bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of F10.7, Sunspot Number and Photon Flux Data for Ionosphere TEC Modeling and Prediction Using Machine Learning Techniques
Authors: Benoit Andres Gilberto Machado da Silva , Petry Adriano
Published: September 2021

Considering the growing volumes and varieties of ionosphere data, it is expected that automation of analytical model building using modern technologies could lead to more accurate results. In this work, machine learning techniques are applied to ionospheric modeling and prediction using sun activity data. We propose Total Electron Content (TEC) spectral analysis, using discrete cosine transform (DCT) to evaluate the relation to the solar features F10.7, sunspot number and photon flux data. The ionosphere modeling procedure presented is based on the assessment of a six-year period (2014–2019) of data. Different multi-dimension regression models were considered in experiments, where each geographic location was independently evaluated using its DCT frequency components. The features correlation analysis has shown that 5-year data seem more adequate for training, while learning curves revealed overfitting for polynomial regression from the 4th to 7th degrees. A qualitative evaluation using reconstructed TEC maps indicated that the 3rd degree polynomial regression also seems inadequate. For the remaining models, it can be noted that there is seasonal variation in root-mean-square error (RMSE) clearly related to the equinox (lower error) and solstice (higher error) periods, which points to possible seasonal adjustment in modeling. Elastic Net regularization was also used to reduce global RMSE values down to 2.80 TECU for linear regression.
Detection of Spatial Rainfall Variation over the Andean Region Demonstrated by Satellite-Based Observations
Authors: Shrestha Dibas , Sharma Shankar , Talchabhadel Rocky , Deshar Rashila , Hamal Kalpana , Khadka Nitesh , Nakamura Kenji
Published: September 2021

Topography has an important role in shaping regional and global climate systems, as it acts as a mechanical barrier to the low-level moisture flow. Thus, a complex spatial pattern of rainfall can exist over the mountainous region. Moreover, it is critical to advance our understanding of the relationship between rainfall and topography in terms of rainfall timing, frequency, and magnitude. In this study, characteristics of austral summer (December–February) precipitation are analyzed using 17-year (1998–2014) high-spatial-resolution (0.05° × 0.05°) data obtained from the Tropical Rainfall Measuring Mission (TRMM) Precipitation Radar (PR) over the Andean region focusing on topographic impact. We observe an interaction between precipitation patterns and topography, with clear precipitation–elevation relationships in the Andes regions. The rainfall maxima zone was observed over the higher terrain of the central and southern Andes, and the zone is attributed to frequency and intensity of rainfall, respectively. In the foothills of the central Andes, we find there was a persistent rain system when a moist, low-level flow was lifted due to topography. In contrast, steep mountain slopes and a relatively dry atmosphere modulate deep convection in the foothills of southern Andes.
Radiological Risk Assessment for Karstic Springs Used as Drinking Water in Rural Romania
Authors: Cucoș Alexandra Laura , Moldovan Mircea Claudiu , Burghele Bety Denissa , Dicu Tiberius , Moldovan Oana Teodora
Published: September 2021

Seasonal variations of the radon and radium activity concentrations in karstic water sources originating in karstic formations were investigated as part of a premiere systematic survey conducted in Romania. A database including a total of 228 drinking water samples collected from 30 distinct water sources adjacent to rural communities was compiled. The radon and radium activity concentrations for all seasons, assessed based on solid scintillation, ranged from 2.1 to 19.7 Bq/L and from 0.6 to 3.0 Bq/L, respectively. Overall, the detected radon and radium contents did not exceed the radioprotection standards recommended by national and European legislation. However, in at least one season, the measured values for 31% of the samples exceeded the 11.1 Bq/L maximum contaminant level for radon in drinking water recommended by the Environmental Protection Agency of the United States. The associated radiological risk, reported in terms of annual effective dose, was calculated to be between 9.8 × 10−6 and 6.0 × 10−5 mSv/y for radon and between 5.9 × 10−5 and 2.7 × 10−4 mSv/y for radium, which are considerably below the WHO (World Health Organization) guidelines at a value of 0.1 mSv/y.
Investigation of Air-Sea Turbulent Momentum Flux over the Aegean Sea with a Wind-Wave Coupling Model
Authors: Portalakis Panagiotis , Tombrou Maria , Kalogiros John , Dandou Aggeliki , Wang Qing
Published: September 2021

Near surface turbulent momentum flux estimates are performed over the Aegean Sea, using two different approaches regarding the drag coefficient formulation, a wave boundary layer model (referred here as KCM) and the most commonly used Coupled Ocean–Atmosphere Response Experiment (COARE) algorithm. The KCM model incorporates modifications in the energy-containing wave spectrum to account for the wave conditions of the Aegean Sea, and surface similarity to account for the stratification effects. Airborne turbulence data during an Etesian outbreak over Aegean Sea, Greece are processed to evaluate the simulations. KCM estimates found up to 10% higher than COARE ones, indicating that the wave-induced momentum flux may be insufficiently parameterized in COARE. Turbulent fluxes measured at about 150 m, and reduced to their surface values accounting for the vertical flux divergence, are consistently lower than the estimates. Under unstable atmospheric stratification and low to moderate wind conditions, the residuals between estimates and measurements are less than 40%. On the other hand, under stable stratification and strong winds, the majority of the residuals are more than 40%. This discrepancy is associated with the relatively high measurement level, shallow boundary layer, and the presence of a low level jet.
Crop Residue Burning in Northeast China and Its Impact on PM2.5 Concentrations in South Korea
Authors: Lee Jin-Ju , Lee Jae-Bum , Kim Okgil , Heo Gookyoung , Lee Hankyung , Lee DaeGyun , Kim Dai-gon , Lee Sang-Deok
Published: September 2021

The impact of crop residue burning in northeastern China on South Korean PM2.5 concentrations was assessed via weather conditions, air quality modeling (AQM), and PM2.5 composition data during two cases exceeding 35 µg·m−3 in November 2015. PM2.5 concentration simulations of Case 1 differed from observations by 3.7–17.6 µg·m−3, overestimating the levels by 6–36%; however, Case 2 varied by 20.0–59.8 µg·m−3 from observations, with a 53–91% underestimation. Case 1 was generally well simulated, whereas the Case 2 simulation failed because the emissions of crop residue burning in northeastern China, as confirmed through satellite analysis (MODIS fires and thermal anomalies) and previous research, were not considered. The portion of organic/elemental carbon ratio during Case 2 was 1.6–2.3 times higher than that of Case 1. These results suggest that it is necessary to consider the effects of crop residue burning in northeast China to establish countermeasures to improve air quality and air quality forecasting in South Korea.
Cognitive Function during the Prodromal Stage of Alzheimer’s Disease in Down Syndrome: Comparing Models
Authors: Hom Christy L. , Kirby Katharine A. , Ricks-Oddie Joni , Keator David B. , Krinsky-McHale Sharon J. , Pulsifer Margaret B. , Rosas Herminia Diana , Lai Florence , Schupf Nicole , Lott Ira T. , Silverman Wayne
Published: September 2021

Accurate identification of the prodromal stage of Alzheimer’s disease (AD), known as mild cognitive impairment (MCI), in adults with Down syndrome (MCI-DS) has been challenging because there are no established diagnostic criteria that can be applied for people with lifelong intellectual disabilities (ID). As such, the sequence of cognitive decline in adults with DS has been difficult to ascertain, and it is possible that domain constructs characterizing cognitive function in neurotypical adults do not generalize to this high-risk population. The present study examined associations among multiple measures of cognitive function in adults with DS, either prior to or during the prodromal stage of AD to determine, through multiple statistical techniques, the measures that reflected the same underlying domains of processing. Participants included 144 adults with DS 40–82 years of age, all enrolled in a larger, multidisciplinary study examining biomarkers of AD in adults with DS. All participants had mild or moderate lifelong intellectual disabilities. Overall AD-related clinical status was rated for each individual during a personalized consensus conference that considered performance as well as health status, with 103 participants considered cognitively stable (CS) and 41 to have MCI-DS. Analyses of 17 variables derived from 10 tests of cognition indicated that performance reflected three underlying factors: language/executive function, memory, and visuomotor. All three domain composite scores significantly predicted MCI-DS status. Based upon path modeling, the language/executive function composite score was the most affected by prodromal AD. However, based upon structural equation modeling, tests assessing the latent construct of memory were the most impacted, followed by those assessing visuomotor, and then those assessing language/executive function. Our study provides clear evidence that cognitive functioning in older adults with DS can be characterized at the cognitive domain level, but the statistical methods selected and the inclusion or exclusion of certain covariates may lead to different conclusions. Best practice requires investigators to understand the internal structure of their variables and to provide evidence that their variables assess their intended constructs.
Olfaction-Related Factors Affecting Chemosensory Dream Content in a Sleep Laboratory
Authors: Martinec Nováková Lenka , Kliková Monika , Miletínová Eva , Bušková Jitka
Published: September 2021

Mental activity in sleep often involves visual and auditory content. Chemosensory (olfactory and gustatory) experiences are less common and underexplored. The aim of the study was to identify olfaction-related factors that may affect the occurrence of chemosensory dream content. Specifically, we investigated the effects of all-night exposure to an ambient odour, participants’ appraisal of their current olfactory environment, their general propensity to notice odours and act on them (i.e., odour awareness), and their olfactory acuity. Sixty pre-screened healthy young adults underwent olfactory assessment, completed a measure of odour awareness, and spent three nights in weekly intervals in a sleep laboratory. The purpose of the first visit was to adapt to the experimental setting. On the second visit, half of them were exposed to the smell of vanillin or thioglycolic acid and the other half to an odourless control condition. On the third visit, they received control or stimulation in a balanced order. On each visit, data were collected twice: once from the first rapid eye movement (REM) stage that occurred after 3 a.m., and then shortly before getting up, usually from a non-REM stage. Participants were asked to report the presence of sensory dream content and to assess their current olfactory environment. Neither exposure, nor participants’ assessments of the ambient odour, or olfactory acuity affected reports of chemosensory dream content but they were more frequent in individuals with greater odour awareness. This finding may have implications for treatment when such experiences become unwanted or bothersome.
Onsite Quality Check for Installation of Prefabricated Wall Panels Using Laser Scanning
Authors: Wang Mudan , Wang Cynthia Changxin , Zlatanova Sisi , Sepasgozar Samad , Aleksandrov Mitko
Published: September 2021

Prefabricated construction has gained increasing popularity to meet the needs of rapid city development in recent years. Installation quality check is a critical task in prefabricated construction, and currently mostly still carried out manually, which is slow and ineffective. To provide an efficient and practical quality check method to replace the current manual method, this paper elaborates on an approach for checking prefabricated wall panels using laser scanning. The approach is validated in an actual case study. A common laser scanner BLK 360 is adopted to collect onsite 3D scenes after panel installation. The point clouds collected are co-roistered, classified, and segmented. Geometric parameters such as angles and distances allow for determining whether the installation meets the quality requirement. The outcome is compared with the quality check results using the conventional manual method. The results show that the panels, which need rectification, are correctly identified by the proposed approach. The major contribution of this study is determining the set of segmentation parameters to be adopted in similar quality check-up procedures. A practical and efficient quality check process is also proposed and can be readily implemented for certain prefabricated elements in many construction cases.
Reproducibility of CT-Based Hepatocellular Carcinoma Radiomic Features across Different Contrast Imaging Phases: A Proof of Concept on SORAMIC Trial Data
Authors: Ibrahim Abdalla , Widaatalla Yousif , Refaee Turkey , Primakov Sergey , Miclea Razvan L. , Öcal Osman , Fabritius Matthias P. , Ingrisch Michael , Ricke Jens , Hustinx Roland , Mottaghy Felix M. , Woodruff Henry C. , Seidensticker Max , Lambin Philippe
Published: September 2021

Handcrafted radiomic features (HRFs) are quantitative imaging features extracted from regions of interest on medical images which can be correlated with clinical outcomes and biologic characteristics. While HRFs have been used to train predictive and prognostic models, their reproducibility has been reported to be affected by variations in scan acquisition and reconstruction parameters, even within the same imaging vendor. In this work, we evaluated the reproducibility of HRFs across the arterial and portal venous phases of contrast-enhanced computed tomography images depicting hepatocellular carcinomas, as well as the potential of ComBat harmonization to correct for this difference. ComBat harmonization is a method based on Bayesian estimates that was developed for gene expression arrays, and has been investigated as a potential method for harmonizing HRFs. Our results show that the majority of HRFs are not reproducible between the arterial and portal venous imaging phases, yet a number of HRFs could be used interchangeably between those phases. Furthermore, ComBat harmonization increased the number of reproducible HRFs across both phases by 1%. Our results guide the pooling of arterial and venous phases from different patients in an effort to increase cohort size, as well as joint analysis of the phases.
CRISPR/Cas13-Based Platforms for a Potential Next-Generation Diagnosis of Colorectal Cancer through Exosomes Micro-RNA Detection: A Review
Authors: Durán-Vinet Benjamín , Araya-Castro Karla , Calderón Juan , Vergara Luis , Weber Helga , Retamales Javier , Araya-Castro Paulina , Leal-Rojas Pamela
Published: September 2021

Colorectal cancer (CRC) is the third most prevalent cancer with the second highest mortality rate worldwide. CRC is a heterogenous disease with multiple risk factors associated, including obesity, smoking, and use of alcohol. Of total CRC cases, 60% are diagnosed in late stages, where survival can drop to about 10%. CRC screening programs are based primarily on colonoscopy, yet this approach is invasive and has low patient adherence. Therefore, there is a strong incentive for developing molecular-based methods that are minimally invasive and have higher patient adherence. Recent reports have highlighted the importance of extracellular vesicles (EVs), specifically exosomes, as intercellular communication vehicles with a broad cargo, including micro-RNAs (miRNAs). These have been syndicated as robust candidates for diagnosis, primarily for their known activities in cancer cells, including immunoevasion, tumor progression, and angiogenesis, whereas miRNAs are dysregulated by cancer cells and delivered by cancer-derived exosomes (CEx). Quantitative polymerase chain reaction (qPCR) has shown good results detecting specific cancer-derived exosome micro-RNAs (CEx-miRNAs) associated with CRC, but qPCR also has several challenges, including portability and sensitivity/specificity issues regarding experiment design and sample quality. CRISPR/Cas-based platforms have been presented as cost-effective, ultrasensitive, specific, and robust clinical detection tools in the presence of potential inhibitors and capable of delivering quantitative and qualitative real-time data for enhanced decision-making to healthcare teams. Thereby, CRISPR/Cas13-based technologies have become a potential strategy for early CRC diagnosis detecting CEx-miRNAs. Moreover, CRISPR/Cas13-based platforms’ ease of use, scalability, and portability also showcase them as a potential point-of-care (POC) technology for CRC early diagnosis. This study presents two potential CRISPR/Cas13-based methodologies with a proposed panel consisting of four CEx-miRNAs, including miR-126, miR-1290, miR-23a, and miR-940, to streamline novel applications which may deliver a potential early diagnosis and prognosis of CRC.
Validation of Gene Expression-Based Predictive Biomarkers for Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer
Authors: Momma Tomoyuki , Okayama Hirokazu , Kanke Yasuyuki , Fukai Satoshi , Onozawa Hisashi , Fujita Shotaro , Sakamoto Wataru , Saito Motonobu , Ohki Shinji , Kono Koji
Published: September 2021

Background: Neoadjuvant chemoradiotherapy (nCRT) followed by surgery is widely used for patients with locally advanced rectal cancer. However, response to nCRT varies substantially among patients, highlighting the need for predictive biomarkers that can distinguish non-responsive from responsive patients before nCRT. This study aimed to build novel multi-gene assays for predicting nCRT response, and to validate our signature and previously-reported signatures in multiple independent cohorts. Methods: Three microarray datasets of pre-therapeutic biopsies containing a total of 61 non-responders and 53 responders were used as the discovery cohorts to screen for genes that were consistently associated with nCRT response. The predictive values of signatures were tested in a meta-analysis using six independent datasets as the validation cohorts, consisted of a total of 176 non-responders and 99 responders. Results: We identified four genes, including BRCA1, GPR110, TNIK, and WDR4 in the discovery cohorts. Although our 4-gene signature and nine published signatures were evaluated, they were unable to predict nCRT response in the validation cohorts. Conclusions: Although this is one of the largest studies addressing the validity of gene expression-based classifiers using pre-treatment biopsies from patients with rectal cancer, our findings do not support their clinically meaningful values to be predictive of nCRT response.
The Analysis of Platelet-Derived circRNA Repertoire as Potential Diagnostic Biomarker for Non-Small Cell Lung Cancer
Authors: D’Ambrosi Silvia , Visser Allerdien , Antunes-Ferreira Mafalda , Poutsma Ankie , Giannoukakos Stavros , Sol Nik , Sabrkhany Siamack , Bahce Idris , Kuijpers Marijke J. E. , Oude Egbrink Mirjam G. A. , Griffioen Arjan W. , Best Myron G. , Koppers-Lalic Danijela , Oudejans Cees , Würdinger Thomas
Published: September 2021

Tumor-educated Platelets (TEPs) have emerged as rich biosources of cancer-related RNA profiles in liquid biopsies applicable for cancer detection. Although human blood platelets have been found to be enriched in circular RNA (circRNA), no studies have investigated the potential of circRNA as platelet-derived biomarkers for cancer. In this proof-of-concept study, we examine whether the circRNA signature of blood platelets can be used as a liquid biopsy biomarker for the detection of non-small cell lung cancer (NSCLC). We analyzed the total RNA, extracted from the platelet samples collected from NSCLC patients and asymptomatic individuals, using RNA sequencing (RNA-Seq). Identification and quantification of known and novel circRNAs were performed using the accurate CircRNA finder suite (ACFS), followed by the differential transcript expression analysis using a modified version of our thromboSeq software. Out of 4732 detected circRNAs, we identified 411 circRNAs that are significantly (p-value < 0.05) differentially expressed between asymptomatic individuals and NSCLC patients. Using the false discovery rate (FDR) of 0.05 as cutoff, we selected the nuclear receptor-interacting protein 1 (NRIP1) circRNA (circNRIP1) as a potential biomarker candidate for further validation by reverse transcription–quantitative PCR (RT-qPCR). This analysis was performed on an independent cohort of platelet samples. The RT-qPCR results confirmed the RNA-Seq data analysis, with significant downregulation of circNRIP1 in platelets derived from NSCLC patients. Our findings suggest that circRNAs found in blood platelets may hold diagnostic biomarkers potential for the detection of NSCLC using liquid biopsies.
Targeted Therapies for the Evolving Molecular Landscape of Acute Myeloid Leukemia
Authors: Ahmadmehrabi Khashayar , Haque Ali R. , Aleem Ahmed , Griffiths Elizabeth A. , Roloff Gregory W.
Published: September 2021

Despite considerable growth in our understanding of the heterogeneous biology and pathogenesis of acute myeloid leukemia (AML) in recent decades, for nearly forty years, little progress was gained in the realm of novel therapeutics. Since 2017, however, nine agents have been FDA-approved for patients with AML in both the upfront and relapsed/refractory (R/R) settings. Most of these compounds function as inhibitors of key cell cycle enzymatic pathways or mediators of leukemic proliferation and survival. They have been approved both as single agents and in combination with conventional or reduced-intensity conventional chemotherapeutics. In this article, we review the molecular landscape of de novo vs. R/R AML and highlight the potential translational impact of defined molecular disease subsets. We also highlight several recent agents that have entered the therapeutic armamentarium and where they fit in the AML treatment landscape, with a focus on FLT3 inhibitors, IDH1 and IDH2 inhibitors, and venetoclax. Finally, we close with a survey of two promising novel agents under investigation that are poised to enter the mainstream clinical arena in the near future.
A New Player in Neuroblastoma: YAP and Its Role in the Neuroblastoma Microenvironment
Authors: Shim Jenny , Goldsmith Kelly C.
Published: September 2021

Neuroblastoma is the most common extra-cranial pediatric solid tumor that accounts for more than 15% of childhood cancer-related deaths. High risk neuroblastomas that recur during or after intense multimodal therapy have a <5% chance at a second sustained remission or cure. The solid tumor microenvironment (TME) has been increasingly recognized to play a critical role in cancer progression and resistance to therapy, including in neuroblastoma. The Yes-Associated Protein (YAP) in the Hippo pathway can regulate cancer proliferation, tumor initiation, and therapy response in many cancer types and as such, its role in the TME has gained interest. In this review, we focus on YAP and its role in neuroblastoma and further describe its demonstrated and potential effects on the neuroblastoma TME. We also discuss the therapeutic strategies for inhibiting YAP in neuroblastoma.
Metastasis Risk Assessment Using BAG2 Expression by Cancer-Associated Fibroblast and Tumor Cells in Patients with Breast Cancer
Authors: Yoon Chang-Ik , Ahn Sung-Gwe , Cha Yoon-Jin , Kim Dooreh , Bae Soong-June , Lee Ji-Hyung , Ooshima Akira , Yang Kyung-Min , Park Seok-Hee , Kim Seong-Jin , Jeong Joon
Published: September 2021

Few studies have examined the role of BAG2 in malignancies. We investigated the prognostic value of BAG2-expression in cancer-associated fibroblasts (CAFs) and tumor cells in predicting metastasis-free survival in patients with breast cancer. Tissue-microarray was constructed using human breast cancer tissues obtained by surgical resection between 1992 and 2015. BAG2 expression was evaluated by immunohistochemistry in CAFs or the tumor cells. BAG2 expression in the CAFs and cytoplasm of tumor cells was classified as positive and negative, and low and high, respectively. BAG2-CAF was evaluated in 310 patients and was positive in 67 (21.6%) patients. Kaplan–Meier plots showed that distant metastasis-free survival (DMFS) was lesser in patients with BAG2(+) CAF than in patients with BAG2(−) CAF (p = 0.039). Additionally, we classified the 310 patients into two groups: 109 in either BAG2-high or BAG2(+) CAF and 201 in BAG2-low and BAG2(−) CAF. DMFS was significantly reduced in patients with either BAG2-high or BAG2(+) CAF than in the patients of the other group (p = 0.005). Multivariable analysis demonstrated that DMFS was prolonged in patients with BAG2(−) CAF or BAG2-low. Evaluation of BAG2 expression on both CAFs and tumor cells could help in determining the risk of metastasis in breast cancer.
Conceptual Design of a Novel Nozzle Combined with a Clinical Proton Linac for Magnetically Focussed Minibeams
Authors: Schneider Tim , Patriarca Annalisa , Degiovanni Alberto , Gallas Manuel , Prezado Yolanda
Published: September 2021

(1) Background: Proton minibeam radiation therapy (pMBRT) is a novel therapeutic approach with the potential to significantly increase normal tissue sparing while providing tumour control equivalent or superior to standard proton therapy. For reasons of efficiency, flexibility and minibeam quality, the optimal implementation of pMBRT should use magnetically focussed minibeams which, however, could not yet be generated in a clinical environment. In this study, we evaluated our recently proposed minibeam nozzle together with a new clinical proton linac as a potential implementation. (2) Methods: Monte Carlo simulations were performed to determine under which conditions minibeams can be generated and to evaluate the robustness against focussing magnet errors. Moreover, an example of conventional pencil beam scanning irradiation was simulated. (3) Results: Excellent minibeam sizes between 0.6 and 0.9 mm full width at half maximum could be obtained and a good tolerance to errors was observed. Furthermore, the delivery of a 10 cm × 10 cm field with pencil beams was demonstrated. (4) Conclusion: The combination of the new proton linac and minibeam nozzle could represent an optimal implementation of pMBRT by allowing the generation of magnetically focussed minibeams with clinically relevant parameters. It could furthermore be used for conventional pencil beam scanning.
Whole Blood Transcriptome Profiling Identifies DNA Replication and Cell Cycle Regulation as Early Marker of Response to Anti-PD-1 in Patients with Urothelial Cancer
Authors: van Wilpe Sandra , Wosika Victoria , Ciarloni Laura , Hosseinian Ehrensberger Sahar , Jeitziner Rachel , Angelino Paolo , Duiveman-de Boer Tjitske , Koornstra Rutger H. T. , de Vries I. Jolanda M. , Gerritsen Winald R. , Schalken Jack , Mehra Niven
Published: September 2021

Although immune checkpoint inhibitors improve median overall survival in patients with metastatic urothelial cancer (mUC), only a minority of patients benefit from it. Early blood-based response biomarkers may provide a reliable way to assess response weeks before imaging is available, enabling an early switch to other therapies. We conducted an exploratory study aimed at the identification of early markers of response to anti-PD-1 in patients with mUC. Whole blood RNA sequencing and phenotyping of peripheral blood mononuclear cells were performed on samples of 26 patients obtained before and after 2 to 6 weeks of anti-PD-1. Between baseline and on-treatment samples of patients with clinical benefit, 51 differentially expressed genes (DEGs) were identified, of which 37 were upregulated during treatment. Among the upregulated genes was PDCD1, the gene encoding PD-1. STRING network analysis revealed a cluster of five interconnected DEGs which were all involved in DNA replication or cell cycle regulation. We hypothesized that the upregulation of DNA replication/cell cycle genes is a result of T cell proliferation and we were able to detect an increase in Ki-67+ CD8+ T cells in patients with clinical benefit (median increase: 1.65%, range −0.63 to 7.06%, p = 0.012). In patients without clinical benefit, no DEGs were identified and no increase in Ki-67+ CD8+ T cells was observed. In conclusion, whole blood transcriptome profiling identified early changes in DNA replication and cell cycle regulation genes as markers of clinical benefit to anti-PD-1 in patients with urothelial cancer. Although promising, our findings require further validation before implementation in the clinic.
Understanding the Catalytic Activity of Microporous and Mesoporous Zeolites in Cracking by Experiments and Simulations
Authors: Li Shih-Cheng , Lin Yen-Chun , Li Yi-Pei
Published: September 2021

Porous zeolite catalysts have been widely used in the industry for the conversion of fuel-range molecules for decades. They have the advantages of higher surface area, better hydrothermal stability, and superior shape selectivity, which make them ideal catalysts for hydrocarbon cracking in the petrochemical industry. However, the catalytic activity and selectivity of zeolites for hydrocarbon cracking are significantly affected by the zeolite topology and composition. The aim of this review is to survey recent investigations on hydrocarbon cracking and secondary reactions in micro- and mesoporous zeolites, with the emphasis on the studies of the effects of different porous environments and active site structures on alkane adsorption and activation at the molecular level. The pros and cons of different computational methods used for zeolite simulations are also discussed in this review.
All Roads Lead to Rome: Different Molecular Players Converge to Common Toxic Pathways in Neurodegeneration
Authors: Argueti-Ostrovsky Shirel , Alfahel Leenor , Kahn Joy , Israelson Adrian
Published: September 2021

Multiple neurodegenerative diseases (NDDs) such as Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS) and Huntington’s disease (HD) are being suggested to have common cellular and molecular pathological mechanisms, characterized mainly by protein misfolding and aggregation. These large inclusions, most likely, represent an end stage of a molecular cascade; however, the soluble misfolded proteins, which take part in earlier steps of this cascade, are the more toxic players. These pathological proteins, which characterize each specific disease, lead to the selective vulnerability of different neurons, likely resulting from a combination of different intracellular mechanisms, including mitochondrial dysfunction, ER stress, proteasome inhibition, excitotoxicity, oxidative damage, defects in nucleocytoplasmic transport, defective axonal transport and neuroinflammation. Damage within these neurons is enhanced by damage from the nonneuronal cells, via inflammatory processes that accelerate the progression of these diseases. In this review, while acknowledging the hallmark proteins which characterize the most common NDDs; we place specific focus on the common overlapping mechanisms leading to disease pathology despite these different molecular players and discuss how this convergence may occur, with the ultimate hope that therapies effective in one disease may successfully translate to another.
Nicotinamide Adenine Nucleotide—The Fountain of Youth to Prevent Oocyte Aging?
Authors: Kordowitzki Paweł , Ho Wing-Hong Jonathan , Listijono Dave R.
Published: September 2021

According to the U.S. Special Operations Command (SOCOM), new clinical trials of an anti-aging oral treatment using nicotinamide adenine nucleotide are planned for 2022. All over the globe, the discovery of the fountain of youth is still a great goal to reach, not only among aging researchers, since people desire to stay longer healthy and feel young when reaching old age. Since the 1960s, women delaying pregnancy to pursue higher educational levels and a career path has contributed to drastically diminished overall female fertility rates (e.g., number of born offspring/woman). Consequently, a growing number of advanced-aged women depend on assisted reproductive technologies (ART) to become pregnant. In 2019, the Society for Assisted Reproductive Technology reported 293,672 cycles for oocyte retrieval. This change of demographics influenced women’s age of having their first child, which has increased significantly. However, their reproductive tract shows hallmarks of aging very early in life without an effective preventive treatment. Therefore, we will present whether NAD+ could help to prevent oocyte aging.
Establishment and Characterization of a Novel Gill Cell Line, LG-1, from Atlantic Lumpfish (Cyclopterus lumpus L.)
Authors: Sindre Hilde , Gjessing Mona C. , Fosse Johanna Hol , Hermansen Lene C. , Böckerman Inger , Amundsen Marit M. , Dahle Maria K. , Solhaug Anita
Published: September 2021

The use of lumpfish (Cyclopterus lumpus) as a cleaner fish to fight sea lice infestation in farmed Atlantic salmon has become increasingly common. Still, tools to increase our knowledge about lumpfish biology are lacking. Here, we successfully established and characterized the first Lumpfish Gill cell line (LG-1). LG-1 are adherent, homogenous and have a flat, stretched-out and almost transparent appearance. Transmission electron microscopy revealed cellular protrusions and desmosome-like structures that, together with their ability to generate a transcellular epithelial/endothelial resistance, suggest an epithelial or endothelial cell type. Furthermore, the cells exert Cytochrome P450 1A activity. LG-1 supported the propagation of several viruses that may lead to severe infectious diseases with high mortalities in fish farming, including viral hemorrhagic septicemia virus (VHSV) and infectious hematopoietic necrosis virus (IHNV). Altogether, our data indicate that the LG-1 cell line originates from an epithelial or endothelial cell type and will be a valuable in vitro research tool to study gill cell function as well as host-pathogen interactions in lumpfish.
Effects of Fasting and Feeding on Transcriptional and Posttranscriptional Regulation of Insulin-Degrading Enzyme in Mice
Authors: González-Casimiro Carlos M. , Cámara-Torres Patricia , Merino Beatriz , Diez-Hermano Sergio , Postigo-Casado Tamara , Leissring Malcolm A. , Cózar-Castellano Irene , Perdomo Germán
Published: September 2021

Insulin-degrading enzyme (IDE) is a highly conserved and ubiquitously expressed Zn2+-metallopeptidase that regulates hepatic insulin sensitivity, albeit its regulation in response to the fasting-to-postprandial transition is poorly understood. In this work, we studied the regulation of IDE mRNA and protein levels as well as its proteolytic activity in the liver, skeletal muscle, and kidneys under fasting (18 h) and refeeding (30 min and 3 h) conditions, in mice fed a standard (SD) or high-fat (HFD) diets. In the liver of mice fed an HFD, fasting reduced IDE protein levels (~30%); whereas refeeding increased its activity (~45%) in both mice fed an SD and HFD. Likewise, IDE protein levels were reduced in the skeletal muscle (~30%) of mice fed an HFD during the fasting state. Circulating lactate concentrations directly correlated with hepatic IDE activity and protein levels. Of note, L-lactate in liver lysates augmented IDE activity in a dose-dependent manner. Additionally, IDE protein levels in liver and muscle tissues, but not its activity, inversely correlated (R2 = 0.3734 and 0.2951, respectively; p < 0.01) with a surrogate marker of insulin resistance (HOMA index). Finally, a multivariate analysis suggests that circulating insulin, glucose, non-esterified fatty acids, and lactate levels might be important in regulating IDE in liver and muscle tissues. Our results highlight that the nutritional regulation of IDE in liver and skeletal muscle is more complex than previously expected in mice, and that fasting/refeeding does not strongly influence the regulation of renal IDE.
Adaptation to Climate Change by Australian Farmers
Authors: Freebairn John
Published: September 2021

Climate change in the form of higher temperatures, changes of rainfall patterns, and for some, more natural disasters will reduce the returns from current farming choices on what to produce and the production methods. Variation of climate change across regions and uncertainty about the magnitudes of change call for a diverse mix of adaptations to climate change across different regions and individual farms. This paper considers the institutional structure for effective climate change adaptation by Australian farms. It is argued that a rerun of the history of successful adaptation of farms to new technology, changes in output and input prices, natural climate variation, and other circumstances can be repeated for climate change adaptation. Individual farms can benefit from incentives and rewards to revise their decisions, which will combine with better individual outcomes. Complementary support by the government includes the provision of climate change and weather forecast information, support for research into new technology, help to evaluate the pros and cons of alternative choices, and provision of a social safety net for those unable to adapt.
Structural Color Control of CoFeB-Coated Nanoporous Thin Films
Authors: Zhu Xiaomin , Zhao Cuicui , Zhang Weiwei , Zhang Bo , Sun Mengtao , Chen Xinhua , Belotelov Vladimir , Song Yujun
Published: September 2021

Unlike color dyes, structural colors only slightly fade during long-term usage. Here, structural colors were controllably achieved by constructing CoFeB photonic crystal layers on the surface of a nanoporous aluminum oxide (AAO) substrate by magnetron sputtering deposition. The resulting material showed a wide visible spectral response and achieved structural color control with a high resolution, high color purity, and saturation. The angle-dependent color changes of CoFeB@AAO films were further investigated by changing the incident light angle. The simulation results of the model are consistent with the experiments, which is significant in practical applications. This strategy may have great potential applications for solid structure color coatings, anti-counterfeiting and security, information storage, and electromagnetic sensors.
Yttria-Coated Tungsten Fibers for Use in Tungsten Fiber-Reinforced Composites: A Comparative Study on PVD vs. CVD Routes
Authors: Palaniyappan Saravanan , Trautmann Maik , Mao Yiran , Riesch Johann , Gowda Parikshith , Rudolph Nick , Coenen Jan Willem , Neu Rudolf , Wagner Guntram
Published: September 2021

Tungsten fiber-reinforced tungsten (Wf/W) composites are being developed to improve the intrinsic brittleness of tungsten. In these composites, engineered fiber/matrix interfaces are crucial in order to realize toughening mechanisms. For such a purpose, yttria (Y2O3), being one of the suitable interface materials, could be realized through different coating techniques. In this study, the deposition of thin films of yttria on a 150 µm tungsten wire by physical and chemical vapor deposition (PVD and CVD) techniques is comparatively investigated. Although fabrication of yttria is feasible through both CVD and PVD routes, certain coating conditions such as temperature, growth rate, oxidation of Wf, etc., decide the qualitative nature of a coating to a particular extent. In the case of PVD, the oxidation of Wf is highly reduced compared to the WO3 formation in high-temperature CVD coating processes. Yttria-coated tungsten fibers are examined comprehensively to characterize their microstructure, phase, and chemical composition using SEM, XRD, and Raman spectroscopy techniques, respectively.
The Role of Small Lowland Patches of Exotic Forests as Refuges of Rare Endemic Azorean Arthropods
Authors: Tsafack Noelline , Fattorini Simone , Boieiro Mário , Rigal François , Ros-Prieto Alejandra , Ferreira Maria Teresa , Borges Paulo A. V.
Published: September 2021

Islands have been disproportionately affected by the current biodiversity crisis. In island biotas, one of the most recurrent anthropic alterations is species introduction. Invasion of exotic species may represent a major threat for island biotas, because invasive species may change species composition and simplify community dynamics. We investigated diversity patterns of native and introduced species in native and exotic forests of Terceira Island (Azores, Portugal) by using diversity profiles based on Hill numbers. Use of diversity profiles allows for a complete characterization of the community diversity because they combine information on species richness, rarity, and dominance. We found that native forest remnants are crucial for the maintenance of endemic Azorean arthropod diversity. However, we also found that some lowland patches of exotic forests can sustain populations of rare endemic species. Our findings reinforce the importance of the few and small remnants of native forests, which are a pillar to the conservation of Azorean endemic arthropods. However, areas occupied by exotic forests, whether they are large and contiguous or small and isolated, close to native forests, or embedded in a matrix of agriculture activities, can also play a role in the conservation of native species, including endemics.
The Reproducibility of Deep Learning-Based Segmentation of the Prostate Gland and Zones on T2-Weighted MR Images
Authors: Sunoqrot Mohammed R. S. , Selnæs Kirsten M. , Sandsmark Elise , Langørgen Sverre , Bertilsson Helena , Bathen Tone F. , Elschot Mattijs
Published: September 2021

Volume of interest segmentation is an essential step in computer-aided detection and diagnosis (CAD) systems. Deep learning (DL)-based methods provide good performance for prostate segmentation, but little is known about the reproducibility of these methods. In this work, an in-house collected dataset from 244 patients was used to investigate the intra-patient reproducibility of 14 shape features for DL-based segmentation methods of the whole prostate gland (WP), peripheral zone (PZ), and the remaining prostate zones (non-PZ) on T2-weighted (T2W) magnetic resonance (MR) images compared to manual segmentations. The DL-based segmentation was performed using three different convolutional neural networks (CNNs): V-Net, nnU-Net-2D, and nnU-Net-3D. The two-way random, single score intra-class correlation coefficient (ICC) was used to measure the inter-scan reproducibility of each feature for each CNN and the manual segmentation. We found that the reproducibility of the investigated methods is comparable to manual for all CNNs (14/14 features), except for V-Net in PZ (7/14 features). The ICC score for segmentation volume was found to be 0.888, 0.607, 0.819, and 0.903 in PZ; 0.988, 0.967, 0.986, and 0.983 in non-PZ; 0.982, 0.975, 0.973, and 0.984 in WP for manual, V-Net, nnU-Net-2D, and nnU-Net-3D, respectively. The results of this work show the feasibility of embedding DL-based segmentation in CAD systems, based on multiple T2W MR scans of the prostate, which is an important step towards the clinical implementation.
Intraoperative Lung Ultrasound (ILU) for the Assessment of Pulmonary Nodules
Authors: Taurchini Marco , Quarato Carla , Frongillo Elisabetta , Ferretti Gian , Cipriani Cristiana , Bizzarri Marco , Foschino Barbaro Maria , Lacedonia Donato , Simeone Annalisa , Graziano Paolo , Dimitri Lucia , Maiello Evaristo , Cavaliere Lucio , De Cosmo Salvatore , Sperandeo Marco
Published: September 2021

Background: The primary aim of this study was to confirm the validity of intraoperative lung ultrasound (ILU) as a safe and effective method of localization for difficult to visualize pulmonary nodules during Video-Assisted Thoracoscopic Surgery (VATS) and open thoracotomy. The secondary aim was to enhance knowledge on the morphological patterns of presentation of pulmonary nodules on direct ultrasound examination. Materials and methods: 131 patients with lung nodule and indication for surgery were enrolled. All patients underwent pre-operative imaging of the chest, including Chest Computed Tomography (CT) and Transthoracic Ultrasound (TUS), and surgical procedures for histological assessment of pulmonary nodules (VATS or open thoracotomy). Results: The identification of 100.00% of lung nodules was allowed by ILU, while the detection rate of digital palpation was 94.66%. It was not possible to associate any specific ILU echostructural pattern to both benign or malignant lesions. However, the actual histological margins of the lesions in the operating samples were corresponding to those visualized at ILU in 125/131 (95.42%) cases. No complications have been reported with ILU employment. Conclusions: In our experience, ILU performed during both open surgery and VATS demonstrated to be a reliable and safe method for visualization and localization of pulmonary nodules non previously assessed on digital palpation. In addition, ILU showed to allow a clear nodule’s margins’ definition matching, in most cases, with the actual histological margins.
Associations between LncRNA MALAT1 Polymorphisms and Lymph Node Metastasis in Prostate Cancer
Authors: Hu Ju-Chuan , Wang Shian-Shiang , Chou Ying-Erh , Chiu Kun-Yuan , Li Jian-Ri , Chen Chuan-Shu , Hung Sheng-Chun , Yang Cheng-Kuang , Ou Yen-Chuan , Cheng Chen-Li , Lin Chia-Yen , Yang Shun-Fa
Published: September 2021

Current evidence elucidates that long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) could regulate genetic expression and play a crucial role in both the diagnosis and prognosis of prostate cancer. Single-nucleotide polymorphisms (SNPs) of MALAT1 could alter the oncogenesis in various cancers. However, the associations between MALAT1 SNPs and prostate cancer have barely been investigated to date. This study included 579 patients with prostate cancer who received robotic-assisted radical prostatectomy at Taichung Veterans General Hospital from 2012 to 2017. Three SNPs of MALAT1 were analyzed to identify the impacts of SNPs on the clinicopathologic features in Taiwanese prostate cancer. Our results show that patients with a polymorphic G allele at rs619586 had a significantly higher risk of being in an advanced Gleason grade group (AOR: 1.764; 95% CI: 1.011–3.077; p = 0.046). Moreover, individuals with at least one polymorphic A allele at MALAT1 rs1194338 in the PSA >10 ng/mL group were positively associated with node-positive prostate cancer. In conclusion, MALAT1 SNPs are significantly associated with the susceptibility to both advanced Gleason grade and nodal metastasis in prostate cancer. The presence of MALAT1 SNPs rs619586 and rs1194338 seems to enhance oncogenesis in prostate cancer.