bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between CVDs and initiation and adherence to statin treatment in patients with newly diagnosed hypercholesterolaemia: a retrospective cohort study
Authors: Ryou In Sun , Chang Jooyoung , Son Joung Sik , Ko Ahryoung , Choi Seulggie , Kim Kyuwoong , Kim Sung Min , Park Sang Min
Published: April 2021

Objectives

To evaluate the association between incident cardiovascular disease (CVD) and initiation and adherence to statin treatment for primary prevention of CVD in patients with newly diagnosed hypercholesterolaemia.

Design

A population-based retrospective cohort study.

Setting

This study used National Health Insurance Service-Health Screening Cohort (NHIS-HEALS) from Republic of Korea.

Participants

This study included 11 320 participants without previous history of CVD aged between 40 and 79 years who had elevated total cholesterol level (more than 240 mg/dL) and had initiated statin treatment within 24 months of the national health screening from 2004 to 2012 identified in the NHIS-HEALS.

Primary and secondary outcome measures

The primary outcome, CVD, was defined as first-ever admission or death due to ischaemic heart disease, acute myocardial infarction, revascularisation or stroke, or December 31 2013. The HRs of CVD according to statin adherence were calculated according to stratification by Systematic COronary Risk Evaluation.

Results

Early statin initiation significantly lowered risk of CVD outcomes compared with late initiation (HR of late statin user, 1.24; 95% CI 1.02 to 2.51). Among early initiators, statin discontinuers had a significantly higher risk for CVD compared with persistent users (HR, 1.71; 95% CI 1.10 to 2.67), while statin reinitiators had an attenuated risk increase (HR 1.34, 95% CI 0.79 to 2.30).

Conclusions

Among statin users with newly diagnosed hypercholesterolaemia, early statin initiation is associated with lower CVD risk compared with late initiation. Furthermore, statin discontinuation is associated with increased risk of CVD, but reinitiation attenuated the risk.
Rationale and design of the EMPA-ELDERLY trial: a randomised, double-blind, placebo-controlled, 52-week clinical trial of the efficacy and safety of the sodium–glucose cotransporter-2 inhibitor empagliflozin in elderly Japanese patients with type 2 diabetes
Authors: Yabe Daisuke , Shiki Kosuke , Suzaki Keiko , Meinicke Thomas , Kotobuki Yutaro , Nishida Kenichiro , Clark Douglas , Yasui Atsutaka , Seino Yutaka
Published: April 2021

Introduction

Elderly people (≥65 years) with type 2 diabetes mellitus (T2DM) are becoming increasingly prevalent, notably in Japan. As cardiovascular (CV) risk increases with age and sodium–glucose cotransporter-2 (SGLT2) inhibitors reduce CV risk, elderly patients with T2DM are increasingly likely to be prescribed these glucose-lowering drugs. There is controversy surrounding the effects of SGLT2 inhibitors on muscle mass, particularly in elderly patients for whom loss of muscle is especially undesirable; however, robust evidence on this important issue is lacking. Consequently, we have designed a clinical trial of the SGLT2 inhibitor empagliflozin in elderly Japanese patients with T2DM (Empagliflozin in Elderly T2DM Patients (EMPA-ELDERLY)) to assess its effects on body composition as well as glycaemic control. EMPA-ELDERLY will be the first randomised clinical trial of an SGLT2 inhibitor in elderly patients with T2DM to evaluate effects on skeletal muscle mass, muscle strength and physical performance concurrently.

Methods and analysis

EMPA-ELDERLY is a randomised, double-blind, placebo-controlled, parallel-group clinical trial to be conducted in Japan. Patients with T2DM aged ≥65 years are eligible if they are Japanese with a body mass index of ≥22 kg/m2and glycated haemoglobin (HbA1c) levels from ≥7.0% to ≤10.0% from either diet and exercise alone or treatment with oral glucose-lowering drugs. Approximately 128 participants will be randomised 1:1 to once per day, oral, double-blind treatment with empagliflozin 10 mg or matching placebo for 52 weeks. The primary endpoint is the change in HbA1c level from baseline at week 52. Secondary endpoints include changes from baseline to 52 weeks in body composition, including muscle mass and body fat, measured by bioelectrical impedance analysis, as well as skeletal muscle index, grip strength and time in the five-time chair stand test. Other endpoints include changes in patient-reported outcomes (including quality of life), cognitive function and safety.

Ethics and dissemination

We will submit the trial results to conferences and peer-reviewed journals.

Trial registration number

NCT04531462.
Multi-stakeholder perspectives in defining health services quality indicators and dimensions: a concept mapping based comparison for cataract care between Singapore and The Netherlands
Authors: Stolk-Vos Aline , De Korne Dirk , Lamoureux Ecosse , Wai Charity , Busschbach Jan JV , van de Klundert Joel Joris
Published: April 2021

Objective

This study aims to advance understanding of globally valid versus country-specific quality dimensions and indicators, as perceived by relevant stakeholders. It specifically addresses patient-level indicators for cataract surgery.

Design

A mixed-methods case study comparing Singapore and The Netherlands

Setting

Singapore (2017–2019) and The Netherlands (2014–2015).

Participants

Stakeholder representatives of cataract care in Singapore and The Netherlands.

Intervention

Based on the previously identified complete set of stakeholders in The Netherlands, we identified stakeholders of cataract care in Singapore. Stakeholder representatives then established a multi-stakeholder perspective on the quality of cataract care using a concept mapping approach. This yielded a multidimensional cluster map based on multivariate statistical analyses. Consensus-based quality dimensions were subsequently defined during a plenary session. Thereafter, Singaporean dimensions were matched with dimensions obtained in The Netherlands to identify commonalities and differences.

Main outcome measure

Health-services quality dimensions of cataract care.

Results

19 Singaporean stakeholders representing patients, general practitioners, ophthalmologists, nurses, care providers, researchers and clinical auditors defined health-services quality of cataract care using the following eight dimensions: clinical outcome, patient outcomes, surgical process, surgical safety, patient experience, access, cost and standards of care. Compared with the Dutch results, 61% of the indicators were allocated to dimensions of comparable names and compositions. Considerable differences also existed in the composition of some dimensions and the importance attached to indicators.

Conclusions and relevance

This study on cataract care in Singapore and The Netherlands shows that cataract care quality measurement instruments can share a common international core. At the same time, it emphasises the importance of taking a country-specific multi-stakeholder approach to quality definition and measurement. Complementing an international core set with country-specific measures is required to ensure that the included dimensions and indicators adequately capture the country-specific quality views.
Sociodemographic differences in self-reported exposure to high fat, salt and sugar food and drink advertising: a cross-sectional analysis of 2019 UK panel data
Authors: Yau Amy , Adams Jean , Boyland Emma J , Burgoine Thomas , Cornelsen Laura , de Vocht Frank , Egan Matt , Er Vanessa , Lake Amelia A , Lock Karen , Mytton Oliver , Petticrew Mark , Thompson Claire , White Martin , Cummins Steven
Published: April 2021

Objectives

To explore sociodemographic differences in exposure to advertising for foods and drinks high in fat, salt and sugar (HFSS) and whether exposure is associated with body mass index (BMI).

Design

Cross-sectional survey.

Setting

UK.

Participants

1552 adults recruited to the Kantar Fast Moving Consumer Goods panel for London and the North of England.

Outcome measures

Self-reported advertising exposure stratified by product/service advertised (processed HFSS foods; sugary drinks; sugary cereals; sweet snacks; fast food or digital food delivery services) and advertising setting (traditional; digital; recreational; functional or transport); BMI and sociodemographic characteristics.

Results

Overall, 84.7% of participants reported exposure to HFSS advertising in the past 7 days. Participants in the middle (vs high) socioeconomic group had higher odds of overall self-reported exposure (OR 1.48; 95% CI 1.06 to 2.07). Participants in the low (vs high) socioeconomic group had higher odds of reporting exposure to advertising for three of five product categories (ORs ranging from 1.41 to 1.67), advertising for digital food delivery services (OR 1.47; 95% CI 1.05 to 2.05), traditional advertising (OR 1.44; 95% CI 1.00 to 2.08) and digital advertising (OR 1.50; 95% CI 1.06 to 2.14). Younger adults (18–34 years vs ≥65 years) had higher odds of reporting exposure to advertising for digital food delivery services (OR 2.08; 95% CI 1.20 to 3.59), digital advertising (OR 3.93; 95% CI 2.18 to 7.08) and advertising across transport networks (OR 1.96; 95% CI 1.11 to 3.48). Exposure to advertising for digital food delivery services (OR 1.40; 95% CI 1.05 to 1.88), digital advertising (OR 1.80; 95% CI 1.33 to 2.44) and advertising in recreational environments (OR 1.46; 95% CI 1.02 to 2.09) was associated with increased odds of obesity.

Conclusions

Exposure to less healthy product advertising was prevalent, with adults in lower socioeconomic groups and younger adults more likely to report exposure. Broader restrictions may be needed to reduce sociodemographic differences in exposure to less healthy product advertising.
Questionnaire to Assess Life Impact of Treatment by Intravitreal Injections (QUALITII): Development of a patient-reported measure to assess treatment burden of repeat intravitreal injections
Authors: McClard Cynthia K , Wang Rui , Windham Victoria , Munoz Jose , Gomez Samuel , Fried Sagit , Saroj Namrata , Regillo Carl , Wykoff Charles Clifton , Strutt Adriana M
Published: April 2021

Objective

To understand patient burden of treatment of repeated intravitreal injections (IVI) in the management of exudative retinal diseases.

Methods and analysis

Participants were sampled from a large urban retina specialty practice in Houston, Texas, USA, based on history of ongoing receipt of IVI. The 50-item Questionnaire to Assess Life Impact of Treatment by Intravitreal Injections questionnaire was developed to evaluate the patient experience including discomfort, anxiety, inconvenience and satisfaction. Categorial principal components analysis (CATPCA) was performed to assess construct validity and internal consistency. A subset of these items was used to establish a measure of total treatment burden, referred to as the IVI Treatment Burden Score (TBS).

Results

142 patients participated in this study. CATPCA analysis revealed five dimensions of patient burden: disruption of normal routine or capacity, anxiety, frequency of visits, chronicity of disease and perceived treatment value or satisfaction. Together, these dimensions accounted for 67% of variance explained. Cronbach’s alpha was 0.97. The most frequently cited cause of discomfort was the feeling after anaesthetic wore off. The most common source of anxiety was fear of injection and associated discomfort or pain. Regarding inconvenience, patients reported temporary postinjection debilitation, requiring an average of 8 hours for recovery per treatment. The most frequently identified sources of satisfaction were confidence in the provider or treatment and interactions with staff.

Conclusions

Understanding and quantifying the patient burden associated with repeated IVI for exudative retinal diseases can reveal opportunities to improve delivery methods. The TBS could serve to inform strategies to maximise treatment adherence and optimise patient experiences.
Exosome-delivered CD44v6/C1QBP complex drives pancreatic cancer liver metastasis by promoting fibrotic liver microenvironment
Authors: Xie Zhibo , Gao Ya , Ho Chiakang , Li Lequn , Jin Chen , Wang Xiaoyi , Zou Caifeng , Mao Yishen , Wang Xiaobo , Li Qingfeng , Fu Deliang , Zhang Yi-Fan
Published: April 2021

Objective

Pancreatic ductal adenocarcinoma (PDAC) shows a remarkable predilection for liver metastasis. Pro-oncogenic secretome delivery and trafficking via exosomes are crucial for pre-metastatic microenvironment formation and metastasis. This study aimed to explore the underlying mechanisms of how PDAC-derived exosomes (Pex) modulate the liver microenvironment and promote metastasis.

Design

C57BL/6 mice were ‘educated’ by tail vein Pex injection. The intrasplenic injection liver metastasis and PDAC orthotopic transplantation models were used to evaluate liver metastasis. Stable cell lines CD44v6 (CD44 variant isoform 6) or C1QBP (complement C1q binding protein) knockdown or overexpression was established using lentivirus transfection or gateway systems. A total of 142 patients with PDAC in Huashan Hospital were retrospectively enrolled. Prognosis and liver metastasis were predicted using Kaplan-Meier survival curves and logistic regression models.

Results

Pex tail vein injection induced the deposition of liver fibrotic extracellular matrix, which promoted PDAC liver metastasis. Specifically, the exosomal CD44v6/C1QBP complex was delivered to the plasma membrane of hepatic satellite cells (HSCs), leading to phosphorylation of insulin-like growth factor 1 signalling molecules, which resulted in HSC activation and liver fibrosis. Expression of Pex CD44v6 and C1QBP in PDAC patients with liver metastasis was significantly higher than in PDAC patients without liver metastasis, and simultaneous high expression of exosomal CD44v6 and C1QBP correlated with a worse prognosis and a higher risk of postoperative PDAC liver metastasis.

Conclusion

The Pex-derived CD44v6/C1QBP complex is essential for the formation of a fibrotic liver microenvironment and PDAC liver metastasis. Highly expressed exosomal CD44v6 and C1QBP are promising biomarkers for predicting prognosis and liver metastasis in patients with PDAC.
Correlation of BRAF mutational status with clinical characteristics and survival outcomes of patients with ameloblastoma: the experience of 11 Italian centres
Authors: Bonacina Riccardo , Indini Alice , Massazza Gabriella , Rulli Eliana , Gianatti Andrea , Mandalà Mario
Published: April 2021

Aims

Ameloblastoma is a rare odontogenic tumour with an aggressive local behaviour. Mutations in the mitogen-activated protein kinase pathway, namely BRAF V600E mutations, are a common finding. To date, there is no clear correlation between BRAF V600 mutation and clinical outcome.

Methods

We retrospectively reviewed the medical records of patients who underwent surgery for ameloblastoma between May 1998 and June 2018, at 11 participating Italian centres. BRAF mutational status was evaluated by quantitative PCR/pyrosequencing. The primary end points were to determine BRAF mutational status in primitive and recurrent ameloblastoma, and to assess the relapse-free interval (RFI); the secondary end point was to investigate the correlation of BRAF mutational status with the clinical features of the tumour and survival outcomes.

Results

Overall, 74 patients were included: 33 (44.5%) were BRAF wild type and 41 (55.4%) BRAF V600 mutated. BRAF V600 mutated ameloblastomas occurred more frequently in younger patients (p=0.0031), were located at the mandible (p=0.0009) and presented with unicystic variant. After a median follow-up of 60 months, 21 (28.3%) patients relapsed (30.3% and 26.8% in the BRAF wild type and BRAF mutated group, respectively). At univariable Cox models, none of the investigated variables, including microscopic margin involvement, was associated with RFI.

Conclusions

Local recurrence occurs in 30% of patients with ameloblastoma. BRAFV600 mutation is associated with younger age, mandibular localisation and with unicystic ameloblastoma. Neither BRAF mutation nor microscopically positive surgical margins were associated with RFI. Further studies are needed to elucidate outcomes of this rare disease according to clinical, histopathological and comprehensive molecular features.
Sex-based differences in helmet performance in bicycle trauma
Authors: Feler Joshua , Maung Adrian A , O'Connor Rick , Davis Kimberly A , Gerrard Jason
Published: April 2021

Objectives

To determine the existence of sex-based differences in the protective effects of helmets against common injuries in bicycle trauma.

Methods

In a retrospective cohort study, we identified patients 18 years or older in the 2017 National Trauma Database presenting after bicycle crash. Sex-disaggregated and sex-combined multivariable logistic regression models were calculated for short-term outcomes that included age, involvement with motor vehicle collision, anticoagulant use, bleeding disorder and helmet use. The sex-combined model included an interaction term for sex and helmet use. The resulting exponentiated model parameter yields an adjusted OR ratio of the effects of helmet use for females compared with males.

Results

In total, 18 604 patients of average age 48.1 were identified, and 18% were female. Helmet use was greater in females than males (48.0% vs 34.2%, p<0.001). Compared with helmeted males, helmeted females had greater rates of serious head injury (37.7% vs 29.9%, p<0.001) despite less injury overall. In sex-disaggregated models, helmet use reduced odds of intracranial haemorrhage and death in males (p<0.001) but not females. In sex-combined models, helmets conferred to females significantly less odds reduction for severe head injury (p=0.002), intracranial bleeding (p<0.001), skull fractures (p=0.001), cranial surgery (p=0.006) and death (p=0.017). There was no difference for cervical spine fracture.

Conclusions

Bicycle helmets may offer less protection to females compared with males. The cause of this sex or gender-based difference is uncertain, but there may be intrinsic incompatibility between available helmets and female anatomy and/or sex disparity in helmet testing standards.
Assessment of impact of the COVID-19 pandemic from the perspective of patients with rheumatic and musculoskeletal diseases in Europe: results from the REUMAVID study (phase 1)
Authors: Garrido-Cumbrera Marco , Marzo-Ortega Helena , Christen Laura , Plazuelo-Ramos Pedro , Webb Dale , Jacklin Clare , Irwin Shantel , Grange Laurent , Makri Souzi , Frazão Mateus Elsa , Mingolla Serena , Antonopoulou Katy , Sanz-Gómez Sergio , Correa-Fernández José , Carmona Loreto , Navarro-Compán Victoria
Published: April 2021

Aim

To assess the impact of the COVID-19 pandemic on patients with rheumatic and musculoskeletal diseases (RMDs).

Methods

REUMAVID is a cross-sectional study using an online survey developed by an international multidisciplinary patient-led collaboration across seven European countries targeting unselected patients with RMDs. Healthcare access, daily activities, disease activity and function, well-being (WHO Five Well-Being Index (WHO-5)), health status, anxiety/depression (Hospital Anxiety and Depression Scale (HADS)) and access to information were evaluated. Data were collected in April–July 2020 (first phase).

Results

Data from the first phase included 1800 patients with 15 different RMDs (37.2% axial spondyloarthritis, 29.2% rheumatoid arthritis, 17.2% osteoarthritis and others). Mean age was 53, 80% female and 49% had undertaken university studies. During the beginning of the pandemic, 58.4% had their rheumatology appointment cancelled and 45.6% reported not having received any information relating to the possible impact of SARS-CoV-2 infection in their RMDs, with the main source being patient organisations (27.6%).

Regarding habits, 24.6% increased smoking, 18.2% raised their alcohol consumption, and 45.6% were unable to continue exercising. Self-reported disease activity was high (5.3±2.7) and 75.6% reported elevated pain. Half the patients (49.0%) reported poor well-being (WHO-5) and 46.6% that their health had changed for the worse during lockdown. According to HADS, 57.3% were at risk of anxiety and 45.9% of depression.

Conclusion

Throughout the first wave of the COVID-19 pandemic, patients with RMDs have experienced disruption in access to healthcare services, poor lifestyle habits and negative effects on their overall health, well-being and mental health. Furthermore, information on COVID-19 has not reached patients appropriately.
Regional stagnation of the western Keewatin ice sheet and the significance of meltwater corridors and eskers, northern Canada
Authors: Sharpe D.R. , Lesemann J.-E. , Knight R.D. , Kjarsgaard B.A.
Published: April 2021

The glacial land system of western Keewatin region, northern Canada, consists of three significant events: (1) regional emplacement of subglacial sediments, mainly till; (2) landscape erosion with development of an integrated, anabranched network of meltwater drainage routes leading to meltwater corridors; and (3) deposition of an extensive array of eskers, and related landforms, within meltwater corridors. Integration of extensive field observations, mapping, and remotely sensed data allow us to link scoured bedrock and till surfaces, truncated drumlins, scour pits, glaciofluvial terraces, boulder lags, and a large-scale network of corridors, as part of regional meltwater erosion events. The network of long (∼100–200 km), relatively wide (∼1–3 km) meltwater corridors record confined subglacial erosion that scoured sediment (and bedrock) prior to glaciofluvial sedimentation (predominately eskers). Despite considerable sediment erosion along meltwater corridors, moraines and other ice-marginal deposits are rarely observed on the western Keewatin landscape. The absence of these features is inconsistent with deglacial models relying on step-wise active retreat of the ice margin. Instead, we propose that deglaciation of the western Keewatin sector of the Laurentide Ice Sheet was predominantly controlled by regional thinning and stagnation. These findings raise fundamental questions about deglacial patterns and processes and thus suggest that further evaluation and revision of existing models of deglacial chronology for this sector of the Laurentide Ice Sheet is needed.
Effects of simulated hail damage and foliar-applied recovery treatments on growth and grain yield of wheat, field pea, and dry bean crops
Authors: Dhillon Gurbir Singh , Gretzinger Mike , Baarda Lewis , Lange Ralph , Singh Gill Kabal , Yaremko Vance , Harding Michael W. , Coles Ken
Published: April 2021

Hailstorms can be responsible for significant economic loss to the agricultural sector in Alberta, Canada. Foliar applications of certain fungicides and nutrient blends have been advocated to promote recovery and yield of hail-damaged crops. Proper understanding of different crop and hail-related factors is required for an accurate assessment of hail damage to crops and for evaluations of hail-recovery product claims. This study was undertaken at three locations in Alberta during three growing seasons (2016–2018) to determine the effects of two levels of simulated hail severity at three different crop developmental stages, including the early growth (BBCH 30 for wheat; BBCH 14–16 for pulses), mid-growth (BBCH 39 for wheat; BBCH 60 for pulses), and late growth (BBCH 60 for wheat; BBCH 71 for pulses) stages. Plant growth and yield parameters of wheat (Triticum aestivum L.), field pea (Pisum sativum L.), and dry bean (Phaseolus vulgaris L.) crops were measured. Simulated hail damage led to reductions in height, biomass, NDVI, grain yield, and kernel weight of all three crops. Average yield decreased by 24% and 35% for wheat, 17% and 35% for dry beans, and 37% and 45% for field peas for light and heavy hail severity, respectively. Hail timing was a critical factor influencing the extent of crop damage, with hail damage during the early growth stage leading to a lesser yield reduction compared with hail damage at the mid-growth and late growth stages. Fungicides and nutrient blends applications did not significantly improve crop recovery, grain yield, or kernel weight for any of the crops in this study.
Z-boson hadronic decay width up to $${{\mathcal {O}}}(\alpha _s^4)$$-order QCD corrections using the single-scale approach of the principle of maximum conformality
Authors: Huang Xu-Dong , Wu Xing-Gang , Zheng Xu-Chang , Yu Qing , Wang Sheng-Quan , Shen Jian-Ming
Published: April 2021

In the paper, we study the properties of the Z-boson hadronic decay width by using the $$\mathcal {O}(\alpha _s^4)$$

O
(

α
s
4

)

-order quantum chromodynamics (QCD) corrections with the help of the principle of maximum conformality (PMC). By using the PMC single-scale approach, we obtain an accurate renormalization scale-and-scheme independent perturbative QCD (pQCD) correction for the Z-boson hadronic decay width, which is independent to any choice of renormalization scale. After applying the PMC, a more convergent pQCD series has been obtained; and the contributions from the unknown $$\mathcal {O}(\alpha _s^5)$$

O
(

α
s
5

)

-order terms are highly suppressed, e.g. conservatively, we have $$\Delta \Gamma _{\mathrm{Z}}^{\mathrm{had}}|^{{{\mathcal {O}}}(\alpha _s^5)}_{\mathrm{PMC}}\simeq \pm 0.004$$

Δ

Γ

Z

had

|

PMC

O
(

α
s
5

)

≃
±
0.004

MeV. In combination with the known electro-weak (EW) corrections, QED corrections, EW–QCD mixed corrections, and QED–QCD mixed corrections, our final prediction of the hadronic Z decay width is $$\Gamma _{\mathrm{Z}}^{\mathrm{had}}=1744.439^{+1.390}_{-1.433}$$

Γ

Z

had

=
1744
.

439

-
1.433

+
1.390

MeV, which agrees with the PDG global fit of experimental measurements, $$1744.4\pm 2.0$$

1744.4
±
2.0

MeV.
An investigation on gravitational entropy of cosmological models
Authors: Chakraborty Samarjit , Guha Sarbari , Goswami Rituparno
Published: April 2021

In this paper, we investigate the entropy of the free gravitational field for a given epoch for some well-known isotropic and anisotropic cosmologies. We use the definition of gravitational entropy proposed by Clifton, Ellis and Tavakol, where the 2-index square root of the 4-index Bel–Robinson tensor is taken to be the energy– momentum tensor for the free gravity. We examine whether in the vicinity of the initial singularity, the ratio of energy density of free gravity to that of matter density goes to zero, validating Penrose conjecture on Weyl curvature. Whenever this is true, the gravitational entropy increases monotonically with time, leading to structure formation. For the models considered by us, we identify the conditions for which the Weyl curvature hypothesis is valid, and the assumptions under which it is validated, or otherwise.
Intra-salt structure and strain partitioning in layered evaporites: implications for drilling through Messinian salt in the eastern Mediterranean
Authors: Evans Sian L. , Jackson Christopher A.-L.
Published: April 2021

We use 3D seismic reflection data from the Levant margin, offshore Lebanon to investigate the structural evolution of the Messinian evaporite sequence, and how intra-salt structure and strain varies within a thick salt sheet during early-stage salt tectonics. Intra-Messinian reflectivity reveals lithological heterogeneity within the otherwise halite-dominated sequence. This leads to rheological heterogeneity, with the different mechanical properties of the various units controlling strain accommodation within the deforming salt sheet. We assess the distribution and orientation of structures, and show how intra-salt strain varies both laterally and vertically along the margin. We argue that units appearing weakly strained in seismic data may in fact accommodate considerable subseismic or cryptic strain. We also discuss how the intra-salt stress state varies through time and space in response to the gravitational forces driving deformation. We conclude that efficient drilling through thick, heterogeneous salt requires a holistic understanding of the mechanical and kinematic development of the salt and its overburden. This will also enable us to build better velocity models that account for intra-salt lithological and structural complexity in order to accurately image sub-salt geological structures.
Quality Control of Procollagen in Cells
Authors: Ito Shinya , Nagata Kazuhiro
Published: April 2021

Collagen is the most abundant protein in mammals. A unique feature of collagen is its triple-helical structure formed by the Gly-Xaa-Yaa repeats. Three single chains of procollagen make a trimer, and the triple-helical structure is then folded in the endoplasmic reticulum (ER). This unique structure is essential for collagen's functions in vivo, including imparting bone strength, allowing signal transduction, and forming basement membranes. The triple-helical structure of procollagen is stabilized by posttranslational modifications and intermolecular interactions, but collagen is labile even at normal body temperature. Heat shock protein 47 (Hsp47) is a collagen-specific molecular chaperone residing in the ER that plays a pivotal role in collagen biosynthesis and quality control of procollagen in the ER. Mutations that affect the triple-helical structure or result in loss of Hsp47 activity cause the destabilization of procollagen, which is then degraded by autophagy. In this review, we present the current state of the field regarding quality control of procollagen.
Cullin-RING Ubiquitin Ligase Regulatory Circuits: A Quarter Century Beyond the F-Box Hypothesis
Authors: Harper J. Wade , Schulman Brenda A.
Published: April 2021

Cullin-RING ubiquitin ligases (CRLs) are dynamic modular platforms that regulate myriad biological processes through target-specific ubiquitylation. Our knowledge of this system emerged from the F-box hypothesis, posited a quarter century ago: Numerous interchangeable F-box proteins confer specific substrate recognition for a core CUL1-based RING E3 ubiquitin ligase. This paradigm has been expanded through the evolution of a superfamily of analogous modular CRLs, with five major families and over 200 different substrate-binding receptors in humans. Regulation is achieved by numerous factors organized in circuits that dynamically control CRL activation and substrate ubiquitylation. CRLs also serve as a vast landscape for developing small molecules that reshape interactions and promote targeted ubiquitylation-dependent turnover of proteins of interest. Here, we review molecular principles underlying CRL function, the role of allosteric and conformational mechanisms in controlling substrate timing and ubiquitylation, and how the dynamics of substrate receptor interchange drives the turnover of selected target proteins to promote cellular decision-making.
Ethnography, Data Transparency, and the Information Age
Authors: Murphy Alexandra K. , Jerolmack Colin , Smith DeAnna
Published: April 2021

The conventions ethnographers follow to gather, write about, and store their data are increasingly out of sync with contemporary research expectations and social life. Despite technological advancements that allow ethnographers to observe their subjects digitally and record interactions, few follow subjects online and many still reconstruct quotes from memory. Amid calls for data transparency, ethnographers continue to conceal subjects’ identities and keep fieldnotes private. But things are changing. We review debates, dilemmas, and innovations in ethnography that have arisen over the past two decades in response to new technologies and calls for transparency. We focus on emerging conversations around how ethnographers record, collect, anonymize, verify, and share data. Considering the replication crisis in the social sciences, we ask how ethnographers can enable others to reanalyze their findings. We address ethical implications and offer suggestions for how ethnographers can develop standards for transparency that are consistent with their commitment to their subjects and interpretive scholarship.
Implication of Lithium Excess Induced Structure and Electrochemical Behavior Changes of LiNi0.5Mn1.5O4 Spinel
Authors: Luo Rongjie , Chen Wei , Fang Haisheng
Published: April 2021

Cubic spinel LiNi0.5Mn1.5O4 is one of the most promising cathode materials for high energy density lithium ion batteries because of its higher voltage plateau at around 4.7 V vs Li+/Li. In this paper, LiNi0.5Mn1.5O4 spinels are synthesized with different lithium excess, and their composition, structure, morphology and electrochemical behavior are measured and compared. The results show that all samples have an ordered cubic spinel structure with Ni/Mn ordering in the octahedral sites, and the change of lithium excess can induce variations in phase composition and purity, Mn3+ amount, cation mixing and electrochemical behavior of the prepared LiNi0.5Mn1.5O4. Even with the least amount of Mn3+ and a higher amount of impurity, the sample with the least occupation of transition metal ions in the tetrahedral Li sites gives the best rate performance, justifying that the occupation of transition metal ions in the tetrahedral Li sites play a critical role in affecting the kinetics of lithium ion extraction/insertion for LiNi0.5Mn1.5O4 spinel.
Analysis of Galvanic Corrosion Current between an Aluminum Alloy and Stainless-Steel Exposed to an Equilibrated Droplet Electrolyte
Authors: Policastro Steven A. , Anderson Rachel M. , Hangarter Carlos M.
Published: April 2021

Measurements of galvanic corrosion between UNS S13800 and UNS A97075 in bulk and equilibrated droplet electrolytes are compared with theoretical predictions of the corrosion current using calculations of the static diffusion-limited current, the classic Cottrell equation, and chemical reaction pathway models. The droplet electrolyte experiments use disks of stainless steel embedded in the aluminum alloy but isolated from electrical contact by an epoxy ring and connected via a zero-resistance ammeter potentiostat. Discrepancies between the measured and expected corrosion current for the droplet electrolyte are analyzed and a mechanism that relies on chemical reactions in the electrolyte to form corrosion products that block ion transport and suppress further oxidation is proposed. Electrochemical impedance spectroscopy and mass measurements are used to monitor changing solution properties in the equilibration of the droplet with the temperature and relative humidity environment of the atmospheric corrosion chamber.
In-Situ Detection of Early Corrosion of Ferritic Cr-Mo Steel in Aqueous Solutions of different Anions using Laser Raman Spectroscopy
Authors: Thinaharan C. , George R. P. , Philip John
Published: April 2021

We report the early-stage corrosion of modified 9Cr-1Mo ferritic steel in aqueous environments at natural corroding conditions. Uniform, pitting, and crevice corrosion was observed in acidic sulphate, neutral chloride, and fresh water environments, respectively. In-situ laser Raman spectroscopy (LRS) studies revealed the formation of Fe3O4, γ−Fe2O3, γ−FeOOH phases, and stable heterogeneous corrosion products of γ−FeOOH and α−FeOOH in all media, except in an alkaline solution. A stable passive film, composed of oxide and oxy-hydroxides of chromium and iron, is formed in an alkaline solution. X-ray photoelectron spectroscopy (XPS) results confirm the presence of Cr and Fe oxide and oxy-hydroxides in all corrosion products and enrichment of Mn and Nb oxides on the corroded surface in neutral chloride solution, but only Mn oxy-hydroxide in acidic solution. Chloride ion in the corroded surface in neutral chloride solution indicates a chloride-induced corrosion attack. In-situ LRS, together with ex-situ XPS enabled the identification of all corrosion products formed on modified 9Cr-1Mo steel. The presence of laminar γ−FeOOH and acicular α−FeOOH phases are confirmed from the FESEM images. Our results indicate that except in alkaline solution, the corrosive ions deteriorate the integrity of native film on modified 9Cr-1Mo steel.
Next-generation inward rectifier potassium channel modulators: discovery and molecular pharmacology
Authors: Weaver C. David , Denton Jerod S.
Published: April 2021

Inward rectifying potassium (Kir) channels play important roles in both excitable and nonexcitable cells of various organ systems and could represent valuable new drug targets for cardiovascular, metabolic, immune, and neurological diseases. In nonexcitable epithelial cells of the kidney tubule, for example, Kir1.1 ( KCNJ1) and Kir4.1 ( KCNJ10) are linked to sodium reabsorption in the thick ascending limb of Henle’s loop and distal convoluted tubule, respectively, and have been explored as novel-mechanism diuretic targets for managing hypertension and edema. G protein-coupled Kir channels (Kir3) channels expressed in the central nervous system are critical effectors of numerous signal transduction pathways underlying analgesia, addiction, and respiratory-depressive effects of opioids. The historical dearth of pharmacological tool compounds for exploring the therapeutic potential of Kir channels has led to a molecular target-based approach using high-throughput screen (HTS) of small-molecule libraries and medicinal chemistry to develop “next-generation” Kir channel modulators that are both potent and specific for their targets. In this article, we review recent efforts focused specifically on discovery and improvement of target-selective molecular probes. The reader is introduced to fluorescence-based thallium flux assays that have enabled much of this work and then provided with an overview of progress made toward developing modulators of Kir1.1 (VU590, VU591), Kir2.x (ML133), Kir3.X (ML297, GAT1508, GiGA1, VU059331), Kir4.1 (VU0134992), and Kir7.1 (ML418). We discuss what is known about the small molecules’ molecular mechanisms of action, in vitro and in vivo pharmacology, and then close with our view of what critical work remains to be done.
Carbonic anhydrase inhibition improves pulmonary artery reactivity and nitric oxide-mediated relaxation in sugen-hypoxia model of pulmonary hypertension
Authors: Christou Helen , Michael Zoe , Spyropoulos Fotios , Chen Yunfei , Rong Dan , Khalil Raouf A.
Published: April 2021

Pulmonary hypertension (PH) is a serious disease with pulmonary arterial fibrotic remodeling and limited responsiveness to vasodilators. Our data suggest that mild acidosis induced by carbonic anhydrase inhibition could ameliorate PH, but the vascular mechanisms are unclear. We tested the hypothesis that carbonic anhydrase inhibition ameliorates PH by improving pulmonary vascular reactivity and relaxation mechanisms. Male Sprague–Dawley rats were either control normoxic (Nx), or injected with Sugen 5416 (20 mg/kg, sc) and subjected to hypoxia (9% O2) (Su + Hx), or Su + Hx treated with acetazolamide (ACTZ, 100 mg/kg/day, in drinking water). After measuring the hemodynamics, right ventricular hypertrophy was assessed by Fulton’s Index; vascular function was measured in pulmonary artery, aorta, and mesenteric arteries; and pulmonary arteriolar remodeling was assessed in lung sections. Right ventricular systolic pressure and Fulton’s Index were increased in Su + Hx and reduced in Su + Hx + ACTZ rats. Pulmonary artery contraction to KCl and phenylephrine were reduced in Su + Hx and improved in Su + Hx + ACTZ. Acetylcholine (ACh)-induced relaxation and nitrate/nitrite production were reduced in pulmonary artery of Su + Hx and improved in Su + Hx + ACTZ. ACh relaxation was blocked by nitric oxide (NO) synthase and guanylate cyclase inhibitors, supporting a role of NO-cGMP. Sodium nitroprusside (SNP)-induced relaxation was reduced in pulmonary artery of Su + Hx, and ACTZ enhanced relaxation to SNP. Contraction/relaxation were not different in aorta or mesenteric arteries of all groups. Pulmonary arterioles showed wall thickening in Su + Hx that was ameliorated in Su + Hx + ACTZ. Thus, amelioration of pulmonary hemodynamics during carbonic anhydrase inhibition involves improved pulmonary artery reactivity and NO-mediated relaxation and may enhance responsiveness to vasodilator therapies in PH.
Exploring the Pharmacological Mechanism of Duhuo Jisheng Decoction in Treating Osteoporosis Based on Network Pharmacology
Authors: Xiong Zhencheng , Zheng Can , Chang Yanan , Liu Kuankuan , Shu Li , Zhang Chi
Published: April 2021

Objective. The purpose of this work is to study the mechanism of action of Duhuo Jisheng Decoction (DHJSD) in the treatment of osteoporosis based on the methods of bioinformatics and network pharmacology. Methods. In this study, the active compounds of each medicinal ingredient of DHJSD and their corresponding targets were obtained from TCMSP database. Osteoporosis was treated as search query in GeneCards, MalaCards, DisGeNET, Therapeutic Target Database (TTD), Comparative Toxicogenomics Database (CTD), and OMIM databases to obtain disease-related genes. The overlapping targets of DHJSD and osteoporosis were identified, and then GO and KEGG enrichment analysis were performed. Cytoscape was employed to construct DHJSD-compounds-target genes-osteoporosis network and protein-protein interaction (PPI) network. CytoHubba was utilized to select the hub genes. The activities of binding of hub genes and key components were confirmed by molecular docking. Results. 174 active compounds and their 205 related potential targets were identified in DHJSD for the treatment of osteoporosis, including 10 hub genes (AKT1, ALB, IL6, MAPK3, VEGFA, JUN, CASP3, EGFR, MYC, and EGF). Pathway enrichment analysis of target proteins indicated that osteoclast differentiation, AGE-RAGE signaling pathway in diabetic complications, Wnt signaling pathway, MAPK signaling pathway, PI3K-Akt signaling pathway, JAK-STAT signaling pathway, calcium signaling pathway, and TNF signaling pathway were the specifically major pathways regulated by DHJSD against osteoporosis. Further verification based on molecular docking results showed that the small molecule compounds (Quercetin, Kaempferol, Beta-sitosterol, Beta-carotene, and Formononetin) contained in DHJSD generally have excellent binding affinity to the macromolecular target proteins encoded by the top 10 genes. Conclusion. This study reveals the characteristics of multi-component, multi-target, and multi-pathway of DHJSD against osteoporosis and provides novel insights for verifying the mechanism of DHJSD in the treatment of osteoporosis.
A Framework for Automatic Burn Image Segmentation and Burn Depth Diagnosis Using Deep Learning
Authors: Liu Hao , Yue Keqiang , Cheng Siyi , Li Wenjun , Fu Zhihui
Published: April 2021

Burn is a common traumatic disease with high morbidity and mortality. The treatment of burns requires accurate and reliable diagnosis of burn wounds and burn depth, which can save lives in some cases. However, due to the complexity of burn wounds, the early diagnosis of burns lacks accuracy and difference. Therefore, we use deep learning technology to automate and standardize burn diagnosis to reduce human errors and improve burn diagnosis. First, the burn dataset with detailed burn area segmentation and burn depth labelling is created. Then, an end-to-end framework based on deep learning method for advanced burn area segmentation and burn depth diagnosis is proposed. The framework is firstly used to segment the burn area in the burn images. On this basis, the calculation of the percentage of the burn area in the total body surface area (TBSA) can be realized by extending the network output structure and the labels of the burn dataset. Then, the framework is used to segment multiple burn depth areas. Finally, the network achieves the best result with IOU of 0.8467 for the segmentation of burn and no burn area. And for multiple burn depth areas segmentation, the best average IOU is 0.5144.
The Optimal Adaptive-Based Neurofuzzy Control of the 3-DOF Musculoskeletal System of Human Arm in a 2D Plane
Authors: Valizadeh Amin , Akbari Ali Akbar
Published: April 2021

Each individual performs different daily activities such as reaching and lifting with his hand that shows the important role of robots designed to estimate the position of the objects or the muscle forces. Understanding the body’s musculoskeletal system’s learning control mechanism can lead us to develop a robust control technique that can be applied to rehabilitation robotics. The musculoskeletal model of the human arm used in this study is a 3-link robot coupled with 6 muscles which a neurofuzzy controller of TSK type along multicritic agents is used for training and learning fuzzy rules. The adaptive critic agents based on reinforcement learning oversees the controller’s parameters and avoids overtraining. The simulation results show that in both states of with/without optimization, the controller can well track the desired trajectory smoothly and with acceptable accuracy. The magnitude of forces in the optimized model is significantly lower, implying the controller’s correct operation. Also, links take the same trajectory with a lower overall displacement than that of the nonoptimized mode, which is consistent with the hand’s natural motion, seeking the most optimum trajectory.
A Compressive Review on High‐ and Low‐Temperature Performance of Asphalt Modified with Nanomodifier
Authors: Li Limin , Yang Lingming , Lin Yuliang , Zhang Xiancai
Published: April 2021

At present, rutting and cracking have become serious issues in asphalt pavement, especially in the areas of summer heat and winter cold. Nanomodifier has been widely used in recent years due to its unique properties in improving the characteristics of asphalt binders. To make better use of nanomodifier to solve the problem of rutting and cracking of pavement, a compressive review on the high‐ and low‐temperature performance of nanomodified asphalt is performed. The results indicate that for high‐ and low‐temperature performance of asphalt binder, the effectiveness of nanomodification is found to be strictly influenced by the combination of original asphalt type, nanomodifier type, nanomodifier dosage, nanoparticle size, and preparation of nanomodified asphalt, and the high‐temperature antirutting performance and low‐temperature crack resistance of final blends are various with the combination. Chemical composition, microstructure, dispersion, and compatibility of final blends were the possible reason causing the difference. The rational selection of the combination can improve the high‐temperature rutting resistance and the low‐temperature cracking resistance of asphalt binder. So far, there is a lack of systematic investigation in this regard. Therefore, it is very necessary to study systematically the original asphalt, nanomodifier, nanomodifier dosage, nanoparticle size, and preparation of nanomodified asphalt effect on the high and low performance of nanomodified asphalt, especially in the modification mechanism in the future.