bluuebunny/crossref_metadata_2025_split huggingface dataset:
Allosteric activation of SARS-CoV-2 RdRp by remdesivir triphosphate and other phosphorylated nucleotides
Authors: Wang Bing , Svetlov Vladimir , Wolf Yuri I , Koonin Eugene V , Nudler Evgeny , Artsimovitch Irina 
Published: January 2021

SUMMARYThe catalytic subunit of SARS-CoV-2 RNA-dependent RNA polymerase (RdRp), Nsp12, has a unique NiRAN domain that transfers nucleoside monophosphates to the Nsp9 protein. The NiRAN and RdRp modules form a dynamic interface distant from their catalytic sites and both activities are essential for viral replication. We report that codon-optimized (for the pause-free translation) Nsp12 exists in inactive state in which NiRAN/RdRp interactions are broken, whereas translation by slow ribosomes and incubation with accessory Nsp7/8 subunits or NTPs partially rescue RdRp activity. Our data show that adenosine and remdesivir triphosphates promote synthesis of A-less RNAs, as does ppGpp, while amino acid substitutions at the NiRAN/RdRp interface augment activation, suggesting that ligand binding to the NiRAN catalytic site modulates RdRp activity. The existence of allosterically-linked nucleotidyl transferase sites that utilize the same substrates has important implications for understanding the mechanism of SARS-CoV-2 replication and design of its inhibitors.HighlightsCodon-optimization of Nsp12 triggers misfolding and activity lossSlow translation, accessory Nsp7 and Nsp8 subunits, and NTPs rescue Nsp12Non-substrate nucleotides activate RNA chain synthesis, likely via NiRAN domainCrosstalk between two Nsp12 active sites that bind the same ligands
Overcoming the impacts of two-step batch effect correction on gene expression estimation and inference
Authors: Li Tenglong , Zhang Yuqing , Patil Prasad , Johnson W. Evan 
Published: January 2021

AbstractNon-ignorable technical variation is commonly observed across data from multiple experimental runs, platforms, or studies. These so-called batch effects can lead to difficulty in merging data from multiple sources, as they can severely bias the outcome of the analysis. Many groups have developed approaches for removing batch effects from data, usually by accommodating batch variables into the analysis (one-step correction) or by preprocessing the data prior to the formal or final analysis (two-step correction). One-step correction is often desirable due it its simplicity, but its flexibility is limited and it can be difficult to include batch variables uniformly when an analysis has multiple stages. Two-step correction allows for richer models of batch mean and variance. However, prior investigation has indicated that two-step correction can lead to incorrect statistical inference in downstream analysis. Generally speaking, two-step approaches introduce a correlation structure in the corrected data, which, if ignored, may lead to either exaggerated or diminished significance in downstream applications such as differential expression analysis. Here, we provide more intuitive and more formal evaluations of the impacts of two-step batch correction compared to existing literature. We demonstrate that the undesired impacts of two-step correction (exaggerated or diminished significance) depend on both the nature of the study design and the batch effects. We also provide strategies for overcoming these negative impacts in downstream analyses using the estimated correlation matrix of the corrected data. We compare the results of our proposed workflow with the results from other published one-step and two-step methods and show that our methods lead to more consistent false discovery controls and power of detection across a variety of batch effect scenarios. Software for our method is available through GitHub (https://github.com/jtleek/sva-devel) and will be available in future versions of the sva R package in the Bioconductor project (https://bioconductor.org/packages/release/bioc/html/sva.html). Batch effect; Two-step batch adjustment; ComBat; Sample correlation adjustment; Generalized least squares
HAR, TAAM and BODD refinements of model crystal structures using Cu Kα and Mo Kα X-ray diffraction data
Authors: Wanat Monika , Malinska Maura , Gutmann Matthias J. , Cooper Richard I. , Wozniak Krzysztof 
Published: January 2021

The Independent Atom Model (IAM) of electron density is used in routine X-ray data analysis. However, this model does not give a quantitative description of the electron-density distribution. A better model that allows for modelling of aspherical charge density deformations is introduced by the Hansen–Coppens variant of the multipole model of electron density. However, the application of this model requires crystals of excellent quality and high-resolution XRD data which are quite often difficult criteria to fulfil. Therefore, Mo Kα and Cu Kα data of three model compounds (tricyclic imide, xylitol and methyluracil) were refined using IAM and new methods which enabled the refinement and reconstruction of charge density based on the Cu Kα data. These methods were the Bond-Oriented Deformation Density (BODD) model, Hirshfeld Atom Refinement (HAR) and the Transferable Aspherical Atom Model (TAAM). The final results were compared to the model obtained from neutron diffraction experiments. Our results demonstrated not only that Cu Kα data may be refined using BODD, HAR and TAAM methods, but also revealed systematic errors arising from the use of Cu Kα data. These errors were a result of the limited information in the low-resolution data set that manifested as higher values for the anisotropic displacement parameters (ADPs) and smaller maxima and minima of the residual electron density for the Cu Kα data compared to the Mo Kα data. Notably, these systematic errors were much less significant than those found for the IAM. Therefore, the application of BODD, HAR and TAAM on Cu Kα data has a more significant influence on the final results of refinement than for the Mo Kα data.
One-dimensional composite host–guest structure in BaVS3
Authors: Arakcheeva Alla , Pattison Phil , Chapuis Gervais , Berger Helmuth , Barisic Neven , Forro Laszlo 
Published: January 2021

A detailed synchrotron X-ray diffraction (XRD) study performed with a single crystal of BaVS3 (barium vanadium trisulfide) in the temperature range between 10 and 295 K is reported. Aside from the known tetragonal–orthorhombic (240 K) and orthorhombic–monoclinic (69 K) phase transitions, in the 130 < T ≤ 295 K range the overall structure can be viewed as a host–guest (H–G) composite. The BaS3 matrix is the host, while the V-chains form the guest. The two subsystems lock in at T
LOCK = 130 ± 20 K. This temperature is marked by a symmetry change from orthorhombic to monoclinic. This results in the formation of twins, implying a structural phase transition identified here for the first time. From the refined structural data, it is possible to follow, starting already at 295 K downwards, the stepwise transformation of VS6 octahedra into VS5 tetragonal pyramids as the origin of the structure evolution. The new findings will yield a better understanding of the complex electronic phase diagram of BaVS3.
Show me! Using digital figures to facilitate conversations in systemic therapy
Authors: Balmbra Steven Macgregor , Raimundo Carlos A. 
Published: January 2021

This paper is about the value of using small figures and props in systemic therapy and presents two novel digital programs designed for data tablets and personal computers. People in my Life and Play of Life have been developed independently by the authors to facilitate communication and insight and they are presented together with their different theoretical and methodological backgrounds and brief case studies. The authors point to the general contribution of figures in conversation and comment on why digital versions can also have their place in a therapist’s repertoire, no matter what their approach.Practitioner points

Presenting two novel digital methods for systemic therapy

Provision of visual, spatial, and temporal cues can enhance therapeutic conversations with clients with a range of communication styles and abilities

Active and playful digital methods can engage children and families in systemic practice
Variation of IgG N‐linked glycosylation profile in diabetic retinopathy
Authors: Wu Zhiyuan , Pan Huiying , Liu Di , Zhou Di , Tao Lixin , Zhang Jie , Wang Xiaonan , Li Xia , Wang Youxin , Wang Wei , Guo Xiuhua 
Published: January 2021

AbstractBackgroundThe relationship of immunoglobulin G (IgG) glycosylation with diabetes and diabetic nephropathy has been reported, but its role in diabetic retinopathy (DR) remains unclear. We aimed to investigate and validate the association of IgG glycosylation with DR.MethodsWe analyzed the IgG N‐linked glycosylation profile and primarily selected candidate glycans by lasso (least absolute shrinkage and selection operator) regression analysis in the discovery population. The findings were validated in the replication population using a binary logistics model. The association between the significant glycosylation panel and clinical features was illustrated with Spearman's coefficient. The results were confirmed by sensitivity analyses.ResultsAmong 16 selected glycan candidates using lasso, two IgG glycans (GP15, GP20) and two derived traits (IGP32, IGP54) were identified and validated to be significantly associated with DR (P < .05), and the combined adjusted odds ratios (ORs) were 0.587, 0.613, 1.970, and 0.593, respectively. The glycosylation panel showed a weak correlation with clinical features, except for age. In addition, the results remained consistent when the subjects with prediabetes were excluded from the controls, and the adjusted ORs were 0.677, 0.738, 1.597, and 0.678 in the whole population. Furthermore, in the 1:3 rematched population, a significant association was observed, apart from GP20.ConclusionsThe IgG glycosylation profile, reflecting an aging and pro‐inflammatory status, was significantly associated with DR. The variation in the IgG glycome deserves more attention in diabetic complications.
Addressing priorities for surgical research in Africa: implementation of a multicentre cloud‐based peri‐operative registry in Ethiopia
Authors:   Network for Peri‐operative Critical care (N4PCc)*
Published: January 2021

SummaryIn resource‐constrained settings, where inequalities in access to and quality of surgical care results in excess mortality, peri‐operative care registries are uncommon. A south‐south collaboration supported the implementation of a context specific, clinician‐led, multicentre real‐time peri‐operative registry in Ethiopia. Peri‐operative information, including the Ethiopian Ministry of Health’s national ‘Saving Lives through Safe Surgery initiative’, was linked to real‐time dashboards, providing clinicians and administrators with information on service utilisation, surgical access, national surgical key performance indicators and measures of quality of care. We recruited four hospitals representing 285 in‐patient beds from the Amhara and Southern Nations Nationalities and Peoples regions and Addis Ababa city, and reported on 1748 consecutive surgical cases from April 2019 to April 2020. Key performance indicators included: compliance with the World Health Organization’s Surgical Safety Checklist in 1595 (92.1%) surgical cases; adverse events during anaesthesia in 33 (3.1%) cases; and surgical site infections in 21 (2.0%) patients. This collaboration has successfully implemented a multicentre digital surgical registry that can enable measurement of key performance indicators for surgery and evaluation of peri‐operative outcomes. The peri‐operative registry is currently being rolled out across the Amhara region and Addis Ababa city administration. It will provide continuous granular healthcare information necessary to empower clinicians to drive context‐specific priorities for service improvement and research, in collaboration with national stakeholders and international research consortiums.
Child Language Difficulties and Internalizing and Externalizing Symptoms: A Meta‐Analysis
Authors: Hentges Rochelle F. , Devereux Chloe , Graham Susan A. , Madigan Sheri 
Published: January 2021

This study conducted two meta‐analyses to synthesize the association between children’s language skills and two broad‐band dimensions of psychopathology: internalizing and externalizing. Pooled estimates across 139 samples (externalizing k = 105; internalizing k = 90) and 147,305 participants (age range: 2–17 years old; mean % males: 53.75; mean % White participants: 55.59; mean % minority participants: 43.12) indicated small but significant associations between child language skills and externalizing problems (Hedges’ g = .22) and between language skills and internalizing problems (Hedges’ g = .23). The association between language difficulties and externalizing problems was stronger amongst males and in children with low versus high sociodemographic risk. Implications of the results for theory and practice are discussed.
Has China's Housing Production Peaked?
Authors: Rogoff Kenneth , Yang Yuanchen 
Published: January 2021

AbstractChina's real estate has been a key engine of its sustained economic expansion. This paper argues, however, that even before the COVID‐19 shock, a decades‐long housing boom had given rise to severe price misalignments and regional supply–demand mismatches, making an adjustment both necessary and inevitable. We make use of newly available and updated data sources to analyze supply–demand conditions in the fast‐moving Chinese economy. The imbalances are then compared to benchmarks from other economies. We conclude that the real estate sector is quite vulnerable to a sustained aggregate growth shock, such as COVID‐19 might pose. In our baseline calibration, using input–output tables and taking account of the very large footprint of housing construction and real estate related sectors, the adjustment to a decline in housing activity can easily trim a cumulative 5–10 percent from the level of output over a period of years.
Can Trade Facilitation Prevent the Formation of Zombie Firms? Evidence from the China Railway Express
Authors: Li Juncheng , Hu Jun , Yang Lu 
Published: January 2021

AbstractUsing data on firms listed on Chinese A‐share markets from 2009 to 2017, this paper applies the difference‐in‐difference model to test the effect of trade facilitation on preventing the formation of zombie firms. We find that the China Railway Express (CRE) significantly prevented the formation of such firms. Mechanism tests show: (i) the CRE has accelerated the speed of sales, which increased the overseas sales revenue of firms; (ii) the economies of scale and the capital accumulation effect caused by the CRE can help increase firms’ solvency and development ability. Heterogeneity analysis indicates that the effect of the CRE on preventing the formation of zombie firms is mainly reflected in non‐state‐owned firms, firms in highly competitive industries, and firms in the eastern region of China. We suggest that China should continue to promote trade facilitation by expanding the CRE and strengthening the market's dominant role in preventing the formation of zombie firms. Disadvantaged firms should seize the development opportunities brought by the CRE.
Patientenpräferenzen für die Therapie fortgeschrittener Melanome: Einfluss von Komorbidität
Authors: Weilandt Juliane , Diehl Katharina , Schaarschmidt Marthe‐Lisa , Kiecker Felix , Sasama Bianca , Pronk Melanie , Ohletz Jan , Könnecke Andreas , Müller Verena , Utikal Jochen , Hillen Uwe , Harth Wolfgang , Peitsch Wiebke K. 
Published: January 2021

ZusammenfassungHintergrund und ZieleDie Wahl der Therapie für fortgeschrittene Melanome wird entscheidend von Komorbidität und Patientenpräferenzen beeinflusst. Ziel unserer Studie war, den Einfluss von Komorbidität auf Präferenzen zu untersuchen.Patienten und Methoden150 Patienten mit Melanom im Stadium IIC–IV führten ein Discrete‐Choice‐Experiment durch, um Präferenzen für Ergebnisattribute (Gesamtansprechrate [ORR], 2‐Jahres‐Überlebensrate, progressionsfreies Überleben [PFS], Zeit bis zum Ansprechen [time to response, TTR], Art der Nebenwirkungen, Therapieabbruch aufgrund von Nebenwirkungen) und Prozessattribute (Applikationsweise und ‐häufigkeit, Häufigkeit von Arztbesuchen) systemischer Melanomtherapien zu bestimmen. Der Einfluss von Komorbidität wurde mit Varianzanalysen und multivariaten Regressionen ermittelt.ErgebnisseTeilnehmer mit Hypertonie und anderen kardiovaskulären Erkrankungen legten signifikant größeren Wert auf TTR und Applikationsweise als andere. Befragte mit Gelenkerkrankungen sorgten sich stärker um TTR (β = 0,179, P = 0,047) und Applikationsweise, aber weniger um die ORR (ß = –0,209, P = 0,021). Diabetiker erachteten Nebenwirkungen (ß = 0,185, P = 0,039) und Häufigkeit von Arztbesuchen als entscheidender, die ORR dagegen als weniger relevant. Patienten mit anderen Krebserkrankungen waren besonders über Therapieabbrüche (ß = 0,219, P = 0,008) und weniger über die ORR (ß = –0,202, P = 0,015) besorgt. Teilnehmer mit Depressionen legten mehr Wert auf PFS (ß = 0,201, P = 0,025) und weniger auf TTR (ß = –0,201, P = 0,023) und Applikationsweise (ß = –0,167, P = 0,050).SchlussfolgerungenTherapiepräferenzen von Patienten mit Melanom variieren abhängig von der Komorbidität signifikant.
HIV‐Medizin in der Dermatologie und Venerologie
Authors: Esser Stefan , Sammet Stefanie 
Published: January 2021

ZusammenfassungDurch die antiretrovirale Kombinationstherapie (ART) konnten Mortalität und Morbidität der HIV‐Infektion drastisch gesenkt und die Lebenserwartung von Menschen, die mit einer HIV‐Infektion leben (people living with HIV; PLWH), erheblich verbessert werden. Effektiv behandelte HIV‐Infizierte (HIV+) gelten heute als nicht mehr ansteckend. Als Standardtherapie werden meist Eintabletten‐Regimes (STR, single tablet regimen) verordnet. Seit 2015 nimmt die Zahl der HIV‐Neudiagnosen in Deutschland laut Robert Koch‐Institut leicht ab, jedoch bleibt der Anteil der Late Presenter (Erstdiagnose in fortgeschrittenen Stadien der Infektion) seit 2005 mit rund 32 % konstant hoch. Bei 10.800 PLWH wurde in Deutschland deren HIV‐Infektion noch nicht diagnostiziert. Im Vergleich zur Normalbevölkerung leiden HIV+ häufiger unter Dermatosen. Abhängig vom Stadium der Immundefizienz treten im Verlauf einer unbehandelten HIV‐Infektion typische Markererkrankungen an Haut und Schleimhäuten auf. Diese zu (er)kennen und Betroffenen einen HIV‐Test anzubieten ermöglicht eine frühere Diagnose bisher unerkannter HIV‐Infektionen. Durch die frühe Einleitung einer effektiven ART können die Weiterverbreitung von HIV verhindert und die mit Spätdiagnosen verbundenen höheren Sterblichkeitsraten und Behandlungskosten reduziert werden. HIV wird überwiegend sexuell übertragen. Durch eine gezielte Sexualanamnese sowie Diagnosen von HIV‐Markererkrankungen und sexuell übertragbaren Infektionen (STI) können gerade Dermatovenerologen PLWH und Personen mit erhöhtem HIV‐Infektionsrisiko identifizieren, um erstere einer zeitnahen Einleitung der ART zuzuführen und letztere über eine Präexpositionsprophylaxe (PrEP) aufzuklären.
The COVID‐19 Worsening Score (COWS)—a predictive bedside tool for critical illness
Authors: Boero Enrico , Rovida Serena , Schreiber Annia , Berchialla Paola , Charrier Lorena , Cravino Marta Maria , Converso Marcella , Gollini Paola , Puppo Mattia , Gravina Angela , Fornelli Giorgia , Labarile Giulia , Sciacca Santi , Bove Tiziana , Karakitsos Dimitrios , Aprà Franco , Blaivas Michael , Vetrugno Luigi 
Published: January 2021

AbstractObjectivesTo evaluate the accuracy of a new COVID‐19 prognostic score based on lung ultrasound (LUS) and previously validated variables in predicting critical illness.MethodsWe conducted a single‐center retrospective cohort development and internal validation study of the COVID‐19 Worsening Score (COWS), based on a combination of the previously validated COVID‐GRAM score (GRAM) variables and LUS. Adult COVID‐19 patients admitted to the emergency department (ED) were enrolled. Ten variables previously identified by GRAM, days from symptom onset, LUS findings, and peripheral oxygen saturation/fraction of inspired oxygen (P/F) ratio were analyzed. LUS score as a single predictor was assessed. We evaluated GRAM model's performance, the impact of adding LUS, and then developed a new model based on the most predictive variables.ResultsAmong 274 COVID‐19 patients enrolled, 174 developed critical illness. The GRAM score identified 51 patients at high risk of developing critical illness and 132 at low risk. LUS score over 15 (range 0 to 36) was associated with a higher risk ratio of critical illness (RR, 2.05; 95% confidence interval [CI], 1.52‐2.77; area under the curve [AUC], 0.63; 95% CI 0.676‐0.634). The newly developed COVID‐19 Worsening Score relies on five variables to classify high‐ and low‐risk patients with an overall accuracy of 80% and negative predictive value of 93% (95% CI, 87%‐98%). Patients scoring more than 0.183 on COWS showed a RR of developing critical illness of 8.07 (95% CI, 4.97‐11.1).ConclusionsCOWS accurately identify patients who are unlikely to need intensive care unit (ICU) admission, preserving resources for the remaining high‐risk patients.
Hypertensive hypertrophic obstructive cardiomyopathy crisis resolved with transvenous pacing guided by bedside echocardiography
Authors: Spindel Jeffrey F , Mathbout Mohammad , Ghafghazi Shahab 
Published: January 2021

AbstractCardiogenic shock due to hypertrophic obstructive cardiomyopathy (HoCM) crisis presents a clinical challenge as pharmacologic vasopressor and/or inotropic support can compromise hemodynamics and acute afterload reduction worsens left ventricular outflow tract (LVOT) obstruction. Hypertensive hypertrophic obstructive cardiomyopathy (HHoCM) is an entity mostly affecting elderly hypertensive women and could present with a clinical phenotype similar to HoCM crisis. We present a case of an 81‐year‐old female patient with HHoCM complicated by severe mitral regurgitation, in cardiogenic shock, in whom hemodynamic stability was restored with transvenous pacing guided by bedside echocardiography to optimize rate, left ventricle (LV) filling time, and cardiac output.
Evaluation of left and right ventricular functions with three‐dimensional speckle tracking in patients with mitral stenosis
Authors: Seçkin Göbüt Özden , Ünlü Serkan , Taçoy Gülten 
Published: January 2021

AbstractBackgroundThe function of both ventricles has been suggested to be affected in patients with mitral stenosis. In this study, it was aimed to investigate deformation properties of right (RV) and left ventricle (LV) in rheumatic mitral stenosis (MS) patients with three‐dimensional speckle tracking echocardiography (3D‐STE).MethodsA total of 60 patients were included in the study (20 patients with mild MS diagnosis, 20 patients with moderate MS diagnosis, and 20 healthy volunteers). Three‐dimensional echocardiography datasets were obtained for both ventricles in all patients. LV global longitudinal strain (GLS), LV torsion, RV free wall (FW) LS, and interventricular septal (IVS) LS measurements were analyzed.ResultsThe LV ejection fraction (EF), RV fractional area change, peak systolic velocity of the tricuspit annulus, isovolumic acceleration, and tricuspid annular plane systolic excursion values were statistically similar and in the normal range. The LV GLS measurements were significantly different among the groups by being highest in the control group and least in the moderate stenosis group. Patients with MS showed higher torsional values, correlated with MS severity. IVS LS, RVFW LS values obtained by RV analysis also differed significantly among groups. The RVFW‐GLS values only showed significant difference between the control group and moderate MS group.ConclusionPatients with MS showed lower LV‐GLS and higher LV torsion values. RV deformation indices showed significant decrease in correlation with the severity of the mitral stenosis. In conclusion, our data suggest that subclinical LV and RV systolic dysfunction is present in mild‐moderate MS patients and this dysfunction can be detected by 3D‐STE.