bluuebunny/crossref_metadata_2025 huggingface dataset:
A Framework for Pore‐Scale Simulation of Effective Electrical Conductivity and Permittivity of Porous Media in the Frequency Range From 1 mHz to 1 GHz
Authors: Niu Qifei , Zhang Chi , Prasad Manika
Published: October 2020

Geoelectrical methods are broadly used in earth sciences for various purposes. To correctly interpret field geoelectrical data, it is essential to have a mechanistic understanding of the effective electrical conductivity and permittivity of geological materials over a broad frequency range. Recently, the pore‐scale numerical simulation, which utilizes the digital microstructural images of the material, has become a powerful tool in studying the effective electrical properties of geological media. However, it is still difficult to incorporate surface‐related electrochemical processes in a pore‐scale simulation. In this study, we develop a general framework to consider these electrochemical processes in pore‐scale simulations, which enable the calculation of broadband effective electrical conductivity and permittivity of porous geological media. A Berea sandstone sample is utilized to demonstrate the use of the proposed framework. Laboratory experiments of the effective electrical conductivity and permittivity of the sample in the frequency range from 10−3 to 109 Hz provided valuable measurement data for validating the simulation. The good agreement between our simulated spectra and the experimental data provides validation for the numerical simulation to reproduce the variations in the effective electrical conductivity and permittivity of porous geological materials induced by both the electrochemical polarizations and the interfacial polarization. This work thus provides a useful tool for studying the effective electrical properties of porous geological materials featuring complex microstructures.
Linking Mesoscale Meteorology With Extreme Landscape Response: Effects of Narrow Cold Frontal Rainbands (NCFR)
Authors: Collins Brian D. , Oakley Nina S. , Perkins Jonathan P. , East Amy E. , Corbett Skye C. , Hatchett Benjamin J.
Published: October 2020

Landscapes evolve in response to prolonged and/or intense precipitation resulting from atmospheric processes at various spatial and temporal scales. Whereas synoptic (large‐scale) features (e.g., atmospheric rivers and hurricanes) govern regional‐scale hydrologic hazards such as widespread flooding, mesoscale features such as thunderstorms or squall lines are more likely to trigger localized geomorphic hazards such as landslides. Thus, to better understand relations between hydrometeorological drivers and landscape response, a knowledge of mesoscale meteorology and its impacts is needed. Here we investigate the extreme geomorphic response associated with one type of mesoscale meteorological feature, the narrow cold frontal rainband (NCFR). Resulting from low‐level convergence and shallow convection along a cold front, NCFRs are narrow bands of high‐intensity rainfall that occur in midlatitude areas of the world. Our study examines an NCFR impacting the Sierra Nevada foothills (California, USA) that initiated over 500 landslides, mobilized ~360,000 metric tons of sediment to the fluvial system (as much as 16 times the local annual sediment yield), and severely damaged local infrastructure and regional water transport facilities. Coupling geomorphological field investigations with meteorological analyses, we demonstrate that precipitation associated with the NCFR was both intense (maximum 15 min intensity of 70 mm/hr) and localized, resulting in a highly concentrated band of shallow landsliding. This meteorological phenomenon likely plays an important role in landscape evolution and hazard initiation. Other types of mesoscale meteorological features also occur globally and offer new avenues for understanding the effects of storms on landscapes.
The Late Jurassic to Early Cretaceous Strike‐Slip Faults in the Subei‐South Yellow Sea Basin, Eastern China: Constraints From Seismic Data
Authors: Yang Fengli , Hu Panpan , Zhou Xinhuai , Zhang Ruoyu , Peng Yunxin , Li Xiao , Qiu Dan
Published: October 2020

Late Jurassic‐Early Cretaceous strike‐slip faults play an important role in basin formation and igneous activities in eastern China and the adjacent areas. Because of the lack of seismic data, their distribution and effect on the formation of basins and igneous activities in the Subei‐South Yellow Sea Basin (SB‐SYSB) are still poorly understood. In this study, based on systematic analyses of the acquired seismic data, the Late Jurassic‐Early Cretaceous strike‐slip faults in the SB‐SYSB were identified and characterized. The strike‐slip faults can be divided into two sets, a NE‐NNE trending sinistral strike‐slip fault system and a NW trending dextral fault system. They present in seismic sections as a flower structure or Y/V‐shaped structure, respectively. In map view, they show horsetail splay faults, en echelon reverse faults, pull‐apart structure, linear structure, or curvilinear structure. These faults resulted in different types of subbasins in the SB‐SYSB, such as transpressional/transtensional subbasins and pull‐apart subbasins. The close relationship between the strike‐slip faults and the distribution of igneous rocks in the SB‐SYSB suggest that the strike‐slip faults probably acted as efficient pathways for magma intrusion during the Late Jurassic‐Early Cretaceous. The sinistral displacement was characterized by thrusting‐folding deformation structures, which show a tendency to decrease toward the Sulu orogenic belt, indicating that the Sulu orogenic belt has probably weakened the strike‐slip movement in the basin. We infer that the sinistral strike‐slip movement in the SB‐SYSB was most likely controlled by the subduction of the paleo‐Pacific plate and the Tan‐Lu strike‐slip faulting.
Surfaceome dynamics reveal proteostasis-independent reorganization of neuronal surface proteins during development and synaptic plasticity
Authors: van Oostrum Marc , Campbell Benjamin , Seng Charlotte , Müller Maik , tom Dieck Susanne , Hammer Jacqueline , Pedrioli Patrick G. A. , Földy Csaba , Tyagarajan Shiva K. , Wollscheid Bernd
Published: October 2020

Neurons are highly compartmentalized cells with tightly controlled subcellular protein organization. While brain transcriptome, connectome and global proteome maps are being generated, system-wide analysis of temporal protein dynamics at the subcellular level are currently lacking. Here, we perform a temporally-resolved surfaceome analysis of primary neuron cultures and reveal dynamic surface protein clusters that reflect the functional requirements during distinct stages of neuronal development. Direct comparison of surface and total protein pools during development and homeostatic synaptic scaling demonstrates system-wide proteostasis-independent remodeling of the neuronal surface, illustrating widespread regulation on the level of surface trafficking. Finally, quantitative analysis of the neuronal surface during chemical long-term potentiation (cLTP) reveals fast externalization of diverse classes of surface proteins beyond the AMPA receptor, providing avenues to investigate the requirement of exocytosis for LTP. Our resource (neurosurfaceome.ethz.ch) highlights the importance of subcellular resolution for systems-level understanding of cellular processes.
Glioma-derived IL-33 orchestrates an inflammatory brain tumor microenvironment that accelerates glioma progression
Authors: De Boeck Astrid , Ahn Bo Young , D’Mello Charlotte , Lun Xueqing , Menon Shyam V. , Alshehri Mana M. , Szulzewsky Frank , Shen Yaoqing , Khan Lubaba , Dang Ngoc Ha , Reichardt Elliott , Goring Kimberly-Ann , King Jennifer , Grisdale Cameron J. , Grinshtein Natalie , Hambardzumyan Dolores , Reilly Karlyne M. , Blough Michael D. , Cairncross J. Gregory , Yong V. Wee , Marra Marco A. , Jones Steven J. M. , Kaplan David R. , McCoy Kathy D. , Holland Eric C. , Bose Pinaki , Chan Jennifer A. , Robbins Stephen M. , Senger Donna L.
Published: October 2020

Despite a deeper molecular understanding, human glioblastoma remains one of the most treatment refractory and fatal cancers. It is known that the presence of macrophages and microglia impact glioblastoma tumorigenesis and prevent durable response. Herein we identify the dual function cytokine IL-33 as an orchestrator of the glioblastoma microenvironment that contributes to tumorigenesis. We find that IL-33 expression in a large subset of human glioma specimens and murine models correlates with increased tumor-associated macrophages/monocytes/microglia. In addition, nuclear and secreted functions of IL-33 regulate chemokines that collectively recruit and activate circulating and resident innate immune cells creating a pro-tumorigenic environment. Conversely, loss of nuclear IL-33 cripples recruitment, dramatically suppresses glioma growth, and increases survival. Our data supports the paradigm that recruitment and activation of immune cells, when instructed appropriately, offer a therapeutic strategy that switches the focus from the cancer cell alone to one that includes the normal host environment.
Chronic glucose-dependent insulinotropic polypeptide receptor (GIPR) agonism desensitizes adipocyte GIPR activity mimicking functional GIPR antagonism
Authors: Killion Elizabeth A. , Chen Michelle , Falsey James R. , Sivits Glenn , Hager Todd , Atangan Larissa , Helmering Joan , Lee Jae , Li Hongyan , Wu Bin , Cheng Yuan , Véniant Murielle M. , Lloyd David J.
Published: October 2020

Antagonism or agonism of the glucose-dependent insulinotropic polypeptide (GIP) receptor (GIPR) prevents weight gain and leads to dramatic weight loss in combination with glucagon-like peptide-1 receptor agonists in preclinical models. Based on the genetic evidence supporting GIPR antagonism, we previously developed a mouse anti-murine GIPR antibody (muGIPR-Ab) that protected diet-induced obese (DIO) mice against body weight gain and improved multiple metabolic parameters. This work reconciles the similar preclinical body weight effects of GIPR antagonists and agonists in vivo, and here we show that chronic GIPR agonism desensitizes GIPR activity in primary adipocytes, both differentiated in vitro and adipose tissue in vivo, and functions like a GIPR antagonist. Additionally, GIPR activity in adipocytes is partially responsible for muGIPR-Ab to prevent weight gain in DIO mice, demonstrating a role of adipocyte GIPR in the regulation of adiposity in vivo.
Distinct signatures of gut microbiome and metabolites associated with significant fibrosis in non-obese NAFLD
Authors: Lee Giljae , You Hyun Ju , Bajaj Jasmohan S. , Joo Sae Kyung , Yu Junsun , Park Seoyeon , Kang Hyena , Park Jeong Hwan , Kim Jung Ho , Lee Dong Hyeon , Lee Seonhwa , Kim Won , Ko GwangPyo
Published: October 2020

Nonalcoholic fatty liver disease (NAFLD) is associated with obesity but also found in non-obese individuals. Gut microbiome profiles of 171 Asians with biopsy-proven NAFLD and 31 non-NAFLD controls are analyzed using 16S rRNA sequencing; an independent Western cohort is used for external validation. Subjects are classified into three subgroups according to histological spectra of NAFLD or fibrosis severity. Significant alterations in microbiome diversity are observed according to fibrosis severity in non-obese, but not obese, subjects. Ruminococcaceae and Veillonellaceae are the main microbiota associated with fibrosis severity in non-obese subjects. Furthermore, stool bile acids and propionate are elevated, especially in non-obese subjects with significant fibrosis. Fibrosis-related Ruminococcaceae and Veillonellaceae species undergo metagenome sequencing, and four representative species are administered in three mouse NAFLD models to evaluate their effects on liver damage. This study provides the evidence for the role of the microbiome in the liver fibrosis pathogenesis, especially in non-obese subjects.
Fetal whole heart blood flow imaging using 4D cine MRI
Authors: Roberts Thomas A. , van Amerom Joshua F. P. , Uus Alena , Lloyd David F. A. , van Poppel Milou P. M. , Price Anthony N. , Tournier Jacques-Donald , Mohanadass Chloe A. , Jackson Laurence H. , Malik Shaihan J. , Pushparajah Kuberan , Rutherford Mary A. , Razavi Reza , Deprez Maria , Hajnal Joseph V.
Published: October 2020

Prenatal detection of congenital heart disease facilitates the opportunity for potentially life-saving care immediately after the baby is born. Echocardiography is routinely used for screening of morphological malformations, but functional measurements of blood flow are scarcely used in fetal echocardiography due to technical assumptions and issues of reliability. Magnetic resonance imaging (MRI) is readily used for quantification of abnormal blood flow in adult hearts, however, existing in utero approaches are compromised by spontaneous fetal motion. Here, we present and validate a novel method of MRI velocity-encoding combined with a motion-robust reconstruction framework for four-dimensional visualization and quantification of blood flow in the human fetal heart and major vessels. We demonstrate simultaneous 4D visualization of the anatomy and circulation, which we use to quantify flow rates through various major vessels. The framework introduced here could enable new clinical opportunities for assessment of the fetal cardiovascular system in both health and disease.
Immunological fingerprint of 4CMenB recombinant antigens via protein microarray reveals key immunosignatures correlating with bactericidal activity
Authors: Bartolini E. , Borgogni E. , Bruttini M. , Muzzi A. , Giuliani M. , Iozzi S. , Petracca R. , Martinelli M. , Bonacci S. , Marchi S. , Brettoni C. , Donati C. , Torricelli G. , Guidotti S. , Domina M. , Beninati C. , Teti G. , Felici F. , Rappuoli R. , Castellino F. , Del Giudice G. , Masignani V. , Pizza M. , Maione D.
Published: October 2020

Serogroup B meningococcus (MenB) is a leading cause of meningitis and sepsis across the world and vaccination is the most effective way to protect against this disease. 4CMenB is a multi-component vaccine against MenB, which is now licensed for use in subjects >2 months of age in several countries. In this study, we describe the development and use of an ad hoc protein microarray to study the immune response induced by the three major 4CMenB antigenic components (fHbp, NHBA and NadA) in individual sera from vaccinated infants, adolescents and adults. The resulting 4CMenB protein antigen fingerprinting allowed the identification of specific human antibody repertoire correlating with the bactericidal response elicited in each subject. This work represents an example of epitope mapping of the immune response induced by a multicomponent vaccine in different age groups with the identification of protective signatures. It shows the high flexibility of this microarray based methodology in terms of high-throughput information and minimal volume of biological samples needed.
Molecular phenotyping of oxidative stress in diabetes mellitus with point-of-care NMR system
Authors: Peng Weng Kung , Chen Lan , Boehm Bernhard O. , Han Jongyoon , Loh Tze Ping
Published: October 2020

Diabetes mellitus is one of the fastest-growing health burdens globally. Oxidative stress, which has been implicated in the pathogenesis of diabetes complication (e.g., cardiovascular event), remains poorly understood. We report a new approach to rapidly manipulate and evaluate the redox states of blood using a point-of-care NMR system. Various redox states of the hemoglobin were mapped out using the newly proposed (pseudo) two-dimensional map known as T1–T2 magnetic state diagram. We exploit the fact that oxidative stress changes the subtle molecular motion of water proton in the blood, and thus inducing a measurable shift in magnetic resonance relaxation properties. We demonstrated the clinical utilities of this technique to rapidly stratify diabetes subjects based on their oxidative status in conjunction to the traditional glycemic level to improve the patient stratification and thus the overall outcome of clinical diabetes care and management.
Genomic testing in 1019 individuals from 349 Pakistani families results in high diagnostic yield and clinical utility
Authors: Cheema Huma , Bertoli-Avella Aida M. , Skrahina Volha , Anjum Muhammad Nadeem , Waheed Nadia , Saeed Anjum , Beetz Christian , Perez-Lopez Jordi , Rocha Maria Eugenia , Alawbathani Salem , Pereira Catarina , Hovakimyan Marina , Patric Irene Rosita Pia , Paknia Omid , Ameziane Najim , Cozma Claudia , Bauer Peter , Rolfs Arndt
Published: October 2020

We implemented a collaborative diagnostic program in Lahore (Pakistan) aiming to establish the genetic diagnosis, and to asses diagnostic yield and clinical impact in patients with suspected genetic diseases. Local physicians ascertained pediatric patients who had no previous access to genetic testing. More than 1586 genetic tests were performed in 1019 individuals (349 index cases, 670 relatives). Most frequently performed tests were exome/genome sequencing (ES/GS, 284/78 index cases) and specific gene panels (55 index cases). In 61.3% of the patients (n = 214) a genetic diagnosis was established based on pathogenic and likely pathogenic variants. Diagnostic yield was higher in consanguineous families (60.1 vs. 39.5%). In 27 patients, genetic diagnosis relied on additional biochemical testing, allowing rapid assessment of the functional effect of the variants. Remarkably, the genetic diagnosis had a direct impact on clinical management. Most relevant consequences were therapy related such as initiation of the appropriated treatment in a timely manner in 51.9% of the patients (n = 111). Finally, we report 12 candidate genes among 66 cases with no genetic diagnosis. Importantly, three of these genes were validated as ‘diagnostic’ genes given the strong evidence supporting causality derived from our data repository (CAP2-dilated cardiomyopathy, ITFG2-intellectual disability and USP53-liver cholestasis). The high diagnostic yield, clinical impact, and research findings demonstrate the utility of genomic testing, especially when used as first-line genetic test. For patients with suspected genetic diseases from resource-limited regions, ES can be considered as the test of choice to achieve genetic diagnosis.
Data for training and testing radiation detection algorithms in an urban environment
Authors: Ghawaly James M. , Nicholson Andrew D. , Peplow Douglas E. , Anderson-Cook Christine M. , Myers Kary L. , Archer Daniel E. , Willis Michael J. , Quiter Brian J.
Published: October 2020

The detection, identification, and localization of illicit nuclear materials in urban environments is of utmost importance for national security. Most often, the process of performing these operations consists of a team of trained individuals equipped with radiation detection devices that have built-in algorithms to alert the user to the presence nuclear material and, if possible, to identify the type of nuclear material present. To encourage the development of new detection, radioisotope identification, and source localization algorithms, a dataset consisting of realistic Monte Carlo–simulated radiation detection data from a 2 in. × 4 in. × 16 in. NaI(Tl) scintillation detector moving through a simulated urban environment based on Knoxville, Tennessee, was developed and made public in the form of a Topcoder competition. The methodology used to create this dataset has been verified using experimental data collected at the Fort Indiantown Gap National Guard facility. Realistic signals from special nuclear material and industrial and medical sources are included in the data for developing and testing algorithms in a dynamic real-world background.
Birth control knowledge among freshmen of four Italian universities
Authors: Cegolon L. , Bortolotto M. , Bellizzi S. , Cegolon A. , Mastrangelo G. , Xodo C.
Published: October 2020

Since sexual health education (SHE) is not mandatory in Italian schools, we conducted a survey on freshmen of four Italian university campuses in 2012 to investigate the respective level of sexual health knowledge (SHK) in relation to birth control, with the aim to inform public health policy makers. A convenience strategy was employed to sample 4,552 freshmen registered with various undergraduate courses at four Italian universities: Padua university (Veneto Region); university of Milan (Lombardy Region); university of Bergamo (Lombardy Region); university of Palermo (Sicily Region). We investigated the level of SHK on birth control using 6 proxy indicators: (1) the average length of a woman’s period [outcome with 3 levels: wrong (base) vs. acceptable vs. correct]; (2) the most fertile interval within a woman’s period (binary outcome: correct vs. wrong answer); (3) the event between the end of a period and the beginning of the next cycle (binary outcome: correct vs. wrong answer); (4) the average survival of spermatozoa in the womb (binary outcome: correct vs. wrong answer); (5) the concept of contraception (binary outcome: correct vs. wrong answer); (6) the efficacy of various contraceptives to prevent unintended pregnancies (linear score: 0–17). We fitted 6 separate models of multiple regression: multinomial for outcome 1; logistic for outcomes 2, 3, 4, 6; linear for outcome 6. Statistical estimates were adjusted for a number of socio-demographic factors. Results were expressed as odds ratios (OR) for the 4 multiple logistic regression models, linear coefficients (RC) for the linear regression model and relative risk ratio (RRR) for the multinomial logistic regression model. The level of significance of each risk estimate was set at 0.05. The level of SHK of freshmen sampled was rather low, as 60% interviewees did not know the average length of a woman’s period, the average survival of spermatozoa in the womb and the concept of contraception, whilst the most fertile interval within a woman’s period was known only to 55% of interviewees. The mean score of SHK on the efficacy of various contraceptive methods was only 5 (scale 0–17). Some categories of students were consistently and significantly less knowledgeable on birth control at multivariable analysis: males; students from the university of Palermo; those with vocational secondary school education and those not in a romantic relationship at the time the survey was conducted. The results of this survey clearly call for the introduction of SHE programs in Italian schools, as already done in several European countries. School SHE should start as early as possible, ideally even before secondary school. SHE should be holistic and delivered with a multiple agency coordinated approach involving the Ministry of Health, the Ministry of Education, University and Scientific Research (MIUR), families, schools, public health departments, primary health care providers, pharmacists, media, other.
Effects of Alzheimer’s disease and formalin fixation on the different mineralised-iron forms in the human brain
Authors: van der Weerd Louise , Lefering Anton , Webb Andrew , Egli Ramon , Bossoni Lucia
Published: October 2020

Iron accumulation in the brain is a phenomenon common to many neurodegenerative diseases, perhaps most notably Alzheimer’s disease (AD). We present here magnetic analyses of post-mortem brain tissue of patients who had severe Alzheimer’s disease, and compare the results with those from healthy controls. Isothermal remanent magnetization experiments were performed to assess the extent to which different magnetic carriers are affected by AD pathology and formalin fixation. While Alzheimer’s brain material did not show higher levels of magnetite/maghemite nanoparticles than corresponding controls, the ferrihydrite mineral, known to be found within the core of ferritin proteins and hemosiderin aggregates, almost doubled in concentration in patients with Alzheimer’s pathology, strengthening the conclusions of our previous studies. As part of this study, we also investigated the effects of sample preparation, by performing experiments on frozen tissue as well as tissue which had been fixed in formalin for a period of 5 months. Our results showed that the two different preparations did not critically affect the concentration of magnetic carriers in brain tissue, as observable by SQUID magnetometry.
Development of a novel molecular probe for the detection of liver mitochondrial redox metabolism
Authors: Hosain Md. Zahangir , Hyodo Fuminori , Mori Takeshi , Takahashi Koyo , Nagao Yusuke , Eto Hinako , Murata Masaharu , Akahoshi Tomohiko , Matsuo Masayuki , Katayama Yoshiki
Published: October 2020

Redox status influences the course of the inflammatory, metabolic, and proliferative liver diseases. Oxidative stress is thought to play a crucial and sustained role in the pathological progression of early steatosis to severe hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. Oxidative stress induced by reactive oxygen species which are generated in the mitochondria can lead to chronic organelle damage in hepatocytes. Currently, the diagnosis of liver disease requires liver biopsy, which is invasive and associated with complications. The present report describes the development of a novel molecular probe, EDA-PROXYL, with higher reactivity and mitochondrial selectivity than standard carboxyl-PROXYL and carbamoyl-PROXYL probes. The membrane permeability of our probe improved in aqueous environments which led to increased accumulation in the liver and interaction of EDA-PROXYL with the carnitine transporter via the amine (NH3+) group further increased accumulation. This increased mitochondrial sensitivity and enhanced accumulation highlight the potential of EDA-PROXYL as a molecular probe for determining metabolic reactions of the mitochondria. Thus, this novel probe could be a tool for the evaluation of redox status of the mitochondria to assess the degree of liver injury and, ultimately, the response to pharmacological therapy.
Fast and antibiotic free genome integration into Escherichia coli chromosome
Authors: Egger Esther , Tauer Christopher , Cserjan-Puschmann Monika , Grabherr Reingard , Striedner Gerald
Published: October 2020

Genome-based Escherichia coli expression systems are superior to conventional plasmid-based systems as the metabolic load triggered by recombinant compounds is significantly reduced. The efficiency of T7-based transcription compensates for low gene dosage (single copy) and facilitates high product formation rates. While common Gene Bridges’ λ-red mediated recombination technique for site directed integration of genes into the host genome is very efficient, selection for positive clones is based on antibiotic resistance markers and removal thereof is often time consuming. For the generation of industrial production strains, flexibility in terms of integration site is not required, yet time from gene design to a stable clone is a quite relevant parameter. In this study, we developed a fast, efficient and antibiotic-free integration method for E. coli as production strain. We combined the λ-red recombination system with the site-directed homing endonuclease I from Saccharaomyces cerevisiae (I-SceI) for selection. In a first step, λ-red proteins are performing genome integration of a linear, antibiotic marker-free integration cassette. The engineered host strain carries the I-SceI restriction sequence at the attTn7 site, where the integration event happens. After homologous recombination and integration at the target site, site-specific genome cleavage by endonuclease I-SceI is induced, thereby killing all cells still containing an intact I-SceI site. In case of positive recombination events, the genomic I-SceI site is deleted and cleavage is no longer possible. Since plasmids are designed to contain another I-SceI restriction site they are destroyed by self-cleavage, a procedure replacing the time-consuming plasmid curing. The new plasmid-based “All-In-One” genome integration method facilitates significantly accelerated generation of genome-integrated production strains in 4 steps.
Germline BRCA 1-2 status prediction through ovarian ultrasound images radiogenomics: a hypothesis generating study (PROBE study)
Authors: Nero Camilla , Ciccarone Francesca , Boldrini Luca , Lenkowicz Jacopo , Paris Ida , Capoluongo Ettore Domenico , Testa Antonia Carla , Fagotti Anna , Valentini Vincenzo , Scambia Giovanni
Published: October 2020

Radiogenomics is a specific application of radiomics where imaging features are linked to genomic profiles. We aim to develop a radiogenomics model based on ovarian US images for predicting germline BRCA1/2 gene status in women with healthy ovaries. From January 2013 to December 2017 a total of 255 patients addressed to germline BRCA1/2 testing and pelvic US documenting normal ovaries, were retrospectively included. Feature selection for univariate analysis was carried out via correlation analysis. Multivariable analysis for classification of germline BRCA1/2 status was then carried out via logistic regression, support vector machine, ensemble of decision trees and automated machine learning pipelines. Data were split into a training (75%) and a testing (25%) set. The four strategies obtained a similar performance in terms of accuracy on the testing set (from 0.54 of logistic regression to 0.64 of the auto-machine learning pipeline). Data coming from one of the tested US machine showed generally higher performances, particularly with the auto-machine learning pipeline (testing set specificity 0.87, negative predictive value 0.73, accuracy value 0.72 and 0.79 on training set). The study shows that a radiogenomics model on machine learning techniques is feasible and potentially useful for predicting gBRCA1/2 status in women with healthy ovaries.
A novel, low cost, and accessible method for rapid fabrication of the modifiable microfluidic devices
Authors: Annabestani Mohsen , Esmaeili-Dokht Pouria , Fardmanesh Mehdi
Published: October 2020

As microfluidic chips are evolving to become a significant analysis tool toward POCT devices, it is crucial to make the cost and the time required for the fabrication process of these chips as low as possible. Because of the multidisciplinary nature of these systems and the collaboration of many different laboratories and organizations from vastly various fields with unequal types of equipment, it is essential to develop new techniques and materials to make the integration of disparate systems together more straightforward, accessible, and economical. In this paper, we present ethylene–vinyl acetate (EVA) as a new polymer-based material for the fabrication of different microfluidic chips, which brings new features and tools in fabrication, integration, and functionality of microfluidic systems. We put this material next to PDMS for comparison between various aspects of these materials. We have shown that besides the low-cost ability, ubiquitousness, geometrical modifiability, and ease of fabrication of EVA chips, due the lower hydrophobicity and lower terahertz (THz) absorption of EVA than PDMS, EVA chips, in comparison to PDMS counterparts, can work faster, have less number of channel blocking and can be used in THz biosensing application like metamaterial-based cancer detection. Finally, several devices are made using EVA to demonstrate the functionality and versatility of this material for the fabrication of microfluidic chips.
Evaluation of real-world early response of DMO to aflibercept therapy to inform future clinical trial design of novel investigational agents
Authors: Halim Sandra , Gurudas Sarega , Chandra Shruti , Greenwood John , Sivaprasad Sobha
Published: October 2020

New clinical trials for diabetic macular oedema (DMO) are being designed to prove superiority over aflibercept when this agent is already very effective in improving visual acuity (VA) and DMO. The aim of this study was to determine the optimal inclusion–exclusion criteria for trials to aim for superiority in visual outcomes with newer agents. As Phase 1 studies are short duration, we aimed to evaluate the early response of aflibercept in a real-world cohort initiated on monthly aflibercept for 3 consecutive injections and observed the effects at 4 months. The sub-optimal responders were pre-defined based on different cut-offs for VA and central sub-field thickness (CST). 200 patients with treatment naïve DMO treated with 3 loading doses of aflibercept were included in the study. We found that those presenting with baseline VA of 35–54 ETDRS letters (n = 43) had higher proportion of sub-optimal responders compared to other categories (p < 0.001). Patients with baseline CST of less than 400 µm (n = 96) responded less well functionally and anatomically to loading dose than eyes with baseline CST of 400 µm or more (n = 104, p = 0.02), indicating that eyes with CST ≥ 400 µm is another inclusion criteria. There was minimal correlation between change in CST and change in VA at 4 months (r = − 0.27), suggesting that both these inclusion criteria are non-exclusive. However, for maximal efficacy, patients that meet both these inclusion criteria are more likely to show benefit from an alternative intervention. New trials should aim to include patients with treatment naïve DMO with VA between 35–54 letters and CST of 400 µm or more when aflibercept is used as the comparator.
Bovine sperm-oviduct interactions are characterized by specific sperm behaviour, ultrastructure and tubal reactions which are impacted by sex sorting
Authors: Camara Pirez Miguel , Steele Heather , Reese Sven , Kölle Sabine
Published: October 2020

To date sperm-oviduct interactions have largely been investigated under in vitro conditions. Therefore we set out to characterize the behaviour of bovine spermatozoa within the sperm reservoir under near in vivo conditions and in real-time using a novel live cell imaging technology and a newly established fluorescent sperm binding assay. Sperm structure and tubal reactions after sperm binding were analysed using scanning and transmission electron microscopy and histochemistry. As a model to specify the impact of stress on sperm-oviduct interactions, frozen-thawed conventional and sex-sorted spermatozoa from the same bulls (n = 7) were co-incubated with oviducts obtained from cows immediately after slaughter. Our studies revealed that within the oviductal sperm reservoir agile (bound at a tangential angle of about 30°, actively beating undulating tail), lagging (bound at a lower angle, reduced tail movement), immotile (absence of tail movement) and hyperactivated (whip-like movement of tail) spermatozoa occur, the prevalence of which changes in a time-dependent pattern. After formation of the sperm reservoir, tubal ciliary beat frequency is significantly increased (p = 0.022) and the epithelial cells show increased activity of endoplasmic reticula. After sex sorting, spermatozoa occasionally display abnormal movement patterns characterized by a 360° rotating head and tail. Sperm binding in the oviduct is significantly reduced (p = 0.008) following sexing. Sex-sorted spermatozoa reveal deformations in the head, sharp bends in the tail and a significantly increased prevalence of damaged mitochondria (p < 0.001). Our results imply that the oviductal cells specifically react to the binding of spermatozoa, maintaining sperm survival within the tubal reservoir. The sex-sorting process, which is associated with mechanical, chemical and time stress, impacts sperm binding to the oviduct and mitochondrial integrity affecting sperm motility and function.
Identification of nitric oxide (NO)-responsive genes under hypoxia in tomato (Solanum lycopersicum L.) root
Authors: Safavi-Rizi Vajiheh , Herde Marco , Stöhr Christine
Published: October 2020

Flooding periods, as one probable consequence of climate change, will lead more frequently to plant hypoxic stress. Hypoxia sensing and signaling in the root, as the first organ encountering low oxygen, is therefore crucial for plant survival under flooding. Nitric oxide has been shown to be one of the main players involved in hypoxia signaling through the regulation of ERFVII transcription factors stability. Using SNP as NO donor, we investigated the NO-responsive genes, which showed a significant response to hypoxia. We identified 395 genes being differentially regulated under both hypoxia and SNP-treatment. Among them, 251 genes showed up- or down-regulation under both conditions which were used for further biological analysis. Functional classification of these genes showed that they belong to different biological categories such as primary carbon and nitrogen metabolism (e.g. glycolysis, fermentation, protein and amino acid metabolism), nutrient and metabolites transport, redox homeostasis, hormone metabolism, regulation of transcription as well as response to biotic and abiotic stresses. Our data shed light on the NO-mediated gene expression modulation under hypoxia and provides potential targets playing a role in hypoxia tolerance. These genes are interesting candidates for further investigating their role in hypoxia signaling and survival.
Rapid identification of the invasive fall armyworm Spodoptera frugiperda (Lepidoptera, Noctuidae) using species-specific primers in multiplex PCR
Authors: Tsai Cheng-Lung , Chu I.-Hsuan , Chou Ming-Hsun , Chareonviriyaphap Theeraphap , Chiang Ming-Yao , Lin Po-An , Lu Kuang-Hui , Yeh Wen-Bin
Published: October 2020

The fall armyworm (FAW), Spodoptera frugiperda (Smith), is a major pest native to the Americas. A recent invasion of FAWs from Africa eastward to South Asia, the Indochina Peninsula, and mainland China has received much attention due to the considerable economic losses in agriculture. FAWs can rapidly colonise a new area, likely due to the wide range of host plants, good flying capability, and high egg production. Therefore, a convenient, quick, and accurate tool for FAW identification is urgently required to establish a FAW invasion management strategy. In this study, FAW-specific primers were designed to recognise FAWs on the basis of internal transcribed spacer 1 (ITS1). The results revealed the accurate FAW recognition of the three congeneric species and eight common corn lepidopteran pests, especially at their larval stage. Furthermore, species-specific primers have confirmed their efficacy by using 69 FAW specimens from Taiwan, Thailand, and the United States, with a 96% success rate, excluding 3 decayed specimens. By using the simple, reliable, and convenient FAW-specific primers, a pest management programme can be developed not only to reduce sequencing costs and experimental time from 2 days to 4 h, but eradicate the FAW as soon as it enters a new area.
Synthesis, reactivity and catalytic activity of Au-PAd3 complexes
Authors: Voloshkin Vladislav A. , Saab Marina , Van Hecke Kristof , Lau Sii Hong , Carrow Bradley P. , Nolan Steven P.
Published: October 2020

Novel Au-PAd3 complexes have been synthesized from the known [Au(PAd3)Cl]. A number of derivatives were deployed as catalysts and compared with NHC and tertiary phosphine congeners.
All ceramic cathode composite design and manufacturing towards low interfacial resistance for garnet-based solid-state lithium batteries
Authors: Kim Kun Joong , Rupp Jennifer L. M.
Published: October 2020

Solution-assisted all-oxide-cathode formation method allows reduction of processing temperature without using sintering additives, demonstrating the lowest interfacial impedance in garnet-based solid-state lithium batteries.
The fabrication of 3D hierarchical flower-like δ-MnO2@COF nanocomposites for the efficient and ultra-fast removal of UO22+ ions from aqueous solution
Authors: Zhong Xin , Lu Zhipeng , Liang Wen , Guo Xiaojie , Hu Baowei
Published: October 2020

3D flower-like δ-MnO2@TpPa-1 composites was constructed though the integration of δ-MnO2 nano-flowers with a covalent organic framework (TpPa-1) via ultrasonication process. δ-MnO2@TpPa-1 a promising adsorbent for spent-nuclear-fuel reprocessing.
Electrochemical coating of different conductive polymers on diverse plasmonic metal nanocrystals
Authors: Lu Wenzheng , Chow Tsz Him , Lu Yao , Wang Jianfang
Published: October 2020

An electrochemical approach is developed for the coating of conductive polymers on various plasmonic metal nanocrystals for active plasmonics.
Bifunctional metal–organic frameworks for the hydrogenation of nitrophenol using methanol as the hydrogen source
Authors: Melillo Arianna , García-Vallés Cristina , Ferrer Belén , Álvaro Mercedes , Navalón Sergio , García Hermenegildo
Published: October 2020

This work reports the reduction of 4-nitrophenol to 4-aminophenol using UiO-66(Zr) as a bifunctional photocatalyst and hydrogenation catalyst using methanol as the hydrogen source.
Rhodium-catalyzed synthesis of substituted isoquinolones via a selective decarbonylation/alkyne insertion cascade of phthalimides
Authors: Xu Fen , Zhu Wen-Jing , Wang Juan , Ma Qi , Shen Li-Jing
Published: October 2020

A rhodium-catalyzed decarbonylation/alkyne insertion cascade of phthalimides with alkynes has been established.
Regioselective synthesis of tetrahydroquinolines via syn- and anti-nucleopalladation-initiated cascade processes
Authors: Karuppasamy Muthu , Vinoth Perumal , Pradeep N. , Nagarajan Subbiah , Maheswari C. Uma , Sridharan Vellaisamy
Published: October 2020

Regioselective synthesis of tetrahydroquinolines via nucleopalladation-initiated cascade sequences was established.
Structural optimization of organic fluorophores for highly efficient photothermal therapy
Authors: Li Chaonan , Lin Wenhai , Liu Shi , Sun Tingting , Xie Zhigang
Published: October 2020

Highly efficient organic photothermal agents (Py-BDP NPs) were prepared from BDP molecules with large conjugate areas via structural optimization.
Visualizing changes of molecular conformation in the solid-state by a common structural determination technique: single crystal X-ray diffraction
Authors: Zhang Jun , Zhang Haoke , Liu Junkai , Lam Jacky Wing Yip , Tang Ben Zhong
Published: October 2020

Changes of molecular conformation in the solid state play a vital role in many advanced technologies.
Carbonate-promoted C–H carboxylation of electron-rich heteroarenes
Authors: Porter Tyler M. , Kanan Matthew W.
Published: October 2020

Carboxylation of heteroarenes with CO2is achieved using alkali carbonate dispersed in mesoporous titania as a regenerable reagent.
Molecularly engineered thienyl-triphenylamine substituted zinc phthalocyanine as dopant free hole transporting materials in perovskite solar cells
Authors: Huang Peng , Hernández Adrián , Kazim Samrana , Ortiz Javier , Sastre-Santos Ángela , Ahmad Shahzada
Published: October 2020

The synthesis and semiconducting properties of thienyl-triphenylamine tetrasubstituted zinc(ii) phthalocyanine and its integration as a dopant-free hole transporting material in perovskite solar cells. Competitive performance and excellent chemical stability were obtained.
Cadmium-based ferroelectrics with the Ruddlesden–Popper and double perovskite structures: a theoretical study
Authors: Marcondes Michel L. , Santos Samuel S. M. , Miranda Ivan P. , Rocha-Rodrigues Pedro , Assali Lucy V. C. , Lopes Armandina M. L. , Araujo Joao P. , Petrilli Helena M.
Published: October 2020

Theoretical study of chemical substitution effects in the ferroelectric properties of Cd-based Ruddlesden–Popper and double perovskite structures.
An updated meta-analysis of the association between fibroblast growth factor receptor 4 polymorphisms and susceptibility to cancer
Authors: Moazeni-Roodi Abdolkarim , Sarabandi Sahel , Karami Shima , Hashemi Mohammad , Ghavami Saeid
Published: October 2020

Fibroblast growth factor receptor 4 (FGFR4) is a cell surface receptor tyrosine kinases (RTKs) for FGFs.

Several studies have focused on the association between FGFR4 polymorphisms and cancer development. This meta-analysis aimed to estimate the association between FGFR4 rs351855 (Gly388Arg), rs1966265 (Val10Ile), rs7708357, rs2011077, and rs376618 polymorphisms and cancer risk. Eligible studies were identified from electronic databases. All statistical analyses were achieved with the STATA 14.0 software. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to quantitatively estimate the association. Overall, no significant association was found among rs351855, rs2011077, and rs376618 polymorphisms with the risk of overall cancer. The rs1966265 polymorphism significantly decreased the risk of cancer in recessive (OR = 0.87, 95% CI = 0.78–0.97, P=0.009, TT vs CT+CC) genetic model. Whereas the rs7708357 polymorphism was positively associated with cancer risk in dominant (OR = 1.17, 95% CI = 1.02–1.36, P=0.028) genetic model. Stratified analysis revealed that rs351855 variant significantly increased the risk of prostate cancer in heterozygous (OR = 1.16, 95% CI = 1.02–1.32, P=0.025 AG vs GG), dominant (OR = 1.20, 95% CI = 1.06–1.35, P=0.004, AG+AA vs GG), and allele (OR = 1.22, 95% CI = 1.06–1.41, P=0.005, A vs G) genetic models.

In summary, the findings of this meta-analysis indicate that rs1966265, rs7708357, and rs351855 polymorphisms are correlated to cancer development. Further well-designed studies are necessary to draw more precise conclusions.
Chlorogenic acid ameliorated allergic rhinitis-related symptoms in mice by regulating Th17 cells
Authors: Shi Zhaohui , Jiang Weihong , Chen Xiaodong , Xu Min , Wang Jian , Lai Yubin , Zha Dingjun
Published: October 2020

Allergic rhinitis (AR) is a non-infectious chronic inflammatory disease of nasal mucosa provoking T helper cell (Th) 17 response. Chlorogenic acid (CGA), one of the most abundant polyphenol compounds in various agricultural products, possesses antiviral, anti-inflammatory, and antibacterial properties. However, the effect of CGA on AR is unclear. Thus, our study explored the effect of CGA in modulating AR-related symptoms and immunoreaction, especially Th17 response. AR mice were induced by ovalbumin (OVA) administration and further treated with CGA or dexamethasone (Dex). The frequencies of rubbing and sneezing of AR mice were recorded. Histopathological analysis of nasal mucosa was conducted by Hematoxylin–Eosin and Periodic acid–Schiff stainings. The serum and nasal mucosa levels of OVA-immunoglobulin (Ig)E, interferon (IFN)-γ, retinoic acid-associated nuclear orphan receptor (ROR)-γt, and interleukin (IL)-17A were measured by enzyme-linked immunosorbent assay, quantitative reverse-transcription polymerase chain reaction (qRT-PCR), or Western blot. The ratio of CD4+IL-17+Th17 cells to CD4+ T cells in peripheral blood of AR mice was assessed by flow cytometer. CGA diminished the frequencies of rubbing and sneezing of AR mice in a concentration-dependent manner. CGA attenuated histopathological abnormalities and decreased goblet cell number in nasal mucosa of AR mice. CGA decreased the serum levels of OVA-IgE, ROR-γt, and IL-17A, while increasing the serum level of IFN-γ in AR mice. Meanwhile, CGA decreased the ratio of CD4+IL-17+Th17 cells to CD4+T cells in peripheral blood and the mRNA and protein levels of IL-17A and ROR-γt in AR mice. CGA ameliorated AR-related symptoms in mice by regulating Th17 cells, which could be a candidate for the treatment of AR.