bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantifying Periodic Variations in Hotspot Melt Production
Authors: Morrow T. A. , Mittelstaedt E. L. 
Published: June 2021

AbstractFluctuations in estimated mantle plume melt production rates suggest complex dynamics in the upper mantle including changes in plume upwelling, compositional heterogeneity within plume stems, entrainment of anomalous mantle, or other processes. Despite the implications for mantle dynamics, differences between previous studies including the methods, study areas, and types of melt volumes estimated, limit inter‐hotspot comparisons and assessment of global variability. Here, we use a consistent methodology to calculate igneous melt production through time across a suite of 12 hotspot chains located in the Pacific, Indian, and Atlantic Ocean basins. Using global data sets of topography, gravity, sediment cover, and seafloor age along with spectral methods for calculating elastic plate flexure and gravity anomalies, we estimate the total volume of igneous material at each hotspot in three components: (a) volcanic edifices, (b) flexural infill, and (c) intrusions (underplating) within the upper mantle and lower crust. Results indicate time‐averaged melt production rates across all studied hotspots range from 3.44 m3 s−1 (Cobb) to 14.75 m3 s−1 (Kerguelen), with underplating making up the largest component. Through time, melt production rates vary from 0.1 to 2.5 times average values with statistically significant periodic fluctuations of 1.1–71.5 Myr. Spectral analysis of estimated melt volumes shows total melt production varies periodically at all 12 hotspots. Excepting Galápagos, the studied hotspots exhibit multiple periodicities of melt production variability, implying complex dynamic, thermal, and/or chemical processes within the plume conduit. Moreover, we find several groups of hotspots exhibiting similar periods of melt production variability.
Tumor-on-a-chip: from bioinspired design to biomedical application
Authors: Liu Xingxing , Fang Jiaru , Huang Shuang , Wu Xiaoxue , Xie Xi , Wang Ji , Liu Fanmao , Zhang Meng , Peng Zhenwei , Hu Ning 
Published: June 2021

AbstractCancer is one of the leading causes of human death, despite enormous efforts to explore cancer biology and develop anticancer therapies. The main challenges in cancer research are establishing an efficient tumor microenvironment in vitro and exploring efficient means for screening anticancer drugs to reveal the nature of cancer and develop treatments. The tumor microenvironment possesses human-specific biophysical and biochemical factors that are difficult to recapitulate in conventional in vitro planar cell models and in vivo animal models. Therefore, model limitations have hindered the translation of basic research findings to clinical applications. In this review, we introduce the recent progress in tumor-on-a-chip devices for cancer biology research, medicine assessment, and biomedical applications in detail. The emerging tumor-on-a-chip platforms integrating 3D cell culture, microfluidic technology, and tissue engineering have successfully mimicked the pivotal structural and functional characteristics of the in vivo tumor microenvironment. The recent advances in tumor-on-a-chip platforms for cancer biology studies and biomedical applications are detailed and analyzed in this review. This review should be valuable for further understanding the mechanisms of the tumor evolution process, screening anticancer drugs, and developing cancer therapies, and it addresses the challenges and potential opportunities in predicting drug screening and cancer treatment.
FURIN and placental syncytialisation: a cautionary tale
Authors: Morosin Saije K. , Delforce Sarah J. , Corbisier de Meaultsart Celine , Lumbers Eugenie R. , Pringle Kirsty G. 
Published: June 2021

AbstractFURIN is a pro-protein convertase previously shown to be important for placental syncytialisation (Zhou et al. [1]), a process of cell fusion whereby placental cytotrophoblast cells fuse to form a multinucleated syncytium. This finding has been broadly accepted however, we have evidence suggesting the contrary. Spontaneously syncytialising term primary human trophoblast cells and BeWo choriocarcinoma cells were treated with either FURIN siRNA or negative control siRNA or the protease inhibitor, DEC-RVKR-CMK, or vehicle. Cells were then left to either spontaneously syncytialise (primary trophoblasts) or were induced to syncytialise with forskolin (BeWo). Effects on syncytialisation were measured by determining human chorionic gonadotrophin secretion and E-cadherin protein levels. We showed that FURIN is not important for syncytialisation in either cell type. However, in primary trophoblasts another protease also inhibited by DEC-RVKR-CMK, may be involved. Our results directly contrast with those published by Zhou et al. Zhou et al. however, used first trimester villous explants to study syncytialisation, and we used term primary trophoblasts. Therefore, we suggest that FURIN may be involved in syncytialisation of first trimester trophoblasts, but not term trophoblasts. What is more concerning is that our results using BeWo cells do not agree with their results, even though for the most part, we used the same experimental design. It is unclear why these experiments yielded different results, however we wanted to draw attention to simple differences in measuring syncytialisation or flaws in method reporting (including omission of cell line source and passage numbers, siRNA concentration and protein molecular weights) and choice of immunoblot loading controls, that could impact on experimental outcomes. Our study shows that careful reporting of methods by authors and thorough scrutiny by referees are vital. Furthermore, a universal benchmark for measuring syncytialisation is required so that various studies of syncytialisation can be validated.
Intraoperative choroidal detachment during small-gauge vitrectomy: analysis of causes, anatomic, and visual outcomes
Authors: Zhang Ting , Wei Yantao , Zhang Zhaotian , Chi Wei , Feng Lujia , Xiang Wu , Wang Li , Fang Dong , Shi Yunhong , Zhang Shaochong 
Published: June 2021

Abstract
Introduction
To investigate the incidence and causes of intraoperative choroidal detachment (CD) during small-gauge vitrectomy, as well as the anatomic and visual outcomes.

Methods
We retrospectively reviewed the medical records of 1026 consecutive patients who underwent small-gauge vitrectomy from June 2017 to December 2018 at Zhongshan Ophthalmic Centre, Guangzhou, China. Data on the presence, location, and extent of intraoperative CD and its relationship to the infusion cannula were collected. Patient demographic characteristics and postoperative anatomic and visual outcomes were also assessed.

Results
A total of six cases were found to have intraoperative CD, including two with serous CD, three with limited haemorrhagic CD, and one with CD caused by inadvertent perfusion of gas during air/fluid exchange. Retraction of the infusion cannula and acute ocular hypotony were found to be the main causes of intraoperative CD in five out of the six cases. The best-corrected visual acuity of all cases significantly improved after the surgery.

Conclusion
The incidence of intraoperative CD during small-gauge vitrectomy is low; the predominant causes are retraction of the infusion cannula and acute ocular hypotony. Immediate awareness and timely closure of the incision may contribute to a better surgical prognosis.
Phenotypic manifestation of α-synuclein strains derived from Parkinson’s disease and multiple system atrophy in human dopaminergic neurons
Authors: Tanudjojo Benedict , Shaikh Samiha S. , Fenyi Alexis , Bousset Luc , Agarwal Devika , Marsh Jade , Zois Christos , Heman-Ackah Sabrina , Fischer Roman , Sims David , Melki Ronald , Tofaris George K. 
Published: June 2021

Abstractα-Synuclein is critical in the pathogenesis of Parkinson’s disease and related disorders, yet it remains unclear how its aggregation causes degeneration of human dopaminergic neurons. In this study, we induced α-synuclein aggregation in human iPSC-derived dopaminergic neurons using fibrils generated de novo or amplified in the presence of brain homogenates from Parkinson’s disease or multiple system atrophy. Increased α-synuclein monomer levels promote seeded aggregation in a dose and time-dependent manner, which is associated with a further increase in α-synuclein gene expression. Progressive neuronal death is observed with brain-amplified fibrils and reversed by reduction of intraneuronal α-synuclein abundance. We identified 56 proteins differentially interacting with aggregates triggered by brain-amplified fibrils, including evasion of Parkinson’s disease-associated deglycase DJ-1. Knockout of DJ-1 in iPSC-derived dopaminergic neurons enhance fibril-induced aggregation and neuronal death. Taken together, our results show that the toxicity of α-synuclein strains depends on aggregate burden, which is determined by monomer levels and conformation which dictates differential interactomes. Our study demonstrates how Parkinson’s disease-associated genes influence the phenotypic manifestation of strains in human neurons.
ERRγ enhances cardiac maturation with T-tubule formation in human iPSC-derived cardiomyocytes
Authors: Miki Kenji , Deguchi Kohei , Nakanishi-Koakutsu Misato , Lucena-Cacace Antonio , Kondo Shigeru , Fujiwara Yuya , Hatani Takeshi , Sasaki Masako , Naka Yuki , Okubo Chikako , Narita Megumi , Takei Ikue , Napier Stephanie C. , Sugo Tsukasa , Imaichi Sachiko , Monjo Taku , Ando Tatsuya , Tamura Norihisa , Imahashi Kenichi , Nishimoto Tomoyuki , Yoshida Yoshinori 
Published: June 2021

AbstractOne of the earliest maturation steps in cardiomyocytes (CMs) is the sarcomere protein isoform switch between TNNI1 and TNNI3 (fetal and neonatal/adult troponin I). Here, we generate human induced pluripotent stem cells (hiPSCs) carrying a TNNI1EmGFP and TNNI3mCherry double reporter to monitor and isolate mature sub-populations during cardiac differentiation. Extensive drug screening identifies two compounds, an estrogen-related receptor gamma (ERRγ) agonist and an S-phase kinase-associated protein 2 inhibitor, that enhances cardiac maturation and a significant change to TNNI3 expression. Expression, morphological, functional, and molecular analyses indicate that hiPSC-CMs treated with the ERRγ agonist show a larger cell size, longer sarcomere length, the presence of transverse tubules, and enhanced metabolic function and contractile and electrical properties. Here, we show that ERRγ-treated hiPSC-CMs have a mature cellular property consistent with neonatal CMs and are useful for disease modeling and regenerative medicine.
Engineered ACE2 receptor therapy overcomes mutational escape of SARS-CoV-2
Authors: Higuchi Yusuke , Suzuki Tatsuya , Arimori Takao , Ikemura Nariko , Mihara Emiko , Kirita Yuhei , Ohgitani Eriko , Mazda Osam , Motooka Daisuke , Nakamura Shota , Sakai Yusuke , Itoh Yumi , Sugihara Fuminori , Matsuura Yoshiharu , Matoba Satoaki , Okamoto Toru , Takagi Junichi , Hoshino Atsushi 
Published: June 2021

AbstractSARS-CoV-2 has mutated during the global pandemic leading to viral adaptation to medications and vaccinations. Here we describe an engineered human virus receptor, ACE2, by mutagenesis and screening for binding to the receptor binding domain (RBD). Three cycles of random mutagenesis and cell sorting achieved sub-nanomolar affinity to RBD. Our structural data show that the enhanced affinity comes from better hydrophobic packing and hydrogen-bonding geometry at the interface. Additional disulfide mutations caused the fixing of a closed ACE2 conformation to avoid off-target effects of protease activity, and also improved structural stability. Our engineered ACE2 neutralized SARS-CoV-2 at a 100-fold lower concentration than wild type; we also report that no escape mutants emerged in the co-incubation after 15 passages. Therapeutic administration of engineered ACE2 protected hamsters from SARS-CoV-2 infection, decreased lung virus titers and pathology. Our results provide evidence of a therapeutic potential of engineered ACE2.
Phylogenomic analysis reveals persistence of gonococcal strains with reduced-susceptibility to extended-spectrum cephalosporins and mosaic penA-34
Authors: Thomas Jesse C. , Joseph Sandeep J. , Cartee John C. , Pham Cau D. , Schmerer Matthew W. , Schlanger Karen , St. Cyr Sancta B. , Kersh Ellen N. , Raphael Brian H. ,   the Antimicrobial Resistant Neisseria gonorrhoeae Working Group, Dominguez Cathy , Patel Ami , Loomis Jillian , Hun Sopheay , Ruiz Ryan , Talosig Nicole , Hua Chi , Zhang Jenny , Oh Bonnie , Leavitt John , Moore Christina , Perry Zach 
Published: June 2021

AbstractThe recent emergence of strains of Neisseria gonorrhoeae associated with treatment failures to ceftriaxone, the foundation of current treatment options, has raised concerns over a future of untreatable gonorrhea. Current global data on gonococcal strains suggest that several lineages, predominately characterized by mosaic penA alleles, are associated with elevated minimum inhibitory concentrations (MICs) to extended spectrum cephalosporins (ESCs). Here we report on whole genome sequences of 813 N. gonorrhoeae isolates collected through the Gonococcal Isolate Surveillance Project in the United States. Phylogenomic analysis revealed that one persisting lineage (Clade A, multi-locus sequence type [MLST] ST1901) with mosaic penA-34 alleles, contained the majority of isolates with elevated MICs to ESCs. We provide evidence that an ancestor to the globally circulating MLST ST1901 clones potentially emerged around the early to mid-20th century (1944, credibility intervals [CI]: 1935–1953), predating the introduction of cephalosporins, but coinciding with the use of penicillin. Such results indicate that drugs with novel mechanisms of action are needed as these strains continue to persist and disseminate globally.
Quasi-graphitic carbon shell-induced Cu confinement promotes electrocatalytic CO2 reduction toward C2+ products
Authors: Kim Ji-Yong , Hong Deokgi , Lee Jae-Chan , Kim Hyoung Gyun , Lee Sungwoo , Shin Sangyong , Kim Beomil , Lee Hyunjoo , Kim Miyoung , Oh Jihun , Lee Gun-Do , Nam Dae-Hyun , Joo Young-Chang 
Published: June 2021

AbstractFor steady electroconversion to value-added chemical products with high efficiency, electrocatalyst reconstruction during electrochemical reactions is a critical issue in catalyst design strategies. Here, we report a reconstruction-immunized catalyst system in which Cu nanoparticles are protected by a quasi-graphitic C shell. This C shell epitaxially grew on Cu with quasi-graphitic bonding via a gas–solid reaction governed by the CO (g) - CO2 (g) - C (s) equilibrium. The quasi-graphitic C shell-coated Cu was stable during the CO2 reduction reaction and provided a platform for rational material design. C2+ product selectivity could be additionally improved by doping p-block elements. These elements modulated the electronic structure of the Cu surface and its binding properties, which can affect the intermediate binding and CO dimerization barrier. B-modified Cu attained a 68.1% Faradaic efficiency for C2H4 at −0.55 V (vs RHE) and a C2H4 cathodic power conversion efficiency of 44.0%. In the case of N-modified Cu, an improved C2+ selectivity of 82.3% at a partial current density of 329.2 mA/cm2 was acquired. Quasi-graphitic C shells, which enable surface stabilization and inner element doping, can realize stable CO2-to-C2H4 conversion over 180 h and allow practical application of electrocatalysts for renewable energy conversion.
Phenotypic and genomic hallmarks of a novel, potentially pathogenic rapidly growing Mycobacterium species related to the Mycobacterium fortuitum complex
Authors: Gharbi Reem , Khanna Varun , Frigui Wafa , Mhenni Besma , Brosch Roland , Mardassi Helmi 
Published: June 2021

AbstractPreviously, we have identified a putative novel rapidly growing Mycobacterium species, referred to as TNTM28, recovered from the sputum of an apparently immunocompetent young man with an underlying pulmonary disease. Here we provide a thorough characterization of TNTM28 genome sequence, which consists of one chromosome of 5,526,191 bp with a 67.3% G + C content, and a total of 5193 predicted coding sequences. Phylogenomic analyses revealed a deep-rooting relationship to the Mycobacterium fortuitum complex, thus suggesting a new taxonomic entity. TNTM28 was predicted to be a human pathogen with a probability of 0.804, reflecting the identification of several virulence factors, including export systems (Sec, Tat, and ESX), a nearly complete set of Mce proteins, toxin-antitoxins systems, and an extended range of other genes involved in intramacrophage replication and persistence (hspX, ahpC, sodA, sodC, katG, mgtC, ClpR, virS, etc.), some of which had likely been acquired through horizontal gene transfer. Such an arsenal of potential virulence factors, along with an almost intact ESX-1 locus, might have significantly contributed to TNTM28 pathogenicity, as witnessed by its ability to replicate efficiently in macrophages. Overall, the identification of this new species as a potential human pathogen will help to broaden our understanding of mycobacterial pathogenesis.
Factors associated with prognostic or treatment outcomes in HIV/AIDS patients with and without hypertension in Eswatini
Authors: Dlamini Sabelo Bonginkosi , Dahms Hans-Uwe , Wu Ming-Tsang 
Published: June 2021

AbstractNon-communicable diseases are increasing faster in HIV/AIDS patients than in the general population. We studied the association between hypertension and other possible confounding factors on viral load and CD4-cell counts in hypertensive and non-hypertensive HIV/AIDS patients receiving antiretroviral therapy (ART) at a large hospital in Eswatini over a 4-year period. We performed a retrospective longitudinal review of the medical records of 560 ART patients divided into non-hypertension and hypertension groups (n = 325 and n = 235) from July 27 to September 8, 2018. Generalized Estimated Equation was used to analyze the longitudinal data. Hypertensive patients were more likely to have improved CD4-cell counts than non-hypertensive patients (OR = 1.83, [1.37–2.44]). ART patients with hypertension were more likely to have detectable viral loads, though not significant (OR = 1.37 [0.77–2.43]). In non-hypertensive patients, second line ART was significantly associated with viral load (OR = 8.61 [2.93–25.34]) and adverse side effects (OR = 3.50 [1.06–11.54]), while isoniazid preventive therapy was significantly associated with CD4-cell counts (OR = 1.68 [1.16–2.45]). In hypertensive patients, factors associated with viral load were WHO HIV stage (OR = 2.84 [1.03–7.85]) and adherence (OR = 8.08 [1.33–49.04]). In both groups, CD4-cell counts significantly and steadily increased over time (p-value < 0.001). Results show a significant association between hypertension and CD4 cell counts but not viral load. In ART patients with and without hypertension, the factors associated with prognostic markers were different. More attention may need to be paid to ART patients with well controlled HIV status to monitoring and controlling of hypertension status.
Association between household air pollution and child mortality in Myanmar using a multilevel mixed-effects Poisson regression with robust variance
Authors: Rana Juwel , Islam Rakibul M. , Khan Md Nuruzzaman , Aliani Razia , Oulhote Youssef 
Published: June 2021

AbstractHousehold air pollution (HAP) from solid fuel use (SFU) for cooking is a major public health threat for women and children in low and middle-income countries. This study investigated the associations between HAP and neonatal, infant, and under-five child mortality in Myanmar. The study consisted of 3249 sample of under-five children in the households from the first Myanmar Demographic and Health Survey 2016. Fuel types and levels of exposure to SFU (no, moderate and high) were proxies for HAP. We estimated covariate-adjusted relative risks (aRR) of neonatal, infant, and under-five child mortality with 95% confidence intervals, accounting for the survey design. The prevalence of SFU was 79.0%. The neonatal, infant, and under-five child mortality rates were 26, 45, and 49 per 1000 live births, respectively. The risks of infant (aRR 2.02; 95% CI 1.01–4.05; p-value = 0.048) and under-five mortality (aRR 2.16; 95% CI 1.07–4.36; p-value = 0.031), but not neonatal mortality, were higher among children from households with SFU compared to children from households using clean fuel. Likewise, children highly exposed to HAP had higher risks of mortality than unexposed children. HAP increases the risks of infant and under-five child mortality in Myanmar, which could be reduced by increasing access to clean cookstoves and fuels.
Domain knowledge integration into deep learning for typhoon intensity classification
Authors: Higa Maiki , Tanahara Shinya , Adachi Yoshitaka , Ishiki Natsumi , Nakama Shin , Yamada Hiroyuki , Ito Kosuke , Kitamoto Asanobu , Miyata Ryota 
Published: June 2021

AbstractIn this report, we propose a deep learning technique for high-accuracy estimation of the intensity class of a typhoon from a single satellite image, by incorporating meteorological domain knowledge. By using the Visual Geometric Group’s model, VGG-16, with images preprocessed with fisheye distortion, which enhances a typhoon’s eye, eyewall, and cloud distribution, we achieved much higher classification accuracy than that of a previous study, even with sequential-split validation. Through comparison of t-distributed stochastic neighbor embedding (t-SNE) plots for the feature maps of VGG with the original satellite images, we also verified that the fisheye preprocessing facilitated cluster formation, suggesting that our model could successfully extract image features related to the typhoon intensity class. Moreover, gradient-weighted class activation mapping (Grad-CAM) was applied to highlight the eye and the cloud distributions surrounding the eye, which are important regions for intensity classification; the results suggest that our model qualitatively gained a viewpoint similar to that of domain experts. A series of analyses revealed that the data-driven approach using only deep learning has limitations, and the integration of domain knowledge could bring new breakthroughs.
MRI-derived radiomics model for baseline prediction of prostate cancer progression on active surveillance
Authors: Sushentsev Nikita , Rundo Leonardo , Blyuss Oleg , Gnanapragasam Vincent J. , Sala Evis , Barrett Tristan 
Published: June 2021

AbstractNearly half of patients with prostate cancer (PCa) harbour low- or intermediate-risk disease considered suitable for active surveillance (AS). However, up to 44% of patients discontinue AS within the first five years, highlighting the unmet clinical need for robust baseline risk-stratification tools that enable timely and accurate prediction of tumour progression. In this proof-of-concept study, we sought to investigate the added value of MRI-derived radiomic features to standard-of-care clinical parameters for improving baseline prediction of PCa progression in AS patients. Tumour T2-weighted imaging (T2WI) and apparent diffusion coefficient radiomic features were extracted, with rigorous calibration and pre-processing methods applied to select the most robust features for predictive modelling. Following leave-one-out cross-validation, the addition of T2WI-derived radiomic features to clinical variables alone improved the area under the ROC curve for predicting progression from 0.61 (95% confidence interval [CI] 0.481–0.743) to 0.75 (95% CI 0.64–0.86). These exploratory findings demonstrate the potential benefit of MRI-derived radiomics to add incremental benefit to clinical data only models in the baseline prediction of PCa progression on AS, paving the way for future multicentre studies validating the proposed model and evaluating its impact on clinical outcomes.