bluuebunny/crossref_metadata_2025 huggingface dataset:
Solitonic Windkessel Model for Intracranial Aneurysm
Authors: Ujiie Hiroshi , Iwata Yoritaka
Published: August 2022

The Windkessel model, which is known as a successful model for explaining the hemodynamic circulation, is a mathematical model with a direct correspondence with the electric circuit. We propose a theoretical model for the intracranial aneurysm based on the Windkessel-type steady blood flow. Intracranial aneurysms are well known vascular lesions, which cause subarachnoid hemorrhages. Since an aneurysm is an end-sack formed on the blood vessel, it functions as an unusual blood path that has characteristic features such as a reservoir and bottle neck orifice. We simulate an aneurysm by an electric circuit consisting of three different impedances, resistance, capacitance and inductance. A dumbbell-shaped aneurysm is the most dangerous aneurysm to easily rupture. Our aneurysmal model is created as a two-story aneurysm model for this point, thus namely the five-element Windkessel. Then, the mathematical formula was solved in numerical simulations by changing the size of the aneurysm and the elasticity of the aneurysm wall. An analysis of this model provided that the presence of the daughter aneurysm and the thinning of the aneurysm wall are positively correlated with a sharp increase in blood pressure in the aneurysm dome. Our mathematic aneurysm model proposes a good analogue to the real aneurysm and proved that this model includes soliton that is a non-decreasing wave propagation.
Research on Top Archer’s EEG Microstates and Source Analysis in Different States
Authors: Gu Feng , Gong Anmin , Qu Yi , Xiao Hui , Wu Jin , Nan Wenya , Jiang Changhao , Fu Yunfa
Published: August 2022

The electroencephalograph (EEG) microstate is a method used to describe the characteristics of the EEG signal through the brain scalp electrode potential’s spatial distribution; as such, it reflects the changes in the brain’s functional state. The EEGs of 13 elite archers from China’s national archery team and 13 expert archers from China’s provincial archery team were recorded under the alpha rhythm during the resting state (with closed eyes) and during archery aiming. By analyzing the differences between the EEG microstate parameters and the correlation between these parameters with archery performance, as well as by combining our findings through standardized low-resolution brain electromagnetic tomography source analysis (sLORETA), we explored the changes in the neural activity of professional archers of different levels, under different states. The results of the resting state study demonstrated that the duration, occurrence, and coverage in microstate D of elite archers were significantly higher than those of expert archers and that their other microstates had the greatest probability of transferring to microstate D. During the archery aiming state, the average transition probability of the other microstates transferring to microstate in the left temporal region was the highest observed in the two groups of archers. Moreover, there was a significant negative correlation between the duration and coverage of microstates in the frontal region of elite archers and their archery performance. Our findings indicate that elite archers are more active in the dorsal attention system and demonstrate a higher neural efficiency during the resting state. When aiming, professional archers experience an activation of brain regions associated with archery by suppressing brain regions unrelated to archery tasks. These findings provide a novel theoretical basis for the study of EEG microstate dynamics in archery and related cognitive motor tasks, particularly from the perspective of the subject’s mental state.
Progressive Course of Chronic Tick-Borne Encephalitis Manifesting as Amyotrophic Lateral Sclerosis-like Syndrome 35 Years after the Acute Disease
Authors: Volok Viktor P. , Gmyl Larissa V. , Belyaletdinova Ilmira K. , Karganova Galina G. , Dekonenko Evgenii P.
Published: August 2022

The chronic form of tick-borne encephalitis (TBE) is understudied and seems to be linked exclusively to Siberian and Far Eastern TBE virus (TBEV) subtypes. There are limited clinical descriptions demonstrating that chronic TBE can resemble an amyotrophic lateral sclerosis (ALS)-like disease. Here, we present a description of a clinical case of progressive chronic TBEV infection with a relapse 35 years after the initial acute infection following a tick bite. The disease manifested as an ALS-like syndrome with bulbar signs, progressive muscle weakness and atrophy, decreased reflexes, and eventual respiratory failure and death. There is no clear differentiation between chronic TBE and postencephalitic syndrome described in European sources. The reactivation of TBEV infection was supported by the presence of anti-TBEV antibodies in serum and antibodies to E protein and to the nonstructural protein NS1 in the CSF. These findings support the diagnosis of a relapse of chronic TBE in this patient.
Metal-Nails Waste and Steel Slag Aggregate as Alternative and Eco-Friendly Radiation Shielding Composites
Authors: Attia Mohammed M. , Abdelsalam Bassam Abdelsalam , Amin Mohamed , Agwa Ibrahim Saad , Abdelmagied Mohammad Farouk
Published: August 2022

Metal waste recycling has become a global requirement owing to its environmental benefits and powerful economic activity. Metal nail waste (MNW) is a byproduct of metal nail manufacture. MNW has an equal size, contains a high ratio of iron, and has a high specific gravity comparable to normal aggregate. We present MNW recycling as a partial replacement for fine aggregates and electric arc furnace steel slag (EAFSS) as coarse aggregates to produce sustainable heavyweight concrete (HWC). Our main research aim was to study the radiation shielding and mechanical properties of sustainable HWC by partially replacing MNW with 10, 20, 30, and 40% sand. EAFSS is a coarse aggregate for 60% of the total volume. Fresh and hardened properties of HWC are presented. Furthermore, we analysed the internal structure of HWC mixes using a scanning electron microscope. Our results showed the positive effects of MNW on the unit weight of concrete. The density of HWC mixes ranges between 2650 and 3170 kg/m3. In addition, MNW contributes to increasing the compressive strength of concrete mixes with their use of up to 30%. Therefore, the MNW ratios improved the failure behaviour of HWC mixes. The improved linear attenuation coefficient of HWC mixes was due to using MNW ratios and higher densities than the reference mix.
A Business Analysis of Innovations in Aquaculture: Evidence from Israeli Sturgeon Caviar Farm
Authors: Degani Gad , Yom Din Gregory
Published: August 2022

The background of this study is related to the tendencies in caviar production and prices in the world. The objective of the study is to evaluate and compare the profitability of different sturgeon sex determination methods for the conditions of aquaculture farms in northern Israel. We present the economic valuation of the technological innovation of early sex determination in this aquaculture industry. The production of sturgeon biomass exceeded the fishery harvest during the 1970–1980s by more than four times. There was a significant decline in world caviar prices the last time. The aquafarming business has a high potential economic value in the region of northern Israel. Based on the empirical data of the Caviar Galilee farm in this region, we examine the economic benefits of the innovation in sturgeon sex determination, including the case of a possible decrease in caviar price. Using the bio-economic model for a sturgeon caviar farm in two versions (for each of the considered sex determination methods, the endoscopy method and the early sex determination method), we show the economic advantages of this innovation of 9–34% for different financial highlights compared to the traditional method of sturgeon sex determination. The study empirically illustrates the economic advantages of the cooperation between aquaculture farming and research institutes. Our study suggests that additional directions in research should be sought in order to increase the profitability of sturgeon farms, especially when the world caviar prices decline. Further research can be conducted for additional regions and data.
Clinical Outcomes of Patients with Recurrent Microsatellite-Stable Endometrial Cancer in Early-Phase Immunotherapy Clinical Trials
Authors: How Jeffrey A. , Jazaeri Amir A. , Fu Siqing , Rodon Ahnert Jordi , Gong Jing , Stephen Bettzy , Ferreira Dalla Pria Hanna , Bhosale Priya , Johnson Amber , Yuan Ying , Meric-Bernstam Funda , Naing Aung
Published: August 2022

Recurrent microsatellite stable (MSS) endometrial cancer has poor response to conventional therapy and limited efficacy with immune checkpoint monotherapy. We conducted a retrospective study of recurrent MSS endometrial cancer patients enrolled in immunotherapy-based clinical trials at MD Anderson Cancer Center between 1 January 2010 and 31 December 2019. Patients were evaluated for radiologic response using RECIST 1.1 criteria, progression-free survival (PFS), and overall survival (OS). Thirty-five patients were treated with immune checkpoint inhibitors: 8 with monotherapy, 17 with immunotherapy (IO) in combination with another IO-only, and 10 with IO in combination with non-IO therapy. Among those treated with combination IO plus non-IO therapy, one had a partial response but 50% had clinical benefit. Patients who received combination IO plus non-IO therapy had improved PFS compared to those who received monotherapy (HR 0.56, 95% CI 0.33–0.97; p = 0.037) or combination IO-only therapy (HR 0.36, 95% CI 0.15–0.90; p = 0.028) and had improved OS when compared to monotherapy after adjusting for prior lines of therapy (HR 0.50, 95% CI 0.27–0.95; p = 0.036). The potential beneficial clinical outcomes of combination IO plus non-IO therapy in MSS endometrial cancer should be validated in a larger study.
Longitudinal Changes in the Fatty Acid Profile in Patients with Head and Neck Cancer: Associations with Treatment and Inflammatory Response
Authors: Christou Constantina N , Ehrsson Ylva Tiblom , Westerbergh Johan , Risérus Ulf , Laurell Göran
Published: August 2022

Studies on fatty acids (FAs) in patients with head and neck cancer (HNC) are limited. We aimed to investigate the longitudinal changes of circulating FAs in patients with HNC and to examine potential correlations of FA changes with treatment. The secondary aims were to investigate correlations of FAs with cytokines and patient-related factors, and if any FAs correlated with disease recurrence or death. A total of 174 patients with HNC were included before treatment and followed-up at three time points after the start of the treatment through blood sampling and body weight measurements. Serum FA profiling was assessed by gas chromatography. The total follow-up time was 3 years. The levels of almost all FAs changed from baseline to 7 weeks. The change in FA 14:0 was associated with treatment and the change in 18:3n-6 was associated with the patients’ pre-treatment BMI. FAs 14:0 and 18:0 were correlated with weight changes from baseline to 7 weeks. IL-6 was correlated with three FAs at 7 weeks and with two FAs at 1 year. Patients with higher levels 20:5n-3 at 3 months had a higher risk of all-cause death within 3 years (HR 2.75, 95% CI 1.22–6.21). Treatment, inflammation, and weight loss contributed in a complex manner to the altered FA profile in the studied cohort. The association between IL-6 and FAs in patients with HNC is in line with earlier studies and suggests the opportunity for regulating inflammation in HNC patients through modulation of FAs.
Targeted Mutational Analysis of Circulating Tumor DNA to Decipher Temporal Heterogeneity of High-Grade Serous Ovarian Cancer
Authors: Paracchini Lara , Mannarino Laura , Beltrame Luca , Landoni Fabio , Fruscio Robert , Grassi Tommaso , Dalessandro Maria Luisa , D’Incalci Maurizio , Marchini Sergio
Published: August 2022

We have previously demonstrated that longitudinal untargeted analysis of plasma samples withdrawn from patients with high-grade serous ovarian cancer (HGS-EOC) can intercept the presence of molecular recurrence (TRm) earlier than the diagnosis of clinical recurrence (TRc). This finding opens a clinical important temporal window to acquire through plasma sample analysis a real-time picture of those emerging molecular lesions that will drive and sustain the growth of relapsed disease and ultimately will confer resistance. In this proof of principle study, the same genomic libraries obtained at the diagnosis (T0), TRm and TRc were further analyzed by targeted resequencing approach to sequence the coding region of a panel of 65 genes to provide longitudinal analysis of clonal evolution as a novel strategy to support clinical decisions for the second-line treatment. Experiments were performed on plasma and tumor tissues withdrawn on a selection of previously analyzed cohorts of cases (i.e., 33 matched primary and synchronous lesions and 43 plasma samples from 18 patients). At T0, the median concordance of mutations shared by each tumor tissue biopsy and its matched plasma sample was 2.27%. This finding confirms the limit of a single tumor biopsy to be representative of the entire disease, while plasma analysis can recapitulate most of the main molecular lesions of the disease. A comparable scenario was observed during longitudinal analysis, where, with the exception of the TP53 gene and germline mutations in BRCA1/2 genes, no other gene shared the same locus specific gene mutation across T0, TRm and TRc time points. This high level of temporal heterogeneity has important implications for planning second-line treatment. For example, in three out of 13 cases, plasma ctDNA analysis at TRm or TRc reported acquired novel variants in the TP53BP1 gene not present at T0. In particular, patient 21564, potentially eligible for PARP-inhibitor (PARPi) treatment at the time of diagnosis (BRCA1 c.5182delA mutation), would unlikely respond to these drugs in second-line therapy due to the presence of eight distinct TP53BP1 variants in plasma samples collected TRc. This study demonstrates that liquid biopsy provides a real-time molecular picture to intercept those actionable genetic vulnerabilities or drug resistance mechanisms that could be used to plan a more rational second-line treatment.
A Novel Localization in Human Large Extracellular Vesicles for the EGF-CFC Founder Member CRIPTO and Its Biological and Therapeutic Implications
Authors: Mantile Francesca , Kisovec Matic , Adamo Giorgia , Romancino Daniele P. , Hočevar Matej , Božič Darja , Bedina Zavec Apolonija , Podobnik Marjetka , Stoppelli Maria Patrizia , Kisslinger Annamaria , Bongiovanni Antonella , Kralj-Iglič Veronika , Liguori Giovanna L.
Published: August 2022

Tumor growth and metastasis strongly rely on cell–cell communication. One of the mechanisms by which tumor cells communicate involves the release and uptake of lipid membrane encapsulated particles full of bioactive molecules, called extracellular vesicles (EVs). EV exchange between cancer cells may induce phenotype changes in the recipient cells. Our work investigated the effect of EVs released by teratocarcinoma cells on glioblastoma (GBM) cells. EVs were isolated by differential centrifugation and analyzed through Western blot, nanoparticle tracking analysis, and electron microscopy. The effect of large EVs on GBM cells was tested through cell migration, proliferation, and drug-sensitivity assays, and resulted in a specific impairment in cell migration with no effects on proliferation and drug-sensitivity. Noticeably, we found the presence of the EGF-CFC founder member CRIPTO on both small and large EVs, in the latter case implicated in the EV-mediated negative regulation of GBM cell migration. Our data let us propose a novel route and function for CRIPTO during tumorigenesis, highlighting a complex scenario regulating its effect, and paving the way to novel strategies to control cell migration, to ultimately improve the prognosis and quality of life of GBM patients.
Lung Cancer Organoids: The Rough Path to Personalized Medicine
Authors: Rossi Rachele , De Angelis Maria Laura , Xhelili Eljona , Sette Giovanni , Eramo Adriana , De Maria Ruggero , Cesta Incani Ursula , Francescangeli Federica , Zeuner Ann
Published: August 2022

Lung cancer is the leading cause of cancer death worldwide. Despite significant advances in research and therapy, a dismal 5-year survival rate of only 10–20% urges the development of reliable preclinical models and effective therapeutic tools. Lung cancer is characterized by a high degree of heterogeneity in its histology, a genomic landscape, and response to therapies that has been traditionally difficult to reproduce in preclinical models. However, the advent of three-dimensional culture technologies has opened new perspectives to recapitulate in vitro individualized tumor features and to anticipate treatment efficacy. The generation of lung cancer organoids (LCOs) has encountered greater challenges as compared to organoids derived from other tumors. In the last two years, many efforts have been dedicated to optimizing LCO-based platforms, resulting in improved rates of LCO production, purity, culture timing, and long-term expansion. However, due to the complexity of lung cancer, further advances are required in order to meet clinical needs. Here, we discuss the evolution of LCO technology and the use of LCOs in basic and translational lung cancer research. Although the field of LCOs is still in its infancy, its prospective development will likely lead to new strategies for drug testing and biomarker identification, thus allowing a more personalized therapeutic approach for lung cancer patients.
Deep Neural Network Models for Colon Cancer Screening
Authors: Kavitha Muthu Subash , Gangadaran Prakash , Jackson Aurelia , Venmathi Maran Balu Alagar , Kurita Takio , Ahn Byeong-Cheol
Published: August 2022

Early detection of colorectal cancer can significantly facilitate clinicians’ decision-making and reduce their workload. This can be achieved using automatic systems with endoscopic and histological images. Recently, the success of deep learning has motivated the development of image- and video-based polyp identification and segmentation. Currently, most diagnostic colonoscopy rooms utilize artificial intelligence methods that are considered to perform well in predicting invasive cancer. Convolutional neural network-based architectures, together with image patches and preprocesses are often widely used. Furthermore, learning transfer and end-to-end learning techniques have been adopted for detection and localization tasks, which improve accuracy and reduce user dependence with limited datasets. However, explainable deep networks that provide transparency, interpretability, reliability, and fairness in clinical diagnostics are preferred. In this review, we summarize the latest advances in such models, with or without transparency, for the prediction of colorectal cancer and also address the knowledge gap in the upcoming technology.
Adult Medulloblastoma: Updates on Current Management and Future Perspectives
Authors: Franceschi Enrico , Giannini Caterina , Furtner Julia , Pajtler Kristian W. , Asioli Sofia , Guzman Raphael , Seidel Clemens , Gatto Lidia , Hau Peter
Published: August 2022

Medulloblastoma (MB) is a malignant embryonal tumor of the posterior fossa belonging to the family of primitive neuro-ectodermic tumors (PNET). MB generally occurs in pediatric age, but in 14–30% of cases, it affects the adults, mostly below the age of 40, with an incidence of 0.6 per million per year, representing about 0.4–1% of tumors of the nervous system in adults. Unlike pediatric MB, robust prospective trials are scarce for the post-puberal population, due to the low incidence of MB in adolescent and young adults. Thus, current MB treatments for older patients are largely extrapolated from the pediatric experience, but the transferability and applicability of these paradigms to adults remain an open question. Adult MB is distinct from MB in children from a molecular and clinical perspective. Here, we review the management of adult MB, reporting the recent published literature focusing on the effectiveness of upfront chemotherapy, the development of targeted therapies, and the potential role of a reduced dose of radiotherapy in treating this disease.
TP53 Abnormalities Are Underlying the Poor Outcome Associated with Chromothripsis in Chronic Lymphocytic Leukemia Patients with Complex Karyotype
Authors: Ramos-Campoy Silvia , Puiggros Anna , Kamaso Joanna , Beà Sílvia , Bougeon Sandrine , Larráyoz María José , Costa Dolors , Parker Helen , Rigolin Gian Matteo , Blanco María Laura , Collado Rosa , Ancín Idoya , Salgado Rocío , Moro-García Marco A. , Baumann Tycho , Gimeno Eva , Moreno Carol , Salido Marta , Calvo Xavier , Calasanz María José , Cuneo Antonio , Nguyen-Khac Florence , Oscier David , Haferlach Claudia , Strefford Jonathan C. , Schoumans Jacqueline , Espinet Blanca
Published: August 2022

Chromothripsis (cth) has been associated with a dismal outcome and poor prognosis factors in patients with chronic lymphocytic leukemia (CLL). Despite being correlated with high genome instability, previous studies have not assessed the role of cth in the context of genomic complexity. Herein, we analyzed a cohort of 33 CLL patients with cth and compared them against a cohort of 129 non-cth cases with complex karyotypes. Nine cth cases were analyzed using optical genome mapping (OGM). Patterns detected by genomic microarrays were compared and the prognostic value of cth was analyzed. Cth was distributed throughout the genome, with chromosomes 3, 6 and 13 being those most frequently affected. OGM detected 88.1% of the previously known copy number alterations and several additional cth-related rearrangements (median: 9, range: 3–26). Two patterns were identified: one with rearrangements clustered in the region with cth (3/9) and the other involving both chromothriptic and non-chromothriptic chromosomes (6/9). Cases with cth showed a shorter time to first treatment (TTFT) than non-cth patients (median TTFT: 2 m vs. 15 m; p = 0.013). However, when stratifying patients based on TP53 status, cth did not affect TTFT. Only TP53 maintained its significance in the multivariate analysis for TTFT, including cth and genome complexity defined by genomic microarrays (HR: 1.60; p = 0.029). Our findings suggest that TP53 abnormalities, rather than cth itself, underlie the poor prognosis observed in this subset.
Mutations Affecting Genes in the Proximal T-Cell Receptor Signaling Pathway in Peripheral T-Cell Lymphoma
Authors: Liu Xiaoqian , Ning Jinyao , Liu Xuxiang , Chan Wing C. (John)
Published: August 2022

Peripheral T-cell lymphoma (PTCL) comprises a heterogeneous group of mature T-cell malignancies. Recurrent activating mutations and fusions in genes related to the proximal TCR signaling pathway have been identified in preclinical and clinical studies. This review summarizes the genetic alterations affecting proximal TCR signaling identified from different subgroups of PTCL and the functional impact on TCR signaling and downstream pathways. These genetic abnormalities include mostly missense mutations, occasional indels, and gene fusions involving CD28, CARD11, the GTPase RHOA, the guanine nucleotide exchange factor VAV1, and kinases including FYN, ITK, PLCG1, PKCB, and PI3K subunits. Most of these aberrations are activating mutations that can potentially be targeted by inhibitors, some of which are being tested in clinical trials that are briefly outlined in this review. Finally, we focus on the molecular pathology of recently identified subgroups of PTCL-NOS and highlight the unique genetic profiles associated with PTCL-GATA3.
A Digital Cancer Ecosystem to Deliver Health and Psychosocial Education as Preventive Intervention
Authors: Ciria-Suarez Laura , Costas Laura , Flix-Valle Aida , Serra-Blasco Maria , Medina Joan C. , Ochoa-Arnedo Cristian
Published: August 2022

Health education and psychosocial interventions prevent emotional distress, and the latter has been shown to have an impact on survival. In turn, digital health education interventions may help promote equity by reaching a higher number of cancer patients, both because they avoid journeys to the hospital, by and having a better efficiency. A total of 234 women recently diagnosed with breast cancer in a comprehensive cancer center used the digital ecosystem ICOnnecta’t from March 2019 to March 2021. ICOnnecta’t consists of four care levels, provided to patients according to their level of distress. The second level of this intervention consists of an educational campus, which was analyzed to track users’ interests and their information-seeking behavior. Overall, 99 out of 234 women (42.3%) used the educational campus. There were no significant differences in sociodemographic and clinical variables between the campus users and non-users. Among users, the median number of resources utilized per user was four (interquartile range: 2–9). Emotional and medical resources were the contents most frequently viewed and the audiovisual format the most consulted (p < 0.01). Resources were used mainly within the first three months from enrolment. Users who were guided to visit the virtual campus were more active than spontaneous users. Offering an early holistic health educational platform inside a digital cancer ecosystem, with health professionals involved, can reach more patients, promoting equity in the access of cancer information and prevention, from the very beginning of the disease.
Universal Markers Unveil Metastatic Cancerous Cross-Sections at Nanoscale
Authors: Bakalis Evangelos , Ferraro Angelo , Gavriil Vassilios , Pepe Francesco , Kollia Zoe , Cefalas Alkiviadis-Constantinos , Malapelle Umberto , Sarantopoulou Evangelia , Troncone Giancarlo , Zerbetto Francesco
Published: August 2022

The characterization of cancer histological sections as metastatic, M, or not-metastatic, NM, at the cellular size level is important for early diagnosis and treatment. We present timely warning markers of metastasis, not identified by existing protocols and used methods. Digitized atomic force microscopy images of human histological cross-sections of M and NM colorectal cancer cells were analyzed by multifractal detrended fluctuation analysis and the generalized moments method analysis. Findings emphasize the multifractal character of all samples and accentuate room for the differentiation of M from NM cross-sections. Two universal markers emphatically achieve this goal performing very well: (a) the ratio of the singularity parameters (left/right), which are defined relative to weak/strong fluctuations in the multifractal spectrum, is always greater than 0.8 for NM tissues; and (b) the index of multifractality, used to classify universal multifractals, points to log-normal distribution for NM and to log-Cauchy for M tissues. An immediate large-scale screening of cancerous sections is doable based on these findings.
The Hepatic Pre-Metastatic Niche
Authors: Ormseth Benjamin , Onuma Amblessed , Zhang Hongji , Tsung Allan
Published: August 2022

Primary tumors can communicate with the liver to establish a microenvironment that favors metastatic colonization prior to dissemination, forming what is termed the “pre-metastatic niche” (PMN). Through diverse signaling mechanisms, distant malignancies can both influence hepatic cells directly as well as recruit immune cells into the PMN. The result is a set of changes within the hepatic tissue that increase susceptibility of tumor cell invasion and outgrowth upon dissemination. Thus, the PMN offers a novel step in the traditional metastatic cascade that could offer opportunities for clinical intervention. The involved signaling molecules also offer promise as biomarkers. Ultimately, while the existence of the hepatic PMN is well-established, continued research effort and use of innovative models are required to reach a functional knowledge of PMN mechanisms that can be further targeted.
3D In Vivo Models for Translational Research on Pancreatic Cancer: The Chorioallantoic Membrane (CAM) Model
Authors: Pion Eric , Karnosky Julia , Boscheck Sofie , Wagner Benedikt J. , Schmidt Katharina M. , Brunner Stefan M. , Schlitt Hans J. , Aung Thiha , Hackl Christina , Haerteis Silke
Published: August 2022

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with adverse outcomes that have barely improved over the last decade. About half of all patients present with metastasis at the time of diagnosis, and the 5-year overall survival rate across all stages is only 6%. Innovative in vivo research models are necessary to combat this cancer and to discover novel treatment strategies. The chorioallantoic membrane (CAM) model represents one 3D in vivo methodology that has been used in a large number of studies on different cancer types for over a century. This model is based on a membrane formed within fertilized chicken eggs that contain a dense network of blood vessels. Because of its high cost-efficiency, simplicity, and versatility, the CAM model appears to be a highly valuable research tool in the pursuit of gaining more in-depth insights into PDAC. A summary of the current literature on the usage of the CAM model for the investigation of PDAC was conducted and subdivided into angiogenesis, drug testing, modifications, personalized medicine, and further developments. On this comprehensive basis, further research should be conducted on PDAC in order to improve the abysmal prognosis of this malignant disease.
Pan-Cancer Analysis Reveals SH3TC2 as an Oncogene for Colorectal Cancer and Promotes Tumorigenesis via the MAPK Pathway
Authors: Huang Chengzhi , Yi Hui , Zhou Yue , Zhang Qing , Yao Xueqing
Published: August 2022

SH3 domain and tetrapeptide repeat 2 (SH3TC2) is a protein-encoding gene and has previously been described as a critical signaling hub for neurological disorders. Although increasing evidence supports a vital role of SH3TC2 in the tumorigenesis of various kinds of cancer, no systematic analysis of SH3TC2 is available. The function and mechanism of SH3TC2 in other cancers remain unknown. Thus, this study aimed to analyze SH3TC2 in various kinds of cancer to find its tumorigenic role in one or more specific cancers. In the current study, we analyzed the expression level and prognostic value of SH3TC2 in different tumors in the TCGA-GTEx pan-cancer dataset. Subsequently, the prognostic role and mechanism of SH3TC2 in colorectal cancer (CRC) were further explored via clinical samples and in vitro and in vivo experiments. We observed differential expression of SH3TC2 in colon adenocarcinoma (COAD), acute myeloid leukemia (LAML), READ (rectum adenocarcinoma), SKCM (skin cutaneous melanoma), and TGCT (testicular germ cell tumors). Subsequently, SH3TC2 showed a significant effect on the clinical stage and prognostic value in CRC, LAML, and SKCM. Moreover, we found in the TCGA database and seven GEO datasets that SH3TC2 was significantly highly expressed in tumor tissue. Through enrichment analysis of SH3TC2 and its co-expressed genes, we found that SH3TC2 may play a role in the MAPK signaling pathway. Correlation analysis indicated that SH3TC2 was significantly associated with multiple key factors in the MAPK signaling pathway. Additionally, higher expression of SH3TC2 was found in tumor tissue in our cohort including 40 CRC patients. Overexpression of SH3TC2 may imply poor prognosis. Knockdown of SH3TC2 significantly inhibited tumor invasion, migration, and proliferation. More importantly, knockdown of SH3TC2 inhibited tumor growth in a CRC mouse model. The study preliminarily conducted a pan-cancer study of SH3TC2 and further explored the mechanism of SH3TC2 in CRC. Our research revealed that higher expression of SH3TC2 may promote CRC progression and invasion via the MAPK signaling pathway.
Management and Outcomes in Anal Canal Adenocarcinomas—A Systematic Review
Authors: Taliadoros Vasilis , Rafique Henna , Rasheed Shahnawaz , Tekkis Paris , Kontovounisios Christos
Published: August 2022

(1) Background: Anal canal adenocarcinomas constitute 1% of all gastrointestinal tract cancers. There is a current lack of consensus and NICE guidelines in the United Kingdom regarding the management of this disease. The overall objective was to perform a systematic review on the multitude of practice and subsequent outcomes in this group. (2) Methods: The MEDLINE, EMBASE, EMCARE and CINAHL databases were interrogated between 2011 to 2021. PRISMA guidelines were used to select relevant studies. The primary outcome measure was 5-year overall survival (OS). Secondary outcome measures included both local recurrences (LR) and distant metastases (DM). The Newcastle–Ottawa Scale (NOS) was used to assess the quality of studies retrieved. The study was registered on PROSPERO (338286). (3) Results: Fifteen studies were included. Overall, there were 11,967 participants who were demographically matched. There were 2090 subjects in the largest study and five subjects in the smallest study. Treatment modalities varied from neoadjuvant chemoradiotherapy (CRT), CRT and surgery (CRT + S), surgery then CRT (S + CRT) and surgery only (S). Five-year OS ranged from 30.2% to 91% across the literature. LR rates ranged from 22% to 29%; DM ranged from 6% to 60%. Study heterogeneity precluded meta-analysis. (4) Conclusions: Trimodality treatment with neoadjuvant chemoradiotherapy (CRT) followed by radical surgery of abdominoperineal excision of rectum (APER) appeared to be the most effective approach, giving the best survival outcomes according to the current data.
Machine Learning Improves the Prediction Rate of Non-Curative Resection of Endoscopic Submucosal Dissection in Patients with Early Gastric Cancer
Authors: Yun Hae-Ryong , Huh Cheal Wung , Jung Da Hyun , Lee Gyubok , Son Nak-Hoon , Kim Jie-Hyun , Youn Young Hoon , Park Jun Chul , Shin Sung Kwan , Lee Sang Kil , Lee Yong Chan
Published: August 2022

Non-curative resection (NCR) of early gastric cancer (EGC) after endoscopic submucosal dissection (ESD) can increase the burden of additional treatment and medical expenses. We aimed to develop a machine-learning (ML)-based NCR prediction model for EGC prior to ESD. We obtained data from 4927 patients with EGC who underwent ESD between January 2006 and February 2020. Ten clinicopathological characteristics were selected using extreme gradient boosting (XGBoost) and were used to develop a ML-based model. Dataset was divided into the training and internal validation sets and verified using an external validation set. Sensitivity, specificity, and area under the receiver operating characteristic curve (AUROC) were evaluated. The performance of each model was compared by using the Delong test. A total of 1100 (22.1%) patients were identified as being treated non-curatively with ESD. Seven ML-based NCR prediction models were developed. The performance of NCR prediction was highest in the XGBoost model (AUROC, 0.851; 95% confidence interval, 0.837–0.864). When we compared the prediction performance by the Delong test, XGBoost (p = 0.02) and support vector machine (p = 0.02) models showed a significantly higher performance among the NCR prediction models. We developed an ML model capable of accurately predicting the NCR of EGC before ESD. This ML model can provide useful information for decision-making regarding the appropriate treatment of EGC before ESD.
CD44 Depletion in Glioblastoma Cells Suppresses Growth and Stemness and Induces Senescence
Authors: Kolliopoulos Constantinos , Ali Mohamad Moustafa , Castillejo-Lopez Casimiro , Heldin Carl-Henrik , Heldin Paraskevi
Published: August 2022

Glioblastoma multiforme (GBM) is a lethal brain tumor, characterized by enhanced proliferation and invasion, as well as increased vascularization and chemoresistance. The expression of the hyaluronan receptor CD44 has been shown to correlate with GBM progression and poor prognosis. Here, we sought to elucidate the molecular mechanisms by which CD44 promotes GBM progression by knocking out (KO) CD44, employing CRISPR/Cas9 gene editing in U251MG cells. CD44-depleted cells exhibited an impaired proliferation rate, as shown by the decreased cell numbers, decreased Ki67-positive cell nuclei, diminished phosphorylation of CREB, and increased levels of the cell cycle inhibitor p16 compared to control cells. Furthermore, the CD44 KO cells showed decreased stemness and increased senescence, which was manifested upon serum deprivation. In stem cell-like enriched spheres, RNA-sequencing analysis of U251MG cells revealed a CD44 dependence for gene signatures related to hypoxia, the glycolytic pathway, and G2 to M phase transition. Partially similar results were obtained when cells were treated with the γ-secretase inhibitor DAPT, which inhibits CD44 cleavage and therefore inhibits the release of the intracellular domain (ICD) of CD44, suggesting that certain transcriptional responses are dependent on CD44-ICD. Interestingly, the expression of molecules involved in hyaluronan synthesis, degradation, and interacting matrix proteins, as well as of platelet-derived growth factor (PDGF) isoforms and PDGF receptors, were also deregulated in CD44 KO cells. These results were confirmed by the knockdown of CD44 in another GBM cell line, U2990. Notably, downregulation of hyaluronan synthase 2 (HAS2) impaired the hypoxia-related genes and decreased the CD44 protein levels, suggesting a CD44/hyaluronan feedback circuit contributing to GBM progression.
Tertiary Lymphoid Structures as Mediators of Immunotherapy Response
Authors: Vaghjiani Raj G. , Skitzki Joseph J.
Published: August 2022

Since its first application in the treatment of cancer during the 1800s, immunotherapy has more recently become the leading edge of novel treatment strategies. Even though the efficacy of these agents can at times be predicted by more traditional metrics and biomarkers, often patient responses are variable. TLS are distinct immunologic structures that have been identified on pathologic review of various malignancies and are emerging as important determinants of patient outcome. Their presence, location, composition, and maturity are critically important in a host’s response to malignancy. Because of their unique immunogenic niche, they are also prime candidates, not only to predict and measure the efficacy of immunotherapy agents, but also to be potentially inducible gatekeepers to increase therapeutic efficacy. Herein, we review the mechanistic underpinnings of TLS formation, the data on its relationship to various malignancies, and the emerging evidence for the role of TLS in immunotherapy function.
Environmental Remediation through Catalytic Inhibition of Steel Corrosion by Schiff’s Bases: Electrochemical and Biological Aspects
Authors: Farag Ahmed A. , Toghan Arafat , Mostafa Mohsen S. , Lan Chen , Ge Guanglu
Published: August 2022

The environmental impact of corrosion is very dangerous and consumes much of world’s efforts and funds. This work discusses the safeguarding of the environment, metals, and metal-infra structures by efficient Schiff’s base inhibitors. The corrosion inhibitors [(1E,3E)-N1,N3-dibutyl-1-(thiophen-2-yl)butane-1,3-diimine] (GSB-I) and [(1Z,3Z)-N1,N3-bis(4-methylhexan-2-yl)-1-(thiophen-2-yl)butane-1,3-diimine] (GSB-II) were successfully synthesized and evaluated for the protection of API 5L X65 steel (CS) in 1 M HCl media using electrochemical techniques, SEM/EDS, and quantum chemical calculations. GSB-I and GSB-inhibitory I’s efficiency is proportional to the concentration of the test. In the presence of 1 mM GSB-I and GSB-II, the maximum inhibitory efficiency was determined to be 90.6 and 93.8 percent, respectively. According to potentiodynamic polarization tests, the two compounds are effective inhibitors of mixed-type corrosion. The physisorption and chemisorption of both inhibitors followed the Langmuir adsorption isotherm on CS surfaces. The biological reactivity of both GSB has been examined, and encouraging results have been obtained as antifungal, antibacterial, and biocidal agents against sulfate-reducing bacteria (SRB). In addition, using DFT calculations and molecular dynamic (MD) simulation, the effect of GSB-I and GSB-II molecular configuration on corrosion inhibition behavior in acidic environments was investigated.
The Combined Effect of Heat and Osmotic Stress on Suberization of Arabidopsis Roots
Authors: Leal Ana Rita , Belo Joana , Beeckman Tom , Barros Pedro M. , Oliveira M. Margarida
Published: August 2022

The simultaneous occurrence of heat stress and drought is becoming more regular as a consequence of climate change, causing extensive agricultural losses. The application of either heat or osmotic stress increase cell-wall suberization in different tissues, which may play a role in improving plant resilience. In this work, we studied how the suberization process is affected by the combination of drought and heat stress by following the expression of suberin biosynthesis genes, cell-wall suberization and the chemical composition in Arabidopsis roots. The Arabidopsis plants used in this study were at the onset of secondary root development. At this point, one can observe a developmental gradient in the main root, with primary development closer to the root tip and secondary development, confirmed by the suberized phellem, closer to the shoot. Remarkably, we found a differential response depending on the root zone. The combination of drought and heat stress increased cell wall suberization in main root segments undergoing secondary development and in lateral roots (LRs), while the main root zone, at primary development stage, was not particularly affected. We also found differences in the overall chemical composition of the cell walls in both root zones in response to combined stress. The data gathered showed that, under combined drought and heat stress, Arabidopsis roots undergo differential cell wall remodeling depending on developmental stage, with modifications in the biosynthesis and/or assembly of major cell wall components.
hMRP8-ATTAC Mice: A New Model for Conditional and Reversible Neutrophil Ablation
Authors: Duits Danique E. M. , Salvagno Camilla , Raeven Elisabeth A. M. , Vrijland Kim , Stip Marjolein C. , Hau Cheei-Sing , Kaldenbach Daphne , de Visser Karin E.
Published: August 2022

Neutrophils are not only crucial immune cells for the neutralization of pathogens during infections, but they are also key players in tissue repair and cancer. Several methods are available to investigate the in vivo role of neutrophils in these conditions, including the depletion of neutrophils with neutralizing antibodies against Ly6G, or the blockade of neutrophil recruitment with CXCR2 inhibitors. A limited number of transgenic mouse models were generated that rely on the disruption of genes important for neutrophil development or on the injection of diphtheria toxin to induce neutrophil ablation. However, these methods have various limitations, including a lack of neutrophil specificity, a lack of long-term efficacy, or a lack of the ability to conditionally deplete neutrophils. Therefore, we generated a transgenic mouse model for the inducible and reversible ablation of neutrophils using the ATTAC (Apoptosis Through Targeted Activation of Caspase 8) approach. With the ATTAC strategy, which relies on the expression of the caspase 8-FKBP fusion protein, apoptosis is induced upon administration of a chemical dimerizer (FK506 analogue) that facilitates the dimerization and activation of caspase 8. In order to achieve specific neutrophil depletion, we cloned the ATTAC construct under the human migration inhibitory factor-related protein 8 (hMRP8) promotor. The newly generated hMRP8-ATTAC mice expressed high levels of the transgene in neutrophils, and, as a consequence, dimerizer injection induced an efficient reduction of neutrophil levels in all the organs analyzed under homeostatic conditions. In situations with extensive pressure on the bone marrow to mobilize neutrophils, for instance in the context of cancer, effective neutrophil depletion in this model requires further optimization. In conclusion, we here describe the generation and characterization of a new transgenic model for conditional neutrophil ablation and highlight the need to improve the ATTAC strategy for the depletion of large numbers of rapidly generated short-lived cells, such as neutrophils.
Synthesis and Thermal Behaviour of Calcium Alkyl Phosphates as Bioceramic Precursors
Authors: Tikhonov Andrey , Putlayev Valery
Published: August 2022

Powders of alkyl phosphoric acids and calcium alkyl phosphates with various alkyl chains (butyl, octyl, and dodecyl) have been synthesized. The resulting powders were characterized by X-ray phase analysis, electron microscopy, and thermal analysis. It was shown that the calcium alkyl phosphates correspond to the composition of acid salts of calcium alkyl phosphates Ca(RPO4H)2, data on which are not presented in the literature. The thermal behaviour of calcium alkyl phosphates can be described as a complex phase transformation into biphasic calcium phosphate mixture (of Ca2P2O7 and Ca3(PO4)2) with the increase of the Ca to P ratio in comparison to initial materials. The powders thermally treated in the range of 400–600 °C could be recommended as single precursors of biphasic bioceramics.
Current Trends in the Utilization of Photolysis and Photocatalysis Treatment Processes for the Remediation of Dye Wastewater: A Short Review
Authors: Anisuzzaman S M , Joseph Collin G. , Pang Chuan Kian , Affandi Nur Ammarah , Maruja Sitti Nurazida , Vijayan Veena
Published: August 2022

Development in the textile industry leads to an increased demand for the use of various dyes. Moreover, there is the use of some dyes in the food industry as well as medical diagnostics. Thereby, increased demand for dyes in various fields has resulted in dye-containing wastewater. Only a small portion of the generated wastewater is adequately treated. The rest is usually dumped or otherwise directly discharged into the sewage system, which ultimately enters rivers, lakes, and streams. The handling and disposal of such concentrated wastewater, especially the dye-containing wastewater, is considered to be a major environmental issue from the moment of its generation to its ultimate disposal. Conventional water treatment methods such as flotation, filtration, adsorption, etc., are non-destructive physical separation processes. They only transfer the pollutants to other phases, thereby generating concentrated deposits. The advanced oxidation process (AOP) is one of the most effective emerging methods for the treatment of wastewater containing chemical pollutants. The method involves the formation and interaction of highly reactive hydroxyl radicals under suitable activation conditions. These radicals are non-selective and efficient for the destruction and eventual mineralization of recalcitrant organic pollutants. This review aims at the pros and cons of using photocatalysis as an efficient AOP to degrade dye-containing wastewater.