bluuebunny/crossref_metadata_2025 huggingface dataset:
Unveiling a continent
Authors: Kennett Brian
Published: November 2020

Brian Kennett shows what geophysics can reveal about the lithosphere of Australia.
Can Knowledge Exchange Forge a Collaborative Pathway to Policymaking? A Case Study Example of the Recognition Matters Project
Authors: Critchley Ariane , Mitchell Mary
Published: November 2020

Knowledge Exchange is considered a way that research might be operationalised beyond the academy, both within policy and practice. This article seeks to analyse knowledge exchange as a method of bringing field, research and policy together. It does so through the case study of a social work knowledge exchange project, ‘Recognition Matters’. This co-produced project brought together two separate research studies undertaken by the authors. These studies focused on different elements of child welfare and protection: pre-birth child protection and Family Group Conferencing, respectively. The research findings were creatively woven together with the retelling of a mother’s story of child protection proceedings, alongside the practice wisdom and experience of three social work practitioners. In this article, the authors firstly consider the conditions for collaborative knowledge exchange as a commitment to social justice. Using the case study described, the value of this approach as a mechanism for social work to engage in policymaking is then explored. It is argued that in the context of significant challenges to the realisation of social justice, collaborative knowledge exchange activities may represent a genuine avenue for transforming social policy and creating meaningful research impact.
“Green Life Matters”: Place and the Politics of Environmental and Commemorative Justice
Authors: Maurantonio Nicole
Published: November 2020

This article analyzes newspaper discourse in Richmond, Virginia surrounding the placement of a statue to Maggie Lena Walker, the first Black woman bank president in the United States, and the proposed removal of a live oak tree to make way for the installation of the Walker statue in the city’s Jackson Ward neighborhood, once known as the “Harlem of the South.” While at first glance, the heated debate surrounding the live oak tree’s proposed removal might conjure a familiar racial divide between white environmentalists and Black community members, this article suggests that the debate in the majority Black city instead captured a broader tension within Black communities torn between advocating for commemorative and environmental justice.
Rapid High-Performance Liquid Chromatography Method for Levodopa Quantitation at Low UV Wavelength: Application of Pharmacokinetics Study in Rat Following Intranasal Delivery
Authors: Parhizkar Elahehnaz , Mohammadi Zahra , Alipour Shohreh
Published: November 2020

Levodopa is widely administered orally in clinical treatment of Parkinson’s disease; however, due to levodopa various oral absorption and low bioavailability, intranasal delivery seems to be a suitable alternative route of administration. Pluronic F-127 is a thermosensitive polymer, which can form gel at nasal cavity temperature and increase drug residence time. In this study, a rapid High Performance Liquid Chromatography (HPLC) method was validated in presence of internal standard to determine pharmacokinetic parameters following levodopa administration to rats in three different intravenous solution, intranasal solution and intranasal thermosensitive gel groups. A precised (96.7%) and accurate (95.0%) HPLC method was validated at low UltraViolet (UV) wavelength of 208 nm that showed limit of detection and limit of quantitation of 59 and 177 ng/mL, respectively. Specificity results showed no interference for levodopa with endogenous serum materials, and serum extraction efficacy was 93%. Pharmacokinetic parameters including bioavailability of 75 and 85% with mean residence time of 78 and 94 min were estimated for intranasal solution and thermosensitive gel using the validated HPLC method, which indicated that levodopa nasal gel may be a good alternative with appropriate pharmacokinetic outcome. Therefore, the validated levodopa HPLC analysis method at low UV wavelength was efficiently applied in pharmacokinetic study.
Acquisition and Transmission of Carbapenemase-Producing (blaKPC-2) Enterobacter cloacae in a Highly Frequented Outpatient Clinic
Authors: Klein Sabrina , Boutin Sébastien , Späth Isabel , Kimmich Christoph , Brandt Juliane , Müller-Tidow Carsten , Heeg Klaus , Nurjadi Dennis
Published: November 2020

The role of outpatient clinics as a potential transmission ground for multidrug-resistant organisms has not been adequately investigated. Here, we report a transmission cluster of blaKPC-2-positive Enterobacter cloacae among patients treated in a highly frequented outpatient department.
Secondary Attack Rate and Family Clustering of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection in Children of Healthcare Workers With Confirmed Coronavirus Disease 2019 (COVID-19)
Authors: Ladhani Shamez N , Andrews Nick , Aiano Felicity , Baawuah Frances , Amin-Chowdhury Zahin , Brown Kevin E , Amirthalingam Gayatri , Ramsay Mary E , Waterfield Thomas ,   RAPID-19 Investigation Team, Watson Chris , Moore Rebecca , Ferris Kathryn , Tonry Claire , Watt Alison P , McGinn Claire , Foster Steven , Evans Jennifer , Lyttle Mark D , Ahmad Shazaad , Corr Michael , McFetridge Lisa , Mitchell Hannah , Maney Julie-Ann , Christie Sharon
Published: November 2020

We measured serum SARS-CoV-2 antibodies in 215 children of healthcare workers to estimate secondary attack rates. Twenty-one families had a parent with confirmed COVID-19. There was strong evidence of family clustering (P < .001): 20/21 (95.2%) children were seropositive in 9 families and none of 23 children in 12 other families.
Modularity and specialization in bat–fly interaction networks are remarkably consistent across patches within urbanized landscapes and spatial scales
Authors: Urbieta Gustavo Lima , Graciolli Gustavo , Vizentin-Bugoni Jeferson
Published: November 2020

Patterns of specialization and the structure of interactions between bats and ectoparasitic flies have been studied mostly on non-urban environments and at local scales. Thus, how anthropogenic disturbances influence species interactions and network structure in this system remain poorly understood. Here, we investigated patterns of interaction between Phyllostomidae bats and ectoparasitic Streblidae flies, and variations in network specialization and structure across Cerrado patches within urbanized landscapes in Brazil and between local and regional scales. We found high similarity in the richness and composition of bat and fly species across communities, associated with low turnover of interactions between networks. The high specialization of bat–streblid interactions resulted in little connected and modular networks, with the emergence of modules containing subsets of species that interact exclusively or primarily with each other. Such similarities in species and interaction composition and network structure across communities and scales suggest that bat–fly interactions within Cerrado patches are little affected by the degree of human modification in the surrounding matrix. This remarkable consistency is likely promoted by specific behaviors, the tolerance of Phyllostomidae bats to surrounding urbanized landscapes as well as by the specificity of the streblid–bat interactions shaped over evolutionary time.
Automated Detection of Crohn’s Disease Intestinal Strictures on Capsule Endoscopy Images Using Deep Neural Networks
Authors: Klang Eyal , Grinman Ana , Soffer Shelly , Margalit Yehuda Reuma , Barzilay Oranit , Amitai Michal Marianne , Konen Eli , Ben-Horin Shomron , Eliakim Rami , Barash Yiftach , Kopylov Uri
Published: November 2020

Background and Aims

Passable intestinal strictures are frequently detected on capsule endoscopy [CE]. Such strictures are a major component of inflammatory scores. Deep neural network technology for CE is emerging. However, the ability of deep neural networks to identify intestinal strictures on CE images of Crohn’s disease [CD] patients has not yet been evaluated.

Methods

We tested a state-of-the-art deep learning network for detecting CE images of strictures. Images of normal mucosa, mucosal ulcers, and strictures of Crohn’s disease patients were retrieved from our previously described CE image bank. Ulcers were classified as per degree of severity. We performed 10 cross-validation experiments. A clear patient-level separation was maintained between training and testing sets.

Results

Overall, the entire dataset included 27 892 CE images: 1942 stricture images, 14 266 normal mucosa images, and 11 684 ulcer images [mild: 7075, moderate: 2386, severe: 2223]. For classifying strictures versus non-strictures, the network exhibited an average accuracy of 93.5% [±6.7%]. The network achieved excellent differentiation between strictures and normal mucosa (area under the curve [AUC] 0.989), strictures and all ulcers [AUC 0.942], and between strictures and different grades of ulcers [for mild, moderate, and severe ulcers—AUCs 0.992, 0.975, and 0.889, respectively].

Conclusions

Deep neural networks are highly accurate in the detection of strictures on CE images in Crohn’s disease. The network can accurately separate strictures from ulcers across the severity range. The current accuracy for the detection of ulcers and strictures by deep neural networks may allow for automated detection and grading of Crohn’s disease-related findings on CE.
Complete subset averaging with many instruments
Authors: Lee Seojeong , Shin Youngki
Published: November 2020

We propose a two-stage least squares (2SLS) estimator whose first stage is the equal-weighted average over a complete subset with k instruments among K available, which we call the complete subset averaging (CSA) 2SLS. The approximate mean squared error (MSE) is derived as a function of the subset size k by the Nagar (1959) expansion. The subset size is chosen by minimising the sample counterpart of the approximate MSE. We show that this method achieves asymptotic optimality among the class of estimators with different subset sizes. To deal with averaging over a growing set of irrelevant instruments, we generalise the approximate MSE to find that the optimal k is larger than otherwise. An extensive simulation experiment shows that the CSA-2SLS estimator outperforms the alternative estimators when instruments are correlated. As an empirical illustration, we estimate the logistic demand function in Berry et al. (1995) and find that the CSA-2SLS estimate is better supported by economic theory than are the alternative estimates.
Long-term prognostic value of late gadolinium enhancement and periprocedural myocardial infarction after uncomplicated revascularization: MASS-V follow-up
Authors: Linhares-Filho Jaime , Hueb Whady , Lima Eduardo , Rezende Paulo , Azevedo Diogo , Rochitte Carlos , Nomura Cesar , Serrano-Junior Carlos , Ramires José , Kalil-Filho Roberto
Published: November 2020

Aims

Cardiac biomarkers elevation is common after revascularization, even in absence of periprocedural myocardial infarction (PMI) detection by imaging methods. Thus, late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) may be useful on PMI diagnosis and prognosis. We sought to evaluate long-term prognostic value of PMI and new LGE after revascularization.

Methods and results

Two hundred and two patients with multivessel coronary disease and preserved ventricular function who underwent elective revascularization were included, of whom 136 (67.3%) underwent coronary artery bypass grafting and 66 (32.7%) percutaneous coronary intervention. The median follow-up was 5 years (4.8–5.8 years). Cardiac biomarkers measurement and LGE-CMR were performed before and after procedures. The Society for Cardiovascular Angiography and Interventions definition was used to assess PMI. Primary endpoint was composed of death, infarction, additional revascularization, or cardiac hospitalization. Primary endpoint was observed in 29 (14.3%) patients, of whom 13 (14.9%) had PMI and 16 (13.9%) did not (P = 0.93). Thirty-six (17.8%) patients had new LGE. Twenty (12.0%) events occurred in patients without new LGE and 9 (25.2%) in patients with it (P = 0.045). LGE was also associated to increased mortality, with 4 (2.4%) and 4 (11.1%) deaths in subjects without and with it (P = 0.02). LGE was the only independent predictor of primary endpoint and mortality (P = 0.03 and P = 0.02). Median LGE mass was estimated at 4.6 g. Patients with new LGE had a greater biomarkers release (median troponin: 8.9 ng/mL vs. 1.8 ng/mL and median creatine kinase-MB: 38.0 ng/mL vs. 12.3 ng/mL; P < 0.001 in both comparisons).

Conclusions

New LGE was shown to be better prognostic predictor than biomarker-only PMI definition after uncomplicated revascularization. Furthermore, new LGE was the only independent predictor of cardiovascular events and mortality.

Clinical trial registration

http://www.controlled-trials.com/ISRCTN09454308.
Histopathological changes in dilated ascending aorta associated with aortic valve cuspidity
Authors: Karalko Mikita , Stejskal Vaclav , Dergel Martin , Gofus Jan , Timbilla Salifu , Zaloudkova Lenka , Zacek Pavel , Pojar Marek , Vojacek Jan
Published: November 2020

OBJECTIVES

Patients with a bicuspid aortic valve (BAV) often present with a dilated ascending aorta. However, the underlying pathogenesis for the observed changes in the aortic wall and the resulting aneurysmal dilation remains a subject of debate. This study aims to compare the histological abnormalities of the ascending aorta in BAV and tricuspid aortic valve (TAV) patients and their correlation with aortic diameter and patient age.

METHODS

A total of 376 patients from our institution’s clinical database were included in the retrospective analysis. These patients underwent either elective surgery for ascending aorta dilation or emergency surgery for aortic dissection, either isolated or with a structurally diseased aortic valve. After excision, the ascending aorta samples were analysed by a pathologist.

RESULTS

On histological examination, a higher degree of elastic fibre fragmentation and loss and mucoid extracellular matrix accumulation was present in the samples from TAV patients when compared with that from BAV patients (P < 0.001). However, correlation was poor for all variables when considering aortic diameter and histological abnormalities or age and histological abnormalities in both BAV and TAV patients.

CONCLUSIONS

Our study demonstrates a greater incidence of severe histological abnormalities in TAV patients when compared with BAV patients.
The association of amputations and peripheral artery disease in patients with type 2 diabetes mellitus receiving sodium-glucose cotransporter type-2 inhibitors: real-world study
Authors: Paul Sanjoy K , Bhatt Deepak L , Montvida Olga
Published: November 2020

Aims 

The aim of this study was to evaluate the temporal pattern of amputations in patients with type 2 diabetes mellitus (T2DM), the risk of amputations by new and older anti-diabetic drugs (ADDs), and the interplay of peripheral artery disease (PAD) with therapy and amputation risk.

Methods and results 

Using Centricity Electronic Medical Records from USA, 3 293 983 patients with T2DM were identified: 169 739 received sodium-glucose cotransporter type-2 inhibitors (SGLT-2i; no exposure to incretins); 149 826 received glucagon-like peptide 1 receptor agonists [GLP-1RA, no SGLT-2i or dipeptidyl peptidase-4 inhibitor (DPP-4i) exposure]; 448 225 received DPP-4i (no exposure to GLP-1RA or SGLT-2i); and 1 954 353 received other ADDs. The proportion of incident amputations per 10 000 adults ranged between 4.7 and 6.8 during 2000–08 and significantly increased to 12.3 in 2017. Over 17 211 719 person-years follow-up post T2DM diagnosis, the rates per 1000 person-years of any and lower limb amputations (LLAs) were similar between SGLT-2i and incretins [95% confidence interval (CI) range: 1.06–1.67], and significantly higher in other groups (95% CI range: 1.96–2.29). In propensity score-adjusted pairwise analyses, the risk of LLA was not higher in SGLT-2i vs. GLP1-RA [hazard ratio (HR) (95% CI): 0.88 (0.73, 1.05)], and lower in SGLT-2i vs. DPP-4i/other ADD [HR (95% CI): 0.65 (0.56, 0.75)/0.43 (0.37, 0.49)]. The rate of LLA was similar in patients treated with canagliflozin, empagliflozin, or dapagliflozin. Patients with PAD had more than four-fold higher LLA risk (range of 95% CI of HR: 3.6–6.0).

Conclusion 

The risk of amputation in patients treated with SGLT-2i and incretins was not higher compared with other ADDs. Pre-existing PAD was the greatest driver of amputation risk.
Role of genetics in atrial fibrillation management
Authors: Rienstra Michiel , Siland Joylene E , Ellinor Patrick T
Published: November 2020

Atrial fibrillation (AF) management has significantly improved during the career of professor Crijns. Research was implemented into guidelines and clinical practice. However, despite advances in AF management, large differences between individual treatment responses still exist and the mechanisms underlying initiation and perpetuation of AF are not completely understood. International collaborations have revealed the genetic contribution to AF and steps towards improving AF management are being made. In this short review, the most important paradigms shifts in the field of AF genetics are recognized and the future role of genetics in personalized management of AF is discussed.
Distance from the outbreak of infection, ozone pollution and public health consequences of SARS-CoV-2 epidemic: the HOPE method
Authors: Tripepi Giovanni , Plebani Mario , Iervasi Giorgio , Gori Mercedes , Leonardis Daniela , D’Arrigo Graziella , Fusaro Maria
Published: November 2020

Background

Italy was the second country in the world, after China, to be hit by SARS-CoV-2 pandemic. Italy’s experience teaches that steps to limit people’s movement by imposing ‘red zones’ need to be put in place early by carefully identifying the cities to be included within these areas of quarantine. The assessment of the relationship between the distance from an established outbreak of SARS-CoV-2 infection with transmission-linked cases and mortality observed in other sites could provide useful information to identify the optimal radius of red zones.

Methods

We investigated the relationship between SARS-CoV-2 cases and the distance of each Italian province from the first outbreak of SARS-CoV-2 epidemic in Italy (the city of Lodi placed in the Lombardia region). In 38 provinces of Lombardia and neighboring regions, we performed a breakpoint analysis to identify the radius of the red zone around Lodi minimizing epidemic spread and mortality in neighboring cities.

Results

In all Italian provinces, a non-linear relationship was found between SARS-CoV-2 cases and distance from Lodi. In an analysis including the provinces of Lombardia and neighboring regions, SARS-CoV-2 cases and mortality increased when the distance from Lodi reduced below 92 and 140 km, respectively, and such relationships were amplified by ozone (O3) pollution.

Conclusions

The breakpoint analysis identifies the radius around the outbreak of Lodi minimizing the public health consequences of SARS-CoV-2 in neighboring cities. Such an approach can be useful to identify the red zones in future epidemics due to highly infective pathogens similar to SARS-CoV-2.
Identification of a novel type of glucose dehydrogenase involved in the mineral weathering ability of Collimonas pratensis strain PMB3(1)
Authors: Picard L , Turpault M-P , Oger P M , Uroz S
Published: November 2020

The exact molecular mechanisms as well as the genes involved in the mineral weathering (MW) process by bacteria remain poorly characterized. To date, a single type of glucose dehydrogenase (GDH) depending on a particular co-factor named pyrroloquinoline quinone (PQQ) is known. These enzymes allow the production of gluconic acid through the oxidation of glucose. However, it remains to be determined how bacteria missing PQQ-dependent GDH and/or the related pqq biogenesis genes weather minerals. In this study, we considered the very effective mineral weathering bacterial strain PMB3(1) of Collimonas pratensis. Genome analysis revealed that it does not possess the PQQ based system. The use of random mutagenesis, gene complementation and functional assays allowed us to identify mutants impacted in their ability to weather mineral. Among them, three mutants were strongly altered on their acidification and biotite weathering abilities (58 to 75% of reduction compared to WT) and did not produce gluconic acid. The characterization of the genomic regions allowed noticeably to the identification of a Glucose/Methanol/Choline oxidoreductase. This region appeared very conserved among collimonads and related genera. This study represents the first demonstration of the implication of a PQQ-independent GDH in the mineral weathering process and explains how Collimonas weather minerals.
LisRK is required for optimal fitness ofListeria monocytogenesin soil
Authors: Brunhede Maja Z , Santos Patrícia T Dos , Gal Laurent , Garmyn Dominique , Kallipolitis Birgitte H , Piveteau Pascal
Published: November 2020

Listeria monocytogenes is a food-borne pathogen responsible for the disease listeriosis. It is ubiquitously found in the environment and soil is one of its natural habitats. Listeria monocytogenes is highly capable of coping with various stressful conditions. We hypothesized that stress-responsive two-component systems such as LisRK might contribute to the adaptation of L. monocytogenes to the soil environment. Indeed, investigations of the population dynamics of wild-type and mutant strains suggest an important role of LisRK for optimal fitness of L. monocytogenes in sterile soil. Results from non-sterile soil showed that the parental strain was capable of surviving longer than mutant strains lacking lisRK or genes encoding the LisRK-regulated LhrC small RNAs (sRNAs), suggesting that LisRK as well as the LhrC sRNAs were important for survival. Transcription of five LisRK-regulated genes was assessed after 1 h incubation in sterile soil. We observed that LisRK and the LhrC sRNAs contribute to the upregulation of lmo2522 in the soil environment. Notably, lmo2522 encodes an equivalent of the resuscitation promoting factors, Rpfs, in actinobacteria. Collectively, our study demonstrates that LisRK is important for growth and survival in sterile and non-sterile soil and suggests a role for LisRK-regulation of Lmo2522 in resuscitation from dormancy in the soil environment.
Cross-Sectional and Longitudinal Associations Between Plasma Neurodegenerative Biomarkers and Physical Performance Among Community-Dwelling Older Adults
Authors: He Lingxiao , de Souto Barreto Philipe , Giudici Kelly V , Aggarwal Geetika , Nguyen Andrew D , Morley John E , Li Yan , Bateman Randall J , Vellas Bruno ,   for the MAPT/DSA Group, Vellas Bruno , Guyonnet Sophie , Carrié Isabelle , Brigitte Lauréane , Faisant Catherine , Lala Françoise , Delrieu Julien , Villars Hélène , Combrouze Emeline , Badufle Carole , Zueras Audrey , Andrieu Sandrine , Cantet Christelle , Morin Christophe , Abellan Van Kan Gabor , Dupuy Charlotte , Rolland Yves , Caillaud Céline , Ousset Pierre-Jean , Lala Françoise
Published: November 2020

Background

Plasma amyloid-beta (Aβ), neurofilament light chain (NfL), and progranulin (PGRN) have been related to multiple neurodegenerative conditions that might affect physical performance. The aim of this study was to explore the relationship between these plasma neurodegenerative markers and physical performance among community-dwelling older adults.

Methods

Five hundred and seven older adults (aged 76 ± 5 years) previously recruited in the Multidomain Alzheimer’s Preventive Trial, and had received blood and physical performance tests, were included in this study. Plasma Aβ (Aβ 42/Aβ 40 ratio), NfL, and PGRN levels were measured. Physical performance was assessed by handgrip strength and the Short Physical Performance Battery (combining gait speed, chair stands, and balance tests). Physical performance measured at the same time point and after the blood tests were used. Mixed-effect linear models were performed with age, sex, allocation to Multidomain Alzheimer’s Preventive Trial group, body mass index, and Mini-Mental State Examination score as covariates.

Results

The mean values of Aβ 42/Aβ 40 ratio, NfL, and PGRN were 0.11, 84.06 pg/mL, and 45.43 ng/mL, respectively. At the cross-sectional level, higher plasma NfL was associated with a lower Short Physical Performance Battery score (β = −0.004, 95% CI [−0.007, −0.001]). At the longitudinal level, higher PGRN levels were associated with decreasing handgrip strength over time (β = −0.02, 95% CI [−0.04, −0.007]). All the other associations were statistically nonsignificant.

Conclusion

Our findings suggest the possibility of using plasma NfL and PGRN as markers of physical performance in older adults.
Nursing Home Residents With Dementia: Association Between Place of Death and Patient Safety Culture
Authors: Orth Jessica , Li Yue , Simning Adam , Zimmerman Sheryl , Temkin-Greener Helena
Published: November 2020

Background and Objectives

Nursing homes (NHs) care for 70% of Americans dying with dementia. Many consider deaths in NHs rather than hospitals as preferable for most of these residents. NH characteristics such as staff teamwork, communication, and other components of patient safety culture (PSC), together with state minimum NH nurse staffing requirements, may influence location of death. We examined associations between these variables and place of death (NH/hospital) among residents with dementia.

Research Design and Methods

Cross-sectional study of 11,957 long-stay NH residents with dementia, age 65+, who died in NHs or hospitals shortly following discharge from one of 800 U.S. NHs in 2017. Multivariable logistic regression systematically estimated effects of PSC on odds of in-hospital death among residents with dementia, controlling for resident, NH, county, and state characteristics. Logistic regressions also determined moderating effects of state minimum NH nurse staffing requirements on relationships between key PSC domains and location of death.

Results

Residents with dementia in NHs with higher PSC scores in communication openness had lower odds of in-hospital death. This effect was stronger in NHs located in states with higher minimum NH nurse staffing requirements.

Discussion and Implications

Promoting communication openness in NHs across nursing disciplines may help avoid unnecessary hospitalization at the end of life, and merits particular attention as NHs address nursing staff mix while adhering to state staffing requirements. Future research to better understand unintended consequences of staffing requirements is needed to improve end-of-life care in NHs.
Patient-specific 3-dimensional lung modelling: next-generation imaging helps guide precise surgical resection
Authors: Baig Mirza Zain , Muslim Zaid , Weber Joanna F , Bhora Faiz Y
Published: November 2020

Recent strides have allowed the consolidation of routine imaging modalities with highly accurate reconstruction software to aid the operating surgeon generate patient-specific three-dimensional models. In this preliminary report, we describe our initial experience using a patient-specific reconstruction software to guide surgical resection for 2 patients with non-small-cell lung cancer. Digital imaging and communications in medicine data from patient chest CT scans was configured into IQQA BodyImaging Lung software to generate highly accurate maps of airways, vessels and segments as well as estimates of lung volumes. Models generated aided us in planning appropriate lung cancer resection procedures.
Sofosbuvir and daclatasvir for the treatment of COVID-19 outpatients: a double-blind, randomized controlled trial
Authors: Roozbeh Fatemeh , Saeedi Majid , Alizadeh-Navaei Reza , Hedayatizadeh-Omran Akbar , Merat Shahin , Wentzel Hannah , Levi Jacob , Hill Andrew , Shamshirian Amir
Published: November 2020

Introduction

Effective treatments are urgently needed to tackle the novel coronavirus disease 2019 (COVID-19). This trial aims to evaluate sofosbuvir and daclatasvir versus standard care for outpatients with mild COVID-19 infection.

Methods

This was a randomized controlled clinical trial in outpatients with mild COVID-19. Patients were randomized into a treatment arm receiving sofosbuvir/daclatasvir plus hydroxychloroquine or a control arm receiving hydroxychloroquine alone. The primary endpoint of the trial was symptom alleviation after 7 days of follow-up. The secondary endpoint of the trial was hospital admission. Fatigue, dyspnoea and loss of appetite were investigated after 1 month of follow-up. This study is registered with the IRCT.ir under registration number IRCT20200403046926N1.

Results

Between 8 April 2020 and 19 May 2020, 55 patients were recruited and allocated to either the sofosbuvir/daclatasvir treatment arm (n = 27) or the control arm (n = 28). Baseline characteristics were similar across treatment arms. There was no significant difference in symptoms at Day 7. One patient was admitted to hospital in the sofosbuvir/daclatasvir arm and four in the control arm, but the difference was not significant. After 1 month of follow-up, two patients reported fatigue in the sofosbuvir/daclatasvir arm and 16 in the control arm; P < 0.001.

Conclusions

In this study, sofosbuvir/daclatasvir did not significantly alleviate symptoms after 7 days of treatment compared with control. Although fewer hospitalizations were observed in the sofosbuvir/daclatasvir arm, this was not statistically significant. Sofosbuvir/daclatasvir significantly reduced the number of patients with fatigue and dyspnoea after 1 month. Larger, well-designed trials are warranted.
Morphological Alterations of the Sarcotubular System in Permanent Myopathy of Hereditary Hypokalemic Periodic Paralysis with a Mutation in the CACNA1S Gene
Authors: Nagasaka Takamura , Hata Takanori , Shindo Kazumasa , Adachi Yoshiki , Takeuchi Megumi , Saito Kayoko , Takiyama Yoshihisa
Published: November 2020

We investigated the immunohistochemical localization of several proteins related to excitation-contraction coupling and ultrastructural alterations of the sarcotubular system in biopsied muscles from a father and a daughter in a family with permanent myopathy with hypokalemic periodic paralysis (PMPP) due to a mutation in calcium channel CACNA1S; p. R1239H hetero. Immunostaining for L-type calcium channels (LCaC) showed linear hyper-stained regions indicating proliferation of longitudinal t-tubules. The margin of vacuoles was positive for ryanodine receptor, LCaC, calsequestrin (CASQ) 1, CASQ 2, SR/ER Ca2+-ATPase (SERCA) 1, SERCA2, dysferlin, dystrophin, α-actinin, LC3, and LAMP 1. Electron microscopy indicated that the vacuoles mainly originated from the sarcoplasmic reticulum (SR). These findings indicate impairment of the muscle contraction system related to Ca2+ dynamics, remodeling of t-tubules and muscle fiber repair. We speculate that PMPP in patients with a CACNA1S mutation might start with abnormal SR function due to impaired LCaC. Subsequent induction of muscular contractile abnormalities and the vacuoles formed by fused SR in the repair process including autophagy might result in permanent myopathy. Our findings may facilitate prediction of the pathomechanisms of PMPP seen on morphological observation.
Results of definitive radiotherapy with concurrent chemotherapy for maxillary sinus carcinomas with neck lymph node metastasis
Authors: Abe Takanori , Saito Satoshi , Iino Misaki , Aoshika Tomomi , Ryuno Yasuhiro , Ohta Tomohiro , Igari Mitsunobu , Hirai Ryuta , Kumazaki Yu , Ebihara Yasuhiro , Nakahira Mitsuhiko , Sugasawa Masashi , Noda Shin-ei , Kato Shingo
Published: November 2020

The purpose of this study was to describe the results of definitive radiotherapy (RT) with concurrent chemotherapy for maxillary sinus carcinomas (MSCs) with neck lymph node metastasis to clarify its limitation. Local control (LC), progression-free survival (PFS) and overall survival (OS) rates were calculated using the Kaplan–Meier method and were compared between subgroups using the log rank test. Toxicity was classified using common terminology criteria of adverse events version 5.0. Eighteen patients with inoperable MSC with neck lymph node metastasis including 12 men and 6 women with a median age of 67 years were analyzed. The histologic diagnoses were as follows: 16 patients had squamous cell carcinomas and 2 had other histology. Four patients had stage T3 MSC, 6 had T4a and 8 had T4b. Among 18 patients, 7 received concurrent systemic chemotherapy and 11 received selective arterial chemo-infusion. The median follow-up period was 17 months. The 2-year LC, PFS and OS rates for the entire cohort were 34, 31 and 46%, respectively. No significant differences were observed for LC, PFS and OS rates between systemic chemotherapy and selective arterial chemo-infusion cohorts. Grade 3 or higher acute toxicity, including both non-hematological and hematological, was observed in nine patients (50%), while no grade 3 or higher late toxicity was observed. In conclusion, we described the results of definitive RT for MSCs with neck lymph node metastasis. Local recurrence of primary tumor was a frequent pattern of failure and it should be addressed in future study.
A delayed post-operative diaphragmatic hernia with hemothorax due to a strangulated stomach
Authors: Al-Saqqa Rama , Sabouni Rami , Jarad Lana , Abbas Nizar
Published: November 2020

Traumatic diaphragmatic hernias (TDHs) are uncommon, and they mostly occur following blunt or penetrating traumatic injury and rarely as a complication of Iatrogenic procedure. The management of TDHs is through surgical repair. In this article, we present the case of a diaphragmatic herniation presenting 1 year after thoracic surgery in a 16-year-old male. The patient presented with gastrointestinal obstruction symptoms and later developed a hypovolemic shock due to stomach bleeding. Immediate exploratory thoracotomy was performed, and the patient reached a full recovery afterward.
A multiscale assessment of Red-tailed Hawk reproductive success relative to urban density and habitat type
Authors: White Justin H , Brown Jessi L , Ormsby Zachary E
Published: November 2020

Despite the unique threats to wildlife in urban areas, many raptors have established successfully reproducing urban populations. To identify variations in raptor breeding ecology within an urban area, we compared metrics of Red-tailed Hawk reproductive attempts to landscape characteristics in Reno and Sparks, NV, USA during the 2015 and 2016 breeding seasons. We used the Apparent Nesting Success and logistic exposure methods to measure nesting success of the Red-tailed Hawks. We used generalized linear models to relate nesting success and fledge rate to habitat type, productivity to hatch date (Julian day) and hatch date to urban density. Nesting success was 86% and 83% for the respective years. Nesting success increased in grassland-agricultural and shrub habitats and decreased in riparian habitat within the urban landscape. Productivity was 2.23 and 2.03 per nest for the breeding seasons. Fledge rates were 72% and 77%, respectively, and decreased in riparian areas. Nestlings hatched earlier with increased urban density and earliest in suburban areas, following a negative quadratic curve. Nesting success and productivity for this population were high relative to others in North America. Productivity increased in habitats where ground prey was more accessible. We suggest that suburban areas, if not frequently disturbed, provide sufficient resources to sustain Red-tailed Hawks over extended periods. As urban expansion continues in arid environments globally, we stress that researchers monitor reproductive output across the urban predator guild to elucidate patterns in population dynamics and adaptation.
Insights into the evo-devo of plant reproduction using next-generation sequencing approaches
Authors: Preston Jill C
Published: November 2020

The development of plant model organisms has traditionally been analyzed using resource-heavy, tailored applications that are not easily transferable to distantly related non-model taxa. Thus, our understanding of plant development has been limited to a subset of traits, and evolutionary studies conducted most effectively either across very wide [e.g. Arabidopsis thaliana and Oryza sativa (rice)] or narrow (i.e. population level) phylogenetic distances. As plant biologists seek to capitalize on natural diversity for crop improvement, enhance ecosystem functioning, and better understand plant responses to climate change, high-throughput and broadly applicable forms of existing molecular biology assays are becoming an invaluable resource. Next-generation sequencing (NGS) is increasingly becoming a powerful tool in evolutionary developmental biology (evo-devo) studies, particularly through its application to understanding trait evolution at different levels of gene regulation. Here, I review some of the most common and emerging NGS-based methods, using exemplar studies in reproductive plant evo-devo to illustrate their potential.
LeMMINGs – II. The e-MERLIN legacy survey of nearby galaxies. The deepest radio view of the Palomar sample on parsec scale
Authors: Baldi R D , Williams D R A , McHardy I M , Beswick R J , Brinks E , Dullo B T , Knapen J H , Argo M K , Aalto S , Alberdi A , Baan W A , Bendo G J , Corbel S , Fenech D M , Gallagher J S , Green D A , Kennicutt R C , Klöckner H-R , Körding E , Maccarone T J , Muxlow T W B , Mundell C G , Panessa F , Peck A B , Pérez-Torres M A , Romero-Cañizales C , Saikia P , Shankar F , Spencer R E , Stevens I R , Varenius E , Ward M J , Yates J , Uttley P
Published: November 2020

We present the second data release of high-resolution (≤0.2 arcsec) 1.5-GHz radio images of 177 nearby galaxies from the Palomar sample, observed with the e-MERLIN array, as part of the Legacy e-MERLIN Multi-band Imaging of Nearby Galaxies Sample (LeMMINGs) survey. Together with the 103 targets of the first LeMMINGs data release, this represents a complete sample of 280 local active (LINER and Seyfert) and inactive galaxies (H ii galaxies and absorption line galaxies, ALG). This large program is the deepest radio survey of the local Universe, ≳1017.6 W Hz−1, regardless of the host and nuclear type: we detect radio emission ≳0.25 mJy beam−1 for 125/280 galaxies (44.6 per cent) with sizes of typically ≲100 pc. Of those 125, 106 targets show a core which coincides within 1.2 arcsec with the optical nucleus. Although we observed mostly cores, around one third of the detected galaxies features jetted morphologies. The detected radio core luminosities of the sample range between ∼1034 and 1040 erg s−1. LINERs and Seyferts are the most luminous sources, whereas H ii galaxies are the least. LINERs show FR I-like core-brightened radio structures while Seyferts reveal the highest fraction of symmetric morphologies. The majority of H ii galaxies have single radio core or complex extended structures, which probably conceal a nuclear starburst and/or a weak active nucleus (seven of them show clear jets). ALGs, which are typically found in evolved ellipticals, although the least numerous, exhibit on average the most luminous radio structures, similar to LINERs.
Model of heat diffusion in the outer crust of bursting neutron stars
Authors: Yakovlev D G , Kaminker A D , Potekhin A Y , Haensel P
Published: November 2020

We study heat diffusion after an energy release in a deep spherical layer of the outer neutron star crust (107 ≲ ρ ≲ 4 × 1011 g cm−3). We demonstrate that this layer possesses specific heat-accumulating properties, absorbing heat and directing it mostly inside the star. It can absorb up to ∼1043–1044 erg due to its high heat capacity, until its temperature exceeds T ∼ 3 × 109 K and triggers a rapid neutrino cooling. A warm layer (T ∼ 108–3 × 109 K) can serve as a good heat reservoir, which is thermally decoupled from the inner crust and the stellar core for a few months. We present a toy model to explore the heat diffusion within the heat-accumulating layer, and we test this model using numerical simulations. We formulate some generic features of the heat propagation that can be useful, for instance, for the interpretation of superbursts in accreting neutron stars. We present a self-similar analysis of late afterglow after such superbursts, which can be helpful to estimate properties of bursting stars.
On the possibility of probing the flare productivity of an active region in the early stage of emergence
Authors: Kutsenko Alexander S , Abramenko Valentina I , Kutsenko Olga K
Published: November 2020

Prediction of the future flare productivity of an active region (AR) when it is in the early-emergence stage is a longstanding problem. The aim of this study is to probe two parameters of the photospheric magnetic field, both derived during the emergence phase of an AR, and to compare them with the flare productivity of a well developed AR. The parameters are: (i) the index of the magnetic power spectrum (the slope of the spectrum) at the stage of emergence, and (ii) the flux emergence rate. Analysis of 243 emerging ARs showed that the magnetic power index increases from values typical of quiet-Sun regions to those typical of mature ARs within a day, while the emergence proceeds for several days; frequently, after the increase, the value of the power index oscillates around some mean value with the fluctuations being several times smaller than the growth of the power index during the emergence onset. For a subset of 34 flare-productive ARs we found no correlation between the power spectrum index at the stage of emergence and the flare index derived from the entire interval of the AR’s presence on the disc. At the same time, the flux emergence rate correlates well with the flare index (Pearson’s correlation coefficient is 0.74). We conclude that a high flux emergence rate is a necessary condition for an AR to produce strong flares in the future; thus the flux emergence rate can be used to probe the future flare productivity of an AR.
Photometric redshifts in the North Ecliptic Pole Wide field based on a deep optical survey with Hyper Suprime-Cam
Authors: Ho Simon C-C , Goto Tomotsugu , Oi Nagisa , Kim Seong Jin , Malkan Matthew A , Pollo Agnieszka , Hashimoto Tetsuya , Toba Yoshiki , Kim Helen K , Hwang Ho Seong , Shim Hyunjin , Huang Ting-Chi , Kim Eunbin , Wang Ting-Wen , Santos Daryl Joe D , Matsuhara Hideo
Published: November 2020

The AKARI space infrared telescope has performed near-infrared to mid-infrared (MIR) observations on the North Ecliptic Pole Wide (NEPW) field (5.4 deg2) for about 1 yr. AKARI took advantage of its continuous nine photometric bands, compared with NASA's Spitzer and Wide-field Infrared Survey Explorer(WISE) space telescopes, which had only four filters with a wide gap in the MIR. The AKARI NEPW field lacked deep and homogeneous optical data, limiting the use of nearly half of the IR sources for extragalactic studies, because of the absence of photometric redshift (photo-z). To remedy this, we have recently obtained deep optical imaging over the NEPW field with five bands (g, r, i, z and Y) of the Hyper Suprime-Camera (HSC) on the Subaru 8-m telescope. We optically identify AKARI-IR sources along with supplementary Spitzer and WISE data as well as pre-existing optical data. In this work, we derive new photo-z using a χ2 template-fitting method code, PHotometric Analysis for Redshift Estimate (Le Phare) and reliable photometry from 26 selected filters including HSC, AKARI, Canada–France–Hawaii Telescope, Maidanak, Kitt Peak National Observatory, Spitzer and WISE data. We take 2026 spectroscopic redshifts (spec-z) from all available spectroscopic surveys over the NEPW field to calibrate and assess the accuracy of the photo-z. At z < 1.5, we achieve a weighted photo-z dispersion of σΔz/(1+z) = 0.053 with η = 11.3 per cent catastrophic errors.
Non-isotropic feedback from accreting spinning black holes
Authors: Sala Luca , Cenci Elia , Capelo Pedro R , Lupi Alessandro , Dotti Massimo
Published: November 2020

Active galactic nuclei (AGNs) are massive black holes (BHs) caught in the act of accreting gas at the centre of their host galaxies. Part of the accreting mass is converted to energy and released into the surrounding medium, in a process loosely referred to as AGN feedback. Most numerical simulations include AGN feedback as a sub-grid model, wherein energy or momentum (or both) is coupled to the nearby gas. In this work, we implement a new momentum-driven model in the hydrodynamics code gizmo, in which accretion from large scales is mediated by a sub-grid accretion disc model, and gas particles are stochastically kicked over a bi-conical region, to mimic observed kinetic winds. The feedback cone’s axis can be set parallel either to the angular momentum of the gas surrounding the BH or to the BH spin direction, which is self-consistently evolved within the accretion-disc model. Using a circumnuclear disc (CND) as a test bed, we find that (i) the conical shape of the outflow is always visible and is weakly dependent on the launching orientation and aperture, resulting in comparable mass inflows and outflows; (ii) the cone’s orientation is also similar amongst our tests, and it is not always the same as the initial value, due to the interaction with the CND playing a crucial role in shaping the outflow; and (iii) the velocity of the outflow, instead, differs and strongly depends on the interplay with the CND.
Plasmid replication-associated single-strand-specific methyltransferases
Authors: Fomenkov Alexey , Sun Zhiyi , Murray Iain A , Ruse Cristian , McClung Colleen , Yamaichi Yoshiharu , Raleigh Elisabeth A , Roberts Richard J
Published: November 2020

Analysis of genomic DNA from pathogenic strains of Burkholderia cenocepacia J2315 and Escherichia coli O104:H4 revealed the presence of two unusual MTase genes. Both are plasmid-borne ORFs, carried by pBCA072 for B. cenocepacia J2315 and pESBL for E. coli O104:H4. Pacific Biosciences SMRT sequencing was used to investigate DNA methyltransferases M.BceJIII and M.EcoGIX, using artificial constructs. Mating properties of engineered pESBL derivatives were also investigated. Both MTases yield promiscuous m6A modification of single strands, in the context SAY (where S = C or G and Y = C or T). Strikingly, this methylation is asymmetric in vivo, detected almost exclusively on one DNA strand, and is incomplete: typically, around 40% of susceptible motifs are modified. Genetic and biochemical studies suggest that enzyme action depends on replication mode: DNA Polymerase I (PolI)-dependent ColE1 and p15A origins support asymmetric modification, while the PolI-independent pSC101 origin does not. An MTase-PolI complex may enable discrimination of PolI-dependent and independent plasmid origins. M.EcoGIX helps to establish pESBL in new hosts by blocking the action of restriction enzymes, in an orientation-dependent fashion. Expression and action appear to occur on the entering single strand in the recipient, early in conjugal transfer, until lagging-strand replication creates the double-stranded form.