bluuebunny/crossref_metadata_2025_split huggingface dataset:
A clearance period after soluble lead nanoparticle inhalation did not ameliorate the negative effects on target tissues due to decreased immune response
Authors: Dumkova Jana , Smutná Tereza , Vrlikova Lucie , Docekal Bohumil , Kristekova Daniela , Vecera Zbynek , Husakova Zuzana , Jakesova Veronika , Jedlickova Adriena , Mikuska Pavel , Capka Lukas , Coufalik Pavel , Tvrdonova Michaela , Krumal Kamil , Vaculovic Tomas , Kanicky Viktor , Hampl Ales , Buchtova Marcela 
Published: September 2020

Abstract

Background: The inhalation of metal (including lead) nanoparticles poses a real health issue to people and animals living in polluted and/or industrial areas. In this study, we exposed mice to lead(II) nitrate nanoparticles [Pb(NO3)2 NPs], which represent a highly soluble form of lead, by inhalation. We aimed to uncover the effects of their exposure on individual target organs and to reveal potential variability in the lead clearance. Mice were exposed to Pb(NO3)2 NPs in whole-body inhalation chambers for up to 11 weeks. We examined (i) lead biodistribution in target organs using laser ablation and inductively coupled plasma mass spectrometry (LA-ICP-MS) and atomic absorption spectrometry (AAS), (ii) lead effect on histopathological changes and immune cells response in secondary target organs and (iii) the clearance ability of target organs (lung, liver, kidney, spleen, bone and blood). Results: After exposure to Pb(NO3)2 NPs, the lead concentration was the highest in femur at all designated time points with the exception of 3-day inhalation. In contrast to other organs, the ability to clear the lead from the femur was very low. In the lungs, Pb(NO3)2 NP inhalation induced serious structural changes; lung damage was present even after a 5-week clearance period despite the lead being almost completely eliminated from the lung tissue. Furthermore, in secondary target organs (kidney and liver), Pb(NO3)2 NPs induced several morphological defects, with alterations that remained visible after the clearance period even though the tissue lead concentrations decreased to minimal values. The numbers of lung and liver macrophages were significantly decreased after 11-week Pb(NO3)2 NP inhalation; conversely, abundance of alpha-smooth muscle actin (α-SMA)-positive cells, which are responsible for augmented collagen production, was increased in both tissues. Moreover, the expression of nuclear factor κB (NF-κB) and selected cytokines (tumour necrosis factor alpha [TNF-α], transforming growth factor beta 1 [TGFβ1], interleukin 6 [IL-6], IL-1α and IL-1β) displayed a tissue-specific response to lead exposure. Conclusions: Taken together, diminished inflammatory response in lung and liver after Pb(NO3)2 NPs inhalation was associated with prolonged negative effect of lead on tissues, as demonstrated by enhanced pathological changes in target organs, even after a 5-week clearance period.
Influence of Covariates on Involved Lymph Nodes in Primary Breast Cancer Patients: Mixture Distribution Zero-Inflated Modeling Methodological Framework
Authors: Liaqat Madiha , Kamal Shahid , Fischer Florian , Zia Nadeem 
Published: September 2020

Abstract
Background: Involvement of lymph nodes has been an integral part of breast cancer prognosis and survival. This study aimed to explore factors influencing on the number of auxiliary lymph nodes in women diagnosed with primary breast cancer by choosing an efficient model to assess excess of zeros and over-dispersion presented in the study population. Methods: The study is based on a retrospective analysis of hospital records among 5,196 female breast cancer patients in Pakistan. Zero-inflated Poisson and zero-inflated negative binomial modeling techniques are used to assess the association between under-study factors and the number of involved lymph nodes in breast cancer patients. Results: The most common breast cancer was invasive ductal carcinoma (54.5%). Patients median age was 48 years, from which women aged 46 years and above are the majority of the study population (64.8%). Examination of tumors revealed that over 2,662 (51.2%) women were ER-positive, 2,652 (51.0%) PR-positive, and 2,754 (53.0%) were Her2.neu-positive. The mean tumor size was 3.06 cm and histological grade 1 (n=2021, 38.9%) was most common in this sample. The model performance was best in the zero-inflated negative binomial model. Findings indicate that most factors related to breast cancer have a significant impact on the number of involved lymph nodes. Age is not contributed to lymph node status. Women having a larger tumor size suffered from greater number of involved lymph nodes. Tumor grades 11 and 111 contributed to higher numbers of positive lymph node.Conclusions: Zero-inflated models have successfully demonstrated the advantage of fitting count nodal data when both “at-harm” (lymph node involvement) and “not-at-harm” (no lymph node involvement) groups are important in predicting disease on set and disease progression. Our analysis showed that ZINB is the best model for predicting and describing the number of involved nodes in primary breast cancer, when overdispersion arises due to a large number of patients with no lymph node involvement. This is important for accurate prediction both for therapy and prognosis of breast cancer patients.
Dual-comb spectroscopy with spectral acquisition rate surpassing Nyquist-limited trade-off constraint
Authors: Xu Bingxin , Fan Xinyu , Wang Shuai , He Zuyuan 
Published: September 2020

Abstract
Optical frequency comb with evenly spaced lines over a broad bandwidth has revolutionized the fields of optical metrology and spectroscopy. Despite dual-comb spectroscopy (DCS) offers a superb overall performance on spectral resolution, measurement bandwidth and refresh rate, these parameters are still constrained by the Nyquist-limited trade-off. Here, we propose a novel DCS system to overcome this limitation with tens of spectral acquisition rate improvement, which is built with two electro-optic frequency combs seeded by an ultralinearly swept light source. The proposed scheme records a spectrum spanning 304 GHz with a spectral resolution of 10 kHz in 1.6 ms, which achieves a spectral sampling-rate of 1.9×1010 points/s. We also demonstrate the 100-averaged results with 28.9 dB signal-to-noise ratio for high sensitivity measurement. The demonstration shows great prospect for precise measurement with significant performance breakthrough.
Altered ISGylation drives aberrant macrophage-dependent immune responses during SARS-CoV-2 infection
Authors: Sanyal Sumana , Lee Horace , Munnur Deeksha , Teo Qi , Ho Julian , Ng Wilson , Siu Lewis , Spooner Eric , Ploegh Hidde , Pinto-Fernandez Adan , Damianou Andreas , Kessler Benedikt , Mok Chris 
Published: September 2020

Abstract
Interferon stimulated gene 15 (ISG15) is a ubiquitin like modifier frequently induced during virus infections and involved in versatile host defense mechanisms. Not surprisingly, many viruses including SARS-CoV-2 have evolved de-ISGylating activities to antagonize its effect. In this study we compared ISG15-driven macrophage responses upon infection by influenza, Zika and SARS-CoV-2 viruses. ISG15 and its modifying enzymes were upregulated in human macrophages after infection with all three viruses. While influenza and Zika viruses induced cellular ISGylation, SARS-CoV-2 triggered hydrolysis of ISG15 modifications instead, to generate free, extracellular ISG15 from macrophages and dendritic cells, but not from bronchial epithelial cells. Extracellular ISG15 was released independent of the conventional secretory pathway or cell death, but instead, depended on a non-classical autophagy-related secretory process. Increase of extracellular ISG15 was also reflected in serum samples from COVID-19 patients. The high ratio of free versus conjugated ISG15 in SARS-CoV-2 infected cells triggered macrophage polarization towards a M1 phenotype, increased secretion of pro-inflammatory cytokines, e.g. MCP-1 (CCL2), IL-1, TNF and IL-6, and attenuated antigen presentation. Depleting ISG15 conjugating enzymes Ube1L and HERC5 further increased free ISG15 and exacerbated this effect. We could recapitulate this phenomenon by expressing the wild-type but not the catalytically inactive PLpro de-ISGylating enzyme of SARS-CoV-2. Proteomic analyses of the secretome from SARS-CoV-2 infected macrophages revealed that besides ISG15, it displayed significant enrichment in non-classical secretory proteins and inflammatory responses, which was further amplified by free ISG15. Collectively, our results indicate that increased proportions of free ISG15 dramatically alter macrophage responses and is likely a key feature of cytokine storms triggered by highly pathogenic respiratory viruses such as influenza and SARS-CoV-2.
Gender Equity at Last:&nbsp;A National Study of&nbsp;Medical Students Considering a Career in Rural Medicine
Authors: Kim Caleb , Ngo Hanh , Playford Denese 
Published: September 2020

Abstract
Background: The rural medical workforce internationally suffers from a significant gender imbalance. Not only do male doctors outnumber female doctors, but additionally female doctors work fewer hours than their male counterparts. This has health implications for rural communities. In response, In Australia, Rural Clinical Schools (RCSs) are a national training strategy to increase the number of graduates entering the rural medical workforce. It has been observed that RCSs attract a greater number of female students than male students. However, the future work intentions of male versus female RCS students is not known. This paper therefore asked whether male and female RCS students have equivalent intent for future rural practice.Methods: Participants were all students who attended RCSs from 2015-2017, who completed an exit survey that gathered data on demographic, experiential and intentional variables. Univariate analyses examined differences across gender. A multivariate model was constructed to determine the independent predictors for rural intention.Results: There were 2,017 respondents across the three years, of whom 937 were male, and 1,138 female. In univariate analysis, female students had significantly higher rural intention than male students. There were no other gender differences in age, rural background, overall perception of support, and overall excellence of clinical education whilst in RCS. However, in multivariate analysis, gender was not a significant predictor for rural work intention, whereas older age, rural background, and first preference for RCS were all predictive of increased rural intent, as expected from the literature. There were no differences between male and female students in their perceptions of the overall support and the clinical education provided by RCS. Conclusion: We conclude from this national study that gender is not an independent predictor for future rural work intention among RCS students. Considering the disproportionate number of female students entering RCS, this is reassuring for ultimately achieving rural workforce gender equity.
Biomechanical Analysis of Atlantoaxial Dorsal Fixation Using Finite Element Models
Authors: Bae Beomju , Kim Dongwook , Oh Hyejong , Kim Gonhyung 
Published: September 2020

Abstract
Background: Atlantoaxial instability can cause spinal cord compression with clinical signs ranging from cervical pain to tetraplegia and death. Although a variety of dorsal fixation techniques have been described, some of them have been related to the fracture of the dorsal arch of the atlas, leading to surgical failure. We hypothesized that the shape of the dorsal arch of the atlas and types of implants might affect these bone fractures. Thus, the objective of this study was to analyze bone stresses through simulations of the dorsal fixation using finite element models.Results: The width between wires and the length of the bone did not affect the maximum stress on the bone. The maximum bone stress increased as the bone got thinner and the angle of the notch got steeper. The bone with band implant had lower maximum bone stress than that with wire implants. When using wire implants, wires applied beyond the notch of the dorsal arch reduced the maximum bone stress more than wires positioned within it.Conclusions: The fracture of the dorsal arch of the atlas was related to the shape of the bone and types of implant applied. Band implant can effectively reduce the fracture of the dorsal arch compared to wire implant in atlantoaxial dorsal fixation. When considering wire implant, it is recommended to apply wires beyond the notch of the atlas.
Preemptive Intravenous Iron Therapy Versus Autologous Whole Blood Therapy for Early Postoperative Hemoglobin Level in Patients Undergoing Bimaxillary Orthognathic Surgery: A Prospective Randomized Noninferiority Trial
Authors: Chae Min Suk , Lee Mihyun , Choi Min Ho , Park Je Uk , Park Misun , Kim Young Hoon , Choi Hoon , Joo Jin , Moon Young Eun 
Published: September 2020

Abstract
Background: Previous studies have reported the efficacy and safety of intravenous (IV) iron therapy during perioperative period as an alternative and adjunct to allogeneic blood transfusion. Preemptive IV iron therapy provides noninferior hemoglobin levels on postoperative day (POD) 1 compared to autologous whole blood therapy (AWBT) in healthy patients who had undergone bimaxillary orthognathic surgery.Methods: This was a prospective, patient-randomized, noninferiority trial. After excluding 2 patients, 64 patients were divided into two groups: the IV iron therapy group (patients received IV iron infusion 4 weeks before surgery; n = 32) and the AWBT group (2 units of autologous whole blood were collected 4 and 2 weeks before surgery; n = 32). The primary outcome was hemoglobin level on POD 1 and the prespecified noninferiority limit was –1 g/dL.Results: Baseline data were comparable, including hemoglobin and iron levels, between the two groups. Immediately before surgery, the levels of hemoglobin, iron, and ferritin were higher in the IV iron group than in the AWBT group. The mean treatment difference (iron group – whole blood group) in hemoglobin level on POD 1 between the two groups was 0.09 (95% CI = –0.83 to 1.0). As the lower limit of the 95% CI (–0.83) was higher than the prespecified noninferiority margin (δ = –1), noninferiority was established. On POD 2, the hemoglobin level became lower in the iron group, which eventually led to greater requirement of allogeneic blood transfusion compared to the whole blood group. However, the iron group did not require allogeneic blood transfusion during or early after surgery, and the whole blood group showed continuously higher incidence of overt iron deficiency compared to the iron group.Conclusion: As collection of autologous whole blood caused overt iron loss and anemia before surgery and intraoperative transfusion of whole blood was not able to prevent the occurrence of persistent iron deficiency after surgery, IV iron therapy was found to have potential benefits for iron homeostasis and subsequent erythropoiesis in healthy patients early after bimaxillary orthognathic surgery.Trial registration: Clinical Research Information Service, Republic of Korea, approval number: KCT0003680 on March 27, 2019https://cris.nih.go.kr/cris/search/search_result_st01_kren.jsp?seq=15769&sLeft=2&ltype=my&rtype=my
Bacteriological Characteristics of COVID-19 Patients Nosocomially Co-infected at a Designated Hospital: A Retrospective Study
Authors: Yu Jing , Nie Lei , Zhou Xia , Wu Dongde , Chen Jian , Yang Zhifeng , Zhang Ling , Wang Kun 
Published: September 2020

Abstract
Background: Bacterial co-infection in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a critical factor that increases the complexity and treatment of coronavirus disease 2019 (COVID-19). Methods: We collected the clinical laboratory data of 1799 patients with confirmed COVID-19 who were admitted to Jinyintan Hospital in Wuhan, China, between January 1 to April 26, 2020. The bacterial co-infection along with disease progression was analyzed. Other inflammatory markers, including C-reactive protein (CRP), white blood cells (WBC), lymphocytes (L), neutrocytes (N), interleukin-6 (IL-6), and procalcitonin (PCT), were assessed to estimate the progression of COVID-19. Results: We found that 191 of the 1799 (10.62%) patients had bacterial co-infection. The most prevalent causative agents for bacterial co-infection were Klebsiella pneumoniae (91 cases, 5.06%) and Acinetobacter baumannii (66 cases, 3.67%). The most patients with bacterial co-infection showed extensive drug-resistance. The outcomes of patients with bacterial co-infection were worse than those of patients without bacterial co-infection.Conclusions: Secondary bacterial pneumonia during virus infection is a major risk factor for high mortality resulting from severe pneumonia caused by COVID-19.
422 Million Q Planar Integrated All-Waveguide Resonator with a 3.4 Billion Absorption Limited Q, Sub-MHz Linewidth and 3005 Finesse
Authors: Puckett Matthew , Liu Kaikai , Chauhan Nitesh , Zhao Qiancheng , Jin Naijun , Cheng Haotian , Wu Jianfeng , Behunin Ryan , Rakich Peter , Nelson Karl , Blumenthal Daniel 
Published: September 2020

Abstract
High Q optical resonators that are a key component for ultra-narrow linewidth lasers, frequency stabilization, precision spectroscopy and quantum applications. Integration of these resonators in a photonic waveguide wafer-scale platform is key to reducing their cost, size and power as well as sensitivity to environmental disturbances. However, to date, the intrinsic Q of integrated all-waveguide resonators has been relegated to below 150 Million for a non-etched waveguide resonator and 230 Million for a waveguide-coupled etched silica microresonator. Here, we report an all-waveguide Si3N4 resonator with an intrinsic Q of 422 Million and a 3.4 Billion absorption loss limited Q. The resonator linewidth measures at 453 kHz intrinsic linewidth, 906 kHz loaded linewidth with finesse of 3005. The corresponding linear loss of 0.060 dB/m is the lowest reported to date for an all-waveguide design with deposited upper cladding oxide. These are the highest intrinsic and absorption loss limited Q factors and lowest linewidth reported to date for a photonic integrated all-waveguide resonator. This level of performance is achieved through a careful reduction of scattering and absorption loss components and redeposition of a thin nitride layer. We quantify, simulate and measure the various loss contributions including scattering and absorption and describe a surface-state dangling bond absorption that we believe is passivated by the redeposited layer. In addition to the ultra-high Q and narrow linewidth, the resonator has a large optical mode area and volume, both critical for ultra-low laser linewidths and ultra-stable, ultra-low frequency noise reference cavities. These results demonstrate the performance of bulk optic and etched resonators can be realized in a photonic integrated solution, paving the way towards photonic integration compatible Billion Q cavities for precision scientific systems and applications such as nonlinear optics, atomic clocks, quantum photonics and high-capacity fiber communications systems on-chip.
Reversible Ir-based multifunctional electrocatalyst for durable water splitting and fuel cell systems
Authors: Lee Woong Hee , Ko Young-Jin , Kim Jung Hwan , Choi Chang Hyuck , Chae Keun Hwa , Kim Hansung , Hwang Yun Jeong , Min Byoung Koun , Strasser Peter , Oh Hyung-Suk 
Published: September 2020

Abstract
The voltage reversal of water electrolyzers and fuel cells induces a large positive potential on the hydrogen electrodes, followed by severe system degradation. Applying a reversible multifunctional electrocatalyst to the hydrogen electrode is a practical solution. Ir exhibits excellent catalytic reactivity for hydrogen evolution reactions (HER), and hydrogen oxidation reactions (HOR) around 0 V/RHE, yet irreversibly converts to amorphous IrOx at potentials > 0.8 V/RHE, which is an excellent catalyst for oxygen evolution reactions (OER), yet a poor HER and HOR catalyst. Harnessing these multifunctional catalytic characteristics, we designed a unique Ir-based electrocatalyst for OER, HER, and HOR. Under OER operation, the crystalline nanoparticle catalyst generates an atomically-thin, highly active IrOx layer, which reversibly transforms into a metallic Ir surface at more cathodic electrode potentials, restoring high catalytic activity for HER and HOR. Our analysis reveals that a metallic Ir subsurface to the thin IrOx surface layer can act as a catalytic substrate for the reduction of the dissolved Ir ion, creating reversibility. Our work not only uncovers new fundamental, uniquely reversible catalytic properties of nanoparticle catalysts, but also offers a practical materials-based solution to catalyst layer degradation of electrochemical energy conversion devices.
Deep learning on image-omics data in identifying prognostic immune biomarkers for ovarian cancer
Authors: Zhu Ying , Ferri-Borgogno Sammy , Sheng Jianting , Yeung Tsz-Lun , Burks Jared , Cappello Paola , Jazaeri Amir , Kim Jae-Hoon , Han Gwan Hee , Birrer Michael , Mok Samuel , Wong Stephen 
Published: September 2020

Abstract
Although stromal and immune cells in the tumor microenvironment have been shown to directly affect tumor growth and chemoresistance, how the interactions among stromal and immune cells and their spatially resolved cell heterogeneity would influence ovarian patients’ survival remains largely unknown. To fill this gap, we developed a new imageomics method that (i) incorporates an artificial intelligence–based analytics pipeline for imaging mass cytometry (IMC) to increase the accuracy of cell segmentation and spatial information extraction in order to identify immune biomarkers and their interactions that can predict overall survival rates in patients with treatment-naïve ovarian cancer, and (ii) integrates quantitated spatial IMC image data with microdissected tumor and stromal transcriptomic data from the same patients as well as single-cell RNA sequencing data to detect genes correlated with the prognostic features and postulate novel mechanisms by which these genes contribute to the prognostic features.
Nickel Ferrocyanide as High-Performance Next Generation Electrocatalyst for Urea Oxidation
Authors: Geng Shi-Kui , Zheng Yao , Li Shan-Qing , Zhao Xu , Hu Jun , Shu Hai-Bo , Jaroniec Mietek , Chen Ping , Liu Qinghua , Qiao Shizhang 
Published: September 2020

Abstract
Urea oxidation, a key process in energy and environmental science, faces challenges because of the insufficient understanding of its mechanism and the lack of efficient catalysts. Here we demonstrate that nickel ferrocyanide (Ni2Fe(CN)6) molecular catalyst supported on Ni form can drive urea oxidation reaction (UOR) with the record electrochemical activity and stability among all supported catalysts reported so far. A combination of kinetics data, in-situ spectroscopic measurements and energy computations suggests a new UOR pathway that delivers such outstanding performance. Different from most studied Ni-based catalysts with NiOOH derivative as a real catalytically active site for UOR, Ni2Fe(CN)6 appears to be a next-generation catalyst able to directly facilitate a two-step reaction pathway involving a critical reaction of intermediate ammonia’s production (on Ni site) and oxidation (on Fe site). Due to the alternative rate-determining step with a more favorable thermal energetics, Ni2Fe(CN)6 broke the limiting activity of the reported so far UOR catalysts. As a result, the UOR process on Ni2Fe(CN)6 can replace conventional water oxidation process in various energy-saving systems for hydrogen and hydrogen peroxide production.