bluuebunny/crossref_metadata_2025 huggingface dataset:
Rearrangement of T Cell Genome Architecture Regulates GVHD
Authors: Sun Yaping , Dotson Gabrielle A. , Muir Lindsey A. , Ronquist Scott , Oravecz-Wilson Katherine , Peltier Daniel , Seike Keisuke , Li Lu , Meixner Walter , Rajapakse Indika , Reddy Pavan
Published: January 2021

The cohesin complex modulates gene expression and cellular functions by shaping three-dimensional (3D) organization of chromatin. WAPL, cohesin’s DNA release factor, regulates 3D chromatin architecture. The 3D genome structure and its relevance to mature T cell functionsin vivois not well understood. We show thatin vivolymphopenic expansion, and allo-antigen driven proliferation, alters the 3D structure and function of the genome in mature T cells. Conditional deletion ofWaplin T cells reduced long-range genomic interactions, altered chromatin A/B compartments and interactions within topologically associating domains (TADs) of the chromatin in T cells at baseline. Comparison of chromatin structure in normal and WAPL-deficient T cells after lymphopenic and allo-antigen driven stimulation revealed reduced loop extensions with changes in cell cycling genes. WAPL-mediated changes in 3D architecture of chromatin regulated activation, cycling and proliferation of T cellsin vitroandin vivo. Finally, WAPL-deficient T cells demonstrated reduced severity of graft-versus-host disease (GVHD) following experimental allogeneic hematopoietic stem cell transplantation. These data collectively characterize 3D genomic architecture of T cellsin vivoand demonstrate biological and clinical implications for its disruption by cohesin release factor WAPL.
Identification of candidate susceptibility genes toPuccinia graminisf. sp.triticiin wheat
Authors: Henningsen Eva C. , Omidvar Vahid , Coletta Rafael Della , Michno Jean-Michel , Gilbert Erin , Li Feng , Miller Marisa E. , Myers Chad L. , Gordon Sean P. , Vogel John P. , Steffenson Brian J. , Kianian Shahryar F. , Hirsch Cory D. , Figueroa Melania
Published: January 2021

Wheat stem rust disease caused byPuccinia graminisf. sp.tritici(Pgt) is a global threat to wheat production. Fast evolving populations ofPgtlimit the efficacy of plant genetic resistance and constrain disease management strategies. Understanding molecular mechanisms that lead to rust infection and disease susceptibility could deliver novel strategies to deploy crop resistance through genetic loss of disease susceptibility. We used comparative transcriptome-based and orthology-guided approaches to characterize gene expression changes associated withPgtinfection in susceptible and resistantTriticum aestivumgenotypes as well as the non-hostBrachypodium distachyon. We targeted our analysis to genes with differential expression inT. aestivumand genes suppressed or not affected inB. distachyonand report several processes potentially linked to susceptibility toPgt, such as cell death suppression and impairment of photosynthesis. We complemented our approach with a gene co-expression network analysis to identify wheat targets to deliver resistance toPgtthrough removal or modification of putative susceptibility genes.
Launching a saliva-based SARS-CoV-2 surveillance testing program on a university campus
Authors: Ehrenberg Alexander J. , Moehle Erica A. , Brook Cara E. , Doudna Cate Andrew H. , Witkowsky Lea B. , Sachdeva Rohan , Hirsh Ariana , Barry Kerrie , Hamilton Jennifer R. , Lin-Shiao Enrique , McDevitt Shana , Valentin-Alvarado Luis , Letourneau Kaitlyn N. , Hunter Lauren , Keller Amanda , Pestal Kathleen , Frankino Phillip A. , Murley Andrew , Nandakumar Divya , Stahl Elizabeth C. , Tsuchida Connor A. , Gildea Holly K. , Murdock Andrew G. , Hochstrasser Megan L. , O’Brien Elizabeth , Ciling Alison , Tsitsiklis Alexandra , Worden Kurtresha , Dugast-Darzacq Claire , Hays Stephanie G. , Barber Colin C. , McGarrigle Riley , Lam Emily , Ensminger David , Bardet Lucie , Sherry Carolyn ,   the IGI SARS-CoV-2 Testing consortium, Harte Anna , Nicolette Guy , Giannikopoulos Petros , Hockemeyer Dirk , Petersen Maya , Urnov Fyodor D. , Ringeisen Bradley R. , Boots Mike , Doudna Jennifer A.
Published: January 2021

Regular surveillance testing of asymptomatic individuals for SARS-CoV-2 has played a vital role in SARS-CoV-2 outbreak prevention on college and university campuses. Here we describe the voluntary saliva testing program instituted at the University of California, Berkeley during an early period of the SARS-CoV-2 pandemic in 2020. The program was administered as a research study ahead of clinical implementation, enabling us to launch surveillance testing while continuing to optimize the assay. Results of both the testing protocol itself and the study participants’ experience show how the program succeeded in providing routine, robust testing capable of contributing to outbreak prevention within a campus community and offer strategies for encouraging participation and a sense of civic responsibility.
Comparison of Carotid Intima Media Thickness between Women with History of Preeclampsia and Normal Pregnancy: A Meta-Analysis of Systematic Review
Authors: Pikir Budi Susetyo , Subagjo Agus , Wardhani Deasy Eka , Andrianto  , Oktaviono Yudi Her , Nugraha Ricardo Adrian
Published: January 2021

Background

Women with a history of preeclampsia are twice as likely to experience long term cardiovascular disease (CVD) compared to women with unaffected pregnancy. The pathophysiology of preeclampsia is not well understood, however there is general agreement that, similar to cardiovascular disease, endothelial dysfunction plays a crucial role. On a clinical level, preeclampsia and atherosclerotic cardiovascular disease share common risk factors. Carotid intima media thickness (CIMT) is ultrasound-based imaging, non-invasive, simple and reproducible method of subclinical atherosclerosis evaluation. Nowadays, there were studies concerning of CIMT among preeclamptic women, although the results were different.

Objective

To prove that CIMT among women with histories of preeclampsia was greater compared to normal pregnancy.

Methods

We conducted a meta-analysis of studies that reported CIMT, in women who had preeclampsia and had normal pregnancy. Studies were identified through three databases: PubMed, Google Scholar dan SAGE Journals with publication year of 2010- 2020. Heterogeneity was assessed using the I2 statistic. Standardized mean difference was used as measured of effect size.

Results

Nine eligible studies were included in the meta-analysis. This meta-analysis consisted of 439 women with preeclampsia histories and 526 women with normal pregnancy histories. Women who had preeclampsia had significantly higher CIMT compared to those with normal pregnancy with standardized mean difference −0.38 and 95% confidence interval (CI) −0.68 to −0.07 (p=0.02).

Conclusion

CIMT was greater among women with histories of preeclampsia compared to normal pregnancy.

Prospero registration number

ID 228825.
Impact of gastric resection and enteric anastomotic configuration on delayed gastric emptying after pancreaticoduodenectomy: a network meta-analysis of randomized trials
Authors: Varghese Chris , Bhat Sameer , Wang Tim , O’Grady Gregory , Pandanaboyana Sanjay
Published: January 2021

Introduction

Delayed gastric emptying (DGE) is frequent after pancreaticoduodenectomy (PD). Several randomised controlled trials (RCTs) have explored operative strategies to minimise DGE, however, the optimal combination of gastric resection approach, anastomotic route, and configuration, role of Braun enteroenterostomy remains unclear.

Methods

MEDLINE, Embase, and CENTRAL databases were systematically searched for RCTs comparing gastric resection (Classic Whipple, pylorus-resecting, and pylorus-preserving), anastomotic route (antecolicvsretrocolic) and configuration (Billroth IIvsRoux-en-Y), and enteroenterostomy (Braunvsno Braun). A random-effects, Bayesian network meta-analysis with non-informative priors was conducted to determine the optimal combination of approaches to PD for minimising DGE.

Results

Twenty-four RCTs, including 2526 patients and 14 approaches were included. There was some heterogeneity, although inconsistency was low. The overall incidence of DGE was 25.6% (n = 647). Pylorus-resecting, antecolic, Billroth II with Braun enteroenterostomy was associated with the lowest rates of DGE and ranked the best in 35% of comparisons. Classic Whipple, retrocolic, Billroth II with Braun ranked the worst for DGE in 32% of comparisons. Pairwise meta-analysis of retrocolicvsantecolic route of gastro-jejunostomy found increased risk of DGE with the retrocolic route (OR 2.1, 95% CrI; 0.92 - 4.7). Pairwise meta-analysis of Braun enteroenterostomy found a trend towards lower DGE rates with Braun compared to no Braun (OR 1.9, 95% CrI; 0.92 - 3.9). Having a Braun enteroenterostomy ranked the best in 96% of comparisons.

Conclusion

Based on existing RCT evidence, a pylorus-resecting, antecolic, Billroth II with Braun enteroenterostomy may be associated with the lowest rates of DGE.
Mathematical Relationship between Reproduction Number and Epidemic Curve of Daily Cases
Authors: Caudana Bruno
Published: January 2021

The strict mathematical relationship between Rt and the curve of daily cases f (t) is shown. Up to date and statistically robust Rt from the curve of daily cases can be estimated as soon as new cases are added to the curve. That is equivalent to estimating Rt by averaging all detected cases of infection, without any distortion induced by the difficulty of following and weighting trees of secondary cases from original ones, and without needing to wait for secondary cases to manifest infection. With this method, if Rt scaled numbers are of interest, only the average duration of subjects’ infectivity has to be estimated directly, but independently of linking secondary cases to primary ones. A new index, Instantaneous Reproduction Number Rist is introduced, which is mathematically tied to Rt and does not depend on the duration of infectivity of subjects. Rist, Rt and the doubling/halving time of the epidemic may be estimated by simple computations at the very detection time of new daily cases. Any smoothed curve of daily cases gives smooth Rt and Rist. No phase lag on Rt estimate is introduced by this method.
Discerning amyloid network in plants
Authors: Y.Gahane Avinash , Sinha Nabodita , Zahra Talat , K.Thakur Ashwani
Published: January 2021

Amyloids are proteinaceous fibrillar structures and are known for their pathogenic and functional roles across the kingdoms. Besides proteinaceous deposits, amyloid-like structures are present in small metabolite assemblies and fibrillar hydrogels. Recent cryoelectron microscopy studies have shed light on the heterogeneous nature of the amyloid structures and their association with carbohydrate or lipid molecules, suggesting that amyloids are not exclusively proteinaceous. The association of amyloids with carbohydrates is further supported because the gold-standard dye of amyloid detection, Congo red, also binds to carbohydrates, probably due to similar stacking interactions. We name the association between amyloids, carbohydrates and other biomolecules as amyloid-network and propose that plants might contain such structures. Specifically, we hypothesize that cereal seeds containing glutamine-repeat-rich granules of storage proteins may have amyloid-like structures. This is because, polyQ repeats are associated with protein aggregation and amyloid formation in humans and are linked to multiple neurodegenerative conditions. Also seed storage proteins and seed cell wall proteins possess carbohydrate affinity. Thus, plant seeds might contain an intercalated network of proteins and carbohydrates, lending strength, stability and dynamics to these structures. In this paper, we show that, plant seeds have a mesh-like network that shows apple-green birefringence on staining with Congo red, a characteristic of amyloids. This congophilic network is more prominent in protein-rich seed sections of wheat and lentils, as compared to starch-rich compartments of potato. The findings suggest an amyloid network in the seeds and might be extended to other plant tissues. Further investigation with mass spectrometry and other techniques would detail the exact compositional analysis of these networks.
Postdiction: when temporal regularity drives space perception through pre-stimulus alpha oscillations
Authors: Grabot Laetitia , Kayser Christoph , van Wassenhove Virginie
Published: January 2021

During postdiction, the last stimulus of a sequence changes the perception of the preceding ones: in therabbitillusion, a three-flash series presented regularly in time, but not in space, is – illusory - perceived as spatially regular. Such a reorganization of (spatial) perception could be driven by internal priors, e.g. favoring slow motion for therabbitillusion. Although postdiction is a ubiquitous phenomenon, its neural underpinnings remain poorly understood. Here, we focused on the role of priors during postdiction and hypothesized that these could be reflected by alpha oscillations (8-12Hz), previously observed to correlate with idiosyncratic biases. We presented human participants with ambiguous visual stimuli that elicited therabbitillusion on about half the trials, allowing us to contrast MEG-EEG brain responses to the same physical events causing distinct percepts. Given that a strong prior will increase the overall probability of perceiving the illusion, we used the percentage of perceived illusion as a proxy for an individual’s prior. We found that high fronto-parietal alpha power was associated with perceiving the sequence according to individual biases: participants with high susceptibility to the illusion would report the illusion, while participants with low susceptibility would report the veridical sequence. Additionally, we found that pre-stimulus alpha phase in occipital and frontal areas dissociated illusory from non-illusory trials. These results point to a dissociated relation of the power and timing of alpha band activity to illusory perception, with power reflecting prior expectations and phase influencing behavioral performance, potentially due to the modulation of sensory uncertainty.

Significance Statement

Late events may sometimes influence how earlier events are perceived, as if the arrow of time was reversed in the brain. This surprising phenomenon, called postdiction, is observed in the rabbit illusion, and highlights a predominant mechanism for perceptual processes. Perception builds up from the combination of prior expectations with incoming sensory evidence, which takes time. We showed that pre-stimulus neural activity, and more specifically alpha oscillations (8-12Hz), play a double role in postdiction. Fronto-parietal alpha power reflects individual prior expectation, while occipital and frontal alpha phase predicts illusory perception. Postdiction might actually be a means of compensating for the neural delays inherent in perceptual processes, so that the arrow of perceptual time matches the arrow of physical time.
Host-directed therapies against early-lineage SARS-CoV-2 retain efficacy against B.1.1.7 variant
Authors: Reuschl Ann-Kathrin , Thorne Lucy G. , Zuliani-Alvarez Lorena , Bouhaddou Mehdi , Obernier Kirsten , Hiatt Joseph , Soucheray Margaret , Turner Jane , Fabius Jacqueline M. , Nguyen Gina T. , Swaney Danielle L. , Rosales Romel , White Kris M. , Avilés Pablo , Kirby Ilsa T. , Melnyk James E. , Shi Ying , Zhang Ziyang , Shokat Kevan M. , García-Sastre Adolfo , Jolly Clare , Towers Gregory J. , Krogan Nevan J.
Published: January 2021

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in millions of deaths worldwide and massive societal and economic burden. Recently, a new variant of SARS-CoV-2, known as B.1.1.7, was first detected in the United Kingdom and is spreading in several other countries, heightening public health concern and raising questions as to the resulting effectiveness of vaccines and therapeutic interventions. We and others previously identified host-directed therapies with antiviral efficacy against SARS-CoV-2 infection. Less prone to the development of therapy resistance, host-directed drugs represent promising therapeutic options to combat emerging viral variants as host genes possess a lower propensity to mutate compared to viral genes. Here, in the first study of the full-length B.1.1.7 variant virus, we find two host-directed drugs, plitidepsin (aplidin; inhibits translation elongation factor eEF1A) and ralimetinib (inhibits p38 MAP kinase cascade), as well as remdesivir, to possess similar antiviral activity against both the early-lineage SARS-CoV-2 and the B.1.1.7 variant, evaluated in both human gastrointestinal and lung epithelial cell lines. We find that plitidepsin is over an order of magnitude more potent than remdesivir against both viruses. These results highlight the importance of continued development of host-directed therapeutics to combat current and future coronavirus variant outbreaks.
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

The 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.

Highlights

Codon-optimization of Nsp12 triggers misfolding and activity loss

Slow translation, accessory Nsp7 and Nsp8 subunits, and NTPs rescue Nsp12

Non-substrate nucleotides activate RNA chain synthesis, likely via NiRAN domain

Crosstalk 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

Non-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
Effect of disordered imidazole substructure on proton dynamics in imidazolium malonic acid salt
Authors: Ławniczak Paweł , Pogorzelec-Glaser Katarzyna , Pietraszko Adam , Hilczer Bożena
Published: January 2021

The influence of a disorder in cation substructure on proton conductivity of imidazolium malonate (Im-MAL) is studied. Imidazolium in salts with dicarboxylic acids have been found to have a well ordered hydrogen-bond network and only in Im-MAL [Pogorzelec-Glaser et al. (2006). Mater. Sci.-Pol. (2006), 24, 245–252] were two types of cation observed: ordered Im-I and disordered Im-II. Im-I is involved in hydrogen bonds with malonic acid molecules, whereas Im-II is disordered between two symmetrically equivalent positions with occupancy of 0.5. NMR studies by Mizuno et al. [Hyperfine Interact. (2015), 230, 95–100] showed an 180° flip of ordered Im-I and calculated contribution of Im-I flipping to proton conductivity of Im-MAL. Ławniczak et al. [Solid State Ionics (2017), 306, 25] reported that temperature variation of the proton conductivity by impedance spectroscopy yielded the conductivity value higher than that calculated by Mizuno for Im-I. Moreover these detailed structure studies at 240 K and 280 K excluded any phase transition. Repeated X-ray studies from 14 K to 360 K show a continuous increase in anisotropic displacement factors. The half-occupied hydrogen bonds linking the Im-II nitrogen atoms with hydroxyl oxygen atoms may be considered as electric dipoles and the interbond proton transfer as dipolar switching. It assumed here a coherent switching at low temperatures and a decrease of the coupling at higher temperatures with the disappearance at cross-over temperature at 318 K. The possible proton pathway in the crystal structure is determined and the contribution of the proton dynamics of Im-II to phonon-assisted proton diffusion in the ordered substructure is estimated.
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

Background

The 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.

Methods

We 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.

Results

Among 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.

Conclusions

The 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

In 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

China'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

Using 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

Hintergrund und Ziele

Die 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 Methoden

150 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.

Ergebnisse

Teilnehmer 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).

Schlussfolgerungen

Therapiepräferenzen 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

Durch 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

Objectives

To evaluate the accuracy of a new COVID‐19 prognostic score based on lung ultrasound (LUS) and previously validated variables in predicting critical illness.

Methods

We 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.

Results

Among 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).

Conclusions

COWS 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

Cardiogenic 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

Background

The 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).

Methods

A 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.

Results

The 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.

Conclusion

Patients 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.
Informational capital and the transition to university: First‐in‐family students' experiences in Austrian higher education
Authors: Lessky Franziska , Nairz‐Wirth Erna , Feldmann Klaus
Published: January 2021

The agenda for widening participation in higher education has led to increasing numbers of students with a broader range of education and family backgrounds. However, transitioning to the university landscape remains a highly complex negotiation process, especially for first‐in‐family students, who cannot draw on previous experience from higher education in their families. Gaining access to informational capital—a combination of cultural and social capital—plays a crucial role in managing education transitions. We draw on rich empirical data obtained from 26 autobiographical narrative interviews with first‐in‐family university students in Austria to investigate how transitions to university are affected by informational capital. We also explore how access to informational capital was influenced by (1) institutional practices, such as initiatives to support students, especially first‐year students; and (2) cultural fit—the extent to which a student's cultural capital corresponded with the dominant cultural capital in the field of their chosen discipline or higher education establishment. Our findings show that gaining access to informational capital was strongly affected by the institutional practices at universities within the different disciplines, thus highlighting the importance of higher education institutions in supporting their students during transition processes. We conclude with policy implications for how higher education institutions can assist first‐in‐family students to succeed at university.
The working classes and higher education: Meritocratic fallacies of upward mobility in the United Kingdom
Authors: Reay Diane
Published: January 2021

The uniformly positive view of social mobility in the United Kingdom overlooks the difficulties working‐class young people have in reconciling a working‐class background with the middle‐class environments of the university and the professional labour market. But even more hidden are the subtle processes of exclusion and exclusivity that permeate social life in, particularly, the elite universities. Here, working‐class students' marginalisation in relation to advantageous social activities and networks, compromises their chances of later success in the labour market. This paper scrutinises working‐class students' experiences of elite higher education through the lens of Bourdieu's concepts of habitus, capitals and field. Drawing on a research project on working‐class young people who gain entry to elite universities it analyses the disjunctures between working‐class habitus and the field of elite higher education, focusing on the emotional and social consequences for working‐class students. The findings raise concerns—largely unexplored in existing research—about working‐class reception in elite fields. The paper concludes with a call to look beyond the attitudes and actions of working‐class students to those of their upper‐ and middle‐class peers, and the culture and ethos of the elite universities.
Deficits in attentional modulation of auditory N100 in first‐episode schizophrenia
Authors: Ren Xi , Fribance Sarah N. , Coffman Brian A. , Salisbury Dean F.
Published: January 2021

Reductions of the auditory N100 are present in schizophrenia, even at the first episode (FESz). Because most studies examine auditory N100 on active target detection oddball tasks, it remains unclear if the abnormality in FESz results from sensory deficits or impaired enhancement of N100 by selective attention, or both. N100 was recorded from 21 FESz and 22 matched healthy controls (HC) on a single‐tone task and a two‐tone oddball task. Overall, N100 was smaller in FESz (p = .036). Attention enhanced N100 amplitude (p < .001), but this differed between groups, with FESz impaired in N100 modulation (group x attention, p = .012). The oddball task showed greater N100 enhancement than the single‐tone task (p < .001) in both groups. Group differences in N100 enhancement in the oddball task were large (Cohen's d = 0.85). Exploratory correlations showed that better N100 enhancement on the oddball task in FESz was associated with better MATRICS Overall Composite scores (cognitive tasks highly sensitive to psychosis), lower PANNS Negative factor and SANS scores, and better interpersonal (social) and role functioning in the last year. N100 during ignore conditions showed no significant difference between groups, albeit smaller in FESz, with small to medium effect sizes. Although sensory deficits in N100 are likely present, they are compounded by a failure to enhance N100 with attention. The failure of N100 enhancement by attentional gain control in FESz suggests functional dysconnection between cognitive control areas and the sensory cortex. N100 amplitude on active attention tasks may be a useful outcome biomarker for targeted enhancement of the cognitive control system.