bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trends in the incidence and management of hypoxic-ischaemic encephalopathy in the therapeutic hypothermia era: a national population study
Authors: Shipley Lara , Gale Chris , Sharkey Don 
Published: March 2021

ObjectiveHypoxic-ischaemic encephalopathy (HIE) remains a leading cause of neonatal mortality and neurodisability. We aimed to determine the incidence of HIE and management patterns against national guidelines.DesignRetrospective cohort study using the National Neonatal Research Database.SettingNeonatal units in England and Wales.PatientsInfants 34–42 weeks gestational age (GA) with a recorded diagnosis of HIE.Main outcomesIncidence of HIE, mortality and treatment with therapeutic hypothermia (TH) were the main outcomes. Temporal changes were compared across two epochs (2011–2013 and 2014–2016).ResultsAmong 407 462 infants admitted for neonatal care, 12 195 were diagnosed with HIE. 8166 infants ≥36 weeks GA had moderate/severe HIE, 62.1% (n=5069) underwent TH and mortality was 9.3% (n=762). Of infants with mild HIE (n=3394), 30.3% (n=1027) underwent TH and 6 died. In late preterm infants (34–35 weeks GA) with HIE (n=635, 5.2%), 33.1% (n=210) received TH and 13.1% (n=83) died. Between epochs (2011–2013 vs 2014–2016), mortality decreased for infants ≥36 weeks GA with moderate/severe HIE (17.5% vs 12.3%; OR 0.69, 95% CI 0.59 to 0.81, p<0.001). Treatment with TH increased significantly between epochs in infants with mild HIE (24.9% vs 35.8%, p<0.001) and those born late preterm (34.3% vs 46.6%, p=0.002).ConclusionsMortality of infants ≥36 weeks GA with moderate/severe HIE has reduced over time, although many infants diagnosed with moderate/severe HIE do not undergo TH. Increasingly, mild HIE and late preterm infants with HIE are undergoing TH, where the evidence base is lacking, highlighting the need for prospective studies to evaluate safety and efficacy in these populations.
Association between preconception maternal stress and offspring birth weight: findings from an Australian longitudinal data linkage study
Authors: Harris Melissa L , Hure Alexis J , Holliday Elizabeth , Chojenta Catherine , Anderson Amy E , Loxton Deborah 
Published: March 2021

ObjectiveExamine the relationship between preconception stress and offspring birth weight.SettingPopulation-based cohort study linked with state-based administrative perinatal data.Participants6100 births from 3622 women from the 1973–1978 cohort of the Australian Longitudinal Study of Women’s Health who (1) recorded a singleton birth between January 1997 and December 2011; (2) returned at least one follow-up survey within 3 years of conception; and (3) had complete data on perceived stress prior to conception.Primary outcome measuresLinear generalised estimating equations were used to examine the relationship between preconception stress and a continuous measure of birth weight, exploring differences based on birth order and stress chronicity. The minimal sufficient adjustment set of covariates was determined by a directed acyclic graph.ResultsFor all births, there was no relationship between moderate/high acute or chronic stress and offspring birth weight in grams. Among first births only, there was a trend towards a relationship between moderate/high chronic stress and offspring birth weight. Offspring sex was associated with birth weight in all models, with female babies born lighter than male babies on average, after adjusting for covariates (p<0.0001).ConclusionsEffects of preconception stress on birth weight was largely driven by time to conception. With the timing of stress critical to its impact on obstetrical outcomes, preconception care should involve not only reproductive life planning but the space to provide interventions at critical periods so that optimal outcomes are achieved.
Clinicians’ heuristic assessments of radiographs compared with Kellgren-Lawrence and Ahlbäck ordinal grading: an exploratory study of knee radiographs using paired comparisons
Authors: Pedersen Mads Møller , Geoffroy Mongelard Kristian Breds , Mørup-Petersen Anne , Bang Christensen Karl , Odgaard Anders 
Published: March 2021

ObjectivesOrdinal scales provide means for communicating the severity of a condition, but they are affected by cognitive biases, they introduce statistical problems and they sacrifice resolution. Clinicians discern more details than contained in scales, for example, when assessing radiographs, but clinicians’ distinctions are often based on experience-based rules of thumb, that is, heuristics. The objectives of this study are to compare clinicians’ heuristic assessments to ordinal grading, to identify case elements that influence clinicians’ judgements and to present a method for quantifying heuristic assessments.DesignClinicians were presented with 17 207 random pairs from a set of 1087 knee radiographs. For each pair, the radiograph with more severe osteoarthritis was selected. The Bradley-Terry model was used to calculate an osteoarthritis strength parameter for each radiograph. Similarly, strength parameters were determined for 12 morphological features with five additional features being considered either present or absent. All radiographs were also graded according to conventional ordinal systems (Kellgren-Lawrence and Ahlbäck). Relations between clinicians’ judgements and (1) the heuristics-based osteoarthritis strength, (2) conventional ordinal systems and (3) morphological features were investigated.ResultsReceiver operating characteristic analysis showed that the Bradley-Terry model provided a good description of clinicians’ assessments (area under the curve (AUC)=0.97, 95% CI 0.968 to 0.972). Morphological features (AUC=0.90, 95% CI 0.900 to 0.908) provided a superior description of clinicians’ choices compared with conventional ordinal systems (AUC=0.88, 95% CI 0.878 to 0.887 and AUC=0.80, 95% CI 0.796 to 0.809) for Ahlbäck and Kellgren-Lawrence, respectively). The features most strongly associated with osteoarthritis strength were medial joint space width, flattening of the medial femoral and tibial condyles, medial osteophytes and alignment.ConclusionsHeuristics-based assessments give a better distinction than conventional grading systems of knee osteoarthritis. The example presents a general approach to evaluate which features are part of experts’ heuristics. The data suggest that experts discern more details than included in conventional ordinal grading systems. Quantitative heuristic assessments may replace ordinal scales.
Modelling COVID-19 transmission in Africa: countrywise projections of total and severe infections under different lockdown scenarios
Authors: Frost Isabel , Craig Jessica , Osena Gilbert , Hauck Stephanie , Kalanxhi Erta , Schueller Emily , Gatalo Oliver , Yang Yupeng , Tseng Katie K , Lin Gary , Klein Eili 
Published: March 2021

ObjectivesAs of 13 January 2021, there have been 3 113 963 confirmed cases of SARS-CoV-2 and 74 619 deaths across the African continent. Despite relatively lower numbers of cases initially, many African countries are now experiencing an exponential increase in case numbers. Estimates of the progression of disease and potential impact of different interventions are needed to inform policymaking decisions. Herein, we model the possible trajectory of SARS-CoV-2 in 52 African countries under different intervention scenarios.DesignWe developed a compartmental model of SARS-CoV-2 transmission to estimate the COVID-19 case burden for all African countries while considering four scenarios: no intervention, moderate lockdown, hard lockdown and hard lockdown with continued restrictions once lockdown is lifted. We further analysed the potential impact of COVID-19 on vulnerable populations affected by HIV/AIDS and tuberculosis (TB).ResultsIn the absence of an intervention, the most populous countries had the highest peaks in active projected number of infections with Nigeria having an estimated 645 081 severe infections. The scenario with a hard lockdown and continued post-lockdown interventions to reduce transmission was the most efficacious strategy for delaying the time to the peak and reducing the number of cases. In South Africa, projected peak severe infections increase from 162 977 to 2 03 261, when vulnerable populations with HIV/AIDS and TB are included in the analysis.ConclusionThe COVID-19 pandemic is rapidly spreading across the African continent. Estimates of the potential impact of interventions and burden of disease are essential for policymakers to make evidence-based decisions on the distribution of limited resources and to balance the economic costs of interventions with the potential for saving lives.
Atorvastatin is unlikely to prevent rheumatoid arthritis in high risk individuals: results from the prematurely stopped STAtins to Prevent Rheumatoid Arthritis (STAPRA) trial
Authors: van Boheemen Laurette , Turk Samina , Beers-Tas Marian van , Bos Wouter , Marsman Diane , Griep Ed N , Starmans-Kool Mirian , Popa Calin D , van Sijl Alper , Boers Maarten , Nurmohamed Michael T , van Schaardenburg Dirkjan 
Published: March 2021

ObjectivesPersons at high risk of rheumatoid arthritis (RA) might benefit from a low-risk pharmacological intervention aimed at primary prevention. Previous studies demonstrated disease-modifying effects of statins in patients with RA as well as an association between statin use and a decreased risk of RA development. A randomised, double-blind, placebo-controlled trial investigated whether atorvastatin could prevent arthritis development in high-risk individuals.MethodsArthralgia patients with anticitrullinated protein antibody (ACPA) >3 xULN or ACPA and rheumatoid factor, without (a history of) arthritis, were randomised to receive atorvastatin 40 mg daily or placebo for 3 years. The calculated sample size was 220 participants. The primary endpoint was clinical arthritis. Cox regression analysis was used to determine the effect of atorvastatin on arthritis development.ResultsDue to a low inclusion rate, mainly because of an unwillingness to participate, the trial was prematurely stopped. Data of the 62 randomised individuals were analysed. Median follow-up was 14 (inner quartiles 6–35) months. Fifteen individuals (24%) developed arthritis: 9/31 (29%) in the atorvastatin group; 6/31 (19%) in the placebo group: HR 1.40, 95% CI 0.50 to 3.95.ConclusionsIn this small set of randomised high-risk individuals, we did not demonstrate a protective effect of atorvastatin on arthritis development. The main reason for the low inclusion was unwillingness to participate; this may also impede other RA prevention trials. Further research to investigate and solve barriers for prevention trial participation is needed.
Modelling the effect of ribosome mobility on the rate of protein synthesis
Authors: Dauloudet Olivier , Neri Izaak , Walter Jean-Charles , Dorignac Jérôme , Geniet Frédéric , Parmeggiani Andrea 
Published: March 2021

AbstractTranslation is one of the main steps in the synthesis of proteins. It consists of ribosomes that translate sequences of nucleotides encoded on mRNA into polypeptide sequences of amino acids. Ribosomes bound to mRNA move unidirectionally, while unbound ribosomes diffuse in the cytoplasm. It has been hypothesized that finite diffusion of ribosomes plays an important role in ribosome recycling and that mRNA circularization enhances the efficiency of translation, see e.g. Lodish et al. (Molecular cell biology, 8th edn, W.H. Freeman and Company, San Francisco, 2016). In order to estimate the effect of cytoplasmic diffusion on the rate of translation, we consider a totally asymmetric simple exclusion process coupled to a finite diffusive reservoir, which we call the ribosome transport model with diffusion. In this model, we derive an analytical expression for the rate of protein synthesis as a function of the diffusion constant of ribosomes, which is corroborated with results from continuous-time Monte Carlo simulations. Using a wide range of biological relevant parameters, we conclude that diffusion is not a rate limiting factor in translation initiation because diffusion is fast enough in biological cells.Graphic abstract
Flagellar arrangements in elongated peritrichous bacteria: bundle formation and swimming properties
Authors: Clopés Judit , Winkler Roland G. 
Published: March 2021

Abstract
The surface distribution of flagella in peritrichous bacterial cells has been traditionally assumed to be random. Recently, the presence of a regular grid-like pattern of basal bodies has been suggested. Experimentally, the manipulation of the anchoring points of flagella in the cell membrane is difficult, and thus, elucidation of the consequences of a particular pattern on bacterial locomotion is challenging. We analyze the bundle formation process and swimming properties of Bacillus subtilis-like cells considering random, helical, and ring-like arrangements of flagella by means of mesoscale hydrodynamics simulations. Helical and ring patterns preferentially yield configurations with a single bundle, whereas configurations with no clear bundles are most likely for random anchoring. For any type of pattern, there is an almost equally low probability to form V-shaped bundle configurations with at least two bundles. Variation of the flagellum length yields a clear preference for a single major bundle in helical and ring patterns as soon as the flagellum length exceeds the body length. The average swimming speed of cells with a single or two bundles is rather similar, and approximately $$50\%$$

50
%

larger than that of cells of other types of flagellar organization. Considering the various anchoring patterns, rings yield the smallest average swimming speed independent of the type of bundle, followed by helical arrangements, and largest speeds are observed for random anchoring. Hence, a regular pattern provides no advantage in terms of swimming speed compared to random anchoring of flagella, but yields more likely single-bundle configurations.

Graphic abstract
CiliaQ: a simple, open-source software for automated quantification of ciliary morphology and fluorescence in 2D, 3D, and 4D images
Authors: Hansen Jan Niklas , Rassmann Sebastian , Stüven Birthe , Jurisch-Yaksi Nathalie , Wachten Dagmar 
Published: March 2021

AbstractCilia are hair-like membrane protrusions that emanate from the surface of most vertebrate cells and are classified into motile and primary cilia. Motile cilia move fluid flow or propel cells, while also fulfill sensory functions. Primary cilia are immotile and act as a cellular antenna, translating environmental cues into cellular responses. Ciliary dysfunction leads to severe diseases, commonly termed ciliopathies. The molecular details underlying ciliopathies and ciliary function are, however, not well understood. Since cilia are small subcellular compartments, imaging-based approaches have been used to study them. However, tools to comprehensively analyze images are lacking. Automatic analysis approaches require commercial software and are limited to 2D analysis and only a few parameters. The widely used manual analysis approaches are time consuming, user-biased, and difficult to compare. Here, we present CiliaQ, a package of open-source, freely available, and easy-to-use ImageJ plugins. CiliaQ allows high-throughput analysis of 2D and 3D, static or time-lapse images from fluorescence microscopy of cilia in cell culture or tissues, and outputs a comprehensive list of parameters for ciliary morphology, length, bending, orientation, and fluorescence intensity, making it broadly applicable. We envision CiliaQ as a resource and platform for reproducible and comprehensive analysis of ciliary function in health and disease.Graphic abstract
Combined Inhibition of p38MAPK and PIKfyve Synergistically Disrupts Autophagy to Selectively Target Cancer Cells
Authors: O'Connell Constandina E. , Vassilev Alex 
Published: March 2021

Abstract

In nutrient-poor conditions, autophagy buffers metabolic stress and counteracts the effects of chemotherapy and radiation on cancer cells, which depend on autophagy for survival. However, clinical trials targeting autophagy have failed to produce successful anticancer treatments using currently available inhibitors. Recent studies have shown that PIKfyve kinase inhibitors disrupt lysosome function in autophagy and can selectively kill certain cancer cells. Analysis of biochemical changes caused by PIKfyve inhibition revealed that resistant cells contain significantly higher levels of cellular p38MAPK protein and phosphorylation. Expression of the lysosomal protein, lysosomal-associated membrane protein 2, carrying phosphomimetic mutations of the p38MAPK phosphorylation sites prevented all effects caused by PIKfyve inhibition–induced lysosome dysfunction. Thus, the activation of p38MAPK in response to PIKfyve inhibition revealed a novel compensatory role in maintaining lysosome function in autophagy. The functional cooperation between the cellular PIKfyve and p38MAPK pathways in regulating lysosome homeostasis was especially important in cancer cells. Combined inhibition of PIKfyve and p38MAPK activities synergistically blocked autophagy-mediated protein degradation, prevented cathepsin maturation, and markedly reduced the viability of multiple cancer cell types without affecting the viability of normal cells. Furthermore, combined PIKfyve and p38MAPK inhibitors synergistically reduced tumor growth in mice bearing xenografts of human colorectal adenocarcinoma, suggesting a novel way to target cancer cells by prolonged inhibition of autophagy using lower drug concentrations.

Significance:
This study demonstrates that PIKfyve and p38MAPK cooperate to regulate lysosome homeostasis and their combined inhibition synergistically blocks autophagy to reduce cancer cell viability in vitro and in vivo.
Response to Standard Therapies and Comprehensive Genomic Analysis for Patients with Lung Adenocarcinoma with EGFR Exon 20 Insertions
Authors: Choudhury Noura J. , Schoenfeld Adam J. , Flynn Jessica , Falcon Christina J. , Rizvi Hira , Rudin Charles M. , Kris Mark G. , Arcila Maria E. , Heller Glenn , Yu Helena A. , Ladanyi Marc , Riely Gregory J. 
Published: March 2021

Abstract

Purpose:
EGFR exon 20 insertions (ex20ins) are an uncommon genotype in non–small cell lung cancer (NSCLC) for which targeted therapies are under development. We sought to describe treatment outcomes and genomic and immunophenotypic characteristics of these tumors.

Experimental Design:
We identified sequential patients with NSCLC with EGFR ex20ins and compared their clinical outcomes and pathologic features with other patients with NSCLC.

Results:
Among 6,290 patients with NSCLC, 106 (2%) had EGFR ex20ins. Patients with EGFR ex20ins were more likely to be Black (14% vs. 6%; P &lt; 0.001) or Asian (22% vs. 10%; P &lt; 0.001) compared with all other patients with NSCLC. Median tumor mutational burden (TMB; 3.5 vs. 5.9; P &lt; 0.001) and proportion of tumors with PD-L1 expression ≥1% (22% vs. 60%; P &lt; 0.001) were lower in EGFR ex20ins compared with other NSCLCs (TMB, n = 5,851 and PD-L1 expression, n = 282) and EGFR del 19/L858R (median TMB, 3.5; P = 0.001 and 39% PD-L1 ≥ 1%; P = 0.02). Compared with a 2:1 cohort of patients with metastatic NSCLC without targetable alterations (n = 192), EGFR ex20ins patients had longer overall survival (median 20 vs. 12 months; HR, 0.56; P = 0.007) and longer time to treatment discontinuation (TTD) for platinum chemotherapy (median, 7 vs. 4 months; HR, 0.6; P = 0.02) and no improvement in TTD for immune checkpoint inhibitors (ICI; HR, 1.75; P = 0.05).

Conclusions:
With better outcomes on platinum chemotherapy, patients with EGFR ex20ins NSCLC have improved prognosis, lower PD-L1 expression and TMB, and derive less benefit from ICIs compared with patients with NSCLC without targetable oncogenes. Improving molecularly targeted therapies could provide greater benefit for patients with EGFR ex20ins.
Linear discriminant analysis and support vector machines for classifying breast cancer
Authors: Rustam Zuherman , Amalia Yasirly , Hartini Sri , Stephani Saragih Glori 
Published: March 2021

<span id="docs-internal-guid-4db59d91-7fff-c659-478a-6dd7456f380f"><span>Breast cancer is an abnormal cell growth in the breast that keeps changed uncontrolled and it forms a tumor. The tumor can be benign or malignant. Benign could not be dangerous to health and cancerous, but malignant could be has a probability dangerous to health and be cancerous. A specialist doctor will diagnose the patient and give treatment based on the diagnosis which is benign or malignant. Machine learning offer times efficiency to determine a cancer cell. The machine will learn the pattern based on the information from the dataset. Support vector machines and linear discriminant analysis are common methods that can be used in the classification of cancer. In this study, both of linear discriminant analysis and support vector machines are compared by looking from accuracy, sensitivity, specificity, and F1-score. We will know which methods are better in classifying breast cancer dataset. The result shows that the support vector machine has better performance than the linear discriminant analysis. It can be seen from the accuracy is 98.77%.</span></span>
Vehicle detection and tracking for traffic management
Authors: Anandhalli Mallikarjun , P. Baligar Vishwanth , Baligar Pavana , Deepsir Pooja , Iti Mithali 
Published: March 2021

<span lang="EN-US">The detection of object with respect to Vehicle and tracking is the most needed step in computer research area as there is wide investment being made form Intelligent Traffic Management. Due to changes in vision or scenes, detection and tracking of vehicle under different drastic conditions has become most challenging process because of the illumination, shadows etc. To overcome this, we propose a method which uses TensorFlow fused with corner points of the vehicles for detection of vehicle and tracking of an vehicle is formulated again, the location of the object which is detected is passed to track the detected object, using the tracking algorithm based on CNN. The proposed algorithm gives result of 90.88% accuracy of detection in video sequences under different conditions of climate.</span>