCM) RCA4. Specifically, we examine the impact of the RCM formulation (reduction of turbulent mixing) on future change in seasonal mean precipitation by comparing the results of the modified model version (RCA4-v4) with those of the standard version (RCA4-v1) used in CORDEX (Coordinated Regional Climate Downscaling Experiment). The two RCM versions are driven by two global climate models participating in the Coupled Model Intercomparison Project phase 5 (CMIP5). The results show that seasonal precipitation is largely affected by modifications in the atmospheric column moisture convergence or divergence, and, in turn, associated with changes in the dynamic (ΔDY) and thermodynamic (ΔTH) components of the moisture-budget equation. Projected decreased precipitation in the dry seasons (December–January–February and June–July–August) is linked to increased moisture divergence driven by dynamic effects (changes in circulation), with most experiments showing ΔDY as the main contributor (>60%) to the total moisture budget. Overall, precipitation is projected to increase in the wet seasons (March–April–May and September–October–November), which can be attributed to both dynamic and thermodynamic effects, but with a larger thermodynamic contribution (changes in specific humidity, ΔTH > 45%), compared to the dynamic one (ΔDY > 40%). Through a comparison of the two model versions, we found that the formulation (reducing turbulent mixing) and boundary conditions (driving GCM) strongly influence precipitation projections. This result holds substantial value for ensuring the fitness of models for future projections intended for decision-makers.
Clinical Features and Risk Factors of Postoperative Stroke in Adult Moyamoya Disease
Authors: Liu Wen , Huang Kaixin , Zhang Jianjian , Zhou Da , Chen Jincao
Published: December 2023

Background and purpose: The clinical features of and risk factors for postoperative stroke after surgical revascularization in adult moyamoya disease (MMD) have not been fully elucidated. To this end, the baseline clinical features were hereby described, and the risk factors for postoperative stroke were determined. Methods: Data of 4078 MMD inpatients were collected retrospectively across all secondary- and higher-level hospitals of Hubei Province from January 2019 to December 2020. In accordance with inclusion and exclusion criteria, 559 adult MMD inpatients were finally enrolled. The associated characteristics and potential risk factors were analyzed, and the Kaplan–Meier risk of stroke was also calculated. Results: The patients consisted of 286 females and 273 males, with a mean age of 49.1 ± 10.0 years, all of whom had at least 1 year of follow-up (median 25.1 months). There were 356 cases of preoperative ischemic symptoms and 203 cases of preoperative hemorrhage symptoms. Indirect, direct, and combined revascularization were conducted on 97, 105 and 357 patients, respectively. Among these patients, 17 had postoperative hemorrhagic stroke (PHS), and 43 had postoperative ischemic stroke (PIS). A comparison between PHS/PIS group and control group (patients without postoperative stroke events) showed that preoperative hemorrhage was significantly associated with PHS (p = 0.003), while hypertension (p = 0.003), diabetes mellitus (p = 0.003) and modified Rankin scale (mRS) (p = 0.034) at admission were associated with a higher rate of PIS. Furthermore, preoperative hemorrhagic stroke was identified as a risk factor for PHS (odds ratio [OR], 4.229 [95% CI, 1.244–14.376]; p = 0.021), while hypertension (odds ratio [OR], 0.424 [95% CI, 0.210–0.855]; p = 0.017), diabetes mellitus (odds ratio [OR], 0.368 [95% CI, 0.163–0.827]; p = 0.016) and admission mRS (odds ratio [OR], 2.301 [95% CI, 1.157–4.575]; p = 0.017) were found to be risk factors for PIS. Conclusions: The age distribution of adult MMD patients with revascularization was predominantly concentrated within the range from 46 to 55 years. Preoperative hemorrhage events were considered the risk factor for PHS. Hypertension, diabetes and admission mRS were correlated with PIS, and were also the risk factors for PIS. These results indicated the possible contribution of enhancing systematic disease management to the prevention of postoperative cerebrovascular accidents.
An Insight into the Prospects and Drawbacks of Stem Cell Therapy for Spinal Cord Injuries: Ongoing Trials and Future Directions
Authors: Khan Shahidul Islam , Ahmed Nazmin , Ahsan Kamrul , Abbasi Mahmud , Maugeri Rosario , Chowdhury Dhiman , Bonosi Lapo , Brunasso Lara , Costanzo Roberta , Iacopino Domenico Gerardo , Umana Giuseppe Emmanuele , Chaurasia Bipin
Published: December 2023

Spinal cord injury (SCI) is a devastating neurological disorder that has a substantial detrimental impact on a person’s quality of life. The estimated global incidence of SCI is 40 to 80 cases per million people and around 90% of cases are traumatic. Various etiologies can be recognized for SCI, and post-traumatic SCI represents the most common of these. Patients worldwide with SCI suffer from a persistent loss of motor and sensory function, which affects every aspect of their personal and social lives. Given the lack of effective treatments, many efforts have been made to seek a cure for this condition. In recent years, thanks to their ability to regenerate tissue and repair lost or damaged cells, much attention has been directed toward the use of stem cells (embryonic, induced pluripotent, mesenchymal, hematopoietic), aimed at restoring the functional integrity of the damaged spinal cord and improving a functional recovery including sensory and motor function. In this paper, we offer an overview of the benefits and drawbacks of stem cell therapy for SCI based on clinical evidence. This report also addresses the characteristics of various stem cell treatments, as well as the field’s likely future. Each cell type targets specific pathological characteristics associated with SCI and demonstrates therapeutic effects via cell replacement, nutritional support, scaffolds, and immunomodulation pathways. SCI accompanied by complex pathological processes cannot be resolved by single treatment measures. Stem cells are associated with the adjustment of the expression of neurotrophic factors that help to achieve better nutrition to damaged tissue. Single-cell treatments have been shown in some studies to provide very minor benefits for SCI in multiple preclinical studies and a growing number of clinical trials. However, SCI damage is complex, and many studies are increasingly recognizing a combination approach such as physical therapy, electrical stimulation, or medication therapy to treatment.
The Impact of Spatial Frequency on the Perception of Crowd Emotion: An fMRI Study
Authors: Zhao Dongfang , Shen Xiangnan , Li Shuaixia , He Weiqi
Published: December 2023

Recognizing the emotions of faces in a crowd is crucial for understanding overall behavior and intention as well as for smooth and friendly social interactions. However, it is unclear whether the spatial frequency of faces affects the discrimination of crowd emotion. Although high- and low-spatial-frequency information for individual faces is processed by distinct neural channels, there is a lack of evidence on how this applies to crowd faces. Here, we used functional magnetic resonance imaging (fMRI) to investigate neural representations of crowd faces at different spatial frequencies. Thirty-three participants were asked to compare whether a test face was happy or more fearful than a crowd face that varied in high, low, and broad spatial frequencies. Our findings revealed that fearful faces with low spatial frequencies were easier to recognize in terms of accuracy (78.9%) and response time (927 ms). Brain regions, such as the fusiform gyrus, located in the ventral visual stream, were preferentially activated in high spatial frequency crowds, which, however, were the most difficult to recognize behaviorally (68.9%). Finally, the right inferior frontal gyrus was found to be better activated in the broad spatial frequency crowds. Our study suggests that people are more sensitive to fearful crowd faces with low spatial frequency and that high spatial frequency does not promote crowd face recognition.
Low-Grade Gliomas: Histological Subtypes, Molecular Mechanisms, and Treatment Strategies
Authors: Toader Corneliu , Eva Lucian , Costea Daniel , Corlatescu Antonio Daniel , Covache-Busuioc Razvan-Adrian , Bratu Bogdan-Gabriel , Glavan Luca Andrei , Costin Horia Petre , Popa Andrei Adrian , Ciurea Alexandru Vlad
Published: December 2023

Low-Grade Gliomas (LGGs) represent a diverse group of brain tumors originating from glial cells, characterized by their unique histopathological and molecular features. This article offers a comprehensive exploration of LGGs, shedding light on their subtypes, histological and molecular aspects. By delving into the World Health Organization’s grading system, 5th edition, various specificities were added due to an in-depth understanding of emerging laboratory techniques, especially genomic analysis. Moreover, treatment modalities are extensively discussed. The degree of surgical resection should always be considered according to postoperative quality of life and cognitive status. Adjuvant therapies focused on chemotherapy and radiotherapy depend on tumor grading and invasiveness. In the current literature, emerging targeted molecular therapies are well discussed due to their succinctly therapeutic effect; in our article, those therapies are summarized based on posttreatment results and possible adverse effects. This review serves as a valuable resource for clinicians, researchers, and medical professionals aiming to deepen their knowledge on LGGs and enhance patient care.
Distinguishing Laparoscopic Surgery Experts from Novices Using EEG Topographic Features
Authors: Manabe Takahiro , Rahul F.N.U. , Fu Yaoyu , Intes Xavier , Schwaitzberg Steven D. , De Suvranu , Cavuoto Lora , Dutta Anirban
Published: December 2023

The study aimed to differentiate experts from novices in laparoscopic surgery tasks using electroencephalogram (EEG) topographic features. A microstate-based common spatial pattern (CSP) analysis with linear discriminant analysis (LDA) was compared to a topography-preserving convolutional neural network (CNN) approach. Expert surgeons (N = 10) and novice medical residents (N = 13) performed laparoscopic suturing tasks, and EEG data from 8 experts and 13 novices were analysed. Microstate-based CSP with LDA revealed distinct spatial patterns in the frontal and parietal cortices for experts, while novices showed frontal cortex involvement. The 3D CNN model (ESNet) demonstrated a superior classification performance (accuracy > 98%, sensitivity 99.30%, specificity 99.70%, F1 score 98.51%, MCC 97.56%) compared to the microstate based CSP analysis with LDA (accuracy ~90%). Combining spatial and temporal information in the 3D CNN model enhanced classifier accuracy and highlighted the importance of the parietal–temporal–occipital association region in differentiating experts and novices.
Impaired Expression of the Salvador Homolog-1 Gene Is Associated with the Development and Progression of Colorectal Cancer
Authors: Kowalczyk Anna Ewa , Krazinski Bartlomiej Emil , Piotrowska Aleksandra , Grzegrzolka Jedrzej , Godlewski Janusz , Dziegiel Piotr , Kmiec Zbigniew
Published: December 2023

Salvador homolog-1 (SAV1) is a component of the Hippo pathway that regulates tissue growth and homeostasis by affecting diverse cell processes, including apoptosis, cell division, and differentiation. The aberrant expression of Hippo pathway components has been observed in various human cancers. This study aimed to examine the expression level of the SAV1 gene in colorectal cancer (CRC) and its prognostic value and associations with tumor progression. We obtained matched pairs of tumor tissue and non-cancerous mucosa of the large intestine from 94 CRC patients as well as 40 colon biopsies of healthy subjects collected during screening colonoscopy. The tissue samples and CRC cell lines were quantified for SAV1 mRNA levels using the quantitative polymerase chain reaction method, while SAV1 protein expression was estimated in the paired tissues of CRC patients using immunohistochemistry. The average level of SAV1 mRNA was decreased in 93.6% of the tumor tissues compared to the corresponding non-cancerous tissues and biopsies of healthy colon mucosa. A downregulated expression of SAV1 mRNA was also noted in the CRC cell lines. Although the average SAV1 immunoreactivity was increased in the CRC samples compared to the non-cancerous tissues, a decreased immunoreactivity of the SAV1 protein in the tumor specimens was associated with lymph node involvement and higher TNM disease stage and histological grade. The results of our study suggest that the impaired expression of SAV1 is involved in CRC progression.
Ampullary Adenocarcinoma: A Review of the Mutational Landscape and Implications for Treatment
Authors: Tsagkalidis Vasileios , Langan Russell C. , Ecker Brett L.
Published: December 2023

Ampullary carcinomas represent less than 1% of all gastrointestinal malignancies with an incidence of approximately 6 cases per 1 million. Histologic examination and immunohistochemistry have been traditionally used to categorize ampullary tumors into intestinal, pancreatobiliary or mixed subtypes. Intestinal-subtype tumors may exhibit improved survival versus the pancreatobiliary subtype, although studies on the prognostic value of immunomorphologic classification have been inconsistent. Genomic classifiers hold the promise of greater reliability, while providing potential targets for precision oncology. Multi-institutional collaboration will be necessary to better understand how molecular classification can guide type and sequencing of multimodality therapy.
Inhibition of Survivin Homodimerization Decreases Neuroblastoma Cell Growth
Authors: Dorneburg Carmen , Galiger Celimene , Stadler Giovanna L. , Westhoff Mike-Andrew , Rasche Volker , Barth Thomas F. E. , Debatin Klaus-Michael , Beltinger Christian
Published: December 2023

Increased expression of BIRC5/survivin, a crucial regulator of the mitotic spindle checkpoint, is associated with poor prognosis in neuroblastoma (NB), the most common extracranial tumor of childhood. Transcriptional inhibitors of survivin have been tested in adult cancers and inhibitors of survivin homodimerization are emerging. We compared genetic inhibition of survivin transcription with the inhibition of survivin homodimerization by S12 and LQZ-7I, chosen from a larger panel of survivin dimerization inhibitors with activity against NB cells. Mice hemizygous for Birc5 were crossed with NB-prone TH-MYCN mice to generate Birc5+/-/MYCNtg/+ mice. The marked decrease of survivin transcription in these mice did not suffice to attenuate the aggressiveness of NB, even when tumors were transplanted into wild-type mice to assure that immune cell function was not compromised by the lack of survivin. In contrast, viability, clonogenicity and anchorage-independent growth of NB cells were markedly decreased by S12. S12 administered systemically to mice with subcutaneous NB xenotransplants decreased intratumoral hemorrhage, albeit not tumor growth. LQZ-7I, which directly targets the survivin dimerization interface, was efficacious in controlling NB cell growth in vitro at markedly lower concentrations compared to S12. LQZ-7I abrogated viability, clonogenicity and anchorage-independent growth, associated with massively distorted mitotic spindle formation. In vivo, LQZ-7I effectively reduced tumor size and cell proliferation of NB cells in CAM assays without apparent toxicity to the developing chick embryo. Collectively, these findings show that inhibiting survivin homodimerization with LQZ-7I holds promise for the treatment of NB and merits further investigation.
Plasma Assay of Cell-Free Methylated DNA Markers of Colorectal Cancer: A Tumor-Agnostic Approach to Monitor Recurrence and Response to Anticancer Therapies
Authors: Zhu Mojun , Taylor William R. , Mahoney Douglas W. , Then Sara S. , Berger Calise K. , Burger Kelli N. , Gonser Anna M. , Doering Karen A. , Xie Hao , Foote Patrick H. , Kaiser Michael W. , Allawi Hatim T. , Hubbard Joleen M. , Kisiel John B.
Published: December 2023

Background: Radiographic surveillance of colorectal cancer (CRC) after curative-intent therapy is costly and unreliable. Methylated DNA markers (MDMs) detected primary CRC and metastatic recurrence with high sensitivity and specificity in cross-sectional studies. This study evaluated using serial MDMs to detect recurrence and monitor the treatment response to anti-cancer therapies. Methods: A nested case-control study was drawn from a prospective cohort of patients with CRC who completed curative-intent therapy for CRC of all stages. Plasma MDMs were assayed vis target enrichment long-probe quantitative-amplified signal assays, normalized to B3GALT6, and analyzed in combination with serum carcinoembryonic antigen to yield an MDM score. Clinical information, including treatment and radiographic measurements of the tumor burden, were longitudinally collected. Results: Of the 35 patients, 18 had recurrence and 17 had no evidence of disease during the study period. The MDM score was positive in 16 out of 18 patients who recurred and only 2 of the 17 patients without recurrence. The MDM score detected recurrence in 12 patients preceding clinical or radiographic detection of recurrent CRC by a median of 106 days (range 90–232 days). Conclusions: Plasma MDMs can detect recurrent CRC prior to radiographic detection; this tumor-agnostic liquid biopsy approach may assist cancer surveillance and monitoring.
In Vitro Three-Dimensional (3D) Models for Melanoma Immunotherapy
Authors: Nomdedeu-Sancho Gemma , Gorkun Anastasiya , Mahajan Naresh , Willson Kelsey , Schaaf Cecilia R. , Votanopoulos Konstantinos I. , Atala Anthony , Soker Shay
Published: December 2023

Melanoma is responsible for the majority of skin cancer-related fatalities. Immune checkpoint inhibitor (ICI) treatments have revolutionized the management of the disease by significantly increasing patient survival rates. However, a considerable number of tumors treated with these drugs fail to respond or may develop resistance over time. Tumor growth and its response to therapies are critically influenced by the tumor microenvironment (TME); it directly supports cancer cell growth and influences the behavior of surrounding immune cells, which can become tumor-permissive, thereby rendering immunotherapies ineffective. Ex vivo modeling of melanomas and their response to treatment could significantly advance our understanding and predictions of therapy outcomes. Efforts have been directed toward developing reliable models that accurately mimic melanoma in its appropriate tissue environment, including tumor organoids, bioprinted tissue constructs, and microfluidic devices. However, incorporating and modeling the melanoma TME and immune component remains a significant challenge. Here, we review recent literature regarding the generation of in vitro 3D models of normal skin and melanoma and the approaches used to incorporate the immune compartment in such models. We discuss how these constructs could be combined and used to test immunotherapies and elucidate treatment resistance mechanisms. The development of 3D in vitro melanoma models that faithfully replicate the complexity of the TME and its interaction with the immune system will provide us with the technical tools to better understand ICI resistance and increase its efficacy, thereby improving personalized melanoma therapy.
Prognostic Factors of Platinum-Refractory Advanced Urothelial Carcinoma Treated with Pembrolizumab
Authors: Akashi Yasunori , Yamamoto Yutaka , Hashimoto Mamoru , Adomi Shogo , Fujita Kazutoshi , Kiba Keisuke , Minami Takafumi , Yoshimura Kazuhiro , Hirayama Akihide , Uemura Hirotsugu
Published: December 2023

Introduction: Immune checkpoint inhibitor (ICI) therapy has significantly improved the prognosis of some patients with advanced urothelial carcinoma (UC), but it does not provide high therapeutic efficacy in all patients. Therefore, identifying predictive biomarkers is crucial in determining which patients are candidates for ICI treatment. This study aimed to identify the predictors of ICI treatment response in patients with platinum-refractory advanced UC treated with pembrolizumab. Methods: Patients with platinum-refractory advanced UC who had received pembrolizumab at two hospitals in Japan were included. Univariate and multivariate analyses were performed to identify biomarkers for progression-free survival (PFS) and overall survival (OS). Results: Forty-one patients were evaluable for this analysis. Their median age was 75 years, and the vast majority of the patients were male (85.4%). The objective response rate was 29.3%, with a median overall survival (OS) of 17.8 months. On multivariate analysis, an Eastern Cooperative Oncology Group performance status (ECOG-PS) ≥ 2 (HR = 6.33, p = 0.03) and a baseline neutrophil-to-lymphocyte ratio (NLR) > 3 (HR = 2.79, p = 0.04) were significantly associated with poor OS. Antibiotic exposure did not have a significant impact on either PFS or OS. Conclusions: ECOG-PS ≥ 2 and baseline NLR > 3 were independent risk factors for OS in patients with platinum-refractory advanced UC treated with pembrolizumab. Antibiotic exposure was not a predictor of ICI treatment response.
How to Manage Philadelphia-Positive Acute Lymphoblastic Leukemia in Resource-Constrained Settings
Authors: Silva Wellington , Rego Eduardo
Published: December 2023

Recent studies have indicated that more than half of adult patients newly diagnosed with Ph+ ALL can now achieve a cure. However, determining the most suitable protocol for less-resourced settings can be challenging. In these situations, we must consider the potential for treatment toxicity and limited access to newer agents and alloSCT facilities. Currently, it is advisable to use less intensive induction regimens for Ph+ ALL. These regimens can achieve high rates of complete remission while causing fewer induction deaths. For consolidation therapy, chemotherapy should remain relatively intensive, with careful monitoring of the BCR-ABL1 molecular transcript and minimal residual disease. AlloSCT may be considered, especially for patients who do not achieve complete molecular remission or have high-risk genetic abnormalities, such as IKZF1-plus. If there is a loss of molecular response, it is essential to screen patients for ABL mutations and, ideally, change the TKI therapy. The T315I mutation is the most common mechanism for disease resistance, being targetable to ponatinib. Blinatumomab, a bispecific antibody, has shown significant synergy with TKIs in treating this disease. It serves as an excellent salvage therapy, aside from achieving outstanding results when incorporated into the frontline.
Current State-of-the-Art Therapy for Malignant Pleural Mesothelioma and Future Options Centered on Immunotherapy
Authors: Cedres Susana , Valdivia Augusto , Iranzo Patricia , Callejo Ana , Pardo Nuria , Navarro Alejandro , Martinez-Marti Alex , Assaf-Pastrana Juan David , Felip Enriqueta , Garrido Pilar
Published: December 2023

Malignant pleural mesothelioma (MPM) is a locally aggressive disease related to asbestos exposure with a median survival for untreated patients of 4–8 months. The combination of chemotherapy based on platinum and antifolate is the standard treatment, and the addition of bevacizumab adds two months to median survival. Recently, in first-line treatment, immunotherapy combining nivolumab with ipilimumab has been shown to be superior to chemotherapy in the CheckMate-743 study in terms of overall survival (18.1 months), leading to its approval by the FDA and EMA. The positive results of this study represent a new standard of treatment for patients with MPM; however, not all patients will benefit from immunotherapy treatment. In an effort to improve the selection of patient candidates for immunotherapy for different tumors, biomarkers that have been associated with a greater possibility of response to treatment have been described. MPM is a type of tumor with low mutational load and neo-antigens, making it a relatively non-immunogenic tumor for T cells and possibly less susceptible to responding to immunotherapy. Different retrospective studies have shown that PD-L1 expression occurs in 20–40% of patients and is associated with a poor prognosis; however, the predictive value of PD-L1 in response to immunotherapy has not been confirmed. The purpose of this work is to review the state of the art of MPM treatment in the year 2023, focusing on the efficacy results of first-line or subsequent immunotherapy studies on patients with MPM and possible chemo-immunotherapy combination strategies. Additionally, potential biomarkers of response to immunotherapy will be reviewed, such as histology, PD-L1, lymphocyte populations, and TMB.
Recurrence Patterns and Risk Factors after Curative Resection for Colorectal Cancer: Insights for Postoperative Surveillance Strategies
Authors: Ryu Hyo Seon , Kim Jin , Park Ye Ryung , Cho Eun Hae , Choo Jeong Min , Kim Ji-Seon , Baek Se-Jin , Kwak Jung-Myun
Published: December 2023

This study aimed to assess recurrence patterns and related risk factors following curative resection of colorectal cancer (CRC). This retrospective observational study was conducted at a tertiary care center, including 2622 patients with stage I–III CRC who underwent curative resection between 2008 and 2018. Hazard rates of recurrence were calculated using a hazard function. The primary outcome was the peak recurrence time after curative resection and secondary outcomes were prognostic factors associated with recurrence. Over a median follow-up period of 53 months, the overall, locoregional and systemic recurrence rates were 8.9%, 0.7%, and 8.5%, respectively. Recurrence rates were significantly higher for rectal cancer (14.9% overall, 4.4% locoregionally, and 12.3% systemically) than for colon cancer (all p < 0.001). The peak recurrence time was 11 months, with variations in hazard rates and curves depending on the tumor location, stage, and risk factors. Patients with AL or CRM involvement exhibited a distinct pattern, with a high hazard rate in the early postoperative period. Understanding these recurrence patterns and risk factors is crucial for establishing effective postoperative surveillance strategies. Our findings suggested that short-interval surveillance should be considered during the first 2 years post-surgery, particularly for high-risk patients who should receive early attention.
Neoadjuvant Chemotherapy Followed by Gastrectomy for Cytology-Positive Gastric Cancer without Any Other Non-Curative Factors in a Western Setting: An International Eastern European Cohort Study
Authors: Bausys Augustinas , Ümarik Toomas , Dobrzhanskyi Oleksii , Luksta Martynas , Kondratskyi Yourii , Reinsoo Arvo , Vassiljev Mihhail , Bausys Bernardas , Bickaite Klaudija , Rauduvyte Kornelija , Luksaite-Lukste Raminta , Bausys Rimantas , Strupas Kestutis
Published: December 2023

The optimal approach for treating cytology-positive (Cy1) gastric cancer (GC) patients without additional non-curative factors remains uncertain. While neoadjuvant chemotherapy followed by gastrectomy shows promise, its suitability for Western patients is not well supported by existing data. To address this knowledge gap, a cohort study was conducted across four major GC treatment centers in Lithuania, Estonia, and Ukraine. Forty-three consecutive Cy1 GC patients who underwent neoadjuvant chemotherapy between 2016 and 2020 were enrolled. The study evaluated overall survival (OS), progression-free survival (PFS), cytology status conversion, and major pathological response rates, along with the factors influencing these outcomes. All patients underwent surgery post-neoadjuvant chemotherapy, with 53.5% experiencing cytological status conversion and 23.3% achieving a major pathological response. The median OS and PFS were 20 (95% CI: 16–25) and 19 (95% CI: 11–20) months, respectively. Conversion to negative cytology significantly reduced the relative risk of peritoneal progression (RR: 0.11; 95% CI: 0.03–0.47, p = 0.002). The study suggests that neoadjuvant chemotherapy followed by gastrectomy holds promise as a treatment option for Cy1 GC without additional non-curative factors, associating cytology status conversion with improved long-term outcomes and reduced peritoneal relapse risk.
Lactate-Induced CCL8 in Tumor-Associated Macrophages Accelerates the Progression of Colorectal Cancer through the CCL8/CCR5/mTORC1 Axis
Authors: Zhou Hui , Yao Jiayi , Zhong Zhaozhong , Wei Hongfa , He Yulong , Li Wenchao , Hu Kunpeng
Published: December 2023

Tumor-associated macrophages (TAMs) play a pivotal role in shaping the tumor microenvironment. Lactic acid (LA) has been identified as an influential factor in promoting immune escape and tumor progression. However, the mechanisms through which LA modulates TAMs in colorectal cancer (CRC) remain poorly understood. We used qRT-PCR to quantify the expression of LA-related genes (LDHA and LAMP2) in CRC tumor tissues and adjacent nontumor tissues (n = 64). The biological effects and mechanisms of LA on macrophages and tumors were evaluated via qRT-PCR, Western blot, RNA-seq, wound healing assay, colony formation assay in vitro, and allograft mouse tumor models in vivo. We found the expression of LDHA and LAMP2 was highly elevated in the tumor regions and positively associated with a poor clinical stage of CRC. A high concentration of LA was generated under hypoxia; it could promote tumor progression and metastasis with the involvement of macrophages. The inhibition of LA release impaired this protumor phenomenon. Mechanically, LA induced M2 macrophages through the AKT/ERK signaling pathway; subsequently, M2 macrophages secreted CCL8 and facilitated the proliferation and metastasis of CRC cells by activating the CCL8/CCR5/mTORC1 axis. This effect was inhibited by the antagonist or knockdown of CCR5. In conclusion, lactate-induced CCL8 in TAMs accelerated CRC proliferation and metastasis through the CCL8/CCR5/mTORC1 axis.
Morbidity of Transrectal MRI-Fusion Targeted Prostate Biopsy at a Tertiary Referral Academic Centre: An Audit to Guide the Transition to the Transperineal Approach
Authors: Alberti Andrea , Nicoletti Rossella , Polverino Paolo , Rivetti Anna , Dibilio Edoardo , Resta Giulio Raffaele , Makrides Pantelis , Caneschi Corso , Cifarelli Andrea , D’Amico Antonino , Moscardi Luisa , Lo Re Mattia , Peschiera Federico , Gallo Maria Lucia , Pecoraro Alessio , Sebastianelli Arcangelo , Masieri Lorenzo , Gacci Mauro , Serni Sergio , Campi Riccardo , Sessa Francesco
Published: December 2023

Despite transrectal prostate biopsy (TRPB) being still widespread globally, the EAU Guidelines strongly recommend the transperineal approach, due to the reported lower infectious risk. Our study aims to evaluate the impact of a standardized clinical pathway for TRPB on post-operative complications. We prospectively collected data from all patients undergoing mpMRI-targeted TRPB at our Academic Centre from January 2020 to December 2022. All patients followed a standardized, structured multistep pathway. Post-procedural complications were collected and classified according to the Clavien–Dindo (CD) Classification. Among 458 patients, post-procedural adverse events were reported by 203 (44.3%), of which 161 (35.2%) experienced CD grade 1 complications (hematuria [124, 27.1%], hematochezia [22, 4.8%], hematospermia [14, 3.1%], or a combination [20, 4.4%]), and 45 (9.0%) reported CD grade 2 complications (acute urinary retention or hematuria needing catheterization, as well as urinary tract infections, of which 2 cases required hospitalization). No major complications, including sepsis, were observed. At uni- and multivariable analysis, age > 70 years and BMI > 25 kg/ m2 for patients were identified as predictors of post-operative complications. The results of our study confirm that TRPB is a safe and cost-effective procedure with a low risk of severe adverse events in experienced hands and following a standardized pathway.
A Comparison of 3D Conformal and Deep Inspiratory Breath Holding vs. 4D-CT Intensity-Modulated Radiation Therapy for Patients with Left Breast Cancer
Authors: Aldaly Moustafa , Hussien Azza , El-nadi Inas Mohsen , Laz Nabila Ibrahim , Said Amira S. A. , Al-Ahmad Mohammad M. , Hussein Raghda R. S. , Rabie Al Shaimaa Ibrahim , Shaaban Ahmed Hassan
Published: December 2023

Background: Multimodality is required for the treatment of breast cancer. Surgery, radiation (RT), and systemic therapy were traditionally used. Pharmacotherapy includes different drug mechanisms, such as chemotherapy, hormone therapy, and targeted therapies, alone or in combination with radiotherapy. While radiation offers numerous benefits, it also has certain harmful risks. such as cardiac and pulmonary toxicity, lymphedema, and secondary cancer. Modern radiation techniques have been developed to reduce organs at risk (OAR) doses. Materials and Methods: This study is a prospective feasibility trial conducted at the Fayium Oncology Center on patients with left breast cancer receiving adjuvant locoregional radiotherapy after either breast conservative surgery (BCS) or modified radical mastectomy (MRM). This study aimed to assess the proportion of patients who are fit both physically and intellectually to undergo breast radiotherapy using the deep inspiratory breath-holding (DIBH) technique, comparing different dosimetric outcomes between the 3D dimensional conformal with DIBH and 4D-CT IMRT plans of the same patient. Results: D95 of the clinical target volume (CTV) of the target is significantly higher in the 3D DIBH plan than in the IMRT plan, with an average of 90.812% vs. 86.944%. The dosimetry of the mean heart dose (MHD) in the 4D-CT IMRT plan was significantly lower than in the 3D conformal with the DIBH plan (2.6224 vs. 4.056 Gy, p < 0.0064), and no significant difference between the two plans regarding mean left anterior descending artery (LAD) (14.696 vs. 13.492 Gy, p < 0.58), maximum LAD (39.9 vs. 43.5 Gy, p < 0.35), and V20 of the ipsilateral lung (18.66% vs. 16.306%, p < 0.88) was observed. Internal mammary chain (IMC) irradiation was better in the 4D-CT IMRT plan. Conclusions: Radiotherapy of the breast and chest wall with the 4D-CT IMRT technique appears not to be inferior to the 3D conformal with the DIBH technique and can be used as an alternative to the 3D conformal with the DIBH technique in patients meeting the exclusion criteria for performing the DIBH maneuver concerning coverage to target volumes or unacceptably high doses to OAR.
Sperm-Induced Ca2+ Release in Mammalian Eggs: The Roles of PLCζ, InsP3, and ATP
Authors: Swann Karl
Published: December 2023

Mammalian egg activation at fertilization is triggered by a long-lasting series of increases in cytosolic Ca2+ concentration. These Ca2+ oscillations are due to the production of InsP3 within the egg and the subsequent release of Ca2+ from the endoplasmic reticulum into the cytosol. The generation of InsP3 is initiated by the diffusion of sperm-specific phospholipase Czeta1 (PLCζ) into the egg after gamete fusion. PLCζ enables a positive feedback loop of InsP3 production and Ca2+ release which then stimulates further InsP3 production. Most cytosolic Ca2+ increases in eggs at fertilization involve a fast Ca2+ wave; however, due to the limited diffusion of InsP3, this means that InsP3 must be generated from an intracellular source rather than at the plasma membrane. All mammalian eggs studied generated Ca2+ oscillations in response to PLCζ, but the sensitivity of eggs to PLCζ and to some other stimuli varies between species. This is illustrated by the finding that incubation in Sr2+ medium stimulates Ca2+ oscillations in mouse and rat eggs but not eggs from other mammalian species. This difference appears to be due to the sensitivity of the type 1 InsP3 receptor (IP3R1). I suggest that ATP production from mitochondria modulates the sensitivity of the IP3R1 in a manner that could account for the differential sensitivity of eggs to stimuli that generate Ca2+ oscillations.
Remarkable Potential of Cold Spray in Overlay Restoration for Power Plants: Key Challenges, Recent Developments, and Future Prospects
Authors: Afandi Nurfanizan , Mahalingam Savisha , Tan Adrian , Manap Abreeza , Mohd Yunus Salmi , Sun Wen , Zulkipli Asiah , Chan Xin , Chong Adrian , Om Nur , Bhowmik Ayan
Published: December 2023

Cold spray has become a prominent deposition technology for coating, repair, and restoration in many industries, such as the aerospace, automotive, and power generation industries. It also has the potential to be used as an alternative overlay restoration for power plant components as it has minimal thermal distortion phase changes, as compared to conventional welding and thermal spray. This article aims to bridge the gap in the scientific literature by presenting a comprehensive review of cold spray in the context of power plant components. Firstly, this review examines the challenges of cold spray and subsequently elucidates effective mitigation strategies. Secondly, the review analyses the recent development of cold spray in the field of coating application. Moving forward, it investigates the integration of cold spray technology in repair applications, focusing on practical implementation and effectiveness. Finally, the review presents the overall impact of cold spray, its current outlook, and discusses future prospects. As such, the review will provide the community with a broad understanding of cold spray applications in the power plant sector.
Failure Mechanism of Thermal Barrier Coatings on Nozzle Guide Vanes Fabricated from Nickel-Based Single-Crystal Superalloy under Gas Thermal Shock Conditions
Authors: Wang Yufeng , Fu Qiangang , Yang Chenxi , Peng Hui , Zhang Hua
Published: December 2023

The objective of this study was to investigate the early failure behavior of thermal barrier coatings on single-crystal nozzle guide vanes under gas thermal shock conditions. The microstructure and mechanical properties of the thermal barrier coating before and after the gas thermal shock tests were analyzed using scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), X-ray diffraction (XRD), and microhardness testing. The results indicate the presence of a mixed layer containing Ni, Cr, Al, Zr, and O at the base of the ceramic layer, and reveal failure behavior in the thermal barrier coating. The analysis suggests that the incomplete formation of the thermal growth oxide layer between the ceramic layer and the bonding layer, before the deposition of the YSZ ceramic layer, led to the easy diffusion of elements from the bonding layer into the root of the ceramic layer during the gas thermal shock process, resulting in the formation of a mixed layer. In the test environment, significant thermal stress was generated in the mixed layer, leading to transverse cracks and ultimately causing early failure of the thermal barrier coating. Consequently, the “incomplete initial TGO layer” model is proposed.
Influence of Substrate Preparation on the Catalytic Activity of Conical Ni Catalysts
Authors: Skibińska Katarzyna , Elsharkawy Safya , Kula Anna , Kutyła Dawid , Żabiński Piotr
Published: December 2023

The production of hydrogen using electrolysis contributes to the development of more important renewable energy sources. Nowadays, the synthesis of alloys, which can be successfully applied as catalysts instead of precious metals, is carefully investigated. One-step electrodeposition is a surface engineering method that allows for the control of the morphology of the deposit by changing deposition parameters. It is a simple and low-cost process based on electrochemical synthesis from electrolytes, usually non-toxic crystal modifiers. In this work, a conical Ni structure on Cu foil was produced using this technique. The effect of the copper substrate on the morphology of the developed nanocones was analyzed using a Scanning Electron Microscope (SEM). Then, the catalytic performance of the synthesized coatings was carefully analyzed based on the results of a linear sweep voltammetry experiment and the measurements of their wettability and electrochemical active surface area. The proposed method of Cu treatment, including polishing with sandpapers, influenced the growth of cones and, consequently, increased the catalytic activity and active surface area of the Ni coatings in comparison to the bulk Ni sample.
Flexible Ultraviolet Sensor Based on Zinc Oxide Nanoparticle Powder
Authors: Munguía-Fernández Nicol , Castillo-Saenz Jhonathan , Perez-Landeros Oscar , Nedev Roumen , Mateos David , Paz Judith , Suárez Mariel , Curiel-Alvarez Mario , Nedev Nicola , Arias Abraham
Published: December 2023

Zinc oxide nanopowder was synthesized by the coprecipitation method. FT-IR and EDS analyses were performed to qualitatively determine the composition of the nanopowder. FE-SEM images revealed the morphology of the nanopowder formed by clusters of nanoparticles. An XRD analysis confirmed the wurtzite structure with a crystallite size of ~21.2 nm. UV–Vis measurements were performed to determine the ZnO bandgap (~3.05 eV) using the Tauc plot method in the absorbance spectra. The ZnO nanopowder and two comb-like metal contacts were confined and compacted between two polymeric layers by a low-temperature thermal lamination method, resulting in a flexible Polymer/ZnO/Metal/ZnO/Polymer structure. Part of each comb-like metal was kept uncovered by a polymeric layer in order to be used for electrical characterization. I-V measurements of the flexible structure were performed in the dark and under UV illumination, showing the capacity to detect UV radiation and its potential application as a visible-blind UV sensor. A facile and low-cost flexible optoelectronic device is presented, avoiding using high-vacuum or high-temperature technology. This new and novel approach to developing optoelectronic devices proposes using powder materials as semiconducting active regions instead of thin films; this could eliminate the cracking and delamination problems of flexible devices based on thin film technology.
Oncology Workforce Crisis: Let’s Work Smarter, Not Harder
Authors: Chaput Genevieve
Published: December 2023

Editorial: Cancer projections in Canada are bleak, with the average annual number of new cancer diagnoses expected to be 79% higher in 2028–2032 compared to 2003–2007 [...]
The Characterization and Phylogenetic Implications of the Mitochondrial Genomes of Antheminia varicornis and Carpocoris purpureipennis (Hemiptera: Pentatomidae)
Authors: Wang Ying , Yang Ruijuan , Zhu Xiuxiu , Zheng Chenguang , Bu Wenjun
Published: December 2023

The mitochondrial genome (mitogenome) has been widely used for structural comparisons and phylogenetic analyses of Hemiptera groups at different taxonomic levels. However, little is known about the mitogenomic characteristics of species from Antheminia and Carpocoris, two morphologically similar genera in the Pentatomidae family, and their phylogenetic relationships need to be further confirmed. In this study, the mitogenomes of Antheminia varicornis (Jakovlev, 1874) and Carpocoris purpureipennis (De Geer, 1773) were sequenced and analyzed. Coupled with previously published mitogenomes of Pentatomidae, we performed a phylogenetic analysis. The mitogenomes of A. varicornis and C. purpureipennis are conserved in terms of genomic structure, base composition, codon usage, and tRNA secondary structure. Each mitogenome contains the typical 37 genes and a control region and all genes are arranged in the same order as in the ancestral insect mitogenome. Nucleotide composition is highly biased with the third codon in PCGs displaying the highest A + T content. Phylogenetic analysis strongly supports the sister relationship between A. varicornis and C. purpureipennis. The phylogenetic trees show a strong support for the monophyly of Asopinae and Phyllocephalinae, while the monophyly of Pentatominae and Podopinae was rejected. Our study enriches the mitochondrial genome database of the genera Antheminia and Carpocoris and provides a valuable resource for further phylogenetic and evolutionary analyses of the Pentatomidae.