bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimal Rate of Printing of 3D Printed Concrete Columns and Walls to Avoid Buckling
Authors: Phadnis K P , Shariff M N , Menon D
Published: October 2020

Extrusion based construction of concrete structures has been identified as one of the alternative construction technologies which reduces the construction costs, delays in construction and the material consumption. The most attractive feature of 3D printed constructions is the ease of developing intricate forms and shapes (which otherwise require skilled manpower). Since this is a relatively new technology, not much research has been done with regard to its structural performance and stability. One of the major concerns is the possibility of buckling (under its self-weight) of the column or wall during the extrusion process. This sets a limitation of the acceptable height, thickness and rate of extrusion process. In this study simple ways (second order analysis using matrix methods) have been explored to determine the critical height and the optimal rate of extrusion. Matrix methods have inherent limitations due to the simplification adopted by ignoring the higher-order terms in Taylor’s series. The study uses the evolution of modulus of elasticity of concrete as proposed in literature. The analysis method has been validated using pertinent buckling tests reported in literature. Parameters such as modulus of elasticity and length are considered to determine the critical height to thickness of the wall and the optimal rate of extrusion. The problem is solved using the MATLAB software. This method requires minimal input from the user such as material properties, geometry and printing speed. The analysis method used in this study provides a useful design tool to estimate the limiting parameters of the structural walls and columns manufactured through the process of 3D printing.
A Comparative Study of Aerodynamic Coefficients on Tall Structures using Experimental Studies with International Codes and Standards
Authors: Nair Shalini R , Rooby Jessy , Branesh R John
Published: October 2020

This paper illustrates the comparison of aerodynamic forces and coefficients on rectangular tall buildings. The forces and coefficients were obtained using Wind Tunnel Experiment and various international code provisions and standards. Rectangular tall building models selected for the study were made of acrylic sheets with various geometric scales. The models were tested using low-speed wind tunnel for various angles of incidents of wind varying from 0° to 90°. Drag coefficients obtained from experiments were compared with values of mean drag coefficients obtained from codes and practices, (a) IS: 875(Part3): Wind Loads on Buildings and Structures (India, 2015), (b) AS/NZS1170.2:2011, the combined Australia/New Zealand Standard on Wind Actions (Standards Australia,2011); (c) ASCE7–10 (ASCE, 2010); and (d) HKCoP-2019, the Code of Practice on Wind Effects in Hong Kong, (Buildings Department HongKong, 2019). Buildings with the same plan aspect ratio show the same aerodynamic behaviour. Wind tunnel study over-predicts the coefficient values compared to standards and practices. The average coefficient of drag values from codes is in good agreement with wind tunnel data with a deviation of less than 15%. The study also includes an examination of parameters such as pitching moment and its coefficient.
A fuller picture of COVID-19 prognosis: the added value of vulnerability measures to predict mortality in hospitalised older adults
Authors: Aliberti Márlon Juliano Romero , Covinsky Kenneth E , Garcez Flavia Barreto , Smith Alexander K , Curiati Pedro Kallas , Lee Sei J , Dias Murilo Bacchini , Melo Victor José Dornelas , Rego-Júnior Otávio Fortes do , Richinho Valéria de Paula , Jacob-Filho Wilson , Avelino-Silva Thiago J
Published: October 2020

Background

Although coronavirus disease 2019 (COVID-19) disproportionally affects older adults, the use of conventional triage tools in acute care settings ignores the key aspects of vulnerability.

Objective

This study aimed to determine the usefulness of adding a rapid vulnerability screening to an illness acuity tool to predict mortality in hospitalised COVID-19 patients.

Design

Cohort study.

Setting

Large university hospital dedicated to providing COVID-19 care.

Participants

Participants included are 1,428 consecutive inpatients aged ≥50 years.

Methods

Vulnerability was assessed using the modified version of PRO-AGE score (0–7; higher = worse), a validated and easy-to-administer tool that rates physical impairment, recent hospitalisation, acute mental change, weight loss and fatigue. The baseline covariates included age, sex, Charlson comorbidity score and the National Early Warning Score (NEWS), a well-known illness acuity tool. Our outcome was time-to-death within 60 days of admission.

Results

The patients had a median age of 66 years, and 58% were male. The incidence of 60-day mortality ranged from 22% to 69% across the quartiles of modified PRO-AGE. In adjusted analysis, compared with modified PRO-AGE scores 0–1 (‘lowest quartile’), the hazard ratios (95% confidence interval) for 60-day mortality for modified PRO-AGE scores 2–3, 4 and 5–7 were 1.4 (1.1–1.9), 2.0 (1.5–2.7) and 2.8 (2.1–3.8), respectively. The modified PRO-AGE predicted different mortality risk levels within each stratum of NEWS and improved the discrimination of mortality prediction models.

Conclusions

Adding vulnerability to illness acuity improved accuracy of predicting mortality in hospitalised COVID-19 patients. Combining tools such as PRO-AGE and NEWS may help stratify the risk of mortality from COVID-19.
Is there a dose–response relationship between musical instrument playing and later-life cognition? A cohort study using EPIC-Norfolk data
Authors: Walsh Sebastian , Luben Robert , Hayat Shabina , Brayne Carol
Published: October 2020

Introduction

Musical instrument playing provides intellectual stimulation, which is hypothesised to generate cognitive reserve that protects against cognitive impairment. Studies to date have classified musicianship as a binary entity. This investigation draws on the dataset of the European Prospective Investigation of Cancer Norfolk study to examine the effect of frequency of playing on later-life cognition.

Methods

We compared three categorisations of self-reported musical playing frequency in late mid-life (12-month period) against cognitive performance measured after a 4–11 year delay, adjusted for relevant health and social confounders. Logistic regression models estimated the adjusted association between frequency of musical playing and the likelihood of being in the top and bottom cognitive deciles.

Results

A total of 5,693 participants (745 musicians) provided data on music playing, cognition and all co-variables. Classification of musicianship by frequency of playing demonstrated key differences in socio-demographic factors. Musicians outperformed non-musicians in cognition generally. Compared with non-musicians, frequent musicians had 80% higher odds of being in the top cognitive decile (OR 1.80 [95% CI 1.19–2.73]), whereas musicians playing at any frequency had 29% higher odds (95% CI 1.03–1.62). There was evidence of a threshold effect, rather than a linear dose–response relationship.

Discussion

This study supports a positive association between late mid-life musical instrument playing and later-life cognition, although causation cannot be assumed. Musicians playing frequently demonstrated the best cognition. ‘Musicians’ are a heterogeneous group and frequency of music playing seems a more informative measure than binary classification. Ideally, this more nuanced measure would be collected for different life course phases.
Review of nonopioid multimodal analgesia for surgical and trauma patients
Authors: George Stephy , Johns Meagan
Published: October 2020

Purpose

Pain is a frequent finding in surgical and trauma patients, and effective pain control remains a common challenge in the hospital setting. Opioids have traditionally been the foundation of pain management; however, these agents are associated with various adverse effects and risks of dependence and diversion.

In response to the rising national opioid epidemic and the various risks associated with opioid use, multimodal pain management through use of nonopioid analgesics such as acetaminophen, nonsteroidal anti-inflammatory drugs, α 2 agonists, N-methyl-d-aspartate (NMDA) receptor antagonists, skeletal muscle relaxants, sodium channel blockers, and local anesthetics has gained popularity recently. Multimodal analgesia has synergistic therapeutic effects and can decrease adverse effects by enabling use of lower doses of each agent in the multimodal regimen. This review discusses properties of the various nonopioid analgesics and encourages pharmacists to play an active role in the selection, initiation, and dose-titration of multimodal analgesia. The choice of nonopioid agents should be based on patient comorbidities, hemodynamic stability, and the agents’ respective adverse effect profiles. A multidisciplinary plan for management of pain should be formulated during transitions of care and is an area of opportunity for pharmacists to improve patient care.

Conclusion

Multimodal analgesia effectively treats pain while decreasing adverse effects. There is mounting evidence to support use of this strategy to decrease opioid use. As medication experts, pharmacists can play a key role in the selection, initiation, and dose-titration of analgesic agents based on patient-specific factors.
Dexmedetomidine as add-on sedation to reduce continuous infusion sedative use in mechanically ventilated patients
Authors: Park Jung Hoon , Derry Katrina L , Owens Robert L
Published: October 2020

Purpose

To characterize the impact of add-on dexmedetomidine therapy on baseline continuous infusion sedative use.

Methods

A retrospective, single-center, chart review–based study was conducted to assess outcomes of and potential predictors of response to add-on dexmedetomidine therapy in mechanically ventilated intensive care unit (ICU) patients who were already receiving continuous infusions of sedatives. Patients were defined as complete, partial, or nonresponders to add-on dexmedetomidine therapy if initial sedative infusion rates were reduced by 100%, by 50% to 99%, and by less than 50%, respectively, at 6 and 24 hours after initiation of dexmedetomidine.

Results

Among the 100 patients included in the study sample, there were 54 complete responders, 21 partial responders, and 25 nonresponders to dexmedetomidine add-on therapy at 6 hours after dexmedetomidine initiation; at 24 hours, there were 65 complete and 12 partial responders and 23 nonresponders. Of the variables tested (ie, baseline characteristics, opioid and antipsychotic use, hemodynamic parameters), none differentiated between complete or partial responders and nonresponders. Ventilator time, ICU length of stay (LOS), and hospital LOS after add-on dexmedetomidine therapy initiation were shorter among both partial responders and complete responders vs nonresponders (median, 1.1 days vs 4.1 days [P = 0.01], 7.0 days vs 14.1 days [P = 0.20], and 11.0 vs 17.0 days [P = 0.58], respectively), with only ventilator time being significantly different.

Conclusion

Add-on dexmedetomidine therapy can obviate or reduce the need for alternate sedation in as many as 75% of mechanically ventilated ICU patients. However, the addition of dexmedetomidine does not allow the reduction of alternate sedation in a substantial minority of patients, and failure to respond to dexmedetomidine can be identified as early at 6 hours after add-on therapy initiation. In the absence of clear predictors of response to dexmedetomidine, these data suggest empiric trials of dexmedetomidine can be considered but should be time-limited.
Treatment of chronic hepatitis C virus infection with crushed ledipasvir/sofosbuvir administered through a percutaneous endoscopic gastrostomy tube in a patient with HIV coinfection
Authors: Huffman Vanessa , Andrade Diana C , Sherman Elizabeth , Niu Jianli , Eckardt Paula A
Published: October 2020

Purpose

Ledipasvir/sofosbuvir is an oral combination therapy containing fixed doses of direct-acting antiviral agents indicated for the treatment of hepatitis C virus (HCV) infection. Currently there are limited data on the clinical efficacy of crushed ledipasvir/sofosbuvir administered via feeding tube.

This case report discusses the successful treatment of chronic HCV genotype 1b infection with crushed ledipasvir/sofosbuvir administered through a percutaneous endoscopic gastrostomy (PEG) tube in a patient with human immunodeficiency virus (HIV) coinfection and high-grade sarcoma who had severe swallowing difficulties. The patient received crushed ledipasvir/sofosbuvir daily for a total of 12 weeks. At 12 weeks the patient had achieved a sustained virologic response.

Conclusion

Currently, ledipasvir/sofosbuvir is available only as a tablet, with limited pharmacokinetic data available to guide clinicians on use of the fixed-dose combination medication in crushed form. This case report highlights our experience treating a patient with HCV/HIV coinfection through administration of crushed ledipasvir/sofosbuvir via PEG tube, which we found to be a safe and effective therapeutic option.
DeepBL: a deep learning-based approach for in silico discovery of beta-lactamases
Authors: Wang Yanan , Li Fuyi , Bharathwaj Manasa , Rosas Natalia C , Leier André , Akutsu Tatsuya , Webb Geoffrey I , Marquez-Lago Tatiana T , Li Jian , Lithgow Trevor , Song Jiangning
Published: October 2020

Beta-lactamases (BLs) are enzymes localized in the periplasmic space of bacterial pathogens, where they confer resistance to beta-lactam antibiotics. Experimental identification of BLs is costly yet crucial to understand beta-lactam resistance mechanisms. To address this issue, we present DeepBL, a deep learning-based approach by incorporating sequence-derived features to enable high-throughput prediction of BLs. Specifically, DeepBL is implemented based on the Small VGGNet architecture and the TensorFlow deep learning library. Furthermore, the performance of DeepBL models is investigated in relation to the sequence redundancy level and negative sample selection in the benchmark dataset. The models are trained on datasets of varying sequence redundancy thresholds, and the model performance is evaluated by extensive benchmarking tests. Using the optimized DeepBL model, we perform proteome-wide screening for all reviewed bacterium protein sequences available from the UniProt database. These results are freely accessible at the DeepBL webserver at http://deepbl.erc.monash.edu.au/.
Single-cell RNA-seq data semi-supervised clustering and annotation via structural regularized domain adaptation
Authors: Chen Liang , He Qiuyan , Zhai Yuyao , Deng Minghua
Published: October 2020

Motivation

The rapid development of single-cell RNA sequencing (scRNA-seq) technologies allows us to explore tissue heterogeneity at the cellular level. The identification of cell types plays an essential role in the analysis of scRNA-seq data, which, in turn, influences the discovery of regulatory genes that induce heterogeneity. As the scale of sequencing data increases, the classical method of combining clustering and differential expression analysis to annotate cells becomes more costly in terms of both labor and resources. Existing scRNA-seq supervised classification method can alleviate this issue through learning a classifier trained on the labeled reference data and then making a prediction based on the unlabeled target data. However, such label transference strategy carries with risks, such as susceptibility to batch effect and further compromise of inherent discrimination of target data.

Results

In this article, inspired by unsupervised domain adaptation, we propose a flexible single cell semi-supervised clustering and annotation framework, scSemiCluster, which integrates the reference data and target data for training. We utilize structure similarity regularization on the reference domain to restrict the clustering solutions of the target domain. We also incorporates pairwise constraints in the feature learning process such that cells belonging to the same cluster are close to each other, and cells belonging to different clusters are far from each other in the latent space. Notably, without explicit domain alignment and batch effect correction, scSemiCluster outperforms other state-of-the-art, single-cell supervised classification and semi-supervised clustering annotation algorithms in both simulation and real data. To the best of our knowledge, we are the first to use both deep discriminative clustering and deep generative clustering techniques in the single-cell field.

Availabilityand implementation

An implementation of scSemiCluster is available from https://github.com/xuebaliang/scSemiCluster.

Supplementary information

Supplementary data are available at Bioinformatics online.
Distort, Extort, Deceive and Exploit: Exploring the Inner Workings of a Romance Fraud
Authors: Carter Elisabeth
Published: October 2020

Romance fraud is a crime where the fraudster must strike a balance between the romantic and financial aspects of the communication for their criminal intent to remain hidden. This discourse analytic research examines the setup of information early in the interaction, the use of visceral language and isolation as key tactics of exploitation enabling the distortion of reality and manipulation of power. With demands shrouded in a health narrative, and secrecy urged for the preservation of the relationship and the victim’s happiness, this research reveals how the language of this financially and emotionally devastating crime involves grooming strategies akin to coercive control and domestic violence and abuse and exposes the inaccuracies of popular narratives surrounding victims and in awareness-raising and crime prevention strategies.
Sewage as a Possible Transmission Vehicle During a Coronavirus Disease 2019 Outbreak in a Densely Populated Community: Guangzhou, China, April 2020
Authors: Yuan Jun , Chen Zongqiu , Gong Chenghua , Liu Hui , Li Baisheng , Li Kuibiao , Chen Xi , Xu Conghui , Jing Qinlong , Liu Guocong , Qin Pengzhe , Liu Yufei , Zhong Yi , Huang Lijuan , Zhu Bao-Ping , Yang Zhicong
Published: October 2020

Background

Sewage transmission of SARS-CoV-2 has never been demonstrated. During a COVID-19 outbreak in Guangzhou, China in April 2020, we investigated the mode of transmission.

Methods

We collected clinical and environmental samples from quarantined residents and their environment for RT-PCR testing and genome sequencing. A case was a resident with a positive RT-PCR test regardless of symptoms. We conducted a retrospective cohort study of all residents of cases’ buildings to identify risk factors.

Results

We found 8 cases (onset: 5–21 April). During incubation period, cases 1 and 2 frequented market T where a COVID-19 outbreak was ongoing; cases 3–8 never visited market T, lived in separate buildings and never interacted with cases 1 and 2. Working as a janitor or wastepicker (RR = 13; 95% CIexact, 2.3–180), not changing to clean shoes (RR = 7.4; 95% CIexact, 1.8–34) and handling dirty shoes by hand (RR = 6.3; 95% CIexact, 1.4–30) after returning home were significant risk factors. RT-PCR detected SARS-CoV-2 in 19% of 63 samples from sewage puddles or pipes, and 24% of 50 environmental samples from cases’ apartments. Viruses from the squat toilet and shoe-bottom dirt inside the apartment of cases 1 and 2 were homologous with those from cases 3–8 and the sewage. Sewage from the apartment of cases 1 and 2 leaked out of a cracked pipe onto streets. Rainfall after the onset of cases 1 and 2 flooded the streets.

Conclusions

SARS-CoV-2 might spread by sewage, highlighting the importance of sewage management during outbreaks.
Differential Effects of AIDS and Chronic Human Immunodeficiency Virus Infection on Gray Matter Volume
Authors: O’Connor Erin E , Zeffiro Thomas A , Lopez Oscar L , Becker James T
Published: October 2020

Background

Age, human immunodeficiency virus (HIV) infection, illicit drug use, and central nervous system (CNS) opportunistic infections can affect brain structure, with the striatum being particularly sensitive to HIV effects. Nevertheless, the impact of non-CNS AIDS-defining illness (ADI) on brain structure has been less investigated. We examined ADI and HIV effects on brain volume.

Methods

In a cross-sectional study, including 95 virally suppressed seropositive and 84 demographically matched, seronegative participants, we examined serostatus and ADI effects. Cortical and subcortical gray matter volume (GMV) regions of interest were estimated with computational neuroanatomy techniques applied to high-resolution, T1-weighted magnetic resonance imaging data. Linear regression was used to model HIV serostatus and ADI effects on global and regional GMV, adjusting for age, sex, CD4 nadir, drug use, and total intracranial volume.

Results

While HIV serostatus was associated with lower striatal volume (B = −.59 [95% confidence interval {CI}, −1.08 to −.10]), co-occurring ADI was independently associated with lower striatal volume (B = −.73 [95% CI, −1.36 to −.09]). ADI was also associated with lower global (B = −19.35 [95% CI, −32.42 to −6.29]) and regional GMV.

Conclusions

While HIV infection is associated with a localized effect on striatal structure, having a prior ADI is a strong predictor of smaller global and regional GMV. The lack of interaction between HIV serostatus or ADI with age suggests that chronic HIV infection and ADI have independent effects on brain structure, without associated accelerated lower volume with age. ADI history should be incorporated into statistical adjustments in HIV neuroimaging analysis. These findings also lend support to current HIV treatment guidelines urging prompt antiretroviral therapy initiation after HIV diagnosis.
The Household Secondary Attack Rate of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): A Rapid Review
Authors: Fung Hannah F , Martinez Leonardo , Alarid-Escudero Fernando , Salomon Joshua A , Studdert David M , Andrews Jason R , Goldhaber-Fiebert Jeremy D ,   Stanford-CIDE Coronavirus Simulation Model (SC-COSMO) Modeling Group, Chin Elizabeth T , Claypool Anneke L , Fernandez Mariana , Gracia Valeria , Luviano Andrea , Rosales Regina Isabel Medina , Reitsma Marissa , Ryckman Theresa
Published: October 2020

Background

Although much of the public health effort to combat coronavirus disease 2019 (COVID-19) has focused on disease control strategies in public settings, transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within households remains an important problem. The nature and determinants of household transmission are poorly understood.

Methods

To address this gap, we gathered and analyzed data from 22 published and prepublished studies from 10 countries (20 291 household contacts) that were available through 2 September 2020. Our goal was to combine estimates of the SARS-CoV-2 household secondary attack rate (SAR) and to explore variation in estimates of the household SAR.

Results

The overall pooled random-effects estimate of the household SAR was 17.1% (95% confidence interval [CI], 13.7–21.2%). In study-level, random-effects meta-regressions stratified by testing frequency (1 test, 2 tests, >2 tests), SAR estimates were 9.2% (95% CI, 6.7–12.3%), 17.5% (95% CI, 13.9–21.8%), and 21.3% (95% CI, 13.8–31.3%), respectively. Household SARs tended to be higher among older adult contacts and among contacts of symptomatic cases.

Conclusions

These findings suggest that SARs reported using a single follow-up test may be underestimated, and that testing household contacts of COVID-19 cases on multiple occasions may increase the yield for identifying secondary cases.
Lipoprotein(a) and Cardiovascular Disease
Authors: Kamstrup Pia R
Published: October 2020

Background

High lipoprotein(a) concentrations present in 10%–20% of the population have long been linked to increased risk of ischemic cardiovascular disease. It is unclear whether high concentrations represent an unmet medical need. Lipoprotein(a) is currently not a target for treatment to prevent cardiovascular disease.

Content

The present review summarizes evidence of causality for high lipoprotein(a) concentrations gained from large genetic epidemiologic studies and discusses measurements of lipoprotein(a) and future treatment options for high values found in an estimated >1 billion individuals worldwide.

Evidence from mechanistic, observational, and genetic studies support a causal role of lipoprotein(a) in the development of cardiovascular disease, including coronary heart disease and peripheral arterial disease, as well as aortic valve stenosis, and likely also ischemic stroke. Effect sizes are most pronounced for myocardial infarction, peripheral arterial disease, and aortic valve stenosis where high lipoprotein(a) concentrations predict 2- to 3-fold increases in risk. Lipoprotein(a) measurements should be performed using well-validated assays with traceability to a recognized calibrator to ensure common cut-offs for high concentrations and risk assessment. Randomized cardiovascular outcome trials are needed to provide final evidence of causality and to assess the potential clinical benefit of novel, potent lipoprotein(a) lowering therapies.
Privacy-Aware Image Authentication from Cryptographic Primitives
Authors: Chen Haixia , Huang Xinyi , Wu Wei , Mu Yi
Published: October 2020

Image authentication is the process of verifying image origin, integrity and authenticity. In many situations, image authentication should allow reasonable image editing, which does not introduce any wrong information against the original one. While it has been studied both extensively and intensively with considerable efforts, there is no satisfactory method supporting region extraction. This paper presents a solution to address the issue of privacy protection in authenticated images. Our scheme allows anyone to extract sub-image blocks from an original image (authenticated by the image producer) and generate a proof tag to prove the credibility of the extracted image blocks. The process of proof tag generation does not require any interaction with the image producer. In addition, the image producer is able to define must-be-preserved image blocks (e.g. producer logo) during the extraction. We define the security property for the authenticated sub-images and give a generic design with two core primitives: an ordinary digital signature scheme and a cryptographic accumulator. The security of our design can be reduced to the underlying cryptographic primitives and its practical performance is demonstrated by a bunch of evaluations. We believe the proposed design, together with other image authentication methods, will further facilitate image relevant services and applications.
An Anti-migration Self-expandable and Removable Metal Stent for Crohn’s Disease Strictures: A Nationwide Study From GETAID and SFED
Authors: Attar Alain , Branche Julien , Coron Emmanuel , Privat Jocelyn , Caillo Ludovic , Chevaux Jean-Baptiste , Vuitton Lucine , Amiot Aurélien , Belkhodja Hichem , Dray Xavier , Ponchon Thierry , Bouhnik Yoram , Baumann Cédric , Peyrin-Biroulet Laurent
Published: October 2020

Background and Aims

In Crohn’s disease, strictures are frequent and may require surgical resection or endoscopic balloon dilation. An anti-migration, removable and shaped self-expandable metal stent is available. We evaluated its effectiveness and safety in a real-life setting.

Methods

All centres were asked to collect retrospectively or prospectively all data on patients who had a stent for a stricture. The anti-migration stent [Hanarostent HRC-20-080-230—MITech, Seoul, South Korea] was maintained 7 days before its extraction during a second colonoscopy. Short- and long-term efficacy and safety outcomes were evaluated.

Results

A total of 46 patients were enrolled. Strictures were anastomotic in 73.9% of cases. The median length of the stricture evaluated by cross-sectional imaging and during colonoscopy was 3.1 ± 1.7 and 2.7 ± 1.4 cm, respectively. Immediate success [no obstructive symptom at Day 30] was reported in 93.5% of cases (95% confidence interval [CI] = [86.3; 99.9]). Sixteen patients needed a new balloon dilation [n = 8] or surgery [n = 8]. The overall success rate [obstruction-free without any intervention] was 58.7% [n = 27] after a median follow-up of 26 months [8–41 months]. No perforation occurred and three migrations were observed [6.5%]. Perianal disease (hazard ratio [HR] = 0.1 [0.02; 0.58]) and discontinuation of an immunosuppressant (0.12 [0.02; 0.86]), were associated with a lower probability of success, whereas performing imaging (HR = 5.3 [1.2; 23.5]) before stent placement was associated with success.

Conclusions

The anti-migration stent is safe and effective in about half of patients, with no perforation reported in this study, and has an extremely low migration rate.
Study design, result posting, and publication of late-stage cardiovascular trials
Authors: Kapelios Chris J , Naci Huseyin , Vardas Panos E , Mossialos Elias
Published: October 2020

Aims

Pre-registration of study protocols in accessible databases is required for publication of study results in high-impact medical journals. Nonetheless, data on characteristics of clinical trials registered in these databases and their outcome, in terms of result reporting and publication are limited.

Methods and results

We searched for interventional, late-phase cardiovascular disease (CVD) studies in adults registered in Clinicaltrials.gov. first posted after 1 January 2013 and completed up to 31 December 2018. Data on study design, result reporting, and publication were collected, and potential associations with a pre-defined set of explanatory factors were examined. In total, 250 CVD trials were included in the analysis. Of these, 193 (77.2%) were randomized studies, 99 (39.6%) open label designs, and 126 (50.4%) had industry as main sponsor. One hundred and seventy-nine trials (71.6%) evaluated the effect of drugs and 27 (10.8%) evaluated devices. The most common primary outcomes were non-clinical endpoints (76.0%), with only 17% of studies evaluating clinical endpoints. Industry-funded trials focused on patent-protected drugs and devices more often than non-industry-funded trials (72.0% vs. 30.6%, P < 0.001 and 55.0% vs. 26.3%, P = 0.033, respectively). Sixty-three studies (25.2%) had results posted on clinicaltrials.gov, and 116 (46.4%) had results published in the scientific literature. In multivariate analysis, industry sponsorship was statistically significantly associated with results posting [odds ratio (OR): 3.38; 95% confidence interval (CI): 1.56–7.30, P = 0.002] and publication (OR: 0.41; 95% CI: 0.23–0.75, P = 0.004).

Conclusion

Among late-stage cardiovascular trials only one-fourth had results posted on clinicaltrials.gov and <50% had results published. Industry sponsors were more likely to invest in research on patent-protected drugs and devices than were non-industry sponsors. Industry-sponsored studies were more likely to have their results posted, but less likely to have their results published in the scientific literature.
Walking Back Human Rights in Europe?
Authors: Helfer Laurence R , Voeten Erik
Published: October 2020

Judges and scholars have long debated whether the European Court of Human Rights (the ECtHR or the Court) can only expand, never diminish, human rights protections in Europe. Recent studies have found that political backlashes and national-level restrictions have influenced ECtHR case law. However, analysing whether the ECtHR is shifting in a regressive direction faces an empirical challenge: How can we observe whether the Court is limiting rights over time if it has never expressly overturned a prior judgment in a way that favours the government? We gain traction on this question by analysing all separate and minority opinions of the ECtHR Grand Chamber between 1998 and 2018. We focus on opinions asserting that the Grand Chamber has tacitly overturned prior rulings or settled doctrine in a way that favours the respondent state, which we label as ‘walking back dissents’. We find that walking back dissents have become significantly more common in the last decade, revealing that some members of the ECtHR themselves believe that the Grand Chamber is increasingly overturning prior judgments in a regressive direction.
Clonal haematopoiesis in chronic ischaemic heart failure: prognostic role of clone size for DNMT3A- and TET2-driver gene mutations
Authors: Assmus Birgit , Cremer Sebastian , Kirschbaum Klara , Culmann David , Kiefer Katharina , Dorsheimer Lena , Rasper Tina , Abou-El-Ardat Khalil , Herrmann Eva , Berkowitsch Alexander , Hoffmann Jedrzej , Seeger Florian , Mas-Peiro Silvia , Rieger Michael A , Dimmeler Stefanie , Zeiher Andreas M
Published: October 2020

Aims

Somatic mutations of the epigenetic regulators DNMT3A and TET2 causing clonal expansion of haematopoietic cells (clonal haematopoiesis; CH) were shown to be associated with poor prognosis in chronic ischaemic heart failure (CHF). The aim of our analysis was to define a threshold of variant allele frequency (VAF) for the prognostic significance of CH in CHF.

Methods and results

We analysed bone marrow and peripheral blood-derived cells from 419 patients with CHF by error-corrected amplicon sequencing. Cut-off VAFs were optimized by maximizing sensitivity plus specificity from a time-dependent receiver operating characteristic (ROC) curve analysis from censored data. 56.2% of patients were carriers of a DNMT3A- (N = 173) or a TET2- (N = 113) mutation with a VAF >0.5%, with 59 patients harbouring mutations in both genes. Survival ROC analyses revealed an optimized cut-off value of 0.73% for TET2- and 1.15% for DNMT3A-CH-driver mutations. Five-year-mortality was 18% in patients without any detected DNMT3A- or TET2 mutation (VAF < 0.5%), 29% with only one DNMT3A- or TET2-CH-driver mutations above the respective cut-off level and 42% in patients harbouring both DNMT3A- and TET2-CH-driver mutations above the respective cut-off levels. In carriers of a DNMT3A mutation with VAF ≥ 1.15%, 5-year mortality was 31%, compared with 18% mortality in those with VAF < 1.15% (P = 0.048). Likewise, in patients with TET2 mutations, 5-year mortality was 32% with VAF ≥ 0.73%, compared with 19% mortality with VAF < 0.73% (P = 0.029).

Conclusion

The present study defines novel threshold levels for clone size caused by acquired somatic mutations in the CH-driver genes DNMT3A and TET2 that are associated with worse outcome in patients with CHF.
DNA cytosine methyltransferase enhances viability during prolonged stationary phase in Escherichia coli
Authors: Militello Kevin T , Finnerty-Haggerty Lara , Kambhampati Ooha , Huss Rebecca , Knapp Rachel
Published: October 2020

In Escherichia coli, DNA cytosine methyltransferase (Dcm) methylates the second cytosine in the sequence 5′CCWGG3′ generating 5-methylcytosine. Dcm is not associated with a cognate restriction enzyme, suggesting Dcm impacts facets of bacterial physiology outside of restriction-modification systems. Other than gene expression changes, there are few phenotypes that have been identified in strains with natural or engineered Dcm loss, and thus Dcm function has remained an enigma. Herein, we demonstrate that Dcm does not impact bacterial growth under optimal and selected stress conditions. However, Dcm does impact viability in long-term stationary phase competition experiments. Dcm+ cells outcompete cells lacking dcm under different conditions. Dcm knockout cells have more RpoS-dependent HPII catalase activity than wild-type cells. Thus, the impact of Dcm on stationary phase may involve changes in RpoS activity. Overall, our data reveal a new role for Dcm during long-term stationary phase.
Schizosaccharomyces pombe Ppr10 is required for mitochondrial translation
Authors: Liu Zecheng , Li Yan , Xie Wanqiu , Huang Ying
Published: October 2020

The mitochondrial genome encodes key components of the oxidative phosphorylation (OXPHOS) system, whose expression is essential for mitochondrial functions. We have previously shown that deletion of the Schizosaccharomyces pombe ppr10 encoding a pentatricopeptide repeat protein severely reduces the mature levels of intron-containing mitochondrial transcripts cox1 and cob1, and severely impairs mitochondrial translation. In this study, we examined the possibility that the reduced levels of Cox1 and Cob1 proteins in cells were due to lowered levels of cox1 and cob1 mRNAs. We found that deletion of ppr10 did not affect the levels of mature cox1 and cob1 mRNAs in a mitochondrial intronless background. However, synthesis of Cox1 and Cob1 proteins were still severely affected by deletion of ppr10 in a mitochondrial intronless background. Consistent with this, we found that deletion of mitochondrial introns could not rescue the respiratory growth defect of Δppr10 cells. Our results reveal that Ppr10 is not required for the stability of cox1 and cob1 mRNAs, and provide further support for the idea that Ppr10 plays a critical role in mitochondrial translation.
The Interconnections Between Somatic and Ovarian Aging in Murine Models
Authors: Schneider Augusto , Saccon Tatiana D , Garcia Driele N , Zanini Bianka M , Isola José V V , Hense Jéssica D , Alvarado-Rincón Joao A , Cavalcante Marcelo B , Mason Jeffrey B , Stout Michael B , Bartke Andrzej , Masternak Michal M
Published: October 2020

The mammalian female is born with a limited ovarian reserve of primordial follicles. These primordial follicles are slowly activated throughout the reproductive lifecycle, thereby determining lifecycle length. Once primordial follicles are exhausted, women undergo menopause, which is associated with several metabolic perturbations and a higher mortality risk. Long before exhaustion of the reserve, females experience severe declines in fertility and health. As such, significant efforts have been made to unravel the mechanisms that promote ovarian aging and insufficiency. In this review, we explain how long-living murine models can provide insights in the regulation of ovarian aging. There is now overwhelming evidence that most life-span–extending strategies, and long-living mutant models simultaneously delay ovarian aging. Therefore, it appears that the same mechanisms that regulate somatic aging may also be modulating ovarian aging and germ cell exhaustion. We explore several potential contributing mechanisms including insulin resistance, inflammation, and DNA damage—all of which are hallmarks of cellular aging throughout the body including the ovary. These findings are in alignment with the disposable soma theory of aging, which dictates a trade-off between growth, reproduction, and DNA repair. Therefore, delaying ovarian aging will not only increase the fertility window of middle age females, but may also actively prevent menopausal-related decline in systemic health parameters, compressing the period of morbidity in mid-to-late life in females.
The Association Between Dietary Pattern Adherence, Cognitive Stimulating Lifestyle, and Cognitive Function Among Older Adults From the Quebec Longitudinal Study on Nutrition and Successful Aging
Authors: Parrott Matthew D , Carmichael Pierre-Hugues , Laurin Danielle , Greenwood Carol E , Anderson Nicole D , Ferland Guylaine , Gaudreau Pierrette , Belleville Sylvie , Morais José A , Kergoat Marie-Jeanne , Fiocco Alexandra J
Published: October 2020

Objectives

This study examined the effect of dietary patterns and engagement in cognitive stimulating lifestyle (CSL) behaviors on the trajectory of global cognition, executive function (EF), and verbal episodic memory (VEM).

Methods

Western and prudent dietary patterns were empirically derived using food frequency questionnaire responses from 350 community-dwelling older adults (mean age: 73.7 years) participating in the Quebec Longitudinal Study on Nutrition and Successful Aging. CSL was represented by a binary composite indicator based on education, occupational complexity, and social engagement. Global cognition, EF, and VEM were assessed prospectively.

Results

Primary effect models revealed an association between higher Western dietary pattern score and a greater rate of decline in global cognition and EF. Higher Western dietary pattern adherence was also associated with poorer baseline VEM. Primary effect models also revealed that CSL was independently associated with baseline global cognition and EF. Effect modification models suggested an interactive effect between Western dietary pattern and CLS on global cognition only. No associations were found for prudent dietary pattern score.

Discussion

Contributing to existing research supporting the negative impact of consuming an unhealthy diet on cognitive function, the current study suggests increased vulnerability among older adults who do not engage in a CSL. These findings can inform the development of lifestyle intervention programs that target brain health in later adulthood.
Shallow slip of blind fault associated with the 2019Ms 6.0 Changning earthquake in fold-and-thrust belt in salt mines of Southeast Sichuan, China
Authors: Yang Ying-Hui , Hu Jyr-Ching , Chen Qiang , Lei Xinglin , Zhao Jingjing , Li Weile , Xu Rui , Chiu Chun-Ying
Published: October 2020

An earthquake with a magnitude of Ms 6.0 and shallow focal depth of ∼4 km struck the Changning county, Sichuan province, China on 2019 June 17. The hypocentre is located in the fold-and-thrust belt with plentiful shale gas and salt mine resources. One hypothesis is that the shallow fault could be affected by the artificial pressure water injection including the disposal of wastewater, fracking shale gas extraction and salt mining in Changning area. In this study, SAR (Synthetic Aperture Radar) images, historical earthquakes, aftershocks and seismic reflection data were collected to jointly investigate the characteristics of the 2019 Changning earthquake. The source model inferred from the InSAR coseismic deformation observation reveals that the 2019 Changning earthquake is attributed to a blind fault dipping to southwest with dominant thrust and sinistral strike slip. Moreover, a small shallow fault developing within the Changning anticline was triggered by the main shock, which contributed to the surface displacements as observed in the north of the epicentre. The estimated maximum slip of 0.49 m is located at the depth of ∼1.9 km, ∼9 km northwest of the epicentre. The Coulomb failure stress change caused by the previous two large earthquakes, which occurred in the hydraulic fracturing area, suggesting that they have little effect on the initial rupture of the 2019 Changning earthquake. Despite this, they have a positive triggering effect on the fault rupture in the northwest of the seismogenic fault. In addition, the analysis on the relation between the positive Coulomb failure stress change and the aftershocks suggests that the aftershocks may have different motion patterns from the main shock. The analysis also shows the earthquakes occurrence in the seismogenic zone may be affected by the high pore pressure due to the long-term injection of salt mining for more than three decades.
Insights from ancient DNA analysis of Egyptian human mummies: clues to disease and kinship
Authors: Gad Yehia Z , Hassan Naglaa Abu-Mandil , Mousa Dalia M , Fouad Fayrouz A , El-Sayed Safaa G , Abdelazeem Marwa A , Mahdy Samah M , Othman Hend Y , Ibrahim Dina W , Khairat Rabab , Ismail Somaia
Published: October 2020

The molecular Egyptology field started in the mid-eighties with the first publication on the ancient DNA (aDNA) analysis of an Egyptian mummy. Egypt has been a major interest for historians, archeologists, laymen as well as scientists. The aDNA research on Egyptian biological remains has been fueled by their abundance and relatively well-preserved states through artificial mummification and by the advanced analytical techniques. Early doubts of aDNA integrity within the Egyptian mummies and data authenticity were later abated with studies proving successfully authenticated aDNA retrieval. The current review tries to recapitulate the published studies presenting paleogenomic evidence of disease diagnosis and kinship establishment for the Egyptian human remains.

Regarding disease diagnosis, the prevailing literature was on paleogenomic evidence of infectious diseases in the human remains. A series of reports presented evidence for the presence of tuberculosis and/or malaria. In addition, there were solitary reports of the presence of leprosy, diphtheria, bacteremia, toxoplasmosis, schistosomiasis and leishmaniasis. On the contrary, paleogenomic evidence of the presence of rare diseases was quite scarce and mentioned only in two articles.

On the other hand, kinship analysis of Egyptian human remains, including that of Tutankhamen, was done using both mitochondrial DNA sequences and nuclear DNA markers, to establish family relationships in four studies.

It is clear that the field of molecular Egyptology is still a largely unexplored territory. Nevertheless, the paleogenomic investigation of Egyptian remains could make significant contributions to biomedical sciences (e.g. elucidation of coevolution of human host–microbe interrelationship) as well as to evidence-based archeology.
The legal supremacy of legislative initiatives in judicial proceedings: The Israeli lesson
Authors: Yosef Bell E
Published: October 2020

This article reveals an evolving judicial doctrine, in which the Supreme Court of Israel postpones, removes, dismisses, or even dismisses in limine petitions, due to the mere existence of legislative initiative with respect to the petition’s issue. The article analyzes the way the Court uses the doctrine, and offers a normative analysis of this phenomenon. The main argument is that the judicial use of the doctrine leads to deprivation of the petitioners’ rights, gives (too) much power to the state legal counsels, leans on uncertain and unforeseeable situations, and damages the fundamental principle of the rule of law. On the other hand, the judicial use of the doctrine promotes and enhances constitutional dialogue, as well as preserving judicial resources (and judicial legitimacy in particular) and the professionality of the legislation. Henceforth, the article also introduces an effort to balance between the doctrine different consequences, by presenting a set of criteria for a more reasoned, coherent, and analytical use of that doctrine.
The Scope of Investors’ Legitimate Expectations under the FET Standard in the European Renewable Energy Cases
Authors: Biggs Jack
Published: October 2020

In the 2000s, several European states sought to increase foreign investment in their renewable energy sectors. Those governments later wound back those financial incentives. This resulted in dozens of investment disputes. One of the key issues in those disputes was whether the decision to amend or withdraw financial incentives breached investors' legitimate expectations under the fair and equitable treatment standard. This article argues that investors' legitimate expectations should operate analogously to the concept of estoppel. Therefore, if a state makes a clear commitment to induce investment (this includes commitments in legislation), and an investor reasonably relies on that commitment, then the state should not be able to renege on that commitment without generating liability for breaching the fair and equitable treatment standard.