bluuebunny/crossref_metadata_2025 huggingface dataset:
A cloud detection neural network for above-aircraft clouds using airborne cameras
Authors: Nied Joseph , Jones Michael , Seaman Shane , Shingler Taylor , Hair Johnathan , Cairns Brian , Gilst David Van , Bucholtz Anthony , Schmidt Sebastian , Chellappan Seethala , Zuidema Paquita , Van Diedenhoven Bastiaan , Sorooshian Armin , Stamnes Snorre
Published: February 2023

For aerosol, cloud, land, and ocean remote sensing, the development of accurate cloud detection methods, or cloud masks, is extremely important. For airborne passive remotesensing, it is also important to identify when clouds are above the aircraft since their presence contaminates the measurements of nadir-viewing passive sensors. We describe the development of a camera-based approach to detecting clouds above the aircraft via a convolutional neural network called the cloud detection neural network (CDNN). We quantify the performance of this CDNN using human-labeled validation data where we report 96% accuracy in detecting clouds in testing datasets for both zenith viewing and forward-viewing models. We present results from the CDNN based on airborne imagery from the NASA Aerosol Cloud meteorology Interactions oVer the western Atlantic Experiment (ACTIVATE) and the Clouds, Aerosol, and Monsoon Processes Philippines Experiment (CAMP2Ex). We quantify the ability of the CDNN to identify the presence of clouds above the aircraft using a forward-looking camera mounted inside the aircraft cockpit compared to the use of an all-sky upward-looking camera that is mounted outside the fuselage on top of the aircraft. We assess our performance by comparing the flight-averaged cloud fraction of zenith and forward CDNN retrievals with that of the prototype hyperspectral total-diffuse Sunshine Pyranometer (SPN-S) instrument’s cloud optical depth data. A comparison of the CDNN with the SPN-S on time-specific intervals resulted in 93% accuracy for the zenith viewing CDNN and 84% for the forward-viewing CDNN. The comparison of the CDNNs with the SPN-S on flight-averaged cloud fraction resulted in an agreement of .15 for the forward CDNN and .07 for the zenith CDNN. For CAMP2Ex, 53% of flight dates had above-aircraft cloud fraction above 50%, while for ACTIVATE, 52% and 54% of flight dates observed above-aircraft cloud fraction above 50% for 2020 and 2021, respectively. The CDNN enables cost-effective detection of clouds above the aircraft using an inexpensive camera installed in the cockpit for airborne science research flights where there are no dedicated upward-looking instruments for cloud detection, the installation of which requires time-consuming and expensive aircraft modifications, in addition to added mission cost and complexity of operating additional instruments.
Case report: Drainage tube penetrating anastomosis as a rare cause for long-term nonunion of esophagogastric anastomosis in neck
Authors: Huang Yaochen , Fu Xiangning , Fu Shengling
Published: February 2023

Anastomotic leakage is a life-threatening complication for esophageal cancer patients who received McKeown esophagectomy. Cervical drainage tube penetrating anastomosis is a rare but noteworthy cause of long-term nonunion of esophagogastric anastomosis. Here we reported two cases of esophageal cancer patients who received McKeown esophagectomy. The first case acquired the anastomotic leakage on postoperative day (POD) 7, and lasted for 56 days. The cervical drainage tube was removed at POD 38, and the leakage healed in 25 days. The second case acquired the anastomotic leakage on POD 8 and lasted for 95 days. The cervical drainage tube was removed at POD 57, and the leakage healed in 46 days. The two cases demonstrated the duration-prolonging effect of drainage tube penetrating anastomosis, which should not be overlooked in clinical practice. We suggested paying attention to the duration of leakage, the drainage fluids amounts and characteristics, and the imaging manifestations to help diagnose. If the cervical drainage tube penetrated the anastomosis, the tube should be eliminated as soon.
Biomarkers and their potential for detecting livestock plant poisonings in Western North America
Authors: Green Benedict T. , Welch Kevin D. , Lee Stephen T. , Stonecipher Clinton A. , Gardner Dale R. , Stegelmeier Bryan L. , Davis T. Zane , Cook Daniel
Published: February 2023

The United States National Cancer Institute defines a biomarker as: “A biological molecule found in blood, other body fluids, or tissues that is a sign of a normal or abnormal process, or of a condition or disease.” In Veterinary Medicine, biomarkers associated with plant poisonings of livestock have great utility. Since grazing livestock poisoned by toxic plants are often found dead, biomarkers of plant poisoning allow for a more rapid postmortem diagnosis and response to prevent further deaths. The presence and concentration of toxins in poisonous plants are biomarkers of risk for livestock poisoning that can be measured by the chemical analysis of plant material. More difficult is, the detection of plant toxins or biomarkers in biological samples from intoxicated or deceased animals. The purpose of this article is to review potential biomarkers of plant poisoning in grazing livestock in the Western North America including recently investigated non-invasive sampling techniques. Plants discussed include larkspur, lupine, water hemlock, swainsonine-containing plants, selenium-containing plants, and pyrrolizidine alkaloid containing plants. Other factors such as animal age and sex that affect plant biomarker concentrations in vivo are also discussed.
Experimental Investigation of Flameholding in Scramjet Combustor by Pylon with Plasma Actuator Based on Q-DC Discharge
Authors: Firsov Aleksandr
Published: February 2023

This paper presents the results of testing and optimization of a plasma-assisted combustion scheme based on a pylon for fuel injection equipped with a plasma actuator. Electrodes were installed behind the stern of the pylon for the creation of Q-DC discharge with voltage U = 200–2500 V and current I = 3–7.5 A. The experiments were performed in the PWT-50 supersonic wind tunnel of the JIHT RAS under the following conditions: Mach number M = 2, static pressure ~200 Torr, stagnation temperature T0 = 300 K. Gaseous fuel ethylene was used and the fuel mass flow rate was 0.5–4 g/s. The pylon had a streamlined shape that prevented the formation of a stagnant zone; plasma-assisted combustion was performed under more difficult conditions compared to plasma-assisted combustion on a flat wall, where separated flows near the wall are easily formed by discharge. In this work, two new geometries of pylon equipped with electrodes were proposed and experimentally tested. A second version providing a longer discharge length demonstrates stable ignition and intense combustion in a fully discussed fuel mass flow rate. The process of ignition in a supersonic flow and flame front pulsations was described. A reduction in the energy input in comparison with the previously considered configurations of plasma-assisted combustion was also demonstrated.
Influence of Non-Uniform Bluntness on Aerodynamic Performance and Aerothermal Characteristics of Waverider
Authors: Qu Zhipeng , Wang Wanyu , Xiao Houdi , Xiao Yao , Li Guangli , Cui Kai
Published: February 2023

The waverider is widely used in hypersonic vehicles with its high aerodynamic performance, but due to the serious aerothermal environment, its sharp leading edge should be blunted. Circular blunt is one of the commonly used aerothermal characteristic protection methods. Circular blunt with larger diameter can reduce peak heat flux, but at the same time, it will lead to larger drag. The existing research shows that under the same blunt diameter in two-dimensions, the non-uniform blunt can reduce the peak heat flux by 20%, and the difference of drag is small. In this paper, the non-uniform blunt profile is applied to the three-dimensional waverider, and the influence of the non-uniform blunt profile on the aerothermal characteristic performance and aerodynamic performance of the waverider is studied, and the results are compared with those of circular blunt. The numerical simulation is used to compare and analyze the waverider under different angles of attack, flight altitudes, and Mach number. The results show that the peak heat flux of the waverider with non-uniform blunt reduces by about 17% compared with that with circular blunt under a small angle of attack range, Mach 2-10, and a flight altitude of 15–35 km. Meanwhile, when the blunt height/diameter is 20 mm, the aerodynamic performance difference between the two different blunt profiles does not exceed 3% within a 15 degrees angle of attack, Mach 2-10, and flight altitude of 15–35 km. The non-uniform blunt profile can be applied to the design of the three-dimensional waverider.
Effect of Antibiotic Compared to Non-Antibiotic Dry Cow Treatment on the Bacteriological Cure of Intramammary Infections during the Dry Period—A Retrospective Cross-Sectional Study
Authors: Müller Stephanie , Nitz Julia , Tellen Anne , Klocke Doris , Krömker Volker
Published: February 2023

Antimicrobials are widely used to cure intramammary infections (IMI) in dairy cows during the dry period (DP). Nevertheless, the IMI cure is influenced by many factors and not all quarters benefit from antimicrobial dry cow treatment (DCT). To evaluate the true effect of antibiotic DCT compared to self-cure and the role of causative pathogens on the IMI cure, a retrospective cross-sectional study was performed. The analysis included 2987 quarters infected at dry-off (DO). Information on DCT, causative pathogens, somatic cell count, milk yield, amount of lactation, Body Condition Score, and season and year of DO were combined into categorical variables. A generalized linear mixed model with a random cow, farm and year effect and the binary outcome of bacteriological cure of IMI during the DP was conducted. In the final model, a significant effect (p < 0.05) on DP cure was seen for the DO season and the category of causative pathogens (categories being: Staphylococcus aureus, non-aureus staphylococci, streptococci, coliforms, ‘other Gram-negative bacteria’, ‘other Gram positive bacteria’, non-bacterial infections and mixed infections), while antibiotic DCT (vs. non-antibiotic DCT) only showed a significant effect in combination with the pathogen categories streptococci and ‘other Gram-positive bacteria’.
Stability of Ampicillin plus Ceftriaxone Combined in Elastomeric Infusion Devices for Outpatient Parenteral Antimicrobial Therapy
Authors: Fernández-Rubio Beatriz , Herrera-Hidalgo Laura , Luque-Márquez Rafael , de Alarcón Arístides , López-Cortés Luis E. , Luque-Pardos Sonia , Gutiérrez-Urbón José María , Fernández-Polo Aurora , Gil-Navarro María V. , Gutiérrez-Valencia Alicia
Published: February 2023

Currently, ampicillin plus ceftriaxone (AC) is one of the preferred treatments for Enterococcus faecalis infective endocarditis. However, there is a lack of stability data for the combination of both drugs in elastomeric devices, so the inclusion of AC in Outpatient Parenteral Antimicrobial Therapy (OPAT) programs is challenging. The objective of the study was to determine the stability of AC in elastomeric pumps when stored at 8 ± 2 °C, 25 ± 2 °C, 30 ± 2 °C and 37 ± 2 °C using LC-MS/MS. The combination was diluted in 0.9% sodium chloride and the final concentrations were ampicillin 24 g/L plus ceftriaxone 8 g/L. Physical and chemical stability were evaluated at 12, 20, 24, 36 and 48 h after preparation. Stability was met at each time point if the percentage of intact drug was ≥90% of its respective baseline concentration and color and clearness remained unchanged. The drug combination was stable for 48 h when it was kept at 8 ± 2 °C. At 25 ± 2 °C and 30 ± 2 °C, they were stable for 24 h of storage. At 37 ± 2 °C, the stability criterion was not met at any time point. These results prove that AC could be included in OPAT programs using elastomeric infusion devices for the treatment of E. faecalis infections.
Influence of Moisture in Concrete on the Photothermal Response—A New Approach for a Measurement Method?
Authors: Krankenhagen Rainer
Published: February 2023

Recently, the photothermal determination of the thermophysical properties of concrete under lab conditions was reported. Their values are mainly needed to look at the energy consumption of buildings. Additionally, changes in their values in relation to the initial state might also be a good indicator for material quality or for moisture. The present contribution explains the photothermal method in a more general way to indicate the potential for on-site application. Secondly, a special application case is regarded: the detection of moisture in concrete. Two concrete samples were soaked with water, followed by a drying period, to obtain different levels of water penetration. The water contents were determined by weighing, and the photothermal response was measured. The results show a large influence on the measured temperature transients, which is larger than expected from the original simple model. They clearly provide two points: the photothermal method is suited to detect moisture in concrete, but the magnitude of the actual measurement effect is not yet understood.
Experimental Investigation of State and Parameter Estimation within Reconfigurable Battery Systems
Authors: Theiler Michael , Schneider Dominik , Endisch Christian
Published: February 2023

The battery system is one of the most-important, but also -critical components in the electric power-train. The battery’s system states and parameters are commonly tracked by the battery monitoring system. However, in reality, the accuracy of the state and parameter estimation may suffer from insufficient excitation of the system. Since the current states and parameters serve as the basis for many battery management system functions, this might lead to incorrect operation and severe damage. Reconfigurable battery systems allow enhancing the system’s excitation by applying a switching operation. In this contribution, the state and parameter estimation of a reconfigurable battery module were simulated and tested experimentally. Thereby, a low-exciting and a high-exciting drive cycle were compared. Furthermore, the switching patterns were applied to enhance the excitation and, hence, improve the estimation of an extended Kalman filter. The cells were switched via a pulse-width modulation signal, and the influence of frequency and duty cycle variation on the estimation accuracy were investigated. Compared to the low-excitation input, a significant improvement in the estimation of up to 46% for the state of charge and 78% for the internal resistance were achieved. Hereby, low frequencies and duty cycles proved to be particularly advantageous. Switching, however, has only a limited influence on an already highly excited system and may lead to additional aging due to higher heat generation.
Inactivation of SARS-CoV-2 on Surfaces by Cold-Plasma-Generated Reactive Species
Authors: Thomas Som V. , Dienger-Stambaugh Krista , Jordan Michael , Wang Yuxin , Hammonds Jason , Spearman Paul , Shi Donglu
Published: February 2023

A Cold Atmospheric Plasma (CAP) apparatus was designed and developed for SARS-CoV-2 killing as evaluated by pseudotyped viral infectivity assays. The reactive species generated by the plasma system was fully characterized by using Optical Emission Spectroscopy (OES) measurement under given conditions such as plasma power, flow rate, and treatment time. A variety of reactive oxygen species (ROS) and reactive nitrogen species (RNS) were identified from plasma plume with energies of 15–72 eV in the frequency range between 500–1000 nm. Systematic virus killing experiments were carried out, and the efficacy of CAP treatment in reducing SARS-CoV-2 viral infectivity was significant following treatment for 8 s, with further enhancement of killing upon longer exposures of 15–120 s. We correlated killing efficacy with the reactive species in terms of type, intensity, energy, and frequency. These experimental results demonstrate effective cold plasma virus killing via ROS and RNS under ambient conditions.
Perceptive SARS-CoV-2 End-To-End Ultrasound Video Classification through X3D and Key-Frames Selection
Authors: Gazzoni Marco , La Salvia Marco , Torti Emanuele , Secco Gianmarco , Perlini Stefano , Leporati Francesco
Published: February 2023

The SARS-CoV-2 pandemic challenged health systems worldwide, thus advocating for practical, quick and highly trustworthy diagnostic instruments to help medical personnel. It features a long incubation period and a high contagion rate, causing bilateral multi-focal interstitial pneumonia, generally growing into acute respiratory distress syndrome (ARDS), causing hundreds of thousands of casualties worldwide. Guidelines for first-line diagnosis of pneumonia suggest Chest X-rays (CXR) for patients exhibiting symptoms. Potential alternatives include Computed Tomography (CT) scans and Lung UltraSound (LUS). Deep learning (DL) has been helpful in diagnosis using CT scans, LUS, and CXR, whereby the former commonly yields more precise results. CXR and CT scans present several drawbacks, including high costs. Radiation-free LUS imaging requires high expertise, and physicians thus underutilise it. LUS demonstrated a strong correlation with CT scans and reliability in pneumonia detection, even in the early stages. Here, we present an LUS video-classification approach based on contemporary DL strategies in close collaboration with Fondazione IRCCS Policlinico San Matteo’s Emergency Department (ED) of Pavia. This research addressed SARS-CoV-2 patterns detection, ranked according to three severity scales by operating a trustworthy dataset comprising ultrasounds from linear and convex probes in 5400 clips from 450 hospitalised subjects. The main contributions of this study are related to the adoption of a standardised severity ranking scale to evaluate pneumonia. This evaluation relies on video summarisation through key-frame selection algorithms. Then, we designed and developed a video-classification architecture which emerged as the most promising. In contrast, the literature primarily concentrates on frame-pattern recognition. By using advanced techniques such as transfer learning and data augmentation, we were able to achieve an F1-Score of over 89% across all classes.
Circulating Biomarkers for Cancer Detection: Could Salivary microRNAs Be an Opportunity for Ovarian Cancer Diagnostics?
Authors: Robotti Marzia , Scebba Francesca , Angeloni Debora
Published: February 2023

MicroRNAs (miRNAs) are small non-coding RNAs with the crucial regulatory functions of gene expression at post-transcriptional level, detectable in cell and tissue extracts, and body fluids. For their stability in body fluids and accessibility to sampling, circulating miRNAs and changes of their concentration may represent suitable disease biomarkers, with diagnostic and prognostic relevance. A solid literature now describes the profiling of circulating miRNA signatures for several tumor types. Among body fluids, saliva accurately reflects systemic pathophysiological conditions, representing a promising diagnostic resource for the future of low-cost screening procedures for systemic diseases, including cancer. Here, we provide a review of literature about miRNAs as potential disease biomarkers with regard to ovarian cancer (OC), with an excursus about liquid biopsies, and saliva in particular. We also report on salivary miRNAs as biomarkers in oncological conditions other than OC, as well as on OC biomarkers other than miRNAs. While the clinical need for an effective tool for OC screening remains unmet, it would be advisable to combine within a single diagnostic platform, the tools for detecting patterns of both protein and miRNA biomarkers to provide the screening robustness that single molecular species separately were not able to provide so far.
Myositis-Specific and Myositis-Associated Antibodies in Fibromyalgia Patients: A Prospective Study
Authors: Sambataro Gianluca , Orlandi Martina , Fagone Evelina , Fruciano Mary , Gili Elisa , Libra Alessandro , Palmucci Stefano , Vancheri Carlo , Malatino Lorenzo , Colaci Michele , Sambataro Domenico
Published: February 2023

Fibromyalgia (FM) is a common rheumatologic disorder characterised by widespread muscular pain. Myalgia is also a common clinical feature in Connective Tissue Disease (CTD), and FM should be studied for the concomitant presence of a CTD. The aim of this study is to evaluate the prevalence of Myositis-Specific and Myositis-Associated Antibodies (MSA/MAA) in a cohort of FM patients. We enrolled 233 consecutive FM patients (defined according to the 2016 criteria) that did not report clinical signs of autoimmune disorders and followed them for at least one year. The patients were tested for MSA/MAA with immunoblotting. FM patients were seropositive for Antinuclear Antibodies (ANA) in 24% of cases, for MSA in 9%, and for MAA in 6%. A specific diagnosis of CTD was made in 12 patients (5.2%), namely, 5 cases of primary Sjögren’s Syndrome and 7 of Idiopathic Inflammatory Myopathy. Seropositive patients showed clinical features similar to those who were seronegative at baseline. A CTD diagnosis was associated with ANA positivity (p = 0.03, X2 4.9), the presence of a speckled pattern (p = 0.02, X2 5.3), positivity for MAA (p = 0.004, X2 8.1), and MSA (p = 0.003, X2 9.2). In conclusion, a non-negligible proportion of FM patients may be seropositive for MSA/MAA, and that seropositivity might suggest a diagnosis of CTD.
Experimental Behavior and Modelling of Steel Bolted T-Stub Connections
Authors: Liu Xiao , Hao Zhiming , Luo Xin , Jin Zhengbao
Published: February 2023

The paper comprehensively investigates the tension performance of Q355 steel T-stubs, whose nonlinear mechanical behavior is modelled by spring-slider elements. First, tension tests were conducted on seven specimens to explore the tension performance of Q355 steel T-stubs. T-stub connections were discussed in terms of their tension characteristics. Second, a numerical simulation was performed to analyze the stress distribution of T-stub components during deformation. Finally, on the basis of the tension characteristics of the T-stub connections, we constructed the constitutive model’s density function. The constitutive model’s force–displacement relationship was derived mathematically. A method for determining parameters was also developed. With the proposed model, the entire tensile behavior of T-stub connections can be described accurately while reducing the degrees of freedom at the contact interfaces, resulting in more efficient computing. Four parameters are defined physically in the model, and their values can be determined directly by macroscopic experiments.
MicroRNAs as Predictive Biomarkers in Patients with Colorectal Cancer Receiving Chemotherapy or Chemoradiotherapy: A Narrative Literature Review
Authors: Yang I-Ping , Yip Kwan-Ling , Chang Yu-Tang , Chen Yen-Cheng , Huang Ching-Wen , Tsai Hsiang-Lin , Yeh Yung-Sung , Wang Jaw-Yuan
Published: February 2023

Colorectal cancer (CRC) is one of the most common malignancies and is associated with high mortality rates worldwide. The underlying mechanism of tumorigenesis in CRC is complex, involving genetic, lifestyle-related, and environmental factors. Although radical resection with adjuvant FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin) chemotherapy and neoadjuvant chemoradiotherapy have remained mainstays of treatment for patients with stage III CRC and locally advanced rectal cancer, respectively, the oncological outcomes of these treatments are often unsatisfactory. To improve patients’ chances of survival, researchers are actively searching for new biomarkers to facilitate the development of more effective treatment strategies for CRC and metastatic CRC (mCRC). MicroRNAs (miRs), small, single-stranded, noncoding RNAs, can post-transcriptionally regulate mRNA translation and trigger mRNA degradation. Recent studies have documented aberrant miR levels in patients with CRC or mCRC, and some miRs are reportedly associated with chemoresistance or radioresistance in CRC. Herein, we present a narrative review of the literature on the roles of oncogenic miRs (oncomiRs) and tumor suppressor miRs (anti-oncomiRs), some of which can be used to predict the responses of patients with CRC to chemotherapy or chemoradiotherapy. Moreover, miRs may serve as potential therapeutic targets because their functions can be manipulated using synthetic antagonists and miR mimics.
Utilization of a Machine Learning Algorithm for the Application of Ancillary Features to LI-RADS Categories LR3 and LR4 on Gadoxetate Disodium-Enhanced MRI
Authors: Park Seongkeun , Byun Jieun , Hwang Sook Min
Published: February 2023

Background: This study aimed to identify the important ancillary features (AFs) and determine the utilization of a machine-learning-based strategy for applying AFs for LI-RADS LR3/4 observations on gadoxetate disodium-enhanced MRI. Methods: We retrospectively analyzed MRI features of LR3/4 determined with only major features. Uni- and multivariate analyses and random forest analysis were performed to identify AFs associated with HCC. A decision tree algorithm of applying AFs for LR3/4 was compared with other alternative strategies using McNemar’s test. Results: We evaluated 246 observations from 165 patients. In multivariate analysis, restricted diffusion and mild–moderate T2 hyperintensity showed independent associations with HCC (odds ratios: 12.4 [p < 0.001] and 2.5 [p = 0.02]). In random forest analysis, restricted diffusion is the most important feature for HCC. Our decision tree algorithm showed higher AUC, sensitivity, and accuracy (0.84, 92.0%, and 84.5%) than the criteria of usage of restricted diffusion (0.78, 64.5%, and 76.4%; all p < 0.05); however, our decision tree algorithm showed lower specificity than the criterion of usage of restricted diffusion (71.1% vs. 91.3%; p < 0.001). Conclusion: Our decision tree algorithm of applying AFs for LR3/4 shows significantly increased AUC, sensitivity, and accuracy but reduced specificity. These appear to be more appropriate in certain circumstances in which there is an emphasis on the early detection of HCC.
Current and Emerging Techniques for Diagnosis and MRD Detection in AML: A Comprehensive Narrative Review
Authors: Teixeira Alexandra , Carreira Luís , Abalde-Cela Sara , Sampaio-Marques Belém , Areias Anabela C. , Ludovico Paula , Diéguez Lorena
Published: February 2023

Acute myeloid leukemia (AML) comprises a group of hematologic neoplasms characterized by abnormal differentiation and proliferation of myeloid progenitor cells. AML is associated with poor outcome due to the lack of efficient therapies and early diagnostic tools. The current gold standard diagnostic tools are based on bone marrow biopsy. These biopsies, apart from being very invasive, painful, and costly, have low sensitivity. Despite the progress uncovering the molecular pathogenesis of AML, the development of novel detection strategies is still poorly explored. This is particularly important for patients that check the criteria for complete remission after treatment, since they can relapse through the persistence of some leukemic stem cells. This condition, recently named as measurable residual disease (MRD), has severe consequences for disease progression. Hence, an early and accurate diagnosis of MRD would allow an appropriate therapy to be tailored, improving a patient’s prognosis. Many novel techniques with high potential in disease prevention and early detection are being explored. Among them, microfluidics has flourished in recent years due to its ability at processing complex samples as well as its demonstrated capacity to isolate rare cells from biological fluids. In parallel, surface-enhanced Raman scattering (SERS) spectroscopy has shown outstanding sensitivity and capability for multiplex quantitative detection of disease biomarkers. Together, these technologies can allow early and cost-effective disease detection as well as contribute to monitoring the efficiency of treatments. In this review, we aim to provide a comprehensive overview of AML disease, the conventional techniques currently used for its diagnosis, classification (recently updated in September 2022), and treatment selection, and we also aim to present how novel technologies can be applied to improve the detection and monitoring of MRD.
A Comprehensive Analysis of Immune Response in Patients with Non-Muscle-Invasive Bladder Cancer
Authors: Celada Luis Guillermo , Albers Acosta Eduardo , de la Fuente Hortensia , Velasco Balanza Clara , Arroyo Correas Montserrat , Romero-Laorden Nuria , Alfranca Arantzazu , Olivier Gómez Carlos
Published: February 2023

Background. Bladder carcinoma has elevated morbimortality due to its high recurrence and progression in localized disease. A better understanding of the role of the tumor microenvironment in carcinogenesis and response to treatment is needed. Methods. Peripheral blood and samples of urothelial bladder cancer and adjacent healthy urothelial tissue were collected from 41 patients and stratified in low- and high-grade urothelial bladder cancer, excluding muscular infiltration or carcinoma in situ. Mononuclear cells were isolated and labeled for flow cytometry analysis with antibodies aimed at identifying specific subpopulations within T lymphocytes, myeloid cells and NK cells. Results. In peripheral blood and tumor samples, we detected different percentages of CD4+ and CD8+ lymphocytes, monocyte and myeloid-derived suppressor cells, as well as differential expression of activation- and exhaustion-related markers. Conversely, only a significant increase in bladder total monocytes was found when comparing bladder and tumor samples. Interestingly, we identified specific markers differentially expressed in the peripheral blood of patients with different outcomes. Conclusion. The analysis of host immune response in patients with NMIBC may help to identify specific markers that allow optimizing therapy and patient follow-up. Further investigation is needed to establish a strong predictive model.
HNRNPA2B1-Mediated MicroRNA-92a Upregulation and Section Acts as a Promising Noninvasive Diagnostic Biomarker in Colorectal Cancer
Authors: Li Yiling , Li Kexin , Lou Xiaoying , Wu Yue , Seery Samuel , Xu Danfei , Pei Yuqing , Qian Benheng , Wu Yuxin , Liang Shuang , Wu Kui , Cui Wei
Published: February 2023

MicroRNA-92a (miR-92a) may serve as a novel promising biomarker in multiple cancers, including colorectal cancer (CRC); however, the diagnostic accuracy and the underlying molecular mechanism of miR-92a in CRC is poorly understood. We first carried out meta-analysis and found that serum/plasma miR-92a yield better diagnostic efficacy when compared to stool samples and CRC tissues, and this finding was validated by our independent study through stool sample. Multiple bioinformatics assay indicated that miR-92a expression was positively correlated with heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1) expression and closely related with the clinical characteristics of CRC. Experimental evidence showed that knockdown of HNRNPA2B1 could significantly decrease miR-92a expression and secretion in RKO cells. HNRNPA2B1 mediated miR-92a via m6A RNA modification. These findings indicate that HNRNPA2B1-m6A RNA modification-derived MicroRNA-92a upregulation and section from the local CRC acts a candidate noninvasive serum biomarker in colorectal cancer. Our study provides a novel insight into miR-92a mechanisms in relation to both expression and secretion for CRC diagnosis.
Contribution of Mitochondrial Activity to Doxorubicin-Resistance in Osteosarcoma Cells
Authors: Giacomini Isabella , Cortini Margherita , Tinazzi Mattia , Baldini Nicola , Cocetta Veronica , Ragazzi Eugenio , Avnet Sofia , Montopoli Monica
Published: February 2023

Osteosarcoma is considered the most common bone tumor affecting children and young adults. The standard of care is chemotherapy; however, the onset of drug resistance still jeopardizes osteosarcoma patients, thus making it necessary to conduct a thorough investigation of the possible mechanisms behind this phenomenon. In the last decades, metabolic rewiring of cancer cells has been proposed as a cause of chemotherapy resistance. Our aim was to compare the mitochondrial phenotype of sensitive osteosarcoma cells (HOS and MG-63) versus their clones when continuously exposed to doxorubicin (resistant cells) and identify alterations exploitable for pharmacological approaches to overcome chemotherapy resistance. Compared with sensitive cells, doxorubicin-resistant clones showed sustained viability with less oxygen-dependent metabolisms, and significantly reduced mitochondrial membrane potential, mitochondrial mass, and ROS production. In addition, we found reduced expression of TFAM gene generally associated with mitochondrial biogenesis. Finally, combined treatment of resistant osteosarcoma cells with doxorubicin and quercetin, a known inducer of mitochondrial biogenesis, re-sensitizes the doxorubicin effect in resistant cells. Despite further investigations being needed, these results pave the way for the use of mitochondrial inducers as a promising strategy to re-sensitize doxorubicin cytotoxicity in patients who do not respond to therapy or reduce doxorubicin side effects.
Methylated Cell-Free DNA Sequencing (MeD-seq) of LpnPI Digested Fragments to Identify Early Progression in Metastatic Renal Cell Carcinoma Patients on Watchful Waiting
Authors: Bos Manouk K. , Verhoeff Sarah R. , Oosting Sjoukje F. , Menke-van der Houven van Oordt Willemien C. , Boers Ruben G. , Boers Joachim B. , Gribnau Joost , Martens John W. M. , Sleijfer Stefan , van Herpen Carla M. L. , Wilting Saskia M.
Published: February 2023

According to the current guidelines, watchful waiting (WW) is a feasible option for patients with good or intermediate prognosis renal-cell carcinoma (RCC). However, some patients rapidly progress during WW, requiring the initiation of treatment. Here, we explore whether we can identify those patients using circulating cell-free DNA (cfDNA) methylation. We first defined a panel of RCC-specific circulating methylation markers by intersecting differentially methylated regions from a publicly available dataset with known RCC methylation markers from the literature. The resulting RCC-specific methylation marker panel of 22 markers was subsequently evaluated for an association with rapid progression by methylated DNA sequencing (MeD-seq) in serum from 10 HBDs and 34 RCC patients with a good or intermediate prognosis starting WW in the IMPACT-RCC study. Patients with an elevated RCC-specific methylation score compared to HBDs had a shorter progression-free survival (PFS, p = 0.018), but not a shorter WW-time (p = 0.15). Cox proportional hazards regression showed that only the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) criteria were significantly associated with WW time (HR 2.01, p = 0.01), whereas only our RCC-specific methylation score (HR 4.45, p = 0.02) was significantly associated with PFS. The results of this study suggest that cfDNA methylation is predictive of PFS but not WW.
The Gut-Prostate Axis: A New Perspective of Prostate Cancer Biology through the Gut Microbiome
Authors: Fujita Kazutoshi , Matsushita Makoto , De Velasco Marco A. , Hatano Koji , Minami Takafumi , Nonomura Norio , Uemura Hirotsugu
Published: February 2023

Obesity and a high-fat diet are risk factors associated with prostate cancer, and lifestyle, especially diet, impacts the gut microbiome. The gut microbiome plays important roles in the development of several diseases, such as Alzheimer’s disease, rheumatoid arthritis, and colon cancer. The analysis of feces from patients with prostate cancer by 16S rRNA sequencing has uncovered various associations between altered gut microbiomes and prostate cancer. Gut dysbiosis caused by the leakage of gut bacterial metabolites, such as short-chain fatty acids and lipopolysaccharide results in prostate cancer growth. Gut microbiota also play a role in the metabolism of androgen which could affect castration-resistant prostate cancer. Moreover, men with high-risk prostate cancer share a specific gut microbiome and treatments such as androgen-deprivation therapy alter the gut microbiome in a manner that favors prostate cancer growth. Thus, implementing interventions aiming to modify lifestyle or altering the gut microbiome with prebiotics or probiotics may curtail the development of prostate cancer. From this perspective, the “Gut–Prostate Axis” plays a fundamental bidirectional role in prostate cancer biology and should be considered when screening and treating prostate cancer patients.
State of the Art: ctDNA in Upper Gastrointestinal Malignancies
Authors: Labiano Ibone , Huerta Ana Elsa , Arrazubi Virginia , Hernandez-Garcia Irene , Mata Elena , Gomez David , Arasanz Hugo , Vera Ruth , Alsina Maria
Published: February 2023

Circulating tumor DNA (ctDNA) has emerged as a promising non-invasive source to characterize genetic alterations related to the tumor. Upper gastrointestinal cancers, including gastroesophageal adenocarcinoma (GEC), biliary tract cancer (BTC) and pancreatic ductal adenocarcinoma (PADC) are poor prognostic malignancies, usually diagnosed at advanced stages when no longer amenable to surgical resection and show a poor prognosis even for resected patients. In this sense, ctDNA has emerged as a promising non-invasive tool with different applications, from early diagnosis to molecular characterization and follow-up of tumor genomic evolution. In this manuscript, novel advances in the field of ctDNA analysis in upper gastrointestinal tumors are presented and discussed. Overall, ctDNA analyses can help in early diagnosis, outperforming current diagnostic approaches. Detection of ctDNA prior to surgery or active treatment is also a prognostic marker that associates with worse survival, while ctDNA detection after surgery is indicative of minimal residual disease, anticipating in some cases the imaging-based detection of progression. In the advanced setting, ctDNA analyses characterize the genetic landscape of the tumor and identify patients for targeted-therapy approaches, and studies show variable concordance levels with tissue-based genetic testing. In this line, several studies also show that ctDNA serves to follow responses to active therapy, especially in targeted approaches, where it can detect multiple resistance mechanisms. Unfortunately, current studies are still limited and observational. Future prospective multi-center and interventional studies, carefully designed to assess the value of ctDNA to help clinical decision-making, will shed light on the real applicability of ctDNA in upper gastrointestinal tumor management. This manuscript presents a review of the evidence available in this field up to date.
The Anti-Tumor Effect of the Newly Developed LAT1 Inhibitor JPH203 in Colorectal Carcinoma, According to a Comprehensive Analysis
Authors: Otani Rina , Takigawa Hidehiko , Yuge Ryo , Shimizu Daisuke , Ariyoshi Misa , Miyamoto Ryo , Kadota Hiroki , Hiyama Yuichi , Hayashi Ryohei , Urabe Yuji , Ishikawa Akira , Oue Naohide , Kitadai Yasuhiko , Oka Shiro , Tanaka Shinji
Published: February 2023

A novel large neutral amino acid transporter 1 (LAT1)-specific inhibitor, JPH203, is expected to cause cancer-specific starvation and possess anti-tumor effects; however, its anti-tumor mechanism for colorectal cancer (CRC) remains unclear. We analyzed LAT family gene expressions in public databases using UCSC Xena and evaluated LAT1 protein expression using immunohistochemistry in 154 cases of surgically resected CRC. We also evaluated mRNA expression using polymerase chain reaction in 10 CRC cell lines. Furthermore, JPH203 treatment experiments were conducted in vitro and in vivo using an allogeneic immune-responsive mouse model with abundant stroma created via the orthotopic transplantation of the mouse-derived CRC cell line CT26 and mesenchymal stem cells. The treatment experiments were followed by comprehensive gene expression analyses with RNA sequencing. Database analyses and immunohistochemistry research on clinical specimens revealed that LAT1 expression was cancer-dominant, and its increase was accompanied by tumor progression. In vitro, JPH203 was effective in an LAT1 expression-dependent manner. In vivo, JPH203 treatment considerably reduced tumor size and metastasis, and RNA sequencing-based pathway analysis showed that not only tumor growth and amino acid metabolism pathways, but also stromal activation-related pathways were suppressed. The results of the RNA sequencing were validated in the clinical specimens, as well as both in vitro and in vivo. LAT1 expression in CRC plays an important role in tumor progression. JPH203 may inhibit the progression of CRC and tumor stromal activity.
Genomic Alterations, Gene Expression Profiles and Functional Enrichment of Normal-Karyotype Acute Myeloid Leukaemia Based on Targeted Next-Generation Sequencing
Authors: Ambayya Angeli , Razali Rozaimi , Sulong Sarina , Zulkefli Ezzanie Suffya , Yap Yee Yee , Sathar Jameela , Hassan Rosline
Published: February 2023

Characterising genomic variants is paramount in understanding the pathogenesis and heterogeneity of normal-karyotype acute myeloid leukaemia (AML-NK). In this study, clinically significant genomic biomarkers were ascertained using targeted DNA sequencing and RNA sequencing on eight AML-NK patients’ samples collected at disease presentation and after complete remission. In silico and Sanger sequencing validations were performed to validate variants of interest, and they were followed by the performance of functional and pathway enrichment analyses for overrepresentation analysis of genes with somatic variants. Somatic variants involving 26 genes were identified and classified as follows: 18/42 (42.9%) as pathogenic, 4/42 (9.5%) as likely pathogenic, 4/42 (9.5%) as variants of unknown significance, 7/42 (16.7%) as likely benign and 9/42 (21.4%) as benign. Nine novel somatic variants were discovered, of which three were likely pathogenic, in the CEBPA gene with significant association with its upregulation. Transcription misregulation in cancer tops the affected pathways involving upstream genes (CEBPA and RUNX1) that were deregulated in most patients during disease presentation and were closely related to the most enriched molecular function gene ontology category, DNA-binding transcription activator activity RNA polymerase II-specific (GO:0001228). In summary, this study elucidated putative variants and their gene expression profiles along with functional and pathway enrichment in AML-NK patients.
The Mother-Baby Bond: Role of Past and Current Relationships
Authors: Bianciardi Emanuela , Ongaretto Francesca , De Stefano Alberto , Siracusano Alberto , Niolu Cinzia
Published: February 2023

During the perinatal period, up to 25% of women experience difficulties in relating to their child. The mother-child bond promotes the transition to motherhood, protects the woman from depression, and protects the child from the intergenerational transmission of the disease. This study prospectively investigated if the relationship with the co-parent, the attachment style, and the bond that women had with their parents influenced the mother-fetus and then mother-child bond. We also explored the role of depression and anxiety. One hundred nineteen pregnant women were enrolled. We administered clinical interviews and psychometric tools. A telephone interview was conducted at 1, 3, and 6 months of follow-up. Maternal insecure attachment style (r = −0.253, p = 0.006) and women’s dyadic adjustment in the couple’s relationships (r = 0.182, p = 0.049) were correlated with lower maternal–fetal attachment. Insecure attachment styles and depression correlate with bottle-feeding rather than breastfeeding. The bond women had with their mothers, not their fathers, was associated with breastfeeding. Depression (OR = 0.243, p = 0.008) and anxiety (OR = 0.185, p = 0.004; OR = 0.304, p < 0.0001) were related to mother-infant bonding. Close relationships, past and present, affect the bond with the fetus and the child differently. Psychotherapy can provide reassuring and restorative intersubjective experiences.
Performances of Holiday Climate Index (HCI) for Urban and Beach Destinations in Sri Lanka under Changing Climate
Authors: Samarasinghe Jayanga T. , Wickramarachchi Charuni P. , Makumbura Randika K. , Meddage Pasindu , Gunathilake Miyuru B. , Muttil Nitin , Rathnayake Upaka
Published: February 2023

Climate change has had a significant impact on the tourism industry in many countries, leading to changes in policies and adaptations to attract more visitors. However, there are few studies on the effects of climate change on Sri Lanka’s tourism industry and income, despite its importance as a destination for tourists. A study was conducted to analyze the holiday climate index (HCI) for Sri Lanka’s urban and beach destinations to address this gap. The analysis covered historical years (2010–2018) and forecasted climatic scenarios (2021–2050 and 2071–2100), and the results were presented as colored maps to highlight the importance of HCI scores. Visual analysis showed some correlation between HCI scores and tourist arrivals, but the result of the overall correlation analysis was not significant. However, a country-specific correlation analysis revealed interesting findings, indicating that the changing climate can be considered among other factors that impact tourist arrivals. The research proposes that authorities assess the outcomes of the study and conduct further research to develop adaptive plans for Sri Lanka’s future tourism industry. The study also investigated potential scenarios for beach and urban destinations under two climate scenarios (RCP 4.5 and RCP 8.5) for the near and far future, presenting the findings to tourism industry stakeholders for any necessary policy changes. As Sri Lanka expects more Chinese visitors in the future due to ongoing development projects, this study could be valuable for policymakers and industry stakeholders when adapting to changing climate and future tourist behavior. While more research is needed to fully understand the effects of climate change on Sri Lanka’s tourism industry, this study serves as a starting point for future investigations.