bluuebunny/crossref_metadata_2025 huggingface dataset:
Characteristics Analysis of the Multi-Channel Ground-Based Microwave Radiometer Observations during Various Weather Conditions
Authors: Liu Meng , Liu Yan-An , Shu Jiong
Published: September 2022

Ground-based multi-channel microwave radiometers (MWRs) can continuously detect atmospheric profiles in the tropospheric atmosphere. This makes MWR an ideal tool to supplement radiosonde and satellite observations in monitoring the thermodynamic evolution of the atmosphere and improving numerical weather prediction (NWP) through data assimilation. The analysis of product characteristics of MWR is the basis for applying its data to real-time monitoring and assimilation. In this paper, observations from the latest generation of ground-based multi-channel MWR RPG-HATPRO-G5 installed in Shanghai, China, are compared with the radiosonde observations (RAOB) observed in the same location. The detection performance, characteristics of various channels, and the accuracy of the retrieval profile products of the MWR RPG are comprehensively evaluated during various weather conditions. The results show that the brightness temperatures (BTs) observed by the ground-based MWR RPG during precipitation conditions were high, which affected its detection performance. The bias and the standard deviation (SD) between the BT observed by MWR RPG and the simulated BT during clear and cloudy sky conditions were slight and large, respectively, and the coefficient of determination (R2) was high and low, respectively. However, when the cloud liquid water (CLW) information was added when simulating BT, the bias and the SD of the observed BT and the simulated BT during cloudy days were reduced and the R2 value improved, which indicated that CLW information should be taken into account when simulating BT during cloudy conditions. The temperature profiles of the MWR retrieval had the same accuracy of RMSEs (root-mean-square error) with heights during both clear-sky and cloudy sky conditions, where the RMSEs were below 2 K when the heights were below 4 km. In addition, the MWR RPG has the potential ability to retrieve the temperature inversion in the boundary layer, which has important application value for fog and air pollution monitoring.
Application of Empirical Orthogonal Function Analysis to 1 km Ensemble Simulations and Himawari–8 Observation in the Intensification Phase of Typhoon Hagibis (2019)
Authors: Wada Akiyoshi , Hayashi Masahiro , Yanase Wataru
Published: September 2022

An empirical orthogonal function (EOF) analysis was performed for the inner core of Typhoon Hagibis (2019) in the intensification phase. The Himawari–8 geostationary infrared (IR) brightness temperature (BT) collocated at the Hagibis’s center was combined with the IR BT simulated by a radiative transfer model, with 1 km ensemble simulations conducted by an atmosphere model and the coupled atmosphere–wave–ocean model. The ensemble simulations were conducted under one control atmospheric initial condition and the 26 perturbed ones with two different oceanic initial conditions. The first four EOF modes showed symmetric and asymmetric patterns such as a curved band, cloud dense overcast, and eye pattern used in the classification of the Dvorak technique. The influence of ocean coupling on the modes appeared only in the early intensification phase but was relatively small compared to the difference from the Himawari–8 observations. While ocean coupling and different oceanic initial condition quantitatively affected the IR BT, the normalized amplitude for the first EOF mode did not become close to that of the Himawari–8 observation in the late intensification phase. The intensification rate in the late intensification phase was inconsistent between the simulation results and the estimate from the Himawari–8 normalized amplitude by multiple linear regression analysis.
Measurement of Indoor-Outdoor Carbonyls in Three Different Universities Located in the Metropolitan Zone of Mexico Valley during the First Period of Confinements Due to COVID-19
Authors: García Rocío , Gómez Sandra Silva , Andraca Gema , Jardón Ricardo Torres , Reynoso Agustín García , Cerón Julia Griselda , Cerón Rosa María , Alvarez Violeta Mugica
Published: September 2022

Carbonyl concentrations in indoor-outdoor air were measured at three urban sites in the Metropolitan Zone of Mexico Valley (MZMV) during the first period of confinements due to COVID-19; the exposure for people living in indoor environments was also assessed. Indoor and outdoor samples were simultaneously collected sequentially with Sep-Pack DNPH-Silica cartridges. Formaldehyde, acetaldehyde, acetone, propionaldehyde, butyraldehyde and acrolein were quantified according to the US-EPA TO-11A method. Acrolein and acetone were the most abundant carbonyls in indoor air, with average concentrations of 55.5 µg m−3 and 46.4 µg m−3, respectively, followed by formaldehyde (29.1 µg m−3), acetaldehyde (21.4 µg m−3) and butyraldehyde (7.31 µg m−3). Propionaldehyde was not detected. Acetone was the dominant carbonyl in outdoor samples with an average concentration of 8.4 µg m−3, followed by formaldehyde (2.8 µg m−3) and acetaldehyde (0.7 µg m−3). Butyraldehyde and acrolein were not detected in outdoor air. Indoor/outdoor (I/O) ratios showed that indoor sources prevail for most aldehydes. Statistical analysis of simple correlations showed that the measured carbonyls were influenced by the presence of indoor sources. The average cancer risk coefficients (LTCR) for formaldehyde and acetaldehyde and the non-cancer risk coefficients (HQ) for acrolein and formaldehyde were higher than the recommended limits, which should be a cause for public concern.
Ozone-Induced Lung and Bronchial Injury: A Mouse Model Study
Authors: Liang Shi , Sha Yan , Yang Chuanhong , Lai Huangwen , Sun Chong , Zhao Weisen , Zhang An , Qi Qingwen , Xie Ying
Published: September 2022

Ozone pollution is a prominent public health issue, but there are few studies on the effect of ozone on the ultrastructure of respiratory system; we conducted this research. Exposed to 1.1 ppm O3 4 h per day, the mice lungs and bronchi were taken on the 15th or 30th day. The sections stained with HE and immunohistochemical streptavidin–peroxidase methods for NQO1, Nrf2, and Keap1 were observed and measured under the optical microscope. TEM was used for ultrastructure observation. The animals’ serums were detected for CRP and IL-6 levels. The HE-stained sections showed no obvious micromorphological changes in the O3 exposure, but the NQO1 average optical density was higher than the control on the 15th day (p < 0.05). The ultrastructural changes were found in the O3 exposure group, such as bulges and vacuoles in type I alveolar cells, the increased evacuation of substance from lamellar bodies in the type II alveolar cells, the increased space around the goblet nucleus, binuclear goblet, and columnar cells. CRP and IL-6 levels increased compared with the control (p < 0.05). Although inhaling 1.1 ppm O3 had no significant effect on the micromorphology of the mice lungs and bronchi, it did affect the ultrastructure with oxidative stress and inflammatory responses.
Electric Vehicle Batteries: Status and Perspectives of Data-Driven Diagnosis and Prognosis
Authors: Zhao Jingyuan , Burke Andrew F.
Published: September 2022

Mass marketing of battery-electric vehicles (EVs) will require that car buyers have high confidence in the performance, reliability and safety of the battery in their vehicles. Over the past decade, steady progress has been made towards the development of advanced battery diagnostic and prognostic technologies using data-driven methods that can be used to inform EV owners of the condition of their battery over its lifetime. The research has shown promise for accurately predicting battery state of health (SOH), state of safety (SOS), cycle life, the remaining useful life (RUL), and indicators of cells with high risk of failure (i.e., weak cells). These methods yield information about the battery that would be of great interest to EV owners, but at present it is not shared with them. This paper is concerned with the present status of the information available on the battery with a focus on data-driven diagnostic and prognostic approaches, and how the information would be generated in the future for the millions of EVs that will be on the road in the next decade. Finally, future trends and key challenges for the prognostics and health management of the batteries in real-world EV applications are presented from four perspectives (cloud-edge interaction, full-scale diagnosis, artificial intelligence and electronic health reports) are discussed.
Neurotrauma Prevention Review: Improving Helmet Design and Implementation
Authors: Goutnik Michael , Goeckeritz Joel , Sabetta Zackary , Curry Tala , Willman Matthew , Willman Jonathan , Currier Thomas Theresa , Lucke-Wold Brandon
Published: September 2022

Neurotrauma continues to contribute to significant mortality and disability. The need for better protective equipment is apparent. This review focuses on improved helmet design and the necessity for continued research. We start by highlighting current innovations in helmet design for sport and subsequent utilization in the lay community for construction. The current standards by sport and organization are summarized. We then address current standards within the military environment. The pathophysiology is discussed with emphasis on how helmets provide protection. As innovative designs emerge, protection against secondary injury becomes apparent. Much research is needed, but this focused paper is intended to serve as a catalyst for improvement in helmet design and implementation to provide more efficient and reliable neuroprotection across broad arenas.
Effect of Diclofenac and Simvastatin on Bone Defect Healing—An In Vivo Animal Study
Authors: Karanikola Theodora , Cheva Angeliki , Sarafidou Katia , Myronidou-Tzouveleki Maria , Tsavdaridis Ioannis , Kontonasaki Eleana , Tsirlis Anastasios
Published: September 2022

Non-steroidal, anti-inflammatory drugs and statins are two widely prescribed drug classes that affect bone formation. The aim of this study was to elucidate the effect of diclofenac and simvastatin in artificial bone defect healing. One hundred and forty-four male Wistar rats were used, and the specimens were divided into groups, with respect to the route of drug administration and the type of defect healing (with or without collagen membrane), and subgroups, with respect to the study duration (2, 4 or 8 weeks). Diclofenac was intramuscularly administered while simvastatin was administered both systemically and locally. Animals were euthanized and specimens were histomorphometrically analyzed to evaluate the percentage of new bone formation (%). Bone healing that occurred without any intervention developed more steadily than that of all other groups. Diclofenac exerted a clear, direct inhibitory effect on bone healing and its systemic administration should be avoided. The systemic administration of simvastatin was related to severe myopathy, while the solvent for the local administration of simvastatin seemed to play significant role in bone growth, as simvastatin, when it is administered intraperitoneally in a DMSO solution, appeared to promote bone healing. Local administration may have a significant impact on bone healing and it should be further investigated with the type of solvent or carrier that is used, which both may play a significant role in bone repair induction.
Comparative Characteristics of Biomaterials from Juvenile Dentin and Brefomatrix Using Raman Spectroscopy
Authors: Timchenko Elena V. , Bazhutova Irina V. , Timchenko Pavel Е. , Frolov Oleg О. , Volova Larisa Т.
Published: September 2022

The results of studies on the assessment of new biomaterials from juvenile teeth for further use in surgical dentistry for bone tissue repair are presented in this work. The comparative assessment of these materials and brefomatrices used in dentistry was carried out. It was shown that spectral properties of new biomaterials from juvenile dentin were similar to the spectral properties of brefomatrices from cortical tissue according to the developed discriminant model of the characteristic changes of Raman line intensities. The calculated accuracy of the discriminant model was 82.7 ± 3.2%.
Staging of Skin Cancer Based on Hyperspectral Microscopic Imaging and Machine Learning
Authors: Liu Lixin , Qi Meijie , Li Yanru , Liu Yujie , Liu Xing , Zhang Zhoufeng , Qu Junle
Published: September 2022

Skin cancer, a common type of cancer, is generally divided into basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and malignant melanoma (MM). The incidence of skin cancer has continued to increase worldwide in recent years. Early detection can greatly reduce its morbidity and mortality. Hyperspectral microscopic imaging (HMI) technology can be used as a powerful tool for skin cancer diagnosis by reflecting the changes in the physical structure and microenvironment of the sample through the differences in the HMI data cube. Based on spectral data, this work studied the staging identification of SCC and the influence of the selected region of interest (ROI) on the staging results. In the SCC staging identification process, the optimal result corresponded to the standard normal variate transformation (SNV) for spectra preprocessing, the partial least squares (PLS) for dimensionality reduction, the hold-out method for dataset partition and the random forest (RF) model for staging identification, with the highest staging accuracy of 0.952 ± 0.014, and a kappa value of 0.928 ± 0.022. By comparing the staging results based on spectral characteristics from the nuclear compartments and peripheral regions, the spectral data of the nuclear compartments were found to contribute more to the accurate staging of SCC.
Statins Use in Alzheimer Disease: Bane or Boon from Frantic Search and Narrative Review
Authors: Alsubaie Nawal , Al-kuraishy Hayder M. , Al-Gareeb Ali I. , Alharbi Bandar , De Waard Michel , Sabatier Jean-Marc , Saad Hebatallah M. , Batiha Gaber El-Saber
Published: September 2022

Alzheimer’s disease (AD) was used to describe pre-senile dementia to differentiate it from senile dementia, which develops in the adult age group of more than 65 years. AD is characterized by the deposition of amyloid beta (Aβ) plaque and tau-neurofibrillary tangles (TNTs) in the brain. The neuropathological changes in AD are related to the deposition of amyloid plaques, neurofibrillary tangles, and progression of neuroinflammation, neuronal mitochondrial dysfunction, autophagy dysfunction, and cholinergic synaptic dysfunction. Statins are one of the main cornerstone drugs for the management of cardiovascular disorders regardless of dyslipidemia status. Increasing the use of statins, mainly in the elderly groups for primary and secondary prevention of cardiovascular diseases, may affect their cognitive functions. Extensive and prolonged use of statins may affect cognitive functions in healthy subjects and dementia patients. Statins-induced cognitive impairments in both patients and health providers had been reported according to the post-marketing survey. This survey depends mainly on sporadic cases, and no cognitive measures were used. Evidence from prospective and observational studies gives no robust conclusion regarding the beneficial or detrimental effects of statins on cognitive functions in AD patients. Therefore, this study is a narrative review aimed with evidences to the beneficial, detrimental, and neutral effects of statins on AD.
Multiple Case Studies in German Children with Dyslexia: Characterization of Phonological, Auditory, Visual, and Cerebellar Processing on the Group and Individual Levels
Authors: Ligges Carolin , Lehmann Thomas
Published: September 2022

Background: The underlying mechanisms of dyslexia are still debated. The question remains as to whether there is evidence of a predominant type of deficit or whether it is a multideficit disorder with individual profiles. The assumptions of which mechanism causes the disorder influences the selection of the training approach. Methods: A sample of German neurotypical reading children (NT) and children with dyslexia (DYSL) was investigated with a comprehensive behavioral test battery assessing phonological, auditory, visual, and cerebellar performance, thus addressing performance described in three major theories in dyslexia. Results: In the present sample using the test battery of the present study, DYSL had the strongest impairment in phonological and auditory processing, accompanied by individual processing deficits in cerebellar performance, but only a few in the investigated visual domains. Phonological awareness and auditory performance were the only significant predictors for reading ability. Conclusion: These findings point out that those reading difficulties were associated with phonological as well as auditory processing deficits in the present sample. Future research should investigate individual deficit profiles longitudinally, with studies starting before literacy acquisition at as many processing domains as possible. These individual deficit profiles should then be used to select appropriate interventions to promote reading and spelling.
A Microfluidic In Vitro Three-Dimensional Dynamic Model of the Blood–Brain Barrier to Study the Transmigration of Immune Cells
Authors: Meena Megha , Vandormael Robin , De Laere Maxime , Pintelon Isabel , Berneman Zwi , Watts Regan , Cools Nathalie
Published: September 2022

To study the biodistribution of new chemical and biological entities, an in vitro model of the blood–brain barrier (BBB) may become an essential tool during early phases of drug discovery. Here, we present a proof-of-concept of an in-house designed three-dimensional BBB biochip designed by us. This three-dimensional dynamic BBB model consists of endothelial cells and astrocytes, co-cultured on opposing sides of a polymer-coated membrane under flow mimicking blood flow. Our results demonstrate a highly effective BBB as evidenced by (i) a 30-fold increase in transendothelial electrical resistance (TEER), (ii) a significantly higher expression of tight junction proteins, and (iii) the low FITC–dextran permeability of our technical solution as compared to a static in vitro BBB model. Importantly, our three-dimensional BBB model effectively expresses P-glycoprotein (Pg-p), a hallmark characteristic for brain-derived endothelial cells. In conclusion, we provide here a complete holistic approach and insight to the whole BBB system, potentially delivering translational significance in the clinical and pharmaceutical arenas.
Clinical Significance of Tumor Size in Gross Extrathyroidal Extension to Strap Muscles (T3b) in Papillary Thyroid Carcinoma: Comparison with T2
Authors: Park Joonseon , Kang Il Ku , Bae Ja Seong , Kim Jeong Soo , Kim Kwangsoon
Published: September 2022

The purpose of the present study was to compare the risk of recurrence between T2 and T3b papillary thyroid carcinoma (PTC) and the effect of tumor size on survival in T3b disease. A total of 634 patients with PTC who underwent thyroid surgery at a single center were retrospectively analyzed. Clinicopathological characteristics were compared according to the T category in the TNM staging system, with T3b divided into T3b-1 (tumor size, ≤2 cm) and T3b-2 (tumor size, 2–4 cm). Disease-free survival (DFS) and recurrence risk were compared between T2, T3b, T3b-1, and T3b-2. Tumor size was significantly larger in T2 than in T3b. A significant difference in recurrence was observed between T2 and T3b-2 but not between T2 and T3b-1. T3b-2 was identified as a significant risk factor for PTC recurrence. A significant difference in the DFS curve was observed between T2 and T3b-2. However, no significant differences in survival were observed between T2 and T3b or T3b-1. These results indicate that the prognostic impact of T3b may vary depending on tumor size. Further studies are required to determine the need for T classifications that account for tumor size and gETE invasion of the strap muscles.
Mechanisms of Primary and Acquired Resistance to Immune Checkpoint Inhibitors in Patients with Hepatocellular Carcinoma
Authors: De Lorenzo Stefania , Tovoli Francesco , Trevisani Franco
Published: September 2022

Hepatocellular carcinoma (HCC) is the most common liver cancer and a relevant global health problem. Immune checkpoint inhibitors (ICIs) represent the most effective systemic treatment for HCC. However, due to primary resistance, approximately 40% of HCC patients do not achieve a disease control with ICIs. Moreover, a similar proportion will experience disease progression after an initial response caused by secondary resistance. This review describes the mechanisms of primary and secondary resistance and reports the ongoing therapeutic strategies to overcome these obstacles.
Circulating Neoplastic-Immune Hybrid Cells Predict Metastatic Progression in Uveal Melanoma
Authors: Parappilly Michael S. , Chin Yuki , Whalen Riley M. , Anderson Ashley N. , Robinson Trinity S. , Strgar Luke , Sutton Thomas L. , Conley Patrick , Klocke Christopher , Gibbs Summer L. , Chang Young Hwan , Wu Guanming , Wong Melissa H. , Skalet Alison H.
Published: September 2022

Background: Uveal melanoma is an aggressive cancer with high metastatic risk. Recently, we identified a circulating cancer cell population that co-expresses neoplastic and leukocyte antigens, termed circulating hybrid cells (CHCs). In other cancers, CHCs are more numerous and better predict oncologic outcomes compared to circulating tumor cells (CTCs). We sought to investigate the potential of CHCs as a prognostic biomarker in uveal melanoma. Methods: We isolated peripheral blood monocular cells from uveal melanoma patients at the time of primary treatment and used antibodies against leukocyte and melanoma markers to identify and enumerate CHCs and CTCs by immunocytochemistry. Results: Using a multi-marker approach to capture the heterogeneous disseminated tumor cell population, detection of CHCs was highly sensitive in uveal melanoma patients regardless of disease stage. CHCs were detected in 100% of stage I-III uveal melanoma patients (entire cohort, n = 68), whereas CTCs were detected in 58.8% of patients. CHCs were detected at levels statically higher than CTCs across all stages (p = 0.05). Moreover, CHC levels, but not CTCs, predicted 3 year progression-free survival (p < 0.03) and overall survival (p < 0.04). Conclusion: CHCs are a novel and promising prognostic biomarker in uveal melanoma.
Targeting Homologous Recombination Deficiency in Ovarian Cancer with PARP Inhibitors: Synthetic Lethal Strategies That Impact Overall Survival
Authors: Xie Tao , Dickson Kristie-Ann , Yee Christine , Ma Yue , Ford Caroline E. , Bowden Nikola A. , Marsh Deborah J.
Published: September 2022

The advent of molecular targeted therapies has made a significant impact on survival of women with ovarian cancer who have defects in homologous recombination repair (HRR). High-grade serous ovarian cancer (HGSOC) is the most common histological subtype of ovarian cancer, with over 50% displaying defective HRR. Poly ADP ribose polymerases (PARPs) are a family of enzymes that catalyse the transfer of ADP-ribose to target proteins, functioning in fundamental cellular processes including transcription, chromatin remodelling and DNA repair. In cells with deficient HRR, PARP inhibitors (PARPis) cause synthetic lethality leading to cell death. Despite the major advances that PARPis have heralded for women with ovarian cancer, questions and challenges remain, including: can the benefits of PARPis be brought to a wider range of women with ovarian cancer; can other drugs in clinical use function in a similar way or with greater efficacy than currently clinically approved PARPis; what can we learn from long-term responders to PARPis; can PARPis sensitise ovarian cancer cells to immunotherapy; and can synthetic lethal strategies be employed more broadly to develop new therapies for women with ovarian cancer. We examine these, and other, questions with focus on improving outcomes for women with ovarian cancer.
Co-Targeting ErbB Receptors and the PI3K/AKT Axis in Androgen-Independent Taxane-Sensitive and Taxane-Resistant Human Prostate Cancer Cells
Authors: Adediran Samusi , Wang Linbo , Khan Mohammad Afnan , Guang Wei , Fan Xiaoxuan , Dan Hancai , Qi Jianfei , Jay Steven M. , Carrier France , Hussain Arif
Published: September 2022

Using two representative models of androgen-independent prostate cancer (PCa), PC3 and DU145, and their respective paclitaxel- and docetaxel-resistant derivatives, we explored the anti-tumor activity of targeting the ErbB receptors and AKT using small-molecule kinase inhibitors. These cells manifest varying degrees of neuroendocrine differentiation characteristics and differ in their expression of functional PTEN. Although the specific downstream signaling events post the ErbB receptor and AKT co-targeting varied between the PC3- and DU145-lineage cells, synergistic anti-proliferative and enhanced pro-apoptotic responses occurred across the wild-type and the taxane-resistant cells, independent of their basal AKT activation state, their degree of paclitaxel- or docetaxel-resistance, or whether this resistance was mediated by the ATP Binding Cassette transport proteins. Dual targeting also led to enhanced anti-tumor responses in vivo, although there was pharmacodynamic discordance between the PCa cells in culture versus the tumor xenografts in terms of the relative activation and inhibition states of AKT and ERK under basal conditions and upon AKT and/or ErbB targeting. The consistent inhibition, particularly of AKT, occurred both in vitro and in vivo, independent of the underlying PTEN status. Thus, co-targeting AKT with ErbB, and possibly other partners, may be a useful strategy to explore further for potential therapeutic effect in advanced PCa.
Prevalence and Outcomes of COVID-19 among Hematology/Oncology Patients and Providers of a Community-Facing Health System during the B1.1.529 (“Omicron”) SARS-CoV-2 Variant Wave
Authors: Kareff Samuel A. , Khan Aliya , Barreto-Coelho Priscila , Iyer Sunil Girish , Pico Brian , Stanchina Michele , Dutcher Giselle , Monteiro de Oliveira Novaes José , Nallagangula Aparna , Lopes Gilberto
Published: September 2022

(1) Background: the SARS-CoV-2 (COVID-19) pandemic continues, and patients actively receiving chemotherapy are known to be at enhanced risk for developing symptomatic disease with poorer outcomes. Our study evaluated the prevalence of COVID-19 among patients and providers of our community-facing county health system during the B1.1.529 (“Omicron”) COVID-19 variant wave. (2) Methods: We retrospectively analyzed patients that received care and clinical providers whom worked at the Jackson Memorial Hospital Hematology/Oncology clinic in Miami, Florida, USA, from 1 December 2021 through 30 April 2022. We assessed demographic variables and quality outcomes among patients. (3) Results: 1031 patients and 18 providers were retrospectively analyzed. 90 patients tested positive for COVID-19 (8.73%), while 6 providers tested positive (33.3%) (p = 0.038). There were 4 (10.3%) COVID-19-related deaths (and another outside our study timeframe) and 39 non-COVID-19-related deaths (89.7%) in the patient population (p = 0.77). COVID-19 accounted for 4.44% of our clinic’s total mortality, and delayed care in 64.4% of patients. (4) Conclusions: The prevalence of COVID-19 positivity in our patient cohort mirrored local, state, and national trends, however a statistically significant greater proportion of our providers tested positive. Almost two-thirds of patients experienced a cancer treatment delay, significantly impacting oncologic care.
Derivatives of Plastics as Potential Carcinogenic Factors: The Current State of Knowledge
Authors: Baj Jacek , Dring James Curtis , Czeczelewski Marcin , Kozyra Paweł , Forma Alicja , Flieger Jolanta , Kowalska Beata , Buszewicz Grzegorz , Teresiński Grzegorz
Published: September 2022

Micro- and nanoplatics have been already reported to be potential carcinogenic/mutagenic substances that might cause DNA damage, leading to carcinogenesis. Thus, the effects of micro- and nanoplastics exposure on human health are currently being investigated extensively to establish clear relationships between those substances and health consequences. So far, it has been observed that there exists a definite correlation between exposure to micro- and nanoplastic particles and the onset of several cancers. Therefore, we have conducted research using PubMed, Web of Science, and Scopus databases, searching for all the research papers devoted to cancers that could be potentially related to the subject of exposure to nano- and microplastics. Ultimately, in this paper, we have discussed several cancers, including hepatocellular carcinoma, pancreatic cancer, pancreatic ductal adenocarcinoma, biliary tract cancer, and some endocrine-related cancers.
NR2F1 Regulates TGF-β1-Mediated Epithelial-Mesenchymal Transition Affecting Platinum Sensitivity and Immune Response in Ovarian Cancer
Authors: Liang Qiuju , Xu Zhijie , Liu Yuanhong , Peng Bi , Cai Yuan , Liu Wei , Yan Yuanliang
Published: September 2022

The mechanism underlying platinum resistance in ovarian cancer (OC) remains unclear. We used bioinformatic analyses to screen differentially expressed genes responsible for platinum resistance and explore NR2F1′s correlation with prognostic implication and OC staging. Moreover, Gene-set enrichment analysis (GSEA) and Gene Ontology (GO) analyses were used for pathway analysis. Epithelial-mesenchymal transition (EMT) properties, invasion, and migration capacities were analyzed by biochemical methods. The association between NR2F1 and cancer-associated fibroblast (CAF) infiltration and immunotherapeutic responses were also researched. A total of 13 co-upregulated genes and one co-downregulated gene were obtained. Among them, NR2F1 revealed the highest correlation with a poor prognosis and positively correlated with OC staging. GSEA and GO analysis suggested the induction of EMT via TGFβ-1 might be a possible mechanism that NR2F1 participates in resistance. In vitro experiments showed that NR2F1 knockdown did not affect cell proliferation, but suppressed cell invasion and migration with or without cisplatin treatment through the EMT pathway. We also found that NR2F1 could regulate TGF-β1 signaling, and treating with TGF-β1 could reverse these effects. Additionally, NR2F1 was predominantly associated with immunosuppressive CAF infiltration, which might cause a poor response to immune check blockades. In conclusion, NR2F1 regulates TGF-β1-mediated EMT affecting platinum sensitivity and immune response in OC patients.
Richter Syndrome: From Molecular Pathogenesis to Druggable Targets
Authors: Mouhssine Samir , Gaidano Gianluca
Published: September 2022

Richter syndrome (RS) represents the occurrence of an aggressive lymphoma, most commonly diffuse large B-cell lymphoma (DLBCL), in patients with chronic lymphocytic leukemia (CLL). Most cases of RS originate from the direct transformation of CLL, whereas 20% are de novo DLBCL arising as secondary malignancies. Multiple molecular mechanisms contribute to RS pathogenesis. B-cell receptor (BCR) overreactivity to multiple autoantigens is due to frequent stereotyped BCR configuration. Genetic lesions of TP53, CDKN2A, NOTCH1 and c-MYC deregulate DNA damage response, tumor suppression, apoptosis, cell cycle and proliferation. Hyperactivation of Akt and NOTCH1 signaling also plays a role. Altered expression of PD-1/PD-L1 and of other immune checkpoints leads to RS resistance to cytotoxicity exerted by T-cells. The molecular features of RS provide vulnerabilities for therapy. Targeting BCR signaling with noncovalent BTK inhibitors shows encouraging results, as does the combination of BCL2 inhibitors with chemoimmunotherapy. The association of immune checkpoint inhibitors with BCL2 inhibitors and anti-CD20 monoclonal antibodies is explored in early phase clinical trials with promising results. The development of patient-derived xenograft mice models reveals new molecular targets for RS, exemplified by ROR1. Although RS still represents an unmet medical need, understanding its biology is opening new avenues for precision medicine therapy.
Prognostic Role of Molecular and Imaging Biomarkers for Predicting Advanced Hepatocellular Carcinoma Treatment Efficacy
Authors: Cerrito Lucia , Ainora Maria Elena , Mosoni Carolina , Borriello Raffaele , Gasbarrini Antonio , Zocco Maria Assunta
Published: September 2022

Hepatocellular carcinoma (HCC) is the sixth most common malignancy worldwide and the fourth cause of tumor-related death. Imaging biomarkers are based on computed tomography, magnetic resonance, and contrast-enhanced ultrasound, and are widely applied in HCC diagnosis and treatment monitoring. Unfortunately, in the field of molecular biomarkers, alpha-fetoprotein (AFP) is still the only recognized tool for HCC surveillance in both diagnostic and follow-up purposes. Other molecular biomarkers have little roles in clinical practice regarding HCC, mainly for the detection of early-stage HCC, monitoring the response to treatments and analyzing tumor prognosis. In the last decades no important improvements have been achieved in this field and imaging biomarkers maintain the primacy in HCC diagnosis and follow-up. Despite the still inconsistent role of molecular biomarkers in surveillance and early HCC detection, they could play an outstanding role in prognosis estimation and treatment monitoring with a potential reduction in health costs faced by standard radiology. An important challenge resides in identifying sufficiently sensitive and specific biomarkers for advanced HCC for prognostic evaluation and detection of tumor progression, overcoming imaging biomarker sensitivity. The aim of this review is to analyze the current molecular and imaging biomarkers in advanced HCC.
Using Patient-Derived Xenograft (PDX) Models as a ‘Black Box’ to Identify More Applicable Patients for ADP-Ribose Polymerase Inhibitor (PARPi) Treatment in Ovarian Cancer: Searching for Novel Molecular and Clinical Biomarkers and Performing a Prospective Preclinical Trial
Authors: Chen Jiayu , Li Yan , Wang Haiyuan , Li Ting , Gu Yu , Wang Wei , Shan Ying , Yin Jie , Wang Yongxue , Qin Meng , Li Siyi , Pan Lingya , Peng Siying , Jin Ying
Published: September 2022

(1) The accuracy of patient-derived xenografts (PDXs) in predicting ADP-ribose polymerase inhibitor (PARPi) efficacy in ovarian cancer was tested, novel biomarkers were investigated, and whether PARPis could replace platinum-based chemotherapy as a first-line therapy was explored. (2) PDXs were reconstructed for 40 patients with ovarian cancer, and niraparib, olaparib and paclitaxel, and carboplatin (TC) sensitivity tests were conducted. Whole exon sequencing and homologous recombination deficiency (HRD) scores were performed, and patient clinical information was collected. The molecular biomarkers were identified by reverse-transcription quantitative PCR and immunoblotting. (3) Niraparib and olaparib sensitivity were tested in 26 patients and showed high consistency. Approximately half of BRCA wild-type, HRD-negative, and platinum-resistant patients may benefit from PARPis. AKT1 enrichment indicated PARPi resistance; high KRAS expression indicated PARPi sensitivity. CA125 below 10 U/mL during chemotherapy has a sensitivity and specificity similar to platinum sensitivity in predicting PARPi efficacy. Niraparib and TC sensitivity tests were performed on 23 patients, and TC showed a better response in this preclinical trial. (4) PDX can indicate individualized PARPi efficacy. Decreased CA125 levels and KRAS and ATK1 expression levels may be novel biomarkers. The preclinical evidence does not support the implementation of PARPis as the first-line treatment in an unselected population.
How Far beyond Diabetes Can the Benefits of Glucagon-like Peptide-1 Receptor Agonists Go? A Review of the Evidence on Their Effects on Hepatocellular Carcinoma
Authors: Arvanitakis Konstantinos , Koufakis Theocharis , Kotsa Kalliopi , Germanidis Georgios
Published: September 2022

Hepatocellular carcinoma (HCC) is characterized by poor survival rate and quality of life, while available treatments remain generally limited. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) originally emerged as drugs for the management of diabetes, but have also been shown to alleviate cardiorenal risk. Furthermore, they have demonstrated a wide range of extraglycemic effects that led to their evaluation as potential therapies for a variety of diseases beyond diabetes, such as obesity, neurogenerative disorders and nonalcoholic fatty liver disease. Given the presence of the GLP-1 receptor in hepatocytes, animal data suggest that GLP-1 RAs could regulate molecular pathways that are deeply involved in the genesis and progression of HCC, including inflammatory responses, tumor cell proliferation and oxidative stress, through direct and indirect effects on liver cells. However, future studies must assess several aspects of the benefit-to-risk ratio of the use of GLP-1 RAs in patients with HCC, including co-administration with approved systemic therapies, the incidence of gastrointestinal side effects in a high-risk population, and weight loss management in individuals with poor nutritional status and high rates of cancer cachexia. In this narrative review, we discuss the potential role of GLP-1 analogs in the treatment of HCC, focusing on the molecular mechanisms that could justify a possible benefit, but also referring to the potential clinical implications and areas for future research.
Combined Large Cell Neuroendocrine Carcinomas of the Lung: Integrative Molecular Analysis Identifies Subtypes with Potential Therapeutic Implications
Authors: Simbolo Michele , Centonze Giovanni , Giudice Luca , Grillo Federica , Maisonneuve Patrick , Gkountakos Anastasios , Ciaparrone Chiara , Cattaneo Laura , Sabella Giovanna , Giugno Rosalba , Bossi Paola , Spaggiari Paola , Del Gobbo Alessandro , Ferrero Stefano , Mastracci Luca , Fabbri Alessandra , Filugelli Martina , Garzone Giovanna , Prinzi Natalie , Pusceddu Sara , Testi Adele , Monti Valentina , Rolli Luigi , Mangogna Alessandro , Bercich Luisa , Benvenuti Mauro Roberto , Bria Emilio , Pilotto Sara , Berruti Alfredo , Pastorino Ugo , Capella Carlo , Infante Maurizio , Milella Michele , Scarpa Aldo , Milione Massimo
Published: September 2022

Background: Combined large cell neuroendocrine carcinoma (CoLCNEC) is given by the association of LCNEC with adeno or squamous or any non-neuroendocrine carcinoma. Molecular bases of CoLCNEC pathogenesis are scant and no standardized therapies are defined. Methods: 44 CoLCNECs: 26 with adenocarcinoma (CoADC), 7 with squamous cell carcinoma (CoSQC), 3 with small cell carcinoma (CoSCLC), 4 with atypical carcinoid (CoAC) and 4 napsin-A positive LCNEC (NapA+), were assessed for alterations in 409 genes and transcriptomic profiling of 20,815 genes. Results: Genes altered included TP53 (n = 30), RB1 (n = 14) and KRAS (n = 13). Targetable alterations included six KRAS G12C mutations and ALK-EML4 fusion gene. Comparison of CoLCNEC transcriptomes with 86 lung cancers of pure histology (8 AC, 19 ADC, 19 LCNEC, 11 SCLC and 29 SQC) identified CoLCNEC as a separate entity of neuroendocrine tumours with three different molecular profiles, two of which showed a non-neuroendocrine lineage. Hypomethylation, activation of MAPK signalling and association to immunotherapy signature specifically characterized each of three CoLCNEC molecular clusters. Prognostic stratification was also provided. Conclusions: CoLCNECs are an independent histologic category. Our findings support the extension of routine evaluation of KRAS mutations, fusion genes and immune-related markers to offer new perspectives in the therapeutic management of CoLCNEC.
Nanoparticles Design for Theranostic Approach in Cancer Disease
Authors: Carrese Barbara , Sanità Gennaro , Lamberti Annalisa
Published: September 2022

Presently, there are no conclusive treatments for many types of cancer, mainly due to the advanced phase of the disease at the time of diagnosis and to the side effects of existing therapies. Present diagnostic and therapeutic procedures need to be improved to supply early detection abilities and perform a more specific therapy with reduced systemic toxicity. In this review, improvements in nanotechnology allowing the design of multifunctional nanoparticles for cancer detection, therapy, and monitoring are reported. Nanoparticles, thanks to the nanomaterials they are made of, can be used as contrast agents for various diagnostic techniques such as MRI, optical imaging, and photoacoustic imaging. Furthermore, when used as drug carriers, they can accumulate in tumor tissues through the passive or/and active targeting, protect encapsulated drugs from degradation, raise tumor exposure to chemotherapeutic agents improving treatment effects. In addition, nanocarriers can simultaneously deliver more than one therapeutic agent enhancing the effectiveness of therapy and can co-deliver imaging and therapy agents to provide integration of diagnostics, therapy, and follow-up. Furthermore, the use of nanocarriers allows to use different therapeutic approaches, such as chemotherapy and hyperthermia to exploit synergistic effects. Theranostic approach to diagnose and treat cancer show a great potential to improve human health, however, despite technological advances in this field, the transfer into clinical practice is still a long way off.
Apelin, a Circulating Biomarker in Cancer Evaluation: A Systematic Review
Authors: Grinstead Christina , Yoon Saunjoo
Published: September 2022

Apelin is a promising biomarker for the detection and prognosis of cancer. This review aims to synthesize current knowledge on associations of circulating apelin with cancer, illustrate knowledge gaps, and discuss future research. Following PRISMA guidelines, CINAHL, EMBASE, and PubMed were searched using terms “cancer AND apelin” between 2011 and 2021, full text, and English language. Inclusion criteria: measured circulating apelin in adults 18 years or older with cancer, and observational, cross-sectional, longitudinal, case–control, cohort, quasi-experimental, or randomized control trials. Excluded were studies with animal models, tissue samples only, secondary data analyses, systematic reviews, literature reviews, grey literature, and conference abstracts. 16 articles were included. There were significant variations in measurement methods between studies. Comparison of circulating apelin between cases and controls and associations of circulating apelin with clinicopathological characteristics were inconsistent. Variations in results suggest that the relationship between circulating apelin and cancer differs among cancer types. Differences in measurement methods between studies highlight the need for consistency in future research to draw meaningful conclusions. Future research should seek to standardize methods of detecting circulating apelin and examine its associations with specific cancer types to determine what role that circulating apelin may play in cancer development and progression.
Integrative Analysis of N6-Methyladenosine-Related Enhancer RNAs Identifies Distinct Prognosis and Tumor Immune Micro-Environment Patterns in Head and Neck Squamous Cell Carcinoma
Authors: Cai Hongshi , Liang Jianfeng , Jiang Yaoqi , Tan Rukeng , Hou Chen , Hou Jinsong
Published: September 2022

At present, the prognostic value of N6-methyladenosine (m6A)-related enhancer RNAs (eRNAs) for head and neck squamous cell carcinoma (HNSCC) still remains unclear. Our study aims to explore the prognostic value of m6A-related eRNAs in HNSCC patients and their potential significance in immune infiltration and immunotherapy. We constructed a 5 m6A-related eRNAs risk model from The Cancer Genome Atlas (TCGA) HNSCC dataset, using univariate and multivariate Cox and least absolute shrinkage and selection operator (LASSO) regression analysis. Based on the SRAMP website and in vitro experiments, it was verified that these 5 m6A-related eRNAs had m6A sites, the expression of which was regulated by corresponding m6A regulators. Moreover, we constructed a nomogram base on 5 m6A-related eRNAs and confirmed the consistency and robustness of an internal TCGA testing set. Further analysis found that the risk score was positively associated with low overall survival (OS), tumor cell metastasis, metabolic reprogramming, low immune surveillance, lower expression of immune-related genes, and higher expression of targeted genes. Finally, we verified that silencing MIR4435-2HG inhibited HNSCC cell migration and invasion. This study contributes to the understanding of the characteristics of m6A-related eRNAs in HNSCC and provides a reference for effective immunotherapy and targeted therapy.
Adequacy of Pain Treatment in Radiotherapy Departments: Results of a Multicenter Study on 2104 Patients (Arise)
Authors: Donati Costanza M. , Nardi Elena , Zamagni Alice , Siepe Giambattista , Mammini Filippo , Cellini Francesco , Di Rito Alessia , Portaluri Maurizio , De Tommaso Cristina , Santacaterina Anna , Tamburella Consuelo , Di Franco Rossella , Parisi Salvatore , Cossa Sabrina , Fusco Vincenzo , Bianculli Antonella , Ziccarelli Pierpaolo , Ziccarelli Luigi , Genovesi Domenico , Caravatta Luciana , Deodato Francesco , Macchia Gabriella , Fiorica Francesco , Napoli Giuseppe , Buwenge Milly , Rossi Romina , Maltoni Marco , Morganti Alessio G.
Published: September 2022

Aim: The frequent inadequacy of pain management in cancer patients is well known. Moreover, the quality of analgesic treatment in patients treated with radiotherapy (RT) has only been rarely assessed. In order to study the latter topic, we conducted a multicenter, observational and prospective study based on the Pain Management Index (PMI) in RT Italian departments. Methods: We collected data on age, gender, tumor site and stage, performance status, treatment aim, and pain (type: CP—cancer pain, NCP—non-cancer pain, MP—mixed pain; intensity: NRS: Numeric Rating Scale). Furthermore, we analyzed the impact on PMI on these parameters, and we defined a pain score with values from 0 (NRS: 0, no pain) to 3 (NRS: 7–10: intense pain) and an analgesic score from 0 (pain medication not taken) to 3 (strong opioids). By subtracting the pain score from the analgesic score, we obtained the PMI value, considering cases with values < 0 as inadequate analgesic prescriptions. The Ethics Committees of the participating centers approved the study (ARISE-1 study). Results: Two thousand one hundred four non-selected outpatients with cancer and aged 18 years or older were enrolled in 13 RT departments. RT had curative and palliative intent in 62.4% and 37.6% patients, respectively. Tumor stage was non-metastatic in 57.3% and metastatic in 42.7% of subjects, respectively. Pain affected 1417 patients (CP: 49.5%, NCP: 32.0%; MP: 18.5%). PMI was < 0 in 45.0% of patients with pain. At multivariable analysis, inadequate pain management was significantly correlated with curative RT aim, ECOG performance status = 1 (versus both ECOG-PS3 and ECOG- PS4), breast cancer, non-cancer pain, and Central and South Italy RT Departments (versus Northern Italy).Conclusions: Pain management was less adequate in patients with more favorable clinical condition and stage. Educational and organizational strategies are needed in RT departments to reduce the non-negligible percentage of patients with inadequate analgesic therapy.