bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differentially conserved amino acid positions may reflect differences in SARS-CoV-2 and SARS-CoV behaviour
Authors: Bojkova Denisa , McGreig Jake E , McLaughlin Katie-May , Masterson Stuart G , Antczak Magdalena , Widera Marek , Krähling Verena , Ciesek Sandra , Wass Mark N , Michaelis Martin , Cinatl Jindrich 
Published: February 2021

Abstract

Motivation
SARS-CoV-2 is a novel coronavirus currently causing a pandemic. Here, we performed a combined in-silico and cell culture comparison of SARS-CoV-2 and the closely related SARS-CoV.

Results
Many amino acid positions are differentially conserved between SARS-CoV-2 and SARS-CoV, which reflects the discrepancies in virus behaviour, i.e. more effective human-to-human transmission of SARS-CoV-2 and higher mortality associated with SARS-CoV. Variations in the S protein (mediates virus entry) were associated with differences in its interaction with ACE2 (cellular S receptor) and sensitivity to TMPRSS2 (enables virus entry via S cleavage) inhibition. Anti-ACE2 antibodies more strongly inhibited SARS-CoV than SARS-CoV-2 infection, probably due to a stronger SARS-CoV-2 S-ACE2 affinity relative to SARS-CoV S. Moreover, SARS-CoV-2 and SARS-CoV displayed differences in cell tropism. Cellular ACE2 and TMPRSS2 levels did not indicate susceptibility to SARS-CoV-2. In conclusion, we identified genomic variation between SARS-CoV-2 and SARS-CoV that may reflect the differences in their clinical and biological behaviour.

Supplementary information
Supplementary data are available at Bioinformatics online.
Integrating intraspecific variation in species distribution models by quantifying niche differentiation
Authors: Zhang Sheng-Nan , Kubota Kôhei 
Published: February 2021

AbstractIntraspecific variation provides insight into heterogeneous demography and adaptive history across distribution ranges of organisms. Most species distribution models assume that species respond to the environment as a single undifferentiated entity across their entire distribution. However, populations occupying different niches might differ in their ability to cope with climate change. Here, we assessed potential climatic niche differentiation at the species and subspecies levels and identified the palaeoclimatic range of three cold-adapted, low-dispersal beetle species: Carabus irregularis, Platycerus albisomni and Platycerus takakuwai. Our results showed that: (1) MaxEnt models incorporating information derived from intraspecific variation outperformed the species-level models; (2) tests of niche similarity revealed niche conservatism in most subspecies, except for two subspecies of C. irregularis, C. i. irregularis and C. i. bucephalus; and (3) historical predictions suggested substantial shifts within species ranges, with multiple glacial refugia during the Last Glacial Maximum. In conclusion, we recommend closer examination of intraspecific variation when predicting species distributions, in order to obtain more accurate generalizations regarding range shifts under climate change.
Signatures of north-eastern expansion and multiple refugia: genomic phylogeography of the Pine Barrens tree frog,Hyla andersonii(Anura: Hylidae)
Authors: Warwick Alexa R , Barrow Lisa N , Smith Megan L , Means D Bruce , Lemmon Alan R , Lemmon Emily Moriarty 
Published: February 2021

AbstractRange fragmentation poses challenges for species persistence over time and can be caused by both historical and contemporary processes. We combined genomic data, phylogeographical model testing and palaeoclimatic niche modelling to infer the evolutionary history of the Pine Barrens tree frog (Hyla andersonii), a seepage bog specialist, in eastern North America to gain a better understanding of the historical context of its fragmented distribution. We sampled H. andersonii populations across the three disjunct regions of the species range: Alabama/Florida (AF), the Carolinas (CL) and New Jersey (NJ). Phylogenetic relationships within H. andersonii were consistent between the nuclear species tree and mitochondrial analyses, indicating divergence between AF and CL/NJ (Atlantic clade) ~0.9 Mya and divergence of the NJ clade ~0.15 Mya. Several predictions of north-eastern expansion along the Atlantic coast were supported by phylogeographical analyses. Model testing using genome-wide single nucleotide polymorphism data and species distribution models both provided evidence for multiple disjunct refugia. This comprehensive phylogeographical study of H. andersonii demonstrates a long history of range fragmentation within an endemic coastal plain species and highlights the influence of historical climate change on the current distribution of species and their genetic diversity.
Interactions between the introduced European honey bee and native bees in urban areas varies by year, habitat type and native bee guild
Authors: Prendergast Kit S , Dixon Kingsley W , Bateman Philip W 
Published: February 2021

AbstractEuropean honey bees have been introduced across the globe and may compete with native bees for floral resources. Compounding effects of urbanization and introduced species on native bees are, however, unclear. Here, we investigated how honey bee abundance and foraging patterns related to those of native bee abundance and diversity in residential gardens and native vegetation remnants for 2 years in urbanized areas of the Southwest Australian biodiversity hotspot and assessed how niche overlap influenced these relationships. Honey bees did not overtly suppress native bee abundance; however, complex relationships emerged when analysing these relationships according to body size, time of day and floral resource levels. Native bee richness was positively correlated with overall honeybee abundance in the first year, but negatively correlated in the second year, and varied with body size. Native bees that had higher resource overlap with honey bees were negatively associated with honey bee abundance, and resource overlap between honey bees and native bees was higher in residential gardens. Relationships with honey bees varied between native bee taxa, reflecting adaptations to different flora, plus specialization. Thus, competition with introduced bees varies by species and location, mediated by dietary breadth and overlap and by other life-history traits of individual bee species.
Structure-preserving integrated analysis for risk stratification with application to cancer staging
Authors: Wang Tianjie , Chen Rui , Liu Wenshuo , Yu Menggang 
Published: February 2021

Summary
To provide appropriate and practical level of health care, it is critical to group patients into relatively few strata that have distinct prognosis. Such grouping or stratification is typically based on well-established risk factors and clinical outcomes. A well-known example is the American Joint Committee on Cancer staging for cancer that uses tumor size, node involvement, and metastasis status. We consider a statistical method for such grouping based on individual patient data from multiple studies. The method encourages a common grouping structure as a basis for borrowing information, but acknowledges data heterogeneity including unbalanced data structures across multiple studies. We build on the “lasso-tree” method that is more versatile than the well-known classification and regression tree method in generating possible grouping patterns. In addition, the parametrization of the lasso-tree method makes it very natural to incorporate the underlying order information in the risk factors. In this article, we also strengthen the lasso-tree method by establishing its theoretical properties for which Lin and others (2013. Lasso tree for cancer staging with survival data. Biostatistics 14, 327–339) did not pursue. We evaluate our method in extensive simulation studies and an analysis of multiple breast cancer data sets.
Association between Quantitative MR Markers of Cortical Evolving Organization and Gene Expression during Human Prenatal Brain Development
Authors: Vasung Lana , Zhao Chenying , Barkovich Matthew , Rollins Caitlin K , Zhang Jennings , Lepage Claude , Corcoran Teddy , Velasco-Annis Clemente , Yun Hyuk Jin , Im Kiho , Warfield Simon Keith , Evans Alan Charles , Huang Hao , Gholipour Ali , Grant Patricia Ellen 
Published: February 2021

AbstractThe relationship between structural changes of the cerebral cortex revealed by Magnetic Resonance Imaging (MRI) and gene expression in the human fetal brain has not been explored. In this study, we aimed to test the hypothesis that relative regional thickness (a measure of cortical evolving organization) of fetal cortical compartments (cortical plate [CP] and subplate [SP]) is associated with expression levels of genes with known cortical phenotype. Mean regional SP/CP thickness ratios across age measured on in utero MRI of 25 healthy fetuses (20–33 gestational weeks [GWs]) were correlated with publicly available regional gene expression levels (23–24 GW fetuses). Larger SP/CP thickness ratios (more pronounced cortical evolving organization) was found in perisylvian regions. Furthermore, we found a significant association between SP/CP thickness ratio and expression levels of the FLNA gene (mutated in periventricular heterotopia, congenital heart disease, and vascular malformations). Further work is needed to identify early MRI biomarkers of gene expression that lead to abnormal cortical development.
A Phase 3, Randomized, Double-Blind Study Comparing Tedizolid Phosphate and Linezolid for Treatment of Ventilated Gram-Positive Hospital-Acquired or Ventilator-Associated Bacterial Pneumonia
Authors: Wunderink Richard G , Roquilly Antoine , Croce Martin , Rodriguez Gonzalez Daniel , Fujimi Satoshi , Butterton Joan R , Broyde Natasha , Popejoy Myra W , Kim Jason Y , De Anda Carisa 
Published: February 2021

Abstract

Background
Hospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP) are associated with high mortality rates. We evaluated the efficacy and safety of tedizolid (administered as tedizolid phosphate) for treatment of gram-positive ventilated HABP/VABP.

Methods
In this randomized, noninferiority, double-blind, double-dummy, global phase 3 trial, patients were randomized 1:1 to receive intravenous tedizolid phosphate 200 mg once daily for 7 days or intravenous linezolid 600 mg every 12 hours for 10 days. Treatment was 14 days in patients with concurrent gram-positive bacteremia. The primary efficacy end points were day 28 all-cause mortality (ACM; noninferiority margin, 10%) and investigator-assessed clinical response at test of cure (TOC; noninferiority margin, 12.5%) in the intention-to-treat population.

Results
Overall, 726 patients were randomized (tedizolid, n = 366; linezolid, n = 360). Baseline characteristics, including incidence of methicillin-resistant Staphylococcus aureus (31.3% overall), were well balanced. Tedizolid was noninferior to linezolid for day 28 ACM rate: 28.1% and 26.4%, respectively (difference, –1.8%; 95% confidence interval [CI]: –8.2 to 4.7). Noninferiority of tedizolid was not demonstrated for investigator-assessed clinical cure at TOC (tedizolid, 56.3% vs linezolid, 63.9%; difference, –7.6%; 97.5% CI: –15.7 to 0.5). In post hoc analyses, no single factor accounted for the difference in clinical response between treatment groups. Drug-related adverse events occurred in 8.1% and 11.9% of patients who received tedizolid and linezolid, respectively.

Conclusions
Tedizolid was noninferior to linezolid for day 28 ACM in the treatment of gram-positive ventilated HABP/VABP. Noninferiority of tedizolid for investigator-assessed clinical response at TOC was not demonstrated. Both drugs were well tolerated.

Clinical Trials Registration
NCT02019420.
Impact of Severe Acute Respiratory Syndrome Coronavirus 2 Infection on Pregnancy Outcomes: A Population-based Study
Authors: Crovetto Francesca , Crispi Fàtima , Llurba Elisa , Pascal Rosalia , Larroya Marta , Trilla Cristina , Camacho Marta , Medina Carmen , Dobaño Carlota , Gomez-Roig Maria Dolores , Figueras Francesc , Gratacos Eduard ,   KidsCorona Pregnancy COVID-19 Group, Arranz Angela , Cantallops Martí , Casas Irene , Tortajada Marta , Cahuana Àlex , Muro Patricia , Valdés-Bango Marta , Boada David , Mundo Anna , Lopez Marta , Goncé Anna , Santano Rebeca , Mercade Imma , Casals Elena , Marcos Maria Ángeles , Yague Jordi , Renau Montserrat Izquierdo , Fumado Vicky , Muñoz-Almagro Carmen , Jou Cristina , García-Osuna Alvaro , Mora Josefina 
Published: February 2021

Abstract

Background
We performed a population-based study to describe the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on pregnancy outcomes.

Methods
This prospective, population-based study included pregnant women who consecutively presented at first/second trimester visits or at delivery at 3 hospitals in Barcelona, Spain. SARS-CoV-2 antibodies (immunoglobulin [Ig] G and IgM/IgA) were measured in all participants, and nasopharyngeal real-time polymerase chain reaction (RT-PCR) was performed at delivery. The primary outcome was a composite of pregnancy complications in SARS-CoV-2–positive vs negative women that included miscarriage, preeclampsia, preterm delivery, perinatal death, small-for-gestational-age newborn, or neonatal admission. Secondary outcomes were components of the primary outcome plus abnormal fetal growth, malformation, or intrapartum fetal distress. Outcomes were also compared between positive symptomatic and positive asymptomatic SARS-CoV-2 women.

Results
Of 2225 pregnant women, 317 (14.2%) were positive for SARS-CoV-2 antibodies (n = 314, 99.1%) and/or RT-PCR (n = 36, 11.4%). Among positive women, 217 (68.5%) were asymptomatic, 93 (29.3%) had mild coronavirus disease 2019 (COVID-19), and 7 (2.2%) had pneumonia, of whom 3 required intensive care unit admission. In women with and without SARS-CoV-2 infection, the primary outcome occurred in 43 (13.6%) and 268 (14%), respectively (risk difference, –0.4%; 95% confidence interval, –4.1% to 4.1). Compared with noninfected women, those with symptomatic COVID-19 had increased rates of preterm delivery (7.2% vs 16.9%, P = .003) and intrapartum fetal distress (9.1% vs 19.2%, P = .004), while asymptomatic women had rates that were similar to those of noninfected cases. Among 143 fetuses from infected mothers, none had anti–SARS-CoV-2 IgM/IgA in cord blood.

Conclusions
The overall rate of pregnancy complications in women with SARS-CoV-2 infection was similar to that of noninfected women. However, symptomatic COVID-19 was associated with modest increases in preterm delivery and intrapartum fetal distress.
Plasma Citrate and Succinate Are Associated With Neurocognitive Impairment in Older People With HIV
Authors: Hileman Corrilynn O , Kalayjian Robert C , Azzam Sausan , Schlatzer Daniela , Wu Kunling , Tassiopoulos Katherine , Bedimo Roger , Ellis Ronald J , Erlandson Kristine M , Kallianpur Asha , Koletar Susan L , Landay Alan L , Palella Frank J , Taiwo Babafemi , Pallaki Muralidhar , Hoppel Charles L 
Published: February 2021

Abstract

Background
Neurocognitive impairment (NCI) is associated with monocyte activation in people with HIV (PWH). Activated monocytes increase glycolysis, reduce oxidative phosphorylation, and accumulate citrate and succinate, tricarboxylic acid (TCA) cycle metabolites that promote inflammation—this metabolic shift may contribute to NCI and slowed gait speed in PWH.

Methods
Plasma citrate and succinate were assayed by liquid chromatography–mass spectrometry from 957 participants upon entry to a multicenter, prospective cohort of older PWH. Logistic, linear, and mixed-effects linear regression models were used to examine associations between entry/baseline TCA cycle metabolites and cross-sectional and longitudinal NCI, neuropsychological test scores (NPZ-4), and gait speed.

Results
Median age was 51 (range 40–78) years. Each 1 standard deviation (SD) citrate increment was associated with 1.18 higher odds of prevalent NCI at baseline (P = .03), 0.07 SD lower time-updated NPZ-4 score (P = .01), and 0.02 m/s slower time-updated gait speed (P &lt; .0001). Age accentuated these effects. In the oldest age-quartile, higher citrate was associated with 1.64 higher odds of prevalent NCI, 0.17 SD lower NPZ-4, and 0.04 m/s slower gait speed (P ≤ .01 for each). Similar associations were apparent with succinate in the oldest age-quintile, but not with gait speed. In participants without NCI at entry, higher citrate predicted a faster rate of neurocognitive decline.

Conclusions
Higher plasma citrate and succinate are associated with worse cross-sectional and longitudinal measures of neurocognitive function and gait speed that are age-dependent, supporting the importance of altered bioenergetic metabolism in the pathogenesis of NCI in older PWH.
Fine-tuning the cardiac O-GlcNAcylation regulatory enzymes governs the functional and structural phenotype of the diabetic heart
Authors: Prakoso Darnel , Lim Shiang Y , Erickson Jeffrey R , Wallace Rachel S , Lees Jarmon G , Tate Mitchel , Kiriazis Helen , Donner Daniel G , Henstridge Darren C , Davey Jonathan R , Qian Hongwei , Deo Minh , Parry Laura J , Davidoff Amy J , Gregorevic Paul , Chatham John C , De Blasio Miles J , Ritchie Rebecca H 
Published: February 2021

Abstract

Aims
The glucose-driven enzymatic modification of myocardial proteins by the sugar moiety, β-N-acetylglucosamine (O-GlcNAc), is increased in pre-clinical models of diabetes, implicating protein O-GlcNAc modification in diabetes-induced heart failure. Our aim was to specifically examine cardiac manipulation of the two regulatory enzymes of this process on the cardiac phenotype, in the presence and absence of diabetes, utilising cardiac-targeted recombinant-adeno-associated viral-vector-6 (rAAV6)-mediated gene delivery.

Methods and results
In human myocardium, total protein O-GlcNAc modification was elevated in diabetic relative to non-diabetic patients, and correlated with left ventricular (LV) dysfunction. The impact of rAAV6-delivered O-GlcNAc transferase (rAAV6-OGT, facilitating protein O-GlcNAcylation), O-GlcNAcase (rAAV6-OGA, facilitating de-O-GlcNAcylation), and empty vector (null) were determined in non-diabetic and diabetic mice. In non-diabetic mice, rAAV6-OGT was sufficient to impair LV diastolic function and induce maladaptive cardiac remodelling, including cardiac fibrosis and increased Myh-7 and Nppa pro-hypertrophic gene expression, recapitulating characteristics of diabetic cardiomyopathy. In contrast, rAAV6-OGA (but not rAAV6-OGT) rescued LV diastolic function and adverse cardiac remodelling in diabetic mice. Molecular insights implicated impaired cardiac PI3K(p110α)-Akt signalling as a potential contributing mechanism to the detrimental consequences of rAAV6-OGT in vivo. In contrast, rAAV6-OGA preserved PI3K(p110α)-Akt signalling in diabetic mouse myocardium in vivo and prevented high glucose-induced impairments in mitochondrial respiration in human cardiomyocytes in vitro.

Conclusion
Maladaptive protein O-GlcNAc modification is evident in human diabetic myocardium, and is a critical regulator of the diabetic heart phenotype. Selective targeting of cardiac protein O-GlcNAcylation to restore physiological O-GlcNAc balance may represent a novel therapeutic approach for diabetes-induced heart failure.
Tilt testing remains a valuable asset
Authors: Sutton Richard , Fedorowski Artur , Olshansky Brian , Gert van Dijk J , Abe Haruhiko , Brignole Michele , de Lange Frederik , Kenny Rose Anne , Lim Phang Boon , Moya Angel , Rosen Stuart D , Russo Vincenzo , Stewart Julian M , Thijs Roland D , Benditt David G 
Published: February 2021

AbstractHead-up tilt test (TT) has been used for &gt;50 years to study heart rate/blood pressure adaptation to positional changes, to model responses to haemorrhage, to assess orthostatic hypotension, and to evaluate haemodynamic and neuroendocrine responses in congestive heart failure, autonomic dysfunction, and hypertension. During these studies, some subjects experienced syncope due to vasovagal reflex. As a result, tilt testing was incorporated into clinical assessment of syncope when the origin was unknown. Subsequently, clinical experience supports the diagnostic value of TT. This is highlighted in evidence-based professional practice guidelines, which provide advice for TT methodology and interpretation, while concurrently identifying its limitations. Thus, TT remains a valuable clinical asset, one that has added importantly to the appreciation of pathophysiology of syncope/collapse and, thereby, has improved care of syncopal patients.
Smartphone electrocardiogram for detecting atrial fibrillation after a cerebral ischaemic event: a multicentre randomized controlled trial
Authors: Koh Keng Tat , Law Wan Chung , Zaw Win Moe , Foo Diana Hui Ping , Tan Chen Ting , Steven Anderson , Samuel Desmond , Fam Tem Lom , Chai Ching Hua , Wong Zhai Sing , Xaviar Sivaraj , Bhavnani Chandan Deepak , Tan Jason Seng Hong , Oon Yen Yee , Said Asri , Fong Alan Yean Yip , Ong Tiong Kiam 
Published: February 2021

Abstract

Aims
Atrial fibrillation (AF) is a preventable cause of ischaemic stroke but it is often undiagnosed and undertreated. The utility of smartphone electrocardiogram (ECG) for the detection of AF after ischaemic stroke is unknown. The aim of this study is to determine the diagnostic yield of 30-day smartphone ECG recording compared with 24-h Holter monitoring for detecting AF ≥30 s.

Methods and results
In this multicentre, open-label study, we randomly assigned 203 participants to undergo one additional 24-h Holter monitoring (control group, n = 98) vs. 30-day smartphone ECG monitoring (intervention group, n = 105) using KardiaMobile (AliveCor®, Mountain View, CA, USA). Major inclusion criteria included age ≥55 years old, without known AF, and ischaemic stroke or transient ischaemic attack (TIA) within the preceding 12 months. Baseline characteristics were similar between the two groups. The index event was ischaemic stroke in 88.5% in the intervention group and 88.8% in the control group (P = 0.852). AF lasting ≥30 s was detected in 10 of 105 patients in the intervention group and 2 of 98 patients in the control group (9.5% vs. 2.0%; absolute difference 7.5%; P = 0.024). The number needed to screen to detect one AF was 13. After the 30-day smartphone monitoring, there was a significantly higher proportion of patients on oral anticoagulation therapy at 3 months compared with baseline in the intervention group (9.5% vs. 0%, P = 0.002).

Conclusions
Among patients ≥55 years of age with a recent cryptogenic stroke or TIA, 30-day smartphone ECG recording significantly improved the detection of AF when compared with the standard repeat 24-h Holter monitoring.