bluuebunny/crossref_metadata_2025 huggingface dataset:
Stereo Digital Image Correlation in MATLAB
Authors: Atkinson Devan , Becker Thorsten Hermann
Published: May 2021

Digital Image Correlation (DIC) has found widespread use in measuring full-field displacements and deformations experienced by a body from images captured of it. Stereo-DIC has received significantly more attention than two-dimensional (2D) DIC since it can account for out-of-plane displacements. Although many aspects of Stereo-DIC that are shared in common with 2D DIC are well documented, there is a lack of resources that cover the theory of Stereo-DIC. Furthermore, publications which do detail aspects of the theory do not detail its implementation in practice. This literature gap makes it difficult for newcomers to the field of DIC to gain a deep understanding of the Stereo-DIC process, although this knowledge is necessary to contribute to the development of the field by either furthering its capabilities or adapting it for novel applications. This gap in literature acts as a barrier thereby limiting the development rate of Stereo-DIC. This paper attempts to address this by presenting the theory of a subset-based Stereo-DIC framework that is predominantly consistent with the current state-of-the-art. The framework is implemented in practice as a 202 line MATLAB code. Validation of the framework shows that it performs on par with well-established Stereo-DIC algorithms, indicating it is sufficiently reliable for practical use. Although the framework is designed to serve as an educational resource, its modularity and validation make it attractive as a means to further the capabilities of DIC.
Line-of-Sight Winds and Doppler Effect Smearing in ACE-FTS Solar Occultation Measurements
Authors: Boone Chris D. , Steffen Johnathan , Crouse Jeff , Bernath Peter F.
Published: May 2021

Line-of-sight wind profiles are derived from Doppler shifts in infrared solar occultation measurements from the Atmospheric Chemistry Experiment Fourier transform spectrometers (ACE-FTS), the primary instrument on SCISAT, a satellite-based mission for monitoring the Earth’s atmosphere. Comparisons suggest a possible eastward bias from 20 m/s to 30 m/s in ACE-FTS results above 80 km relative to some datasets but no persistent bias relative to other datasets. For instruments operating in a limb geometry, looking through a wide range of altitudes, smearing of the Doppler effect along the line of sight can impact the measured signal, particularly for saturated absorption lines. Implications of Doppler effect smearing are investigated for forward model calculations and volume mixing ratio retrievals. Effects are generally small enough to be safely ignored, except for molecules having a large overhang in their volume mixing ratio profile, such as carbon monoxide.
Special Issue: 10th Anniversary of Atmosphere: Climatology and Meteorology
Authors: Lupo Anthony R. , Chernokulsky Alexander V. , Gimeno Luis , Mao Jiafu , Matzarakis Andreas , Tzanis Chris G. , Yi Chuixiang
Published: May 2021

During the last decade, the number of open access science journals has increased, and these have become an avenue for publishing quality science in a relatively fast and economical way [...]
Model Sensitivity Evaluation for 3DVAR Data Assimilation Applied on WRF with a Nested Domain Configuration
Authors: Lam Mingchun , Fung Jimmy Chihung
Published: May 2021

An initial condition that closely represents the true atmospheric state can minimize errors that propagate into the future, and could theoretically lead to improvements in the forecast. This study aims to evaluate and understand the impacts of 3DVAR on the state-of-the-art Weather Research and Forecasting (WRF) model with a two nested domains setup. The domain configuration of the model covers China with an emphasis on Guangdong province, with a resolution of 27 km, 9 km, and 3 km. Improvements in the forecasts for the Winter and Summer season of all the domains are systematically compared and are quantified in terms of 2 m temperature, 10 m wind speed, sea level pressure, and 2 m relative humidity. The results show that 3DVAR provides significant improvements in the winter case and surprisingly improvements were also found after the 48 h of the forecast. Evaluations of performance of 3DVAR in different domains and between two different seasons were done to further understand the reasons behind the discrepancies.
Towards a Structural Mechanism for Sister Chromatid Cohesion Establishment at the Eukaryotic Replication Fork
Authors: Henrikus Sarah S. , Costa Alessandro
Published: May 2021

Cohesion between replicated chromosomes is essential for chromatin dynamics and equal segregation of duplicated genetic material. In the G1 phase, the ring-shaped cohesin complex is loaded onto duplex DNA, enriching at replication start sites, or “origins”. During the same phase of the cell cycle, and also at the origin sites, two MCM helicases are loaded as symmetric double hexamers around duplex DNA. During the S phase, and through the action of replication factors, cohesin switches from encircling one parental duplex DNA to topologically enclosing the two duplicated DNA filaments, which are known as sister chromatids. Despite its vital importance, the structural mechanism leading to sister chromatid cohesion establishment at the replication fork is mostly elusive. Here we review the current understanding of the molecular interactions between the replication machinery and cohesin, which support sister chromatid cohesion establishment and cohesin function. In particular, we discuss how cryo-EM is shedding light on the mechanisms of DNA replication and cohesin loading processes. We further expound how frontier cryo-EM approaches, combined with biochemistry and single-molecule fluorescence assays, can lead to understanding the molecular basis of sister chromatid cohesion establishment at the replication fork.
Silencing of Histone Deacetylase 6 Decreases Cellular Malignancy and Contributes to Primary Cilium Restoration, Epithelial-to-Mesenchymal Transition Reversion, and Autophagy Inhibition in Glioblastoma Cell Lines
Authors: Urdiciain Alejandro , Erausquin Elena , Zelaya María V. , Zazpe Idoya , Lanciego José L. , Meléndez Bárbara , Rey Juan A. , Idoate Miguel A. , Riobo-Del Galdo Natalia A. , Castresana Javier S.
Published: May 2021

Glioblastoma multiforme, the most common type of malignant brain tumor as well as the most aggressive one, lacks an effective therapy. Glioblastoma presents overexpression of mesenchymal markers Snail, Slug, and N-Cadherin and of the autophagic marker p62. Glioblastoma cell lines also present increased autophagy, overexpression of mesenchymal markers, Shh pathway activation, and lack of primary cilia. In this study, we aimed to evaluate the role of HDAC6 in the pathogenesis of glioblastoma, as HDAC6 is the most overexpressed of all HDACs isoforms in this tumor. We treated glioblastoma cell lines with siHDAC6. HDAC6 silencing inhibited proliferation, migration, and clonogenicity of glioblastoma cell lines. They also reversed the mesenchymal phenotype, decreased autophagy, inhibited Shh pathway, and recovered the expression of primary cilia in glioblastoma cell lines. These results demonstrate that HDAC6 might be a good target for glioblastoma treatment.
In Silico Studies on Sennidines—Natural Dianthrones from Senna
Authors: Szymanski Sebastian , Majerz Irena
Published: May 2021

The rapid development of technology allows for more accurate research of biological systems with the use of in silico methods. One of the tools is the quantum-chemical method used for determining the structure, properties and interactions of molecules of great pharmacological importance. The accuracy of theoretical models is increasing and can be a real help in biology, chemistry and pharmacy. The aim of the study is to determine the spatial structure and intramolecular interactions of sennidines—natural pharmaceutical substances present in Senna species. Calculations carried out in the gas-phase and in the solvent model, compared with the available experimental data indicate the possibility of sennidines to form conformers. QTAIM and NCI analysis suggests the presence of many intramolecular interactions in the sennidin structure. Taking into account the lowest energy optimized structure, it can be predicted that the sennidin in the gauche conformation will be present in the plant material. The single C-C bond connecting the anthrone moieties is elongated and its reduced Bond Dissociation Energy (BDE) could be the cause of an easy breakdown of the sennidin molecule into monoanthrones. This work contains data on theoretical, vibrational and electron excitation spectra, which can be used in the analysis of experimental samples.
Associations between the Severity of the Post-Acute COVID-19 Syndrome and Echocardiographic Abnormalities in Previously Healthy Outpatients Following Infection with SARS-CoV-2
Authors: Tudoran Cristina , Tudoran Mariana , Pop Gheorghe Nicusor , Giurgi-Oncu Catalina , Cut Talida Georgiana , Lazureanu Voichita Elena , Oancea Cristian , Parv Florina , Ciocarlie Tudor , Bende Felix
Published: May 2021

The COVID-19 pandemic affected over 130 million individuals during more than one year. Due to the overload of health-care services, a great number of people were treated as outpatients, many of them subsequently developing post-acute COVID-19 syndrome. Our study was conducted on 150 subjects without a history of cardiovascular diseases, treated as outpatients for a mild/moderate form of COVID-19 4 to 12 weeks prior to study inclusion, and who were diagnosed with post-acute COVID-19 and attended a cardiology evaluation with transthoracic echocardiography (TTE) for persisting symptoms. We detected various cardiac abnormalities in 38 subjects (25.33%), including pulmonary hypertension (9.33%), impaired left ventricular performance (8.66%), diastolic dysfunction (14%) and/or evidence of pericarditis (10%). We highlighted statistically significant correlations between the intensity of symptoms and quality of life scores with the severity of initial pulmonary injury, the number of weeks since COVID-19 and with TTE parameters characterizing the systolic and diastolic performance and pulmonary hypertension (p < 0.001). (Post-acute COVID-19 is a complex syndrome characterized by various symptoms, the intensity of which seem to be related to the severity and the time elapsed since the acute infection, and with persisting cardiac abnormalities.
Biocompatibility and Antibiofilm Properties of Calcium Silicate-Based Cements: An In Vitro Evaluation and Report of Two Clinical Cases
Authors: Bossù Maurizio , Mancini Patrizia , Bruni Erika , Uccelletti Daniela , Preziosi Adele , Rulli Marco , Relucenti Michela , Donfrancesco Orlando , Iaculli Flavia , Di Giorgio Gianni , Matassa Roberto , Salucci Alessandro , Polimeni Antonella
Published: May 2021

Calcium silicate-based cements have reached excellent levels of performance in endodontics, providing predictable and successful results. To better assess the properties of these bioactive materials, the present study aimed to compare the biocompatibility and antibiofilm properties of ProRoot MTA and Biodentine. Human osteogenic sarcoma (Saos-2) cells were cultured on ProRoot MTA and Biodentine samples or in the presence of both cement extracts. Cell viability assay, measurement of reactive oxygen species (ROS), immunofluorescence analysis, as well as morphological evaluations were conducted. Moreover, Streptococcus mutans was used to assess the biofilm forming ability on ProRoot MTA and Biodentine disks. Finally, both cements were applied in vivo to treat immature permanent teeth affected by reversible pulpitis. Results: Cell viability assay demonstrated that Saos-2 cells had a dose- and time-dependent cytotoxicity to both analyzed cements, although cells exposed to ProRoot MTA showed a better cell vitality than those exposed to Biodentine (p < 0.001). Both cements demonstrated ROS production while this was greater in the case of Biodentine than ProRoot MTA (p < 0.001). Immunofluorescence images of the cytoskeleton and focal adhesions showed no differences in Saos-2 cells grown in the presence of ProRoot MTA eluate; whereas in the Biodentine groups, cells showed a morphology and focal adhesions more similar to that of the control sample, as the eluate concentration decreased. Morphological analysis revealed that Saos-2 cells were more flattened and exhibited better spreading when attached to ProRoot MTA disks than to Biodentine ones. The antibiofilm properties showed a time-dependent powerful inhibition of S. mutans superficial colonization and an antibiofilm effect of both cements. Clinically, complete root formation of the treated elements was achieved using the two studied cements, showing stable results over time. ProRoot MTA and Biodentine was demonstrated to be biocompatible and to possess antibiofilm properties. Their clinical application in vital pulp therapy provided successful outcomes after 2 years of follow-up.
Natriuretic Peptides Regulate Prostate Cells Inflammatory Behavior: Potential Novel Anticancer Agents for Prostate Cancer
Authors: Mezzasoma Letizia , Talesa Vincenzo Nicola , Costanzi Egidia , Bellezza Ilaria
Published: May 2021

Inflammation, by inducing a tumor-promoting microenvironment, is a hallmark for prostate cancer (PCa) progression. NOD-like receptor protein 3 (NLRP3)-inflammasome activation, interleukin-1β (IL-1β) secretion, and cancer cell-released extracellular vesicles (EVs) contribute to the establishment of tumor microenvironment. We have shown that PC3-derived EVs (PC3-EVs) activate inflammasome cascade in non-cancerous PNT2 cells. It is known that the endogenous biomolecules and Natriuretic Peptides (NPs), such as ANP and BNP, inhibit inflammasome activation in immune cells. Here we investigated whether ANP and BNP modify PCa inflammatory phenotype in vitro. By using PNT2, LNCaP, and PC3 cell lines, which model different PCa progression stages, we analyzed inflammasome activation and the related pathways by Western blot and IL-1β secretion by ELISA. We found that tumor progression is characterized by constitutive inflammasome activation, increased IL-1β secretion, and reduced endogenous NPs expression. The administration of exogenous ANP and BNP, via p38-MAPK or ERK1/2-MAPK, by inducing NLRP3 phosphorylation, counteract inflammasome activation and IL-1β maturation in PC3 and PC3-EVs-treated PNT2 cells, respectively. Our results demonstrate that NPs, by interfering with cell-specific signaling pathways, exert pleiotropic anti-inflammatory effects converging toward inflammasome phosphorylation and suggest that NPs can be included in a drug repurposing process for PCa.
3D Cell Culture Models in COVID-19 Times: A Review of 3D Technologies to Understand and Accelerate Therapeutic Drug Discovery
Authors: de Dios-Figueroa Guadalupe Tonantzin , Aguilera-Marquez Janette del Rocío , Camacho-Villegas Tanya A. , Lugo-Fabres Pavel H.
Published: May 2021

In the last decades, emerging viruses have become a worldwide concern. The fast and extensive spread of the disease caused by SARS-CoV-2 (COVID-19) has impacted the economy and human activity worldwide, highlighting the human vulnerability to infectious diseases and the need to develop and optimize technologies to tackle them. The three-dimensional (3D) cell culture models emulate major tissue characteristics such as the in vivo virus–host interactions. These systems may help to generate a quick response to confront new viruses, establish a reliable evaluation of the pathophysiology, and contribute to therapeutic drug evaluation in pandemic situations such as the one that humanity is living through today. This review describes different types of 3D cell culture models, such as spheroids, scaffolds, organoids, and organs-on-a-chip, that are used in virus research, including those used to understand the new severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2).
Impact of Carbon Felt Electrode Pretreatment on Anodic Biofilm Composition in Microbial Electrolysis Cells
Authors: Spiess Sabine , Kucera Jiri , Seelajaroen Hathaichanok , Sasiain Amaia , Thallner Sophie , Kremser Klemens , Novak David , Guebitz Georg M. , Haberbauer Marianne
Published: May 2021

Sustainable technologies for energy production and storage are currently in great demand. Bioelectrochemical systems (BESs) offer promising solutions for both. Several attempts have been made to improve carbon felt electrode characteristics with various pretreatments in order to enhance performance. This study was motivated by gaps in current knowledge of the impact of pretreatments on the enrichment and microbial composition of bioelectrochemical systems. Therefore, electrodes were treated with poly(neutral red), chitosan, or isopropanol in a first step and then fixed in microbial electrolysis cells (MECs). Four MECs consisting of organic substance-degrading bioanodes and methane-producing biocathodes were set up and operated in batch mode by controlling the bioanode at 400 mV vs. Ag/AgCl (3M NaCl). After 1 month of operation, Enterococcus species were dominant microorganisms attached to all bioanodes and independent of electrode pretreatment. However, electrode pretreatments led to a decrease in microbial diversity and the enrichment of specific electroactive genera, according to the type of modification used. The MEC containing isopropanol-treated electrodes achieved the highest performance due to presence of both Enterococcus and Geobacter. The obtained results might help to select suitable electrode pretreatments and support growth conditions for desired electroactive microorganisms, whereby performance of BESs and related applications, such as BES-based biosensors, could be enhanced.
Association of Severe Retinopathy of Prematurity and Bronchopulmonary Dysplasia with Adverse Neurodevelopmental Outcomes in Preterm Infants without Severe Brain Injury
Authors: Bae Seong Phil , Shin Seung Han , Yoon Young Mi , Kim Ee-Kyung , Kim Han-Suk
Published: May 2021

Although impaired neurodevelopment is strongly associated with severe brain injury, most preterm infants survive without severe brain injury. In this study, the association of impaired neurodevelopment and neonatal morbidities of preterm infants was assessed after excluding those with severe brain injury. This was a retrospective study of very low birthweight infants in a single tertiary center. After excluding infants with severe brain injury, the study population was categorized as infants without intraventricular hemorrhage (IVH) and with low-grade IVH. Neurodevelopmental outcomes at a corrected age (CA) of 18–24 months were evaluated using the Bayley Scales of Infant and Toddler Development 3rd Edition (Bayley-III). Cerebral palsy (CP), hearing impairment and blindness were also assessed and compared. Of 240 infants, 25 (11.6%) infants had combined neurodevelopmental impairment (NDI). In the multivariate analysis for combined NDI, small for gestational age (SGA) (adjusted OR 6.820, 95% confidence intervals (CI) 1.770–26.307), moderate to severe bronchopulmonary dysplasia (BPD) (aOR 3.21, 95% CI 1.032–9.999) and severe retinopathy of prematurity (ROP) (aOR 5.669, 95% CI 1.132–28.396) were associated with combined NDI. Among neonatal morbidities, moderate to severe BPD and severe ROP were associated with adverse neurodevelopmental outcomes in preterm infants without severe brain injury.
Classification of Prefrontal Cortex Activity Based on Functional Near-Infrared Spectroscopy Data upon Olfactory Stimulation
Authors: Chen Cheng-Hsuan , Shyu Kuo-Kai , Lu Cheng-Kai , Jao Chi-Wen , Lee Po-Lei
Published: May 2021

The sense of smell is one of the most important organs in humans, and olfactory imaging can detect signals in the anterior orbital frontal lobe. This study assessed olfactory stimuli using support vector machines (SVMs) with signals from functional near-infrared spectroscopy (fNIRS) data obtained from the prefrontal cortex. These data included odor stimuli and air state, which triggered the hemodynamic response function (HRF), determined from variations in oxyhemoglobin (oxyHb) and deoxyhemoglobin (deoxyHb) levels; photoplethysmography (PPG) of two wavelengths (raw optical red and near-infrared data); and the ratios of data from two optical datasets. We adopted three SVM kernel functions (i.e., linear, quadratic, and cubic) to analyze signals and compare their performance with the HRF and PPG signals. The results revealed that oxyHb yielded the most efficient single-signal data with a quadratic kernel function, and a combination of HRF and PPG signals yielded the most efficient multi-signal data with the cubic function. Our results revealed superior SVM analysis of HRFs for classifying odor and air status using fNIRS data during olfaction in humans. Furthermore, the olfactory stimulation can be accurately classified by using quadratic and cubic kernel functions in SVM, even for an individual participant data set.
Thrombospondin-2 and LDH Are Putative Predictive Biomarkers for Treatment with Everolimus in Second-Line Metastatic Clear Cell Renal Cell Carcinoma (MARC-2 Study)
Authors: Zeuschner Philip , Hölters Sebastian , Stöckle Michael , Seliger Barbara , Mueller Anja , Bachmann Hagen S. , Grünwald Viktor , Christoph Daniel C. , Stenzl Arnulf , Grimm Marc-Oliver , Brüning Fabian , Goebell Peter J. , Augustin Marinela , Roos Frederik , Harde Johanna , Benz-Rüd Iris , Staehler Michael , Junker Kerstin
Published: May 2021

There is an unmet need for predictive biomarkers in metastatic renal cell carcinoma (mRCC) therapy. The phase IV MARC-2 trial searched for predictive blood biomarkers in patients with predominant clear cell mRCC who benefit from second-line treatment with everolimus. In an exploratory approach, potential biomarkers were assessed employing proteomics, ELISA, and polymorphism analyses. Lower levels of angiogenesis-related protein thrombospondin-2 (TSP-2) at baseline (≤665 parts per billion, ppb) identified therapy responders with longer median progression-free survival (PFS; ≤665 ppb at baseline: 6.9 months vs. 1.8, p = 0.005). Responders had higher lactate dehydrogenase (LDH) levels in serum two weeks after therapy initiation (>27.14 nmol/L), associated with a longer median PFS (3.8 months vs. 2.2, p = 0.013) and improved overall survival (OS; 31.0 months vs. 14.0 months, p < 0.001). Baseline TSP-2 levels had a stronger relation to PFS (HR 0.36, p = 0.008) than baseline patient parameters, including IMDC score. Increased serum LDH levels two weeks after therapy initiation were the best predictor for OS (HR 0.21, p < 0.001). mTOR polymorphisms appeared to be associated with therapy response but were not significant. Hence, we identified TSP-2 and LDH as promising predictive biomarkers for therapy response on everolimus after failure of one VEGF-targeted therapy in patients with clear cell mRCC.
Phosphorous Magnetic Resonance Spectroscopy to Detect Regional Differences of Energy and Membrane Metabolism in Naïve Glioblastoma Multiforme
Authors: Walchhofer Lisa Maria , Steiger Ruth , Rietzler Andreas , Kerschbaumer Johannes , Freyschlag Christian Franz , Stockhammer Günther , Gizewski Elke Ruth , Grams Astrid Ellen
Published: May 2021

Background: Glioblastoma multiforme (GBM) is a highly malignant primary brain tumor with infiltration of, on conventional imaging, normal-appearing brain parenchyma. Phosphorus magnetic resonance spectroscopy (31P-MRS) enables the investigation of different energy and membrane metabolites. The aim of this study is to investigate regional differences of 31P-metabolites in GBM brains. Methods: In this study, we investigated 32 patients (13 female and 19 male; mean age 63 years) with naïve GBM using 31P-MRS and conventional MRI. Contrast-enhancing (CE), T2-hyperintense, adjacent and distant ipsilateral areas of the contralateral brain and the brains of age- and gender-matched healthy volunteers were assessed. Moreover, the 31P-MRS results were correlated with quantitative diffusion parameters. Results: Several metabolite ratios between the energy-dependent metabolites and/or the membrane metabolites differed significantly between the CE areas, the T2-hyperintense areas, the more distant areas, and even the brains of healthy volunteers. pH values and Mg2+ concentrations were highest in visible tumor areas and decreased with distance from them. These results are in accordance with the literature and correlated with quantitative diffusion parameters. Conclusions: This pilot study shows that 31P-MRS is feasible to show regional differences of energy and membrane metabolism in brains with naïve GBM, particularly between the different “normal-appearing” regions and between the contralateral hemisphere and healthy controls. Differences between various genetic mutations or clinical applicability for follow-up monitoring have to be assessed in a larger cohort.
TNFα Enhances Tamoxifen Sensitivity through Dissociation of ERα-p53-NCOR1 Complexes in ERα-Positive Breast Cancer
Authors: Kim Hyunhee , Park Seung-Ho , Lee Jangho , Sung Gi-Jun , Song Ji-Hye , Kwak Sungmin , Jeong Ji-Hoon , Kong Min-Jeong , Hwang Jin-Taek , Choi Hyo-Kyoung , Choi Kyung-Chul
Published: May 2021

Tamoxifen is widely used as a medication for estrogen receptor α (ERα)-positive breast cancer, despite the ~50% incidence of tamoxifen resistance. To overcome such resistance, combining tamoxifen with other agents is considered an effective approach. Here, through in vitro studies with ER-positive MCF7 cells and ER-negative MDA-MB-231 cells, validated by the use of xenograft mice, we investigated the potential of tumor necrosis factor α (TNFα) to enhance tamoxifen sensitivity and identified NCOR1 as a key downstream regulator. TNFα specifically degraded nuclear receptor corepressor 1 (NCOR1) in MCF7 cells. Moreover, knockdown of NCOR1, similar to TNFα treatment, suppressed cancer cell growth and promoted apoptosis only in MCF7 cells and MCF7 xenograft mice through the stabilization of p53, a tumor suppressor protein. Interestingly, NCOR1 knockdown with TNFα treatment increased the occupancy of p53 at the p21 promoter, while decreasing that of ERα. Notably, NCOR1 formed a complex with p53 and ERα, which was disrupted by TNFα. Finally, combinatorial treatment with tamoxifen, TNFα and short–hairpin (sh)-NCOR1 resulted in enhanced suppression of tumor growth in MCF7 xenograft mice compared to single tamoxifen treatment. In conclusion, TNFα promoted tamoxifen sensitivity through the dissociation of the ERα-p53-NCOR1 complex, pointing at NCOR1 as a putative therapeutic target for overcoming tamoxifen resistance in ERα-positive breast cancer.
The Long-Term Prognostic Significance of Circulating Tumor Cells in Ovarian Cancer—A Study of the OVCAD Consortium
Authors: Obermayr Eva , Reiner Angelika , Brandt Burkhard , Braicu Elena Ioana , Reinthaller Alexander , Loverix Liselore , Concin Nicole , Woelber Linn , Mahner Sven , Sehouli Jalid , Vergote Ignace , Zeillinger Robert
Published: May 2021

Introduction: We previously reported the prognostic impact of circulating tumor cells (CTCs) in a multicenter study on minimal residual disease in primary ovarian cancer. With additional follow-up data, we evaluated the combined CTC approach (CTCscombo), in particular for the patients who had survived more than five years. Material and Methods: Blood samples taken at baseline and six months after adjuvant treatment (follow-up) were assessed by quantitative PCR (qPCR) measuring PPIC transcripts and immunofluorescent staining (IF). A positive result with either IF or qPCR was classified as CTCcombo-positive. Further, PPIC was assessed in the primary tumor tissue. Results: The concordance of IF and qPCR was 65% at baseline and 83% after treatment. Results showed that 50.5% of the baseline and 29.5% of the follow-up samples were CTCcombo-positive. CTCscombo after treatment were associated with increased mortality after adjusting for FIGO stage (HR 2.574, 95% CI: 1.227–5.398, p = 0.012), a higher risk of recurrence after adjusting for peritoneal carcinosis (HR 4.068, 95% CI: 1.948–8.498, p < 0.001), and increased mortality after five survived years. Discussion: The two-sided analytical approach revealed CTC subpopulations associated with ovarian cancer progression and may illuminate a potential treatment-related shift in molecular phenotypes. That approach can identify patients who have elevated risk of recurrence and death due to ovarian cancer and who may require risk-adapted treatment strategies.
Comparative Efficacy and Safety of Programmed Death-1 Pathway Inhibitors in Advanced Gastroesophageal Cancers: A Systematic Review and Network Meta-Analysis of Phase III Clinical Trials
Authors: da Silva Laercio Lopes , Aguiar Pedro Nazareth , Park Robin , Edelman Saul Eduardo , Haaland Benjamin , de Lima Lopes Gilberto
Published: May 2021

Background: The use of checkpoint inhibitors has changed the treatment landscape for gastroesophageal cancer in the third-line setting. However, success rates in earlier treatment lines are highly variable across trials. Herein, we compare the efficacy and safety of the different anti-PD-1/PD-L1 regimens with or without chemotherapy; Methods: We performed a network meta-analysis (NMA) of anti-PD-1/PD-L1 monotherapy or combined with chemotherapy (chemoimmunotherapy) for gastroesophageal cancers without ERBB2 overexpression; Results: The first-line NMA included four trials (N = 3817), showing that chemoimmunotherapy improved OS and PFS without significant safety difference: Nivolumab-chemotherapy, OS (HR: 0.83 [95% CI, 0.75–0.92]), PFS (HR 0.68 [95% CI, 0.57–0.81]), Pembrolizumab-chemotherapy: OS (HR 0.77 [95% CI, 0.67–0.88]), PFS (HR: 0.72 [95% CI, 0.60–0.85]. Pembrolizumab monotherapy was the safest first-line treatment, SAE (OR 0.02 [95% CI, 0.00–0.2]) but showed no survival benefit. The second-line NMA encompassed four trials (N = 2087), showing that anti-PD-1 significantly improved safety but not survival: camrelizumab, SAE (OR 0.37; [95% CI, 0.24–0.56]); nivolumab, SAE (OR 0.13, [95% CI, 0.08–0.2]) pembrolizumab, SAE (OR 0.4; [95% CI, 0.30–0.53]); Conclusions: chemoimmunotherapy improves OS and PFS in previously untreated gastroesophageal cancers. Anti-PD-1 monotherapies improve safety in refractory disease, with no significant survival benefit.
Intravesical Bacillus Calmette–Guérin Treatment for T1 High-Grade Non-Muscle Invasive Bladder Cancer with Divergent Differentiation or Variant Morphologies
Authors: Miyake Makito , Nishimura Nobutaka , Iida Kota , Fujii Tomomi , Nishikawa Ryoma , Teraoka Shogo , Takenaka Atsushi , Kikuchi Hiroshi , Abe Takashige , Shinohara Nobuo , Okajima Eijiro , Shimizu Takuto , Hori Shunta , Tsuchiya Norihiko , Owari Takuya , Murakami Yasukiyo , Taoka Rikiya , Kobayashi Takashi , Kojima Takahiro , Nishiyama Naotaka , Kitamura Hiroshi , Nishiyama Hiroyuki , Fujimoto Kiyohide
Published: May 2021

The 2016 World Health Organization classification newly described infiltrating urothelial carcinoma (UC) with divergent differentiation (DD) or variant morphologies (VMs). Data comparing oncological outcomes after bladder-preservation therapy using intravesical Bacillus Calmette–Guérin (BCG) treatment among T1 bladder pure UC (pUC), UC with DD (UC-DD), and UC with VMs (UC-VM) are limited. We evaluated 1490 patients with T1 high-grade bladder UC who received intravesical BCG during 2000–2019. They were classified into three groups: 93.6% with pUC, 4.4% with UC-DD, and 2.0% with UC-VM. Recurrence-free, progression-free, and cancer-specific survival following intravesical BCG were compared among the groups using multivariate Cox regression analysis, also used to estimate inverse probability of treatment weighting-adjusted hazard ratio and 95% confidence interval for the outcomes. Glandular differentiation and micropapillary variant were the most common forms in the UC-DD and UC-VM groups, respectively. Of 1490 patients, 31% and 13% experienced recurrence and progression, respectively, and 5.0% died of bladder cancer. Survival analyses revealed the impact of concomitant VMs was significant for cancer-specific survival, but not recurrence-free and progression-free survival compared with that of pUC. Our analysis clearly demonstrated that concomitant VMs were associated with aggressive behavior in contrast to concomitant DD in patients treated with intravesical BCG.
Complete Metabolic Response in FDG-PET-CT Scan before Discontinuation of Immune Checkpoint Inhibitors Correlates with Long Progression-Free Survival
Authors: Schank Timo E. , Forschner Andrea , Sachse Michael Max , Dimitrakopoulou-Strauss Antonia , Sachpekidis Christos , Stenzinger Albrecht , Volckmar Anna-Lena , Enk Alexander , Hassel Jessica C.
Published: May 2021

Checkpoint inhibitors have revolutionized the treatment of patients with metastasized melanoma. However, it remains unclear when to stop treatment. We retrospectively analyzed 45 patients (median age 64 years; 58% male) with metastasized melanoma from 3 cancer centers that received checkpoint inhibitors and discontinued therapy due to either immune-related adverse events or patient decision after an (18F)2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) combined with a low-dose CT scan (FDG-PET-CT) scan without signs for disease progression. After a median of 21 (range 1–42) months of immunotherapy an FDG-PET-CT scan was performed to evaluate disease activity. In these, 32 patients (71%) showed a complete metabolic response (CMR) and 13 were classified as non-CMR. After a median follow-up of 34 (range 1–70) months, 3/32 (9%) of CMR patients and 6/13 (46%) of non-CMR patients had progressed (p = 0.007). Progression-free survival (PFS), as estimated from the date of last drug administration, was significantly longer among CMR patients than non-CMR (log-rank: p = 0.001; hazard ratio: 0.127; 95% CI: 0.032–0.511). Two-year PFS was 94% among CMR patients and 62% among non-CMR patients. Univariable Cox regression showed that metabolic response was the only parameter which predicted PFS (p = 0.004). Multivariate analysis revealed that metabolic response predicted disease progression (p = 0.008). In conclusion, our findings suggest that patients with CMR in an FDG-PET-CT scan may have a favorable outcome even if checkpoint inhibition is discontinued.
The Clinical Relevance of Target Lymph Node Biopsy after Primary Systemic Therapy in Initially Node-Positive Breast Cancer Patients
Authors: Hartmann Steffi , Stachs Angrit , Schultek Gesche , Gerber Bernd , Reimer Toralf
Published: May 2021

Purpose: To assess the impact of the removal of the target lymph node (TLN) on therapy after the completion of primary systemic therapy (PST) in initially node-positive breast cancer patients. Methods: Pooled data analysis of participants of the prospective CLIP- and TATTOO-study at the University of Rostock was performed. Results: A total of 75 patients were included; 63 of them (84.0%) converted to clinically node-negative after PST. Both TLN and sentinel lymph node (SLN) were identified in 41 patients (51.2%). In five out of 63 patients (7.9%), the TLN was metastatic after PST and the SLN was either tumor-free or not detected. Axillary lymph node dissection (ALND) was conducted in all five patients. In one patient, systemic therapy recommendation was influenced by the TLN; adjuvant radiotherapy was influenced by the TLN in zero patients. For patients with fewer than three removed SLNs, the FNR was 28.6% for the SLN biopsy alone and 7.1% for targeted axillary dissection (TAD). Conclusions: Removal of the TLN in addition to the SLN after PST has only minimal impact on the type of adjuvant systemic therapy and radiotherapy. However, the extent of axillary surgery was relevantly affected and FNR was improved by TAD.
CDH1 Gene Mutation Hereditary Diffuse Gastric Cancer Outcomes: Analysis of a Large Cohort, Systematic Review of Endoscopic Surveillance, and Secondary Cancer Risk Postulation
Authors: Benesch Matthew G. K. , Bursey Stuart R. , O’Connell Andrew C. , Ryan Morag G. , Howard Carrie L. , Stockley Cecily C. , Mathieson Alexander
Published: May 2021

Hereditary diffuse gastric cancer (HDGC) is a rare signet-ring cell adenocarcinoma (SRCC) linked to CDH1 (E-cadherin) inactivating germline mutations, and increasingly other gene mutations. Female CDH1 mutation carriers have additional risk of lobular breast cancer. Risk management includes prophylactic total gastrectomy (PTG). The utility of endoscopic surveillance is unclear, as early disease lacks macroscopic lesions. The current systematic biopsy protocols have unknown efficacy, and other secondary cancer risks are postulated. We conducted a retrospective study of consecutive asymptomatic HDGC patients undergoing PTG, detailing endoscopic, pathologic, and outcome results. A systematic review compared endoscopic biopsy foci detection via random sampling versus Cambridge Protocol against PTG findings. A population-level secondary-cancer-risk postulation among sporadic gastric SRCC patients was completed using the Surveillance, Epidemiology, and End Results database. Of 97 patients, 67 underwent PTG, with 25% having foci detection on random endoscopic biopsy despite 75% having foci on final pathology. There was no improvement in the endoscopic detection rate by Cambridge Protocol. The postulated hazard ratio among sporadic gastric SRCC patients for a secondary colorectal SRCC was three-fold higher, relative to conventional adenocarcinoma patients. Overall, HDGC patients should not rely on endoscopic surveillance to delay PTG, and may have secondary SRCC risks. A definitive determination of actual risk requires collaborative patient outcome data banking.
Experimental and Physico-Chemical Comparison of ZnO Nanoparticles’ Activity for Photocatalytic Applications in Wastewater Treatment
Authors: Alberti Stefano , Basciu Irene , Vocciante Marco , Ferretti Maurizio
Published: May 2021

In this contribution, the photoactivity upon activation by simulated sunlight of zinc oxide (ZnO) obtained from two different synthetic pathways (Acetate and Nitrate) is investigated for water purification. Different reagents and processes were exploited to obtain ZnO nanoparticles. Products have been characterized by means of X-Ray Diffraction, Scanning Electron Microscopy along with Energy Dispersive Spectrometer, Dynamic Light Scattering, and Diffuse Reflectance Measurements, to highlight the different outcomes ascribable to each synthesis. A comparison of characteristics and performances was also carried out with respect to commercial ZnO. Nanoparticles of this semiconductor can be obtained as aggregates with different degrees of purity, porosity, and shape, and their physical-chemical properties have been addressed to the specific use in wastewater treatment, testing their effectiveness on the photocatalytic degradation of methylene blue (MB) as a model pollutant. Excluding the commercial sample, experimental results evidenced a better photocatalytic behavior for the ZnO Nitrate sample annealed at 500 °C, which was found to be pure and stable in water, suggesting that ZnO could be effectively exploited as a heterogeneous photocatalyst for the degradation of emerging pollutants in water, provided that thermal treatment is included in the synthetic process.
Hallmarks of Aging in Macrophages: Consequences to Skin Inflammaging
Authors: Guimarães Gabriela Rapozo , Almeida Palloma Porto , de Oliveira Santos Leandro , Rodrigues Leane Perim , de Carvalho Juliana Lott , Boroni Mariana
Published: May 2021

The skin is our largest organ and the outermost protective barrier. Its aging reflects both intrinsic and extrinsic processes resulting from the constant insults it is exposed to. Aging in the skin is accompanied by specific epigenetic modifications, accumulation of senescent cells, reduced cellular proliferation/tissue renewal, altered extracellular matrix, and a proinflammatory environment favoring undesirable conditions, including disease onset. Macrophages (Mφ) are the most abundant immune cell type in the skin and comprise a group of heterogeneous and plastic cells that are key for skin homeostasis and host defense. However, they have also been implicated in orchestrating chronic inflammation during aging. Since Mφ are related to innate and adaptive immunity, it is possible that age-modified skin Mφ promote adaptive immunity exacerbation and exhaustion, favoring the emergence of proinflammatory pathologies, such as skin cancer. In this review, we will highlight recent findings pertaining to the effects of aging hallmarks over Mφ, supporting the recognition of such cell types as a driving force in skin inflammaging and age-related diseases. We will also present recent research targeting Mφ as potential therapeutic interventions in inflammatory skin disorders and cancer.
The C0-C1f Region of Cardiac Myosin Binding Protein-C Induces Pro-Inflammatory Responses in Fibroblasts via TLR4 Signaling
Authors: Yogeswaran Athiththan , Troidl Christian , McNamara James W. , Wilhelm Jochen , Truschel Theresa , Widmann Laila , Aslam Muhammad , Hamm Christian W. , Sadayappan Sakthivel , Lipps Christoph
Published: May 2021

Myocardial injury is associated with inflammation and fibrosis. Cardiac myosin-binding protein-C (cMyBP-C) is cleaved by µ-calpain upon myocardial injury, releasing C0-C1f, an N-terminal peptide of cMyBP-C. Previously, we reported that the presence of C0-C1f is pathogenic within cardiac tissue and is able to activate macrophages. Fibroblasts also play a crucial role in cardiac remodeling arising from ischemic events, as they contribute to both inflammation and scar formation. To understand whether C0-C1f directly modulates fibroblast phenotype, we analyzed the impact of C0-C1f on a human fibroblast cell line in vitro by performing mRNA microarray screening, immunofluorescence staining, and quantitative real-time PCR. The underlying signaling pathways were investigated by KEGG analysis and determined more precisely by targeted inhibition of the potential signaling cascades in vitro. C0-C1f induced pro-inflammatory responses that might delay TGFβ-mediated myofibroblast conversion. TGFβ also counteracted C0-C1f-mediated fibroblast activation. Inhibition of TLR4 or NFκB as well as the delivery of miR-146 significantly reduced C0-C1f-mediated effects. In conclusion, C0-C1f induces inflammatory responses in human fibroblasts that are mediated via TRL4 signaling, which is decreased in the presence of TGFβ. Specific targeting of TLR4 signaling could be an innovative strategy to modulate C0-C1f-mediated inflammation.
Heterogeneous Photocatalysis
Authors: Muñoz-Batista Mario J. , Luque Rafael
Published: May 2021

Heterogeneous photocatalysis is a subtype of catalysis that refers to chemical processes catalysed by a semiconductor solid under proper illumination conditions [...]
Molecularly Imprinted Polymers for Chemical Sensing: A Tutorial Review
Authors: Leibl Nadja , Haupt Karsten , Gonzato Carlo , Duma Luminita
Published: May 2021

The field of molecularly imprinted polymer (MIP)-based chemosensors has been experiencing constant growth for several decades. Since the beginning, their continuous development has been driven by the need for simple devices with optimum selectivity for the detection of various compounds in fields such as medical diagnosis, environmental and industrial monitoring, food and toxicological analysis, and, more recently, the detection of traces of explosives or their precursors. This review presents an overview of the main research efforts made so far for the development of MIP-based chemosensors, critically discusses the pros and cons, and gives perspectives for further developments in this field.
Baseline Examinations and Autoclave Tests of 65 and 100 dpa Flux Thimble Tube O-Ring Specimens
Authors: Karlsen Wade , Toivonen Aki , Efsing Pål
Published: May 2021

This paper describes the methods and results of analytical TEM examinations and autoclave testing of two highly-irradiated flux thimble tube materials harvested from a commercial pressurized water reactor. The materials are cold-worked 316L, and accumulated 65 dpa and 100 dpa of radiation dose. To set the baseline for a broader study, the materials were examined in the as-irradiated condition and tested as O-ring specimens at relatively high constant loads in simulated PWR water conditions. Tests were also conducted with elevated hydrogen. For a given load, more rapid cracking was associated with higher radiation dose, and with the elevated hydrogen.
Effects of Trace Oxygen Content on Microstructure and Performances of Au-20Sn/Cu Solder Joints
Authors: Li Yang , Wu Di , Zhang Yabin , Wang Liujue , Xue Songbai
Published: May 2021

The Au-20Sn solder is widely used in the packaging of high-end electronic products, and the requirement on the reliability of the solder joints is more and more strict with a continuous increase in the performance of the package products. As the oxygen content in the Au-Sn solder is a key factor dominating the quality of fluxless packaging, in this study, the wettability and spreading performance of the Au-20Sn solder with different oxygen contents and the interfacial microstructure, mechanical properties, gas tightness and ratio of soldering area of the Au-Sn/Cu solder joints prepared using these solders were comprehensively investigated to clarify the effects of trace oxygen content. The results reveal that the wetting and spreading performances of the solder decrease sharply with increasing oxygen conte[nt. When the oxygen content increased from 18 to 77 ppm, the spreading area of the solder on the Cu substrate decreased from 92.8 to 49.2 mm2, reducing by 47%. Meanwhile, pores and microcracks appear in the solder joint with relatively high oxygen content, making the shear strength decrease from 56.6 to 31.7 MPa. The oxygen also greatly affects the gas tightness and ratio of soldering area. For the optical window packaged using Au-Sn solder containing 40 ppm of oxygen, the leakage rate was higher than 5 × 10−11 mbar·m−3·s−1 and cannot fulfill the requirements. With increasing oxygen content in the Au-Sn solder, the cleanliness of the chip packaged with these solders deteriorated, and the solder surface was obviously oxidized. When the oxygen content was 18 ppm, the ratio of soldering area was 92%, but decreased sharply to 53% when the oxygen content increased to 77 ppm. It is demonstrated that an oxygen content lower than 27 ppm is required for the Au-20Sn solder used in fluxless packaging.
Stygobiont Diversity in the San Marcos Artesian Well and Edwards Aquifer Groundwater Ecosystem, Texas, USA
Authors: Hutchins Benjamin T. , Gibson J. Randy , Diaz Peter H. , Schwartz Benjamin F.
Published: May 2021

The Edwards Aquifer and related Edwards-Trinity Aquifer of Central Texas, USA, is a global hotspot of stygobiont biodiversity. We summarize 125 years of biological investigation at the San Marcos Artesian Well (SMAW), the best studied and most biodiverse groundwater site (55 stygobiont taxa: 39 described and 16 undescribed) within the Edwards Aquifer Groundwater Ecosystem. Cluster analysis and redundancy analysis (RDA) incorporating temporally derived, distance-based Moran’s Eigenvector Mapping (dbMem) illustrate temporal dynamics in community composition in 85 high-frequency samples from the SMAW. Although hydraulic variability related to precipitation and discharge partially explained changes in community composition at the SMAW, a large amount of temporal autocorrelation between samples remains unexplained. We summarize potential mechanisms by which hydraulic changes can affect community structure in deep, phreatic karst aquifers. We also compile information on 12 other Edwards and Edwards-Trinity Aquifer sites with 10 or more documented stygobionts and used distance-based RDA to assess the relative influences of distance and site type on three measures of β-diversity. Distance between sites was the most important predictor of total dissimilarity and replacement, although site type was also important. Species richness difference was not predicted by either distance or site type.