bluuebunny/crossref_metadata_2025 huggingface dataset:
From Regulating Emotions to Less Lonely Screen Time: Parents’ Qualitative Perspectives of the Benefits and Challenges of Adolescent Pet Companionship
Authors: Charmaraman Linda , Cobas Stephanie , Weed Jules , Gu Quan , Kiel Elizabeth , Chin Holly , Gramajo Alyssa , Mueller Megan K.
Published: May 2022

Adolescence is a prime developmental period to explore human–pet relationships, particularly given that teens are often relying less on their families, and more on other attachment figures such as peers and pets. However, most research on pet companionship is conducted with adults and young children. Moreover, lived experiences around having pets in households with adolescents are underexplored, particularly from parents’ perspectives. This qualitative interview study of 31 parents/guardians in the Northeast U.S. explored perceptions of the benefits and challenges of having pets for their adolescent’s well-being as well as how adolescents affected their pet’s well-being. Our three main themes for perceived benefits of pets included social (e.g., reducing anxiety), physical (e.g., screen time companionship), and emotional (e.g., regulation of difficult emotions such as anger, loneliness). Challenges to adolescent well-being included such social topics as family tension around unevenly shared responsibilities, physical themes such as problematic animal behaviors, and emotional themes related to grieving the passing of pets. We offer a developmental systems approach to understanding pets within adolescent families, noting future directions for developing family interventions to improve pet–adolescent interactions given the demands of child and pet upbringing during adolescence.
Modeling and Measuring the Leaked-Air Rate into the Insulation Layer of a Single-Aisle Aircraft Cabin
Authors: Zhang Tengfei (Tim) , Dong Jinsong , Liu Sumei
Published: May 2022

Leaked air from an aircraft cabin into its envelope walls through cracks can lead to a large amount of moisture condensation on inner shell skins and in insulation layers. The leaked-air rate is subject to the stack pressure difference and the geometry of the cracks. So far, the impacts of the crack sizes and positions, and the flight conditions on the resulting leaked-air rate have been unclear. This investigation adopts validated computational fluid dynamics (CFD) to model leaked flow, pressure, and temperature distribution in a single-aisle aircraft cabin. Impacts of the flight cruising altitude, crack size and position, and flow blocker on the leaked-air rate were examined. In addition, measurements were conducted in a reduced-scale cabin mockup in an environmental chamber to mimic flight conditions. Obtained test data were adopted to validate CFD modeling. Results reveal that a higher cruising altitude of a flight results in greater leaked-air rate from the cabin to the envelope walls due to the larger temperature difference. The smaller the crack size was, the lower the leaked-air rate. In addition, more cracks farther away from the neutral plane lead to a greater leaked-air rate. A flow blocker in the middle of the insulation layer reduced the leaked-air rate by 34.5%.
The Proportion of Occupationally Related Cholangiocarcinoma: A Tertiary Hospital Study in Northeastern Thailand
Authors: Seeherunwong Anantapat , Chaiear Naesinee , Khuntikeo Narong , Ekpanyaskul Chatchai
Published: May 2022

Northeastern Thailand registers the highest worldwide incidence of cholangiocarcinoma (CCA). Most of the cases are associated with liver flukes, while unknown causes comprise approximately 10–30% of cases, and these could be due to occupational exposures. Our aim was to determine the magnitude of occupational causes of CCA in a tertiary hospital in northeastern Thailand. We conducted a cross-sectional study with a sample of 220 patients between March and November 2021. Descriptive statistics were used to analyze the findings. Clinical information and telephone interviews were used to explore significant occupational histories. An occupational consensus meeting was held with two occupational physicians, an industrial hygienist, and a hepatobiliary surgeon to decide on the final diagnosis. The response rate was 90.9% (200/220). Based on the medical records and telephone interviews, researchers found that 11 participants had significant exposure. After occupational consensus, it was agreed that the eleven had possible occupational causes, 5.5% (11/200)–54.5% (6/11) being due to asbestos fibers, 45.5% (5/11) due to dichloromethane, and 9.1% (1/11) due to 1,2-dichloropropane. Only 4% (8/200) had occupational histories collected by their treating physicians. Taken together, occupationally related CCA appears to have been underestimated, so improving occupational history taking is needed to properly identify and classify work-related CCA—both for patient treatment and occupational hazard prevention.
Feasibility of Rehabilitation during Chemoradiotherapy among Patients with Stage III Non-Small Cell Lung Cancer: A Proof-of-Concept Study
Authors: Voorn Melissa J. J. , Bongers Bart C. , van Kampen-van den Boogaart Vivian E. M. , Driessen Elisabeth J. M. , Janssen-Heijnen Maryska L. G.
Published: May 2022

Rehabilitation during chemoradiotherapy (CHRT) might (partly) prevent reduction in physical fitness and nutritional status and could improve treatment tolerance in patients with stage III non-small cell lung cancer (NSCLC). The aim of this proof-of-concept study was to investigate the feasibility of a multimodal program for rehabilitation during CHRT. A home-based multimodal rehabilitation program (partly supervised moderate-intensity physical exercise training and nutritional support) during CHRT was developed in collaboration with patients with stage III NSCLC and specialized healthcare professionals. A predetermined number of six patients with stage III NSCLC (aged > 50 years) who underwent CHRT and participated in this program were monitored in detail to assess its feasibility for further development and optimization of the program. The patient’s level of physical functioning (e.g., cardiopulmonary exercise test, six-minute walking test, handgrip strength, body mass index, fat free mass index, energy and protein intake) was evaluated in order to provide personalized advice regarding physical exercise training and nutrition. The program appeared feasible and well-tolerated. All six included patients managed to perform the assessments. Exercise session adherence was high in five patients and low in one patient. The performed exercise intensity was lower than prescribed for all patients. Patients were motivated to complete the home-based rehabilitation program during CHRT. Preliminary effects on physical and nutritional parameters revealed relatively stable values throughout CHRT, with inter-individual variation. Supervised and personalized rehabilitation in patients with stage III NSCLC undergoing CHRT seems feasible when the intensity of the physical exercise training was adjusted to the possibilities and preferences of the patients. Future research should investigate the feasibility of a supervised and personalized rehabilitation program during CHRT with a low-to-moderate exercise intensity with the aim to prevent physical decline during CHRT.
Urine Cell-Free MicroRNAs in Localized Prostate Cancer Patients
Authors: Koh Yoko , Bustos Matias A. , Moon Jamie , Gross Rebecca , Ramos Romela Irene , Ryu Suyeon , Choe Jane , Lin Selena Y. , Allen Warren M. , Krasne David L. , Wilson Timothy G. , Hoon Dave S. B.
Published: May 2022

Prostate cancer (PCa) is the most common cancer in men. Prostate-specific antigen screening is recommended for the detection of PCa. However, its specificity is limited. Thus, there is a need to find more reliable biomarkers that allow non-invasive screening for early-stage PCa. This study aims to explore urine microRNAs (miRs) as diagnostic biomarkers for PCa. We assessed cell-free miR (cfmiR) profiles of urine and plasma samples from pre- and post-operative PCa patients (n = 11) and normal healthy donors (16 urine and 24 plasma) using HTG EdgeSeq miRNA Whole Transcriptome Assay based on next-generation sequencing. Furthermore, tumor-related miRs were detected in formalin-fixed paraffin-embedded tumor tissues obtained from patients with localized PCa. Specific cfmiRs signatures were found in urine samples of localized PCa patients using differential expression analysis. Forty-two cfmiRs that were detected were common to urine, plasma, and tumor samples. These urine cfmiRs may have potential utility in diagnosing early-stage PCa and complementing or improving currently available PCa screening assays. Future studies may validate the findings.
Impact of Positive Lymph Nodes and Resection Margin Status on the Overall Survival of Patients with Resected Perihilar Cholangiocarcinoma: The ENSCCA Registry
Authors: Nooijen Lynn E. , Banales Jesus M. , de Boer Marieke T. , Braconi Chiara , Folseraas Trine , Forner Alejandro , Holowko Waclaw , Hoogwater Frederik J. H. , Klümpen Heinz-Josef , Groot Koerkamp Bas , Lamarca Angela , La Casta Adelaida , López-López Flora , Izquierdo-Sánchez Laura , Scheiter Alexander , Utpatel Kirsten , Swijnenburg Rutger-Jan , Kazemier Geert , Erdmann Joris I.
Published: May 2022

Background: Lymph node metastasis and positive resection margins have been reported to be major determinants of overall survival (OS) and poor recurrence-free survival (RFS) for patients who underwent resection for perihilar cholangiocarcinoma (pCCA). However, the prognostic value of positive lymph nodes independently from resection margin status on OS has not been evaluated. Methods: From the European Cholangiocarcinoma (ENSCCA) registry, patients who underwent resection for pCCA between 1994 and 2021 were included in this retrospective cohort study. The primary outcome was OS stratified for resection margin and lymph node status. The secondary outcome was recurrence-free survival. Results: A total of 325 patients from 11 different centers and six European countries were included. Of these, 194 (59.7%) patients had negative resection margins. In 113 (34.8%) patients, positive lymph nodes were found. Lymph node status, histological grade, and ECOG performance status were independent prognostic factors for survival. The median OS for N0R0, N0R1, N+R0, and N+R1 was 38, 30, 18, and 12 months, respectively (p < 0.001). Conclusion: These data indicate that in the presence of positive regional lymph nodes, resection margin status does not determine OS or RFS in patients with pCCA. Achieving negative margins in patients with positive nodes should not come at the expense of more extensive surgery and associated higher mortality.
Liver-Directed Concurrent Chemoradiotherapy versus Sorafenib in Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis
Authors: Kim Jina , Byun Hwa Kyung , Kim Tae Hyung , Kim Sun Il , Kim Beom Kyung , Kim Seung Up , Park Jun Yong , Kim Do Young , Seong Jinsil
Published: May 2022

This study aimed to investigate the efficacy of liver-directed concurrent chemoradiotherapy (LD-CCRT) compared with sorafenib in patients with liver-confined locally advanced hepatocellular carcinoma (HCC) presenting portal vein tumor thrombosis (PVTT). This single institute retrospective cohort study included patients treated with sorafenib or LD-CCRT between 2005 and 2016. Patients with extrahepatic disease and those without PVTT were excluded, leaving 28 and 448 patients in the sorafenib and LD-CCRT groups, respectively. Propensity score matching was performed to balance the differences in clinical features between the two groups. At baseline, the sorafenib group presented higher incidences of unfavorable clinical features, including type III-IV PVTT (53.6% vs. 30.6%, p = 0.048) and bilateral disease extent (64.3% vs. 31.5%, p = 0.001), than the LD-CCRT group. A total of 27 patients from the sorafenib group and 52 patients from the LD-CCRT group were matched. At a median follow-up of 73 months, the median overall survival (OS) was 4.3 and 9.8 months in the sorafenib and LD-CCRT groups, respectively (p = 0.002). Patients with PVTT type II and higher benefited more from LD-CCRT in terms of OS. The Cox proportional hazard model showed that LD-CCRT was a significant prognostic factor for OS. One patient from the sorafenib group and seven patients from the LD-CCRT group underwent curative surgical treatment. Patients who underwent surgical treatment had significantly longer OS. In conclusion, LD-CCRT showed superior survival outcomes to sorafenib in HCC patients with PVTT. LD-CCRT needs further consideration for its substantial local tumor control that can enable curative surgical treatment in selected patients.
Frequent 4EBP1 Amplification Induces Synthetic Dependence on FGFR Signaling in Cancer
Authors: Mohan Prathibha , Pasion Joyce , Ciriello Giovanni , Lailler Nathalie , de Stanchina Elisa , Viale Agnes , van den Berg Anke , Diepstra Arjan , Wendel Hans-Guido , Sanghvi Viraj R. , Singh Kamini
Published: May 2022

The eIF4E translation initiation factor has oncogenic properties and concordantly, the inhibitory eIF4E-binding protein (4EBP1) is considered a tumor suppressor. The exact molecular effects of 4EBP1 activation in cancer are still unknown. Surprisingly, 4EBP1 is a target of genomic copy number gains (Chr. 8p11) in breast and lung cancer. We noticed that 4EBP1 gains are genetically linked to gains in neighboring genes, including WHSC1L1 and FGFR1. Our results show that FGFR1 gains act to attenuate the function of 4EBP1 via PI3K-mediated phosphorylation at Thr37/46, Ser65, and Thr70 sites. This implies that not 4EBP1 but instead FGFR1 is the genetic target of Chr. 8p11 gains in breast and lung cancer. Accordingly, these tumors show increased sensitivity to FGFR1 and PI3K inhibition, and this is a therapeutic vulnerability through restoring the tumor-suppressive function of 4EBP1. Ribosome profiling reveals genes involved in insulin signaling, glucose metabolism, and the inositol pathway to be the relevant translational targets of 4EBP1. These mRNAs are among the top 200 translation targets and are highly enriched for structure and sequence motifs in their 5′UTR, which depends on the 4EBP1-EIF4E activity. In summary, we identified the translational targets of 4EBP1-EIF4E that facilitate the tumor suppressor function of 4EBP1 in cancer.
The Immunological Contribution of a Novel Metabolism-Related Signature to the Prognosis and Anti-Tumor Immunity in Cervical Cancer
Authors: Yu Sihui , Li Xi , Ma Mingjun , Yang Rui , Zhang Jiawen , Wu Sufang
Published: May 2022

Cervical cancer is the most frequently diagnosed malignancy in the female reproductive system. Conventional stratification of patients based on clinicopathological characters has gradually been outpaced by a molecular profiling strategy. Our study aimed to identify a reliable metabolism-related predictive signature for the prognosis and anti-tumor immunity in cervical cancer. In this study, we extracted five metabolism-related hub genes, including ALOX12B, CA9, FAR2, F5 and TDO2, for the establishment of the risk score model. The Kaplan-Meier curve suggested that patients with a high-risk score apparently had a worse prognosis in the cervical cancer training cohort (TCGA, n = 304, p < 0.0001), validation cohort (GSE44001, n = 300, p = 0.0059) and pan-cancer cohorts (including nine TCGA tumors). Using a gene set enrichment analysis (GSEA), we observed that the model was correlated with various immune-regulation-related pathways. Furthermore, pan-cancer cohorts and immunohistochemical analysis showed that the infiltration of tumor infiltrating lymphocytes (TILs) was lower in the high-score group. Additionally, the model could also predict the prognosis of patients with cervical cancer based on the expression of immune checkpoints (ICPs) in both the discovery and validation cohorts. Our study established and validated a metabolism-related prognostic model, which might improve the accuracy of predicting the clinical outcome of patients with cervical cancer and provide guidance for personalized treatment.
Current Trend of Artificial Intelligence Patents in Digital Pathology: A Systematic Evaluation of the Patent Landscape
Authors: Ailia Muhammad Joan , Thakur Nishant , Abdul-Ghafar Jamshid , Jung Chan Kwon , Yim Kwangil , Chong Yosep
Published: May 2022

The integration of digital pathology (DP) with artificial intelligence (AI) enables faster, more accurate, and thorough diagnoses, leading to more precise personalized treatment. As technology is advancing rapidly, it is critical to understand the current state of AI applications in DP. Therefore, a patent analysis of AI in DP is required to assess the application and publication trends, major assignees, and leaders in the field. We searched five major patent databases, namely, those of the USPTO, EPO, KIPO, JPO, and CNIPA, from 1974 to 2021, using keywords such as DP, AI, machine learning, and deep learning. We discovered 6284 patents, 523 of which were used for trend analyses on time series, international distribution, top assignees; word cloud analysis; and subject category analyses. Patent filing and publication have increased exponentially over the past five years. The United States has published the most patents, followed by China and South Korea (248, 117, and 48, respectively). The top assignees were Paige.AI, Inc. (New York City, NY, USA) and Siemens, Inc. (Munich, Germany) The primary areas were whole-slide imaging, segmentation, classification, and detection. Based on these findings, we expect a surge in DP and AI patent applications focusing on the digitalization of pathological images and AI technologies that support the vital role of pathologists.
Unsupervised Deep Learning Registration of Uterine Cervix Sequence Images
Authors: Guo Peng , Xue Zhiyun , Angara Sandeep , Antani Sameer K.
Published: May 2022

During a colposcopic examination of the uterine cervix for cervical cancer prevention, one or more digital images are typically acquired after the application of diluted acetic acid. An alternative approach is to acquire a sequence of images at fixed intervals during an examination before and after applying acetic acid. This approach is asserted to be more informative as it can capture dynamic pixel intensity variations on the cervical epithelium during the aceto-whitening reaction. However, the resulting time sequence images may not be spatially aligned due to the movement of the cervix with respect to the imaging device. Disease prediction using automated visual evaluation (AVE) techniques using multiple images could be adversely impacted without correction for this misalignment. The challenge is that there is no registration ground truth to help train a supervised-learning-based image registration algorithm. We present a novel unsupervised registration approach to align a sequence of digital cervix color images. The proposed deep-learning-based registration network consists of three branches and processes the red, green, and blue (RGB, respectively) channels of each input color image separately using an unsupervised strategy. Each network branch consists of a convolutional neural network (CNN) unit and a spatial transform unit. To evaluate the registration performance on a dataset that has no ground truth, we propose an evaluation strategy that is based on comparing automatic cervix segmentation masks in the registered sequence and the original sequence. The compared segmentation masks are generated by a fine-tuned transformer-based object detection model (DeTr). The segmentation model achieved Dice/IoU scores of 0.917/0.870 and 0.938/0.885, which are comparable to the performance of our previous model in two datasets. By comparing our segmentation on both original and registered time sequence images, we observed an average improvement in Dice scores of 12.62% following registration. Further, our approach achieved higher Dice and IoU scores and maintained full image integrity compared to a non-deep learning registration method on the same dataset.
Nuclear Receptor Coregulators in Hormone-Dependent Cancers
Authors: Jafari Hedieh , Hussain Shahid , Campbell Moray J.
Published: May 2022

Nuclear receptors (NRs) function collectively as a transcriptional signaling network that mediates gene regulatory actions to either maintain cellular homeostasis in response to hormonal, dietary and other environmental factors, or act as orphan receptors with no known ligand. NR complexes are large and interact with multiple protein partners, collectively termed coregulators. Coregulators are essential for regulating NR activity and can dictate whether a target gene is activated or repressed by a variety of mechanisms including the regulation of chromatin accessibility. Altered expression of coregulators contributes to a variety of hormone-dependent cancers including breast and prostate cancers. Therefore, understanding the mechanisms by which coregulators interact with and modulate the activity of NRs provides opportunities to develop better prognostic and diagnostic approaches, as well as novel therapeutic targets. This review aims to gather and summarize recent studies, techniques and bioinformatics methods used to identify distorted NR coregulator interactions that contribute as cancer drivers in hormone-dependent cancers.
Comparing Outcomes of Oligometastases Treated with Hypofractionated Image-Guided Radiotherapy (HIGRT) with a Simultaneous Integrated Boost (SIB) Technique versus Metastasis Alone: A Multi-Institutional Analysis
Authors: Shenker Rachel F. , Price Jeremy G. , Jacobs Corbin D. , Palta Manisha , Czito Brian G. , Mowery Yvonne M. , Kirkpatrick John P. , Boyer Matthew J. , Oyekunle Taofik , Niedzwiecki Donna , Song Haijun , Salama Joseph K.
Published: May 2022

Purpose: We previously reported on the clinical outcomes of treating oligometastases with radiation using an elective simultaneous integrated boost technique (SIB), delivering higher doses to known metastases and reduced doses to adjacent bone or nodal basins. Here we compare outcomes of oligometastases receiving radiation targeting metastases alone (MA) versus those treated via an SIB. Methods: Oligometastatic patients with ≤5 active metastases treated with either SIB or MA radiation at two institutions from 2013 to 2019 were analyzed retrospectively for treatment-related toxicity, pain control, and recurrence patterns. Tumor metastasis control (TMC) was defined as an absence of progression in the high dose planning target volume (PTV). Marginal recurrence (MR) was defined as recurrence outside the elective PTV but within the adjacent bone or nodal basin. Distant recurrence (DR) was defined as any recurrence that is not within the PTV or surrounding bone or nodal basin. The outcome rates were estimated using the Kaplan–Meier method and compared between the two techniques using the log-rank test. Results: 101 patients were treated via an SIB to 90 sites (58% nodal and 42% osseous) and via MA radiation to 46 sites (22% nodal and 78% osseous). The median follow-up among surviving patients was 24.6 months (range 1.4–71.0). Of the patients treated to MA, the doses ranged from 18 Gy in one fraction (22%) to 50 Gy in 10 fractions (50%). Most patients treated with an SIB received 50 Gy to the treated metastases and 30 Gy to the elective PTV in 10 fractions (88%). No acute grade ≥3 toxicities occurred in either cohort. Late grade ≥3 toxicity occurred in 3 SIB patients (vocal cord paralysis and two vertebral body compression), all related to the high dose PTV and not the elective volume. There was similar crude pain relief between cohorts. The MR-free survival rate at 2 years was 87% (95% CI: 70%, 95%) in the MA group and 98% (95% CI: 87%, 99%) in the SIB group (p = 0.07). The crude TMC was 89% (41/46) in the MA group and 94% (85/90) in the SIB group. There were no significant differences in DR-free survival (65% (95% CI: 55–74%; p = 0.24)), disease-free survival (60% (95% CI: 40–75%; p = 0.40)), or overall survival (88% (95% CI: 73–95%; p = 0.26)), between the MA and SIB cohorts. Conclusion: Both SIB and MA irradiation of oligometastases achieved high rates of TMC and similar pain control, with a trend towards improved MR-free survival for oligometastases treated with an SIB. Further investigation of this technique with prospective trials is warranted.
Ligustilide Inhibits Tumor Angiogenesis by Downregulating VEGFA Secretion from Cancer-Associated Fibroblasts in Prostate Cancer via TLR4
Authors: Ma Jing , Chen Xu , Chen Yumo , Tao Ning , Qin Zhihai
Published: May 2022

CAFs secrete VEGFA in the tumor microenvironment to induce angiogenesis and promote tumor growth. The downregulation of VEGFA secretion from CAFs helps block angiogenesis and exerts an anti-tumor effect. In vivo experiments showed that the angiogenesis of the tumor-bearing mice in the ligustilide group was significantly reduced. The results of MTT, tube formation, Transwell and scratch experiments showed that ligustilide did not affect the proliferation of HUVECs in a certain concentration range (<60 μM), but it inhibited the proliferation, tube formation and migration of HUVECs induced by CAFs. At this concentration, ligustilide did not inhibit CAF proliferation. The qPCR and WB results revealed that ligustilide downregulated the level of VEGFA in CAFs via the TLR4-ERK/JNK/p38 signaling pathway, and the effect was attenuated by blockers of the above molecules. Ligustilide also downregulated the autocrine VEGFA of HUVECs induced by CAFs, which inhibited angiogenesis more effectively. In addition, ligustilide inhibited glycolysis and HIF-1 expression in CAFs. Overall, ligustilide downregulated the VEGFA level in CAFs via the TLR4-ERK/JNK/p38 signaling pathway and inhibited the promotion of angiogenesis. This study provides a new strategy for the anti-tumor effect of natural active molecules, namely, blockade of angiogenesis, and provides a new candidate molecule for blocking angiogenesis in the tumor microenvironment.
The Role of Indocyanine Green Fluorescence in Rectal Cancer Robotic Surgery: A Narrative Review
Authors: Belloni Elena , Muttillo Edoardo Maria , Di Saverio Salomone , Gasparrini Marcello , Brescia Antonio , Nigri Giuseppe
Published: May 2022

Background: In rectal cancer surgery, anastomotic leakage (AL) remains the most feared complication, with a frequency of up to 30% in non-high-volume centers. The preservation of proper vascularization is a key factor for successful anastomosis. The use of fluorescence with indocyanine green (ICG) as an intraoperative method to verify optimal perfusion is becoming an interesting tool in rectal surgery. Today, robotic surgery, together with the use of the intraoperative evaluation of the perfusion with ICG, could be a real strategy to deal with AL, allowing for a more delicate and less traumatic surgical technique. This strategy may allow for an extremely accurate surgery, and for optimal control of the proper vascularization of the rectum. Methods: The purpose of this descriptive review is to analyze the impact of fluorescence and robotic surgery on short-term surgical outcomes for rectal cancer. Results: We performed a systematic literature search using the PubMed, Embase and Cochrane library databases. The primary endpoints were to evaluate the application of ICG fluorescence in robotic rectal surgery and the rate of anastomotic leakage when using these technological implementations. The secondary endpoints were to evaluate the dosage of ICG and the timing of application by different surgeons. Conclusions: ICG fluorescence is an inexpensive and quick method to assess bowel perfusion, providing immediate feedback to the surgeon, even if its role has not been proven. A quantitative system must be systematically introduced to minimize the subjectiveness of the visualized image.
Epidemiology of Glioblastoma Multiforme–Literature Review
Authors: Grochans Szymon , Cybulska Anna Maria , Simińska Donata , Korbecki Jan , Kojder Klaudyna , Chlubek Dariusz , Baranowska-Bosiacka Irena
Published: May 2022

Glioblastoma multiforme (GBM) is one of the most aggressive malignancies, with a median overall survival of approximately 15 months. In this review, we analyze the pathogenesis of GBM, as well as epidemiological data, by age, gender, and tumor location. The data indicate that GBM is the higher-grade primary brain tumor and is significantly more common in men. The risk of being diagnosed with glioma increases with age, and median survival remains low, despite medical advances. In addition, it is difficult to determine clearly how GBM is influenced by stimulants, certain medications (e.g., NSAIDs), cell phone use, and exposure to heavy metals.
Gold Glyconanoparticles Combined with 91–99 Peptide of the Bacterial Toxin, Listeriolysin O, Are Efficient Immunotherapies in Experimental Bladder Tumors
Authors: Terán-Navarro Hector , Zeoli Andrea , Salines-Cuevas David , Marradi Marco , Montoya Noemi , Gonzalez-Lopez Elena , Ocejo-Vinyals Javier Gonzalo , Dominguez-Esteban Mario , Gutierrez-Baños Jose Luis , Campos-Juanatey Felix , Yañez-Diaz Sonsoles , Garcia-Castaño Almudena , Rivera Fernando , Duran Ignacio , Alvarez-Dominguez Carmen
Published: May 2022

This study presents proof of concept assays to validate gold nanoparticles loaded with the bacterial peptide 91–99 of the listeriolysin O toxin (GNP-LLO91–99 nanovaccines) as immunotherapy for bladder tumors. GNP-LLO91–99 nanovaccines showed adjuvant abilities as they induce maturation and activation of monocyte-derived dendritic cells (MoDCs) to functional antigen-presenting cells in healthy donors and patients with melanoma or bladder cancer (BC), promoting a Th1 cytokine pattern. GNP-LLO91–99 nanovaccines were also efficient dendritic cell inducers of immunogenic tumor death using different bladder and melanoma tumor cell lines. The establishment of a pre-clinical mice model of subcutaneous BC confirmed that a single dose of GNP-LLO91–99 nanovaccines reduced tumor burden 4.7-fold and stimulated systemic Th1-type immune responses. Proof of concept assays validated GNP-LLO91–99 nanovaccines as immunotherapy by comparison to anti-CTLA-4 or anti-PD-1 antibodies. In fact, GNP-LLO91–99 nanovaccines increased percentages of CD4+ and CD8+ T cells, B cells, and functional antigen-presenting DCs in tumor-infiltrated lymphocytes, while they reduced the levels of myeloid-derived suppressor cells (MDSC) and suppressor T cells (Treg). We conclude that GNP-LLO91–99 nanovaccines can work as monotherapies or combinatory immunotherapies with anti-CTLA-4 or anti-PD-1 antibodies for solid tumors with high T cell infiltration, such as bladder cancer or melanoma.
Identification of Carcinogenesis and Tumor Progression Processes in Pancreatic Ductal Adenocarcinoma Using High-Throughput Proteomics
Authors: Trilla-Fuertes Lucía , Gámez-Pozo Angelo , Lumbreras-Herrera María Isabel , López-Vacas Rocío , Heredia-Soto Victoria , Ghanem Ismael , López-Camacho Elena , Zapater-Moros Andrea , Miguel María , Peña-Burgos Eva M. , Palacios Elena , De Uribe Marta , Guerra Laura , Dittmann Antje , Mendiola Marta , Fresno Vara Juan Ángel , Feliu Jaime
Published: May 2022

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with an overall 5-year survival rate of just 5%. A better understanding of the carcinogenesis processes and the mechanisms of the progression of PDAC is mandatory. Fifty-two PDAC patients treated with surgery and adjuvant therapy, with available primary tumors, normal tissue, preneoplastic lesions (PanIN), and/or lymph node metastases, were selected for the study. Proteins were extracted from small punches and analyzed by LC-MS/MS using data-independent acquisition. Proteomics data were analyzed using probabilistic graphical models, allowing functional characterization. Comparisons between groups were made using linear mixed models. Three proteomic tumor subtypes were defined. T1 (32% of patients) was related to adhesion, T2 (34%) had metabolic features, and T3 (34%) presented high splicing and nucleoplasm activity. These proteomics subtypes were validated in the PDAC TCGA cohort. Relevant biological processes related to carcinogenesis and tumor progression were studied in each subtype. Carcinogenesis in the T1 subtype seems to be related to an increase of adhesion and complement activation node activity, whereas tumor progression seems to be related to nucleoplasm and translation nodes. Regarding the T2 subtype, it seems that metabolism and, especially, mitochondria act as the motor of cancer development. T3 analyses point out that nucleoplasm, mitochondria and metabolism, and extracellular matrix nodes could be involved in T3 tumor carcinogenesis. The identified processes were different among proteomics subtypes, suggesting that the molecular motor of the disease is different in each subtype. These differences can have implications for the development of future tailored therapeutic approaches for each PDAC proteomics subtype.
Role of Pre-Operative Brain Imaging in Patients with NSCLC Stage I: A Retrospective, Multicenter Analysis
Authors: Azenha Luis Filipe , Bertoglio Pietro , Kestenholz Peter , Gonzalez Michel , Pal Matyas , Krueger Thorsten , Redwan Bassam , Koesek Volkan , Masri Eyad Al , Miyazaki Takuro , Beigee Farahnaz Sadegh , Bedetti Benedetta , Schnorr Philipp , Schmidt Joachim , Zardo Patrick , Boschetti Laura , Schumann Sven Oliver , Minervini Fabrizio
Published: May 2022

Background: Lung cancer is the worldwide leading oncological cause of death in both genders combined and accounts for around 40–50% of brain metastases in general. In early-stage lung cancer, the incidence of brain metastases is around 3%. Since the early detection of asymptomatic cerebral metastases is of prognostic value, the aim of this study was to analyze the incidence of brain metastases in early-stage lung cancer and identify possible risk factors. Methods: We conducted a retrospective multicentric analysis of patients with Stage I (based on T and N stage only) Non-Small Cell Lung Cancer (NSCLC) who had received preoperative cerebral imaging in the form of contrast-enhanced CT or MRI. Patients with a history of NSCLC, synchronous malignancy, or neurological symptoms were excluded from the study. Analyzed variables were gender, age, tumor histology, cerebral imaging findings, smoking history, and tumor size. Results were expressed as mean with standard deviation or median with range. Results: In total, 577 patients were included in our study. Eight (1.4%) patients were found to have brain metastases in preoperative brain imaging. Tumor histology was adenocarcinoma in all eight cases. Patients were treated with radiotherapy (five), surgical resection (two), or both (one) prior to thoracic surgical treatment. Other than tumor histology, no statistically significant characteristics were found to be predictive of brain metastases. Conclusion: Given the low incidence of brain metastases in patients with clinical Stage I NSCLC, brain imaging in this cohort could be avoided.
Possible Role of Insulin-Degrading Enzyme in the Physiopathology of Retinitis Pigmentosa
Authors: Sánchez-Cruz Alonso , Hernández-Fuentes María D. , Murillo-Gómez Cayetana , de la Rosa Enrique J. , Hernández-Sánchez Catalina
Published: May 2022

Insulin-degrading enzyme (IDE) was named after its role as a proteolytic enzyme of insulin. However, recent findings suggest that IDE is a widely expressed, multitask protein, with both proteolytic and non-proteolytic functions. Here, we characterize the expression of IDE in the mammalian retina in both physiological and pathological conditions. We found that IDE was enriched in cone inner segments. IDE levels were downregulated in the dystrophic retina of several mouse models of retinitis pigmentosa carrying distinct mutations. In rd10 mice, a commonly studied mouse model of retinitis pigmentosa, treatment with an IDE activator (a synthetic peptide analog of preimplantation factor) delayed loss of visual function and preserved photoreceptor cells. Together, these results point to potential novel roles for IDE in retinal physiology and disease, further extending the list of diverse functions attributed to this enzyme.
Pathogenic T-Cell Responses in Immune-Mediated Glomerulonephritis
Authors: Linke Alexandra , Tiegs Gisa , Neumann Katrin
Published: May 2022

Glomerulonephritis (GN) comprises a group of immune-mediated kidney diseases affecting glomeruli and the tubulointerstitium. Glomerular crescent formation is a histopathological characteristic of severe forms of GN, also referred to as crescentic GN (cGN). Based on histological findings, cGN includes anti-neutrophil cytoplasmic antibody (ANCA)-associated GN, a severe form of ANCA-associated vasculitis, lupus nephritis associated with systemic lupus erythematosus, Goodpasture’s disease, and IgA nephropathy. The immunopathogenesis of cGN is associated with activation of CD4+ and CD8+ T cells, which particularly accumulate in the periglomerular and tubulointerstitial space but also infiltrate glomeruli. Clinical observations and functional studies in pre-clinical animal models provide evidence for a pathogenic role of Th1 and Th17 cell-mediated immune responses in cGN. Emerging evidence further argues that CD8+ T cells have a role in disease pathology and the mechanisms of activation and function of recently identified tissue-resident CD4+ and CD8+ T cells in cGN are currently under investigation. This review summarizes the mechanisms of pathogenic T-cell responses leading to glomerular damage and renal inflammation in cGN. Advanced knowledge of the underlying immune mechanisms involved with cGN will enable the identification of novel therapeutic targets for the replacement or reduction in standard immunosuppressive therapy or the treatment of refractory disease.
Single-Cell and Single-Nucleus RNAseq Analysis of Adult Neurogenesis
Authors: Kalinina Alena , Lagace Diane
Published: May 2022

The complexity of adult neurogenesis is becoming increasingly apparent as we learn more about cellular heterogeneity and diversity of the neurogenic lineages and stem cell niches within the adult brain. This complexity has been unraveled in part due to single-cell and single-nucleus RNA sequencing (sc-RNAseq and sn-RNAseq) studies that have focused on adult neurogenesis. This review summarizes 33 published studies in the field of adult neurogenesis that have used sc- or sn-RNAseq methods to answer questions about the three main regions that host adult neural stem cells (NSCs): the subventricular zone (SVZ), the dentate gyrus (DG) of the hippocampus, and the hypothalamus. The review explores the similarities and differences in methodology between these studies and provides an overview of how these studies have advanced the field and expanded possibilities for the future.
Ultrastructural Evaluation of the Human Oocyte at the Germinal Vesicle Stage during the Application of Assisted Reproductive Technologies
Authors: Palmerini Maria Grazia , Antonouli Sevastiani , Macchiarelli Guido , Cecconi Sandra , Bianchi Serena , Khalili Mohammad Ali , Nottola Stefania Annarita
Published: May 2022

After its discovery in 1825 by the physiologist J.E. Purkinje, the human germinal vesicle (GV) attracted the interest of scientists. Discarded after laparotomy or laparoscopic ovum pick up from the pool of retrieved mature oocytes, the leftover GV was mainly used for research purposes. After the discovery of Assisted Reproductive Technologies (ARTs) such as in vitro maturation (IVM), in vitro fertilization and embryo transfer (IVF-ET) and intracytoplasmic sperm injection (ICSI), its developing potential was explored, and recognized as an important source of germ cells, especially in the case of scarce availability of mature oocytes for pathological/clinical conditions or in the case of previous recurrent implantation failure. We here review the ultrastructural data available on GV-stage human oocytes and their application to ARTs.
Solid-Solution-Based Metal Coating Enables Highly Reversible, Dendrite-Free Aluminum Anode
Authors: Hu Bo , Han Kang , Han Chunhua , Geng Lishan , Li Ming , Hu Ping , Wang Xuanpeng
Published: May 2022

Aluminum-ion batteries have attracted great interest in the grid-scale energy storage field due to their good safety, low cost and the high abundance of Al. However, Al anodes suffer from severe dendrite growth, especially at high deposition rates. Here, we report a simple strategy for constructing a highly reversible, dendrite-free, Al-based anode through directly introducing a solid-solution-based metal coating to a Zn foil substrate. Compared with Cu foil substrates and bare Al, a Zn foil substrate shows a lower nucleation barrier of Al deposition due to the intrinsic, definite solubility between Al and Zn. During Al deposition, a thin, solid-solution alloy phase is first formed on the surface of the Zn foil substrate and then guides the parallel growth of flake-like Al on Zn substrate. The well-designed, Zn-coated Al (Zn@Al) anode can effectively inhibit dendrite growth and alleviate the corrosion of the Al anode. The fabricated Zn@Al–graphite battery exhibits a high specific capacity of 80 mAh·g−1 and an ultra-long lifespan over 10,000 cycles at a high current density of 20 A·g−1 in low-cost molten salt electrolyte. This work opens a new avenue for the development of stable Al anodes and can provide insights for other metal anode protection.
MG-63 and FetMSC Cell Response on Atomic Layer Deposited TiO2 Nanolayers Prepared Using Titanium Tetrachloride and Tetraisopropoxide
Authors: Nazarov Denis , Ezhov Ilya , Yudintceva Natalia , Mitrofanov Ilya , Shevtsov Maxim , Rudakova Aida , Maximov Maxim
Published: May 2022

Titanium oxide nanocoatings were synthesized on the surface of monocrystalline silicon and ultra-fine-grained titanium by atomic layer deposition (ALD) using titanium tetrachloride (TiCl4) and titanium tetraisopropoxide (TTIP). The morphology of the samples was studied by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The structure and composition were studied by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), contact angle measurements, and energy-dispersive spectroscopy (EDS). The cytological response of osteosarcoma MG-63 and human fetal mesenchymal stem cells (FetMSCs) were studied by analyzing their morphology, viability, and alkaline phosphatase activity with and without the use of medium-induced differentiation in the osteogenic direction. A significant influence of the precursor type and ALD temperature on the crystal structure, morphology, composition, and surface free energy of TiO2 nanocoatings was found. The biocompatibility of amorphous non-stoichiometric and partially crystalline stoichiometric TiO2 coatings was compared. Both types of cells showed faster adhesion and improved spreading on the surface for the samples from TTIP compared to those from TiCl4 at the early stages of cultivation (2 h) due to the difference in composition and higher surface free energy. No cytotoxic effect was found on both types of coatings, nor was there a noticeable difference in cell differentiation. All ALD coatings provided excellent biocompatibility and osteoconductive properties.
tRNA Fusion to Streamline RNA Structure Determination: Case Studies in Probing Aminoacyl-tRNA Sensing Mechanisms by the T-Box Riboswitch
Authors: Grigg Jason C. , Price Ian R. , Ke Ailong
Published: May 2022

RNAs are prone to misfolding and are often more challenging to crystallize and phase than proteins. Here, we demonstrate that tRNA fusion can streamline the crystallization and structure determination of target RNA molecules. This strategy was applied to the T-box riboswitch system to capture a dynamic interaction between the tRNA 3′-UCCA tail and the T-box antiterminator, which senses aminoacylation. We fused the T-box antiterminator domain to the tRNA anticodon arm to capture the intended interaction through crystal packing. This approach drastically improved the probability of crystallization and successful phasing. Multiple structure snapshots captured the antiterminator loop in an open conformation with some resemblance to that observed in the recent co-crystal structures of the full-length T box riboswitch–tRNA complex, which contrasts the resting, closed conformation antiterminator observed in an earlier NMR study. The anticipated tRNA acceptor–antiterminator interaction was captured in a low-resolution crystal structure. These structures combined with our previous success using prohead RNA–tRNA fusions demonstrates tRNA fusion is a powerful method in RNA structure determination.
Genomics and Immunomics in the Treatment of Urothelial Carcinoma
Authors: Mollica Veronica , Massari Francesco , Rizzo Alessandro , Ferrara Roberto , Menta Arjun K. , Adashek Jacob J.
Published: May 2022

Urothelial carcinoma is a complex cancer with genomic immunomic drivers that have prognostic and predictive treatment implications. Identifying potential targetable alterations via next-generation sequencing and RNA sequencing may allow for elucidation of such targets and exploitation with targeted therapeutics. The role of immunotherapy in treating urothelial carcinoma has shown benefit, but it is unclear in which patients immunotherapeutics have the highest yield. Continuing efforts into better identifying which patients may benefit most from targeted therapies, immunotherapies, and combination therapies may ultimately lead to improved outcomes for patients with this disease.
Invasive Alien Plant Species—Raising Awareness of a Threat to Biodiversity and Ecological Connectivity (EC) in the Adriatic-Ionian Region
Authors: Gazoulis Ioannis , Antonopoulos Nikolaos , Kanatas Panagiotis , Karavas Nikolas , Bertoncelj Irena , Travlos Ilias
Published: May 2022

Improving ecological connectivity (EC) within landscapes by establishing corridors and ecological networks has been proposed to counteract the negative effects of habitat fragmentation and climate change on biodiversity. To be functional, ecological networks should be kept free of opportunistic invasive species that can disrupt EC between protected areas and cause biodiversity loss. The present study focused on perennial herbaceous species whose occurrence in the Adriatic-Ionian region has increased in the last two decades, namely common milkweed (Asclepias syriaca), Jerusalem artichoke (Helianthus tuberosus), Japanese knotweed (Reynoutria japonica), Bohemian knotweed (Reynoutria × bohemica), giant hogweed (Heracleum mantegazzianum), giant goldenrod (Solidago gigantea), Canadian goldenrod (Solidago canadensis), and Bermuda buttercup (Oxalis pes-caprae). All species have a high potential to spread in grasslands, abandoned agricultural fields, forest edges, and riparian areas and pose a significant threat to native plant communities and biodiversity. Restoring heavily infested sites is a major challenge because these perennial invaders are very persistent and tend to alter the soil environment in invaded habitats and prevent the recolonization of native plant communities. Therefore, early action should be taken to prevent the spread of these environmental weeds in ecological networks and protected areas with high conservation value.