bluuebunny/crossref_metadata_2025 huggingface dataset:
From proband to provider: is there an obligation to inform genetic relatives of actionable risks discovered through direct-to-consumer genetic testing?
Authors: Parsons Jordan A , Baker Philip E
Published: December 2020

Direct-to-consumer genetic testing is a growing phenomenon, fuelled by the notion that knowledge equals control. One ethical question that arises concerns the proband’s duty to share information indicating genetic risks in their relatives. However, such duties are unenforceable and may result in the realisation of anticipated harm to relatives. We argue for a shift in responsibility from proband to provider, placing a duty on test providers in the event of identified actionable risks to relatives. Starting from Parker and Lucassen’s (2004) 'joint account model', we adapt Kilbride’s (2018) application of the rule of rescue and balance it against the relative’s right not to know, placing responsibility on the providers of direct-to-consumer genetic testing. Where the risk of disease to a relative is actionable, we argue providers ought to share results even in the face of the proband’s objections. Confidentiality issues are navigated by a pre-emptive consent model, whereby consumers agree to the sharing of certain information with their relatives ahead of testing and as a condition of testing. When a relative is informed, the proband’s privacy is protected by maximal deidentification, and the rights of the relative are met by a stepwise approach to informing that allows them to decide how much information they receive.
Occupation and risk of severe COVID-19: prospective cohort study of 120 075 UK Biobank participants
Authors: Mutambudzi Miriam , Niedzwiedz Claire , Macdonald Ewan Beaton , Leyland Alastair , Mair Frances , Anderson Jana , Celis-Morales Carlos , Cleland John , Forbes John , Gill Jason , Hastie Claire , Ho Frederick , Jani Bhautesh , Mackay Daniel F , Nicholl Barbara , O'Donnell Catherine , Sattar Naveed , Welsh Paul , Pell Jill P , Katikireddi Srinivasa Vittal , Demou Evangelia
Published: December 2020

Objectives

To investigate severe COVID-19 risk by occupational group.

Methods

Baseline UK Biobank data (2006–10) for England were linked to SARS-CoV-2 test results from Public Health England (16 March to 26 July 2020). Included participants were employed or self-employed at baseline, alive and aged <65 years in 2020. Poisson regression models were adjusted sequentially for baseline demographic, socioeconomic, work-related, health, and lifestyle-related risk factors to assess risk ratios (RRs) for testing positive in hospital or death due to COVID-19 by three occupational classification schemes (including Standard Occupation Classification (SOC) 2000).

Results

Of 120 075 participants, 271 had severe COVID-19. Relative to non-essential workers, healthcare workers (RR 7.43, 95% CI 5.52 to 10.00), social and education workers (RR 1.84, 95% CI 1.21 to 2.82) and other essential workers (RR 1.60, 95% CI 1.05 to 2.45) had a higher risk of severe COVID-19. Using more detailed groupings, medical support staff (RR 8.70, 95% CI 4.87 to 15.55), social care (RR 2.46, 95% CI 1.47 to 4.14) and transport workers (RR 2.20, 95% CI 1.21 to 4.00) had the highest risk within the broader groups. Compared with white non-essential workers, non-white non-essential workers had a higher risk (RR 3.27, 95% CI 1.90 to 5.62) and non-white essential workers had the highest risk (RR 8.34, 95% CI 5.17 to 13.47). Using SOC 2000 major groups, associate professional and technical occupations, personal service occupations and plant and machine operatives had a higher risk, compared with managers and senior officials.

Conclusions

Essential workers have a higher risk of severe COVID-19. These findings underscore the need for national and organisational policies and practices that protect and support workers with an elevated risk of severe COVID-19.
CO2combining power and outcomes in patients with acute ischaemic stroke or transient ischaemic attack
Authors: Wang Anxin , Tian Xue , Gu Hongqiu , Zuo Yingting , Meng Xia , Lv Wei , Li Hao , Wang Yongjun
Published: December 2020

Background and purpose

The clinical significance of carbon dioxide combining power (CO2CP) in ischaemic cerebrovascular disease is not well established, and the role of CO2CP in the prognosis of acute ischaemic stroke (AIS) or transient ischaemic attack (TIA) has not been reported. The objective of the study was to investigate the associations between CO2CP and clinical outcomes in patients with AIS or TIA.

Methods

Data were derived from the China National Stroke Registry III. Patients were classified into five groups by quintiles of CO2CP levels and three groups according to the normal range of CO2CP (23–29 mmol/L). Multivariable Cox and logistic regressions were adopted to explore the associations of CO2CP levels with all-cause death and poor functional outcomes (modified Rankin Scale (mRS) 3–6/2–6) at 3 months and 1 year.

Results

Among 9531 patients included in the study, the median (IQR) CO2CP was 24.9 (23.0–27.0) mmol/L. After adjustment for potential confounders, patients in the first CO2CP quintile (21.1–23.3 mmol/L) had higher risk of all-cause death and poor functional outcomes (mRS score of 3–6/2–6) (HR or OR with 95% CI 2.37 (1.32 to 4.25), 1.49 (1.20 to 1.83) and 1.21 (1.03 to 1.42), respectively) compared with those in the fourth quintile. Similar results were found for outcomes at 1 year. Furthermore, all associations were also significant when CO2CP was <23 mmol/L compared with CO2CP of 23–29 mmol/L.

Conclusions

Decreased CO2CP was associated with high risk of all-cause death and poor functional outcomes in patients with AIS or TIA.
Frailty subtypes and recovery in older survivors of acute respiratory failure: a pilot study
Authors: Baldwin Matthew R , Pollack Lauren R , Friedman Richard A , Norris Simone P , Javaid Azka , O'Donnell Max R , Cummings Matthew J , Needham Dale M , Colantuoni Elizabeth , Maurer Mathew S , Lederer David J
Published: December 2020

Background

Identifying subtypes of acute respiratory failure survivors may facilitate patient selection for post-intensive care unit (ICU) follow-up clinics and trials.

Methods

We conducted a single-centre prospective cohort study of 185 acute respiratory failure survivors, aged
≥
65 years. We applied latent class modelling to identify frailty subtypes using frailty phenotype and cognitive impairment measurements made during the week before hospital discharge. We used Fine-Gray competing risks survival regression to test associations between frailty subtypes and recovery, defined as returning to a basic Activities of Daily Living disability count less than or equal to the pre-hospitalisation count within 6 months. We characterised subtypes by pre-ICU frailty (Clinical Frailty Scale score
≥
5), the post-ICU frailty phenotype, and serum inflammatory cytokines, hormones and exosome proteomics during the week before hospital discharge.

Results

We identified five frailty subtypes. The recovery rate decreased 49% across each subtype independent of age, sex, pre-existing disability, comorbidity and Acute Physiology and Chronic Health Evaluation II score (recovery rate ratio: 0.51, 95% CI 0.41 to 0.63). Post-ICU frailty phenotype prevalence increased across subtypes, but pre-ICU frailty prevalence did not. In the subtype with the slowest recovery, all had cognitive impairment. The three subtypes with the slowest recovery had higher interleukin-6 levels (p=0.03) and a higher prevalence of
≥
2 deficiencies in insulin growth factor-1, dehydroepiandrostersone-sulfate, or free-testosterone (p=0.02). Exosome proteomics revealed impaired innate immunity in subtypes with slower recovery.

Conclusions

Frailty subtypes varied by prehospitalisation frailty and cognitive impairment at hospital discharge. Subtypes with the slowest recovery were similarly characterised by greater systemic inflammation and more anabolic hormone deficiencies at hospital discharge.
CD4+T cells in ageing-associated interstitial lung abnormalities show evidence of pro-inflammatory phenotypic and functional profile
Authors: Machahua Carlos , Buendia-Roldan Ivette , Ocaña-Guzman Ranferi , Molina-Molina María , Pardo Annie , Chavez-Galan Leslie , Selman Moises
Published: December 2020

Background

Interstitial lung abnormalities (ILA) occur in around 10% of subjects over 60 years, and are associated with a higher rate of all-cause mortality. The pathogenic mechanisms are unclear, and the putative contribution of alterations in the immune response has not been explored. Normal ageing is associated with immune deficiencies, including Naïve T-cell decrease and greater expression of the proliferative-limiting, co-inhibitory receptor killer-cell lectin-like receptor G1 (KLRG1).

Objective

To evaluate the frequency and activation state of different T-cell subpopulations in ILA subjects.

Methods

Peripheral blood mononuclear cells were obtained from 15 individuals with ILA, 21 age-matched controls and 28 healthy young subjects. T-cells phenotype was characterised by flow cytometry, and proliferation and activation by stimulation with anti-CD3/anti-CD28 or phorbol myristate acetate/ionomycin; KLRG1 isoforms were evaluated by western blot and cytokines were quantified by ELISA and Multiplex.

Results

A significant increase of Naïve CD4+T cells together with a decrease of central and effector memory CD4+T cells was observed in ILA compared with age-matched controls. CD4+T cells from ILA subjects exhibited greater basal proliferation, which raised after anti-CD3/anti-CD28 stimulation. Additionally, a significant increase in the levels of interleukin-6 and interferon gamma was observed in isolated CD4+T cells and plasma of ILA subjects. They also displayed fewer KLRG1+/CD4+T cells with an increase of circulating E-cadherin, the ligand of KLRG1+. No changes were observed with CD8+T cell subsets.

Conclusion

CD4+T cells from ILA subjects are highly proliferative and show an excessive functional activity, likely related to the loss of KLRG1 expression, which may contribute to an inflammatory state and the development of ILA.
Quality of dying and death in patients with interstitial lung disease compared with lung cancer: an observational study
Authors: Koyauchi Takafumi , Suzuki Yuzo , Sato Kazuki , Hozumi Hironao , Karayama Masato , Furuhashi Kazuki , Fujisawa Tomoyuki , Enomoto Noriyuki , Nakamura Yutaro , Inui Naoki , Yokomura Koshi , Imokawa Shiro , Nakamura Hidenori , Morita Tatsuya , Suda Takafumi
Published: December 2020

Background

There is limited knowledge regarding the quality of dying and death (QODD) and end-of-life interventions in patients with interstitial lung disease (ILD). Hence, differences in QODD and end-of-life interventions between patients with ILD and those with lung cancer (LC) remain poorly understood.

Methods

The primary aim of this study was to explore the differences in QODD and end-of-life interventions among patients dying with ILD versus those dying with LC. We performed a mail survey to quantify the QODD of a bereaved family’s perspective using the Good Death Inventory (GDI) score. Moreover, we examined the end-of-life interventions by medical chart review.

Results

Of 361 consecutive patients analysed for end-of-life interventions, 167 patients whose bereaved families completed questionnaires were analysed for QODD. Patients with ILD had lower GDI scores for QODD than those with LC (p=0.04), particularly in domains related to ‘physical and psychological distress relief’ and ‘prognosis awareness and participation in decision making’ (p=0.02, respectively). In end-of-life interventions, patients with ILD were less likely to receive specialised palliative care services (8.5% vs 54.3%; p<0.001) and opioids (58.2% vs 73.4%; p=0.003). Additionally, lower frequencies of participation of patients with ILD in end-of-life discussion were also observed (40.8% vs 62.4%; p=0.007).

Conclusion

Patients with ILD had lower QODD and poorer access to palliative care and decision making than those with LC. Additional efforts to improve QODD in patients with ILD, particularly in symptom relief and decision-making processes, are urgently warranted.
Unusual case of splenic haemangiosarcoma with suspected scrotal metastasis in a 13‐year‐old English Pointer
Authors: Park Clair S , Sawyere Dominique M
Published: December 2020

Visceral haemangiosarcoma is an aggressive neoplasm, often associated with a high metastatic potential. The most common sites for metastases are the liver, lungs, peritoneum, muscle and lymph nodes. This report describes an unusual presentation of possible visceral haemangiosarcoma metastasis to the scrotum in 13‐year‐old intact male English Pointer. The patient presented with a two‐day history of inappetence. On physical examination, mid‐abdominal and scrotal masses could be palpated. Following staging, a splenectomy and scrotal ablation were performed. Histopathology confirmed splenic and scrotal haemangiosarcoma. Adjuvant chemotherapy was started 20 days postoperatively. A suggestion of progressive disease was suspected at two months postoperatively. The patient was lost to follow‐up following that visit. Metastasis of a splenic haemangiosarcoma to the scrotum is uncommon, and the possibility of the presence of two independent lesions cannot be excluded. This case illustrates the importance of a thorough physical examination and staging.
The development and implementation of a human-caused wildland fire occurrence prediction system for the province of Ontario, Canada
Authors: Woolford Douglas G. , Martell David L. , McFayden Colin B. , Evens Jordan , Stacey Aaron , Wotton B. Michael , Boychuk Dennis
Published: December 2020

We describe the development and implementation of an operational human-caused wildland fire occurrence prediction (FOP) system in the province of Ontario, Canada. A suite of supervised statistical learning models was developed using more than 50 years of high-resolution data over a 73.8 million ha study area, partitioned into Ontario’s Northwest and Northeast Fire Management Regions. A stratified modelling approach accounts for different seasonal baselines regionally and for a set of communities in the Far North. Response-dependent sampling and modelling techniques using logistic generalized additive models are used to develop a fine-scale, spatiotemporal FOP system with models that include nonlinear relationships with key predictors. These predictors include inter- and intra-annual temporal trends, spatial trends, ecological variables, fuel moisture measures, human land-use characteristics, and a novel measure of human activity. The system produces fine-scale, spatially explicit maps of daily probabilistic human-caused FOP based on locally observed conditions along with point and interval predictions for the expected number of fires in each region. A simulation-based approach for generating the prediction intervals is described. Daily predictions were made available to fire management practitioners through a custom dashboard and integrated into daily regional planning to support detection and fire suppression preparedness needs.
Evaluation of a sprayable elemental sulfur fertilizer under field conditions in Alberta
Authors: Bremer E. , Pauly D. , Strydhorst S.M. , McKenzie R.H.
Published: December 2020

Elemental sulfur (ES) fertilizers have high S content but may not be effective in the year of application due to the time required to oxidize. Rapid oxidation may be possible if the ES has a large surface area in contact with the soil. We evaluated the efficacy of Sulgro 70, a micronized ES fertilizer that is sprayed onto the soil surface, in eight field trials in southern and central Alberta over a 2 yr period. Under dry conditions in southern Alberta, the relative efficacy of Sulgro 70 to increase S supply to ion-exchange membranes was 22% during the first 4 wk period after seeding and 53% during the second 4 wk period after seeding, compared with ammonium sulfate (AS) sprayed on the soil surface. Under wetter conditions in central Alberta, the relative efficacy of Sulgro 70 to increase S supply was variable (51%–201%) during the first 4 wk period after seeding and 56% during the second 4 wk period after seeding. Based on increases in biomass S concentration in three trials where the unfertilized control had low S concentration (<3 g S·kg−1), the relative efficacy of Sulgro 70 was 34%. Canola seed yield was not increased by application of AS or Sulgro 70 in any of the trials. Sulgro 70 sprayed on the soil surface oxidized appreciably during the first 8 wk after seeding and, with suitable management, has the potential to meet canola S requirements in the year of application.
Feasibility Study of Super-Long Span Bridges Considering Aerostatic Instability by a Two-Stage Geometric Nonlinear Analysis
Authors: Tsay Jiunn-Yin
Published: December 2020

To meet the need of constructing fixed cross strait links, super-long span bridge with a main span over 2 000[Formula: see text]m is considered as a candidate for their ability to cross deep and wide straits. To this end, some super-long span bridges with proper cable and girder systems were previously proposed and studied. The major design considerations are aimed at adopting new cable material, increasing the entire rigidity of the bridge, stabilizing the dynamic characteristics, strengthening the deck sections, etc. In this paper, a brief review of main cable and girder system is first given of the concepts previously proposed for the design of super-long span bridges. Then some typical examples are studied, focused on various issues related to the design of super-long span bridges, including composite cable, the unstressed length and tension force of the main cable, the stiffness and mass effects of the deck on critical wind speed, and the critical wind speed of various cable systems. The most challenges in super-long span bridges are to solve aerostatic and aerodynamic instability at required design wind speed. In this connection, the wind-induced aerostatic instability of super-long span bridges is studied by a two-stage geometric nonlinear analysis for dead loads and wind loads. The developed program adopted herein for geometric nonlinear analysis was verified and confirmed before. The proposed methods (i.e. composite cable, slotted girder, increasing deck stiffness and mass, cable layout, etc.) obtained for all the examples are in agreement with this study, which indicates applicability of the design approaches presented.
Polynomial and power series ring extensions from sequences
Authors: Chang Gyu Whan , Toan Phan Thanh
Published: December 2020

Let [Formula: see text] be a commutative ring with identity. Let [Formula: see text] and [Formula: see text] be the collection of polynomials and, respectively, of power series with coefficients in [Formula: see text]. There are a lot of multiplications in [Formula: see text] and [Formula: see text] such that together with the usual addition, [Formula: see text] and [Formula: see text] become rings that contain [Formula: see text] as a subring. These multiplications are from a class of sequences [Formula: see text] of positive integers. The trivial case of [Formula: see text], i.e. [Formula: see text] for all [Formula: see text], gives the usual polynomial and power series ring. The case [Formula: see text] for all [Formula: see text] gives the well-known Hurwitz polynomial and Hurwitz power series ring. In this paper, we study divisibility properties of these polynomial and power series ring extensions for general sequences [Formula: see text] including UFDs and GCD-domains. We characterize when these polynomial and power series ring extensions are isomorphic to each other. The relation between them and the usual polynomial and power series ring is also presented.
Generalized fine rings
Authors: Zhou Yiqiang
Published: December 2020

As introduced by Cǎlugǎreanu and Lam in [G. Cǎlugǎreanu and T. Y. Lam, Fine rings: a new class of simple rings, J. Algebra Appl. 15(9) (2016) 1650173, 18 pp.], a fine ring is a ring whose every nonzero element is the sum of a unit and a nilpotent. As a natural generalization of fine rings, a ring is called a generalized fine ring if every element not in the Jacobson radical is the sum of a unit and a nilpotent. Here some known results on fine rings are extended to generalized fine rings. A notable result states that matrix rings over generalized fine rings are generalized fine, extending the important result in [G. Cǎlugǎreanu and T. Y. Lam, Fine rings: a new class of simple rings, J. Algebra Appl. 15(9) (2016) 1650173, 18 pp.] that matrix rings over fine rings are fine.
Asymptotic expansions for Wiener–Hopf equations
Authors: Li Kui , Wong Roderick
Published: December 2020

Wiener–Hopf Equations are of the form [Formula: see text] These equations arise in many physical problems such as radiative transport theory, reflection of an electromagnetive plane wave, sound wave transmission from a tube, and in material science. They are also known as the renewal equations on the half-line in Probability Theory. In this paper, we present a method of deriving asymptotic expansions for the solutions to these equations. Our method makes use of the Wiener–Hopf technique as well as the asymptotic expansions of Stieltjes and Hilbert transforms.
Achieving Secure Search over Encrypted Data for e-Commerce
Authors: Guan Zhitao , Wang Naiyu , Fan Xunfeng , Liu Xueyan , Wu Longfei , Wan Shaohua
Published: December 2020

The advances of Internet technology has resulted in the rapid and pervasive development of e-commerce, which has not only changed the production and operation mode of many enterprises, but also affected the economic development mode of the whole society. This trend has incurred a strong need to store and process large amounts of sensitive data. The traditional data storage and search solutions cannot meet such requirements. To tackle this problem, in this article, we proposed Consortium Blockchain-based Distributed Secure Search (CBDSS) Scheme over encrypted data in e-Commerce environment. By integrating the blockchain and searchable encryption model, sensitive data can be effectively protected. The consortium blockchain can ensure that only authorized nodes can join the system. To fairly assign nodes for the search tasks, we developed an endorsement strategy in which two agent roles are set up to divide and match the search tasks with the virtual resources according to the load capacity of each node. The security analysis and experiments are conducted to evaluate the performance of our proposed scheme. The evaluation results have proved the reliability and security of our scheme over existing methods.
An Enhancement of the Bisection Method Average Performance Preserving Minmax Optimality
Authors: Oliveira I. F. D. , Takahashi R. H. C.
Published: December 2020

We identify a class of root-searching methods that surprisingly outperform the bisection method on the average performance while retaining minmax optimality. The improvement on the average applies for any continuous distributional hypothesis. We also pinpoint one specific method within the class and show that under mild initial conditions it can attain an order of convergence of up to 1.618, i.e., the same as the secant method. Hence, we attain both an improved average performance and an improved order of convergence with no cost on the minmax optimality of the bisection method. Numerical experiments show that, on regular functions, the proposed method requires a number of function evaluations similar to current state-of-the-art methods, about 24% to 37% of the evaluations required by the bisection procedure. In problems with non-regular functions, the proposed method performs significantly better than the state-of-the-art, requiring on average 82% of the total evaluations required for the bisection method, while the other methods were outperformed by bisection. In the worst case, while current state-of-the-art commercial solvers required two to three times the number of function evaluations of bisection, our proposed method remained within the minmax bounds of the bisection method.
Automatic Code Generation for High-performance Discontinuous Galerkin Methods on Modern Architectures
Authors: Kempf Dominic , Heß René , Müthing Steffen , Bastian Peter
Published: December 2020

SIMD vectorization has lately become a key challenge in high-performance computing. However, hand-written explicitly vectorized code often poses a threat to the software’s sustainability. In this publication, we solve this sustainability and performance portability issue by enriching the simulation framework dune-pdelab with a code generation approach. The approach is based on the well-known domain-specific language UFL but combines it with loopy, a more powerful intermediate representation for the computational kernel. Given this flexible tool, we present and implement a new class of vectorization strategies for the assembly of Discontinuous Galerkin methods on hexahedral meshes exploiting the finite element’s tensor product structure. The performance-optimal variant from this class is chosen by the code generator through an auto-tuning approach. The implementation is done within the open source PDE software framework Dune and the discretization module dune-pdelab. The strength of the proposed approach is illustrated with performance measurements for DG schemes for a scalar diffusion reaction equation and the Stokes equation. In our measurements, we utilize both the AVX2 and the AVX512 instruction set, achieving 30% to 40% of the machine’s theoretical peak performance for one matrix-free application of the operator.
Multi-Walled Carbon Nanotubes Decorated with Silver Nanoparticles for Acetone Gas Sensing at Room Temperature
Authors: Young Sheng-Joue , Liu Yi-Hsing , Lin Zheng-Dong , Ahmed Kumkum , Shiblee MD Nahin Islam , Romanuik Sean , Sekhar Praveen Kumar , Thundat Thomas , Nagahara Larry , Arya Sandeep , Ahmed Rafiq , Furukawa Hidemitsu , Khosla Ajit
Published: December 2020

Multi-walled carbon nanotubes (MWCNTs) without and with adsorbed silver nanoparticles (Ag-NPs), are used to detect acetone vapour. MWCNTs are grown on SiO2/Si substrates and silver (Ag) nanoparticles (NPs) are deposited onto some of these MWCNTs using electron beam evaporation method. The sensitivity of CNT based sensors (with and without NPs) increases with the concentration of acetone vapour (50 ppm to 800 ppm) while a substantial rise in sensitivity is obtained from MWCNTs with Ag NPs. Band diagrams of the MWCNTs, with and without NPs, are analyzed to understand the gas molecules adsorption phenomena. This study is the first to establish that such sensors can operate at 27 °C rather than the 180 °C–450 °C used elsewhere, thus offering significant advantages over existing methods. To investigate the sensors’ dependability, they’re exposed to three cycles of 50 ppm acetone gas. These tests show that the devices’ responses remain unchanged, indicating their reliability. The effects of humidity upon MWCNT acetone sensors within 100 ppm of acetone vapour are also studied and improved performance towards stability and response/recovery is observed for the sensors with Ag-NPs. Furthermore, higher selectivity is observed for the Ag-coated sensors for acetone against various target gases (acetone, ethanol, NO2, ammonia, and acetone with water).
Neuronal innervation of the intestinal crypt
Authors: ten Hove Anne S. , Seppen Jurgen , de Jonge Wouter J.
Published: December 2020

Mucosal damage is a key feature of inflammatory bowel diseases (IBD) and healing of the mucosa is an endpoint of IBD treatment that is often difficult to achieve. Autonomic neurons of the parasympathetic and sympathetic nervous system may influence intestinal epithelial cell growth and modulating epithelial innervation could for that reason serve as an interesting therapeutic option to improve mucosal healing. Understanding of the biological processes triggered by nonspecific and specific epithelial adrenergic and cholinergic receptor activation is of key importance. At present, with rising technological advances, bioelectronic neuromodulation as treatment modality has gained momentum. We discuss the current view on state-of-the-art innervation of the intestinal crypt and its impact on epithelial cell growth and differentiation. Furthermore, we outline bioelectronic technology and review its relevance to wound healing processes.
Matrix stiffness and shear stresses modulate hepatocyte functions in a fibrotic liver sinusoidal model
Authors: Li Wang , Li Peiwen , Li Ning , Du Yu , Lü Shouqin , Elad David , Long Mian
Published: December 2020

A fibrotic three-dimensional (3-D) liver sinusoidal model was constructed to mimic different stages of liver fibrosis in vivo and to explore the cooperative effects of matrix stiffness and shear stresses on hepatocyte (HC) functions. Mechanically induced alterations of mass transport mainly contributed to HC functions via typical mechanosensitive signaling.
Clinical and molecular characterization of the R751L-CFTR mutation
Authors: Haq Iram J. , Althaus Mike , Gardner Aaron Ions , Yeoh Hui Ying , Joshi Urjita , Saint-Criq Vinciane , Verdon Bernard , Townshend Jennifer , O’Brien Christopher , Ben-Hamida Mahfud , Thomas Matthew , Bourke Stephen , van der Sluijs Peter , Braakman Ineke , Ward Chris , Gray Michael A. , Brodlie Malcolm
Published: December 2020

Cystic fibrosis (CF) arises from mutations in the CF transmembrane conductance regulator ( CFTR) gene, resulting in progressive and life-limiting respiratory disease. R751L is a rare CFTR mutation that is poorly characterized. Our aims were to describe the clinical and molecular phenotypes associated with R751L. Relevant clinical data were collected from three heterozygote individuals harboring R751L (2 patients with G551D/R751L and 1 with F508del/R751L). Assessment of R751L-CFTR function was made in primary human bronchial epithelial cultures (HBEs) and Xenopus oocytes. Molecular properties of R751L-CFTR were investigated in the presence of known CFTR modulators. Although sweat chloride was elevated in all three patients, the clinical phenotype associated with R751L was mild. Chloride secretion in F508del/R751L HBEs was reduced compared with non-CF HBEs and associated with a reduction in sodium absorption by the epithelial sodium channel (ENaC). However, R751L-CFTR function in Xenopus oocytes, together with folding and cell surface transport of R751L-CFTR, was not different from wild-type CFTR. Overall, R751L-CFTR was associated with reduced sodium chloride absorption but had functional properties similar to wild-type CFTR. This is the first report of R751L-CFTR that combines clinical phenotype with characterization of functional and biological properties of the mutant channel. Our work will build upon existing knowledge of mutations within this region of CFTR and, importantly, inform approaches for clinical management. Elevated sweat chloride and reduced chloride secretion in HBEs may be due to alternative non-CFTR factors, which require further investigation.
E-cigarettes and health risks: more to the flavor than just the name
Authors: Ween M. P. , Moshensky A. , Thredgold L. , Bastian N. A. , Hamon R. , Badiei A. , Nguyen P. T. , Herewane K. , Jersmann H. , Bojanowski C. M. , Shin J. , Reynolds P. N. , Crotty Alexander L. E. , Hodge S. J.
Published: December 2020

The growing interest in regulating flavored E-liquids must incorporate understanding of the “flavoring profile” of each E-liquid—which flavorings (flavoring chemicals) are present and at what concentrations not just focusing on the flavor on the label. We investigated the flavoring profile of 10 different flavored E-liquids. We assessed bronchial epithelial cell viability and apoptosis, phagocytosis of bacteria and apoptotic cells by macrophages after exposure to E-cigarette vapor extract (EVE). We validated our data in normal human bronchial epithelial cells (NHBE) and alveolar macrophages (AM) from healthy donors. We also assessed cytokine release and validated in the saliva from E-cigarette users. Increased necrosis/apoptosis (16.1–64.5% apoptosis) in 16HBE cells was flavor dependent, and NHBEs showed an increased susceptibility to flavors. In THP-1 differentiated macrophages phagocytosis was also flavor dependent, with AM also showing increased susceptibility to flavors. Further, Banana and Chocolate were shown to reduce surface expression of phagocytic target recognition receptors on alveolar macrophages. Banana and Chocolate increased IL-8 secretion by NHBE, whereas all 4 flavors reduced AM IL-1β secretion, which was also reduced in the saliva of E-cigarette users compared with healthy controls. Flavorant profiles of E-liquids varied from simple 2 compound mixtures to complex mixtures containing over a dozen flavorants. E-liquids with high benzene content, complex flavoring profiles, high chemical concentration had the greatest impacts. The Flavorant profile of E-liquids is key to disruption of the airway status quo by increasing bronchial epithelial cell apoptosis, causing alveolar macrophage phagocytic dysfunction, and altering airway cytokines.
The protective role of SOD1 overexpression in central mediation of bradycardia following chronic intermittent hypoxia in mice
Authors: Chen Jin , Gu He , Wurster Robert D. , Cheng Zixi Jack
Published: December 2020

Obstructive sleep apnea (OSA) is a highly prevalent sleep disorder that is associated with many cardiovascular complications. Similar to OSA, chronic intermittent hypoxia (CIH) (a model for OSA) leads to oxidative stress and impairs baroreflex control of the heart rate (HR) in rodents. The baroreflex arc includes the aortic depressor nerve (ADN), vagal efferent, and central neurons. In this study, we used mice as a model to examine the effects of CIH on baroreflex sensitivity, aortic baroreceptor afferents, and central and vagal efferent components of the baroreflex circuitry. Furthermore, we tested whether human Cu/Zn Superoxide Dismutase (SOD1) overexpression in transgenic mice offers protection against CIH-induced deficit of the baroreflex arc. Wild-type C57BL/6J and SOD1 mice were exposed to room air (RA) or CIH and were then anesthetized, ventilated, and catheterized for measurement of mean arterial pressure (MAP) and HR. Compared with wild-type RA control, CIH impaired baroreflex sensitivity but increased maximum baroreceptor gain and bradycardic response to vagal efferent stimulation. Additionally, CIH reduced the bradycardic response to ADN stimulation, indicating a diminished central regulation of bradycardia. Interestingly, SOD1 overexpression prevented CIH-induced attenuation of HR responses to ADN stimulation and preserved HR responses to vagal efferent stimulation in transgenic mice. We suggest that CIH decreased central mediation of the baroreflex and SOD1 overexpression may prevent the CIH-induced central deficit.
Adaptive Variable Neighborhood Search-Based Supply Network Reconfiguration for Robustness Enhancement
Authors: Lou Ping , Chen Yuting , Gao Song
Published: December 2020

Robustness of a supply network highly depends on its structure. Although structural design methods have been proposed to create supply networks with optimal robustness, a real-life supply network can be quite different from these optimal structural designs. Meanwhile, real cases such as Thailand floods and Tohoku earthquake demonstrate the vulnerability of supply networks in real life. Obviously, it is urgent to enhance the robustness of existing real-life supply networks. Thus, in this paper, a supply network reconfiguration method based on adaptive variable neighborhood search (AVNS) is proposed to enhance the structural robustness of supply networks facing both random and target disruptions. Firstly, a supply network model considering the heterogeneous roles of entities is introduced. Based on the model, two robustness metrics, Rr and Rt, are proposed to describe the tolerance of supply networks facing random and target disruptions, respectively. Then, the problem of reconfiguration-based supply network robustness enhancement is described. To solve the problem effectively and efficiently, a new heuristic based on general variable neighborhood search, namely, AVNS, is proposed. Finally, a case study based on three real-life supply networks is presented to verify the applicability and effectiveness of the proposed robustness enhancing method.
Establishment and Validation of Novel Clinical Prognosis Nomograms for Luminal A Breast Cancer Patients with Bone Metastasis
Authors: Tu QiHao , Hu Chuan , Zhang Hao , Peng Chen , Kong Meng , Song MengXiong , Zhao Chong , Wang YuJue , Li Jianyi , Zhou ChuanLi , Wang Chao , Ma XueXiao
Published: December 2020

Purpose. Overall survival (OS) and cancer‐specific survival (CSS) of luminal A breast cancer (BC) patients with bone metastasis remain poor and vary dramatically from person to person. Our goal was to build two universally applicable nomograms to accurately predict OS and CSS for luminal A patients with bone metastasis. Methods. The data were collected from the Surveillance, Epidemiology, and End Results (SEER) database for luminal A BC patients with bone metastasis between 2010 and 2015. Univariate and multivariate Cox regression analyses were to assess and identify independent risk factors of OS and CSS. Integrating all significant predictors, nomograms and risk group stratification model was developed. The performance of the nomogram was validated with concordance index (C‐index), calibration plots, and decision curve analyses (DCA) for discriminative ability, calibration, and clinical utility, respectively. Results. 3171 luminal A BC patients with bone metastasis were included. Through univariate and multivariate Cox regression analyses, 12 variables were identified as both independent OS‐ and CSS‐related factors, including age, race, primary site, histology grade, tumor size, surgery, brain metastasis, liver metastasis, lung metastasis, estrogen receptor status, progesterone receptor status, and insurance. Our nomograms for 1‐, 3‐, and 5‐year survival were based on those significant prognostic factors to develop. The C‐indexes of OS‐ and CSS‐nomograms in the training cohort were 0.701 and 0.704, respectively. Similar results were obtained in the validation cohort. The calibration curves and DCA presented satisfactory calibration and clinical utility. Conclusion. Two nomograms have good discrimination, calibration, and clinical utility, can accurately and effectively predict the prognosis of patients, and may benefit for clinical decision‐making. In high‐risk patients, more aggressive therapy and closer surveillance should be considered.
Identification of the Functional Domain of HPIV3 Matrix Protein Interacting with Nucleocapsid Protein
Authors: Deng Xichuan , Zhang Chaoliang , Zhang Kehan , Lu Nan , He Yonglin , Liu Jia , Yang Zhibang , Zhang Guangyuan
Published: December 2020

Human parainfluenza virus type 3 (HPIV3) is the main pathogen that causes respiratory infections in infants, young children, and the elderly. Currently, there are no vaccines and effective anti‐infective drugs. Studying the replication and proliferation mechanism of HPIV3 is helpful for exploring the targets of anti‐HPIV3 infection. Matrix protein (M) and nucleocapsid protein (N) are two key structural proteins of HPIV3 that exert important functions in HPIV3 proliferation. Herein, we aim to clarify the functional domains of M and N interaction. HPIV3 M and N expression plasmids of pCAGGS‐HA‐M and pCAGGS‐N‐Myc/Flag, M C‐terminal truncation mutant plasmids of pCAGGSHA‐MΔC120, MΔC170, MΔC190, and MΔC210, and M C‐terminal plasmid of pCAGGS‐HA‐MC190 and C‐terminal deletion mutant plasmid of pCAGGS‐MΔN143‐182 were constructed. By using immunoprecipitation, immunofluorescence, and virus‐like particle (VLP) germination experiments, we found that N was encapsulated into M‐mediated VLP through N and M interaction. Moreover, the C‐terminus of the M played a key role in the interaction between M and N. The C‐terminus of the M encapsulated the N into the VLP. We finally determined that the 143‐182 amino acids in the M were the functional regions that encapsulated the N into the M‐mediated VLP. Our findings confirmed the interaction between M and N and for the first time clarified that the 143‐182 amino acid region in M was the functional region that interacted with N, which provides a molecular basis for exploring effective anti‐HPIV3 targets.
Denoising Method of MEMS Gyroscope Based on Interval Empirical Mode Decomposition
Authors: Liu Yang , Chen Guangwu , Wei Zongshou , Yang Juhua , Xing Dongfeng
Published: December 2020

The microelectromechanical system (MEMS) gyroscope has low measurement accuracy and large output noise; the useful signal is often submerged in the noise. A new denoising method of interval empirical mode decomposition (IEMD) is proposed. Firstly, the traditional EMD algorithm is used to decompose the signal into a finite number of intrinsic mode functions (IMFs). Based on the Bhattacharyya distance analysis and the characteristics of the autocorrelation function, a screening mechanism is proposed to divide IMFs into three categories: noise IMFs, mixed IMFs, and signal IMFs. Then, the traditional modelling filtering method is used to filter the mixed IMFs. Finally, the mixed IMFs after modelling and filtering and signal IMFs are reconstructed to obtain the denoised signal. In the experimental analysis, the static denoising experiment of the turntable, the Allan variance analysis, dynamic denoising experiment, and vehicle experiment are set up in this paper, which fully proves that the method has obvious advantages in denoising and greatly improves the quality of signal and the accuracy of the inertial navigation system solution.
Fermented Wheat Germ Extract as a Redox Modulator: Alleviating Endotoxin-Triggered Oxidative Stress in Primary Cultured Rat Hepatocytes
Authors: Mackei Máté , Vörösházi Júlia , Sebők Csilla , Neogrády Zsuzsanna , Mátis Gábor , Jerzsele Ákos
Published: December 2020

Bioactive compounds such as benzoquinone derivates presented in fermented wheat germ extract (FWGE) have several positive effects on overall health status of humans and animals alike. Since available data regarding the antioxidant activity of FWGE are limited, the aim of our study was to investigate its effects on the cellular redox homeostasis applying primary hepatocyte cell cultures of rat origin. Cultures were challenged to lipopolysaccharide (LPS) treatment for 2 or 8 hours to trigger inflammatory response. Further, culture media were concomitantly supplemented with or without FWGE (Immunovet®, 0.1% and 1%). In order to monitor the metabolic activity of the cell cultures, CCK-8 test was applied, while reactive oxygen species (ROS) production was measured using Amplex Red method. Malondialdehyde concentration of culture media as a specific marker of lipid peroxidation and the activity of glutathione peroxidase in cell lysates were also determined to monitor the redox status of the cultures. Based on our findings, it can be concluded that FWGE did not show cytotoxic effects in any applied concentration in cell cultures. Furthermore, FWGE efficiently decreased cellular ROS production and lipid peroxidation rate in case of LPS-induced inflammatory response. However, without LPS treatment, higher concentration of FWGE increased the rate of both ROS and malondialdehyde synthesis. This observation may refer to the prooxidant activity of high dose FWGE, which is an important beneficial effect regarding tumor cells. However, in case of noninflamed hepatocytes, considering the results of glutathione peroxidase activity, the application of the product did not result in severe oxidative distress. In accordance with the abovementioned findings, FWGE as a redox modulator, applied in the appropriate concentration, can serve as a promising candidate in the supplementary therapy of patients suffering from various inflammatory diseases, decreasing the free radical generation, thus avoiding the occurrence of cytotoxic effects.
Histochemical Study of the Rat Uterine Glycoconjugate Alteration following Treatment with Exogenous Gonadotropic Hormones during the Implantation Period
Authors: Aliabadi Elham , Makoolati Zohreh , Talaei-Khozani Tahereh , Ardekani Fakhreddin Mesbah , Aliabadi Arvin
Published: December 2020

One of the female causes of infertility is anovulation which is treatable with gonadotropin hormones. These hormones affect the molecular organization of the uterus such as glycoconjugates that are the first site of contact between the blastocyst and the uterus. The objective of this project was to study the alteration of glycoconjugates on the uterine apical, Golgi zone, and basement membrane of epithelial cells and the uterine gland after hyperstimulation with pregnant mare serum gonadotropin (PMSG) (4, 8, 16, 24, and 40 IU), during the implantation period. Injection of PMSG (in experimental groups) and injection of distilled water (in the control group) were followed by HCG administration (10 IU), mating, isolation of positive vaginal plug rats, and killing at 5.5 days of pregnancy. Histochemistry was done on the pregnant uterine horns with the use of WGA, DBA, PNA, ConA, SBA, and UEA lectins. The intensity of the immunohistochemical staining was scored, and quantitative data were generated. 4 IU did not show any significant differences with the control, 8 IU had less effect on the alteration of the Golgi zone, and apical and basement membrane glycoconjugates and 40 IU had the least effects on the alteration of uterine gland glycoconjugates. Also, 24 IU had the most effect on the alteration of uterine glycoconjugates. Understanding of the effects of gonadotropin hormones at the uterine level in implantation time helps to optimize hormonal manipulation for improving the outcome of assisted reproductive procedures. It seems that the optimal dose for superovulation and less alteration in uterine glycoconjugates of rats at implantation time were induced by the administration of 8 IU PMSG.
Epidemiology and Survival Outcomes for Eyelid Primary Malignant Melanoma: An Analysis of 1397 Cases in the SEER Database
Authors: Shan Yi , Xu Yufeng , Lu Yuexin , Chen Menglu , Cao Jing , Wang Yijie , Lin Xiling , Ye Juan
Published: December 2020

Purpose. There has not been a recent population-based study regarding the epidemiological trend and survival of eyelid primary malignant melanoma (PMM). Our study aims to evaluate the updated incidence trends and discuss the factors affecting the survival outcomes of eyelid PMM. Methods. A total of 1397 eyelid PMM cases diagnosed between 1975 and 2016 were retrospectively identified from the Surveillance, Epidemiology, and End Results (SEER) database. Age-adjusted incidence rates and annual percent changes (APC) were calculated. Kaplan-Meier and Cox proportional hazards regression models were used to calculate survival outcomes and identify potential prognostic factors. Results. The overall age-adjusted incidence of eyelid PMM rose from 0.039 (95% confidence interval [CI], 0.012–0.088) in 1975 to 0.103 (95% CI, 0.070–0.143) per 100 000 population in 2016, with significant APC of 1.313% (p<0.001). Male subjects showed a higher average age-adjusted incidence rate than female subjects (p<0.001). Survival analyses showed that 5-year accumulative overall survival (OS) and disease-specific survival (DSS) for patients with eyelid PMM were 70.5% and 90.6%. Additionally, 10-year OS and DSS were 51.8% and 86.1%, respectively. Analyses of Kaplan-Meier survival curves with the log-rank test revealed that older age, White race, nodular melanoma, higher American Joint Committee on Cancer (AJCC) stage (II to IV), advanced stage, distant metastasis, and no-surgery treatment were associated with lower OS and DSS rates. Age, histology, AJCC stage, and stage at diagnosis were found to be independent predictors of OS and DSS in multivariate models. Conclusion. The incidence of eyelid PMM increased with significant APC and male predominance. Age, histology, AJCC stage, and stage at diagnosis might be independent predictors of prognosis, emphasizing the importance of improved diagnosis of eyelid PMM.