bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparing posaconazole and itraconazole for antifungal prophylaxis in critically ill lung transplant recipients: Efficacy and plasma concentrations
Authors: Kallee Simon , Scharf Christina , Schroeder Ines , Paal Michael , Vogeser Michael , Irlbeck Michael , Zander Johannes , Zoller Michael , Jung Jette , Kneidinger Nikolaus , Schneider Christian , Michel Sebastian , Liebchen Uwe
Published: June 2021

Background

Posaconazole and itraconazole are commonly used for systemic antifungal prophylaxis after lung transplantation. The aim of this study on critically ill lung transplant recipients was to assess the rate of adequate plasma concentrations and the frequency of fungal‐induced transitions from antifungal prophylaxis to therapy after the administration of either posaconazole or itraconazole for systemic prophylaxis.

Methods

Critically ill lung transplant recipients with postoperative posaconazole or itraconazole prophylaxis and therapeutic drug monitoring from February 2016 to November 2019 were retrospectively included in the study. Positive fungal cultures or Aspergillus antigen tests resulting in a transition from antifungal prophylaxis to therapy were analyzed from the first day of prophylaxis until 7 days after the last sample for each patient. Adequate plasma concentrations were defined as ≥500 µg/L for itraconazole and ≥700 µg/L for posaconazole.

Results

Two hundred seventy‐five samples from 73 patients were included in the analysis. Overall, 60% of the posaconazole and 55% of the itraconazole concentrations were subtherapeutic. Administration of posaconazole suspension resulted significantly (P < .01) more often in subtherapeutic concentrations than tablets (68% vs 10%). Patients treated with posaconazole showed less positive fungal records resulting in a transition from prophylaxis to therapy than patients treated with itraconazole (10% vs 33%, P‐value: .029). The detection of a fungal pathogen was not associated with the measured plasma concentrations or the achievement of the target concentrations.

Conclusion

Our findings suggest that posaconazole should be used instead of itraconazole for systemic prophylaxis in critically ill lung transplant recipients.
Theory of Mind From Observation in Cognitive Models and Humans
Authors: Nguyen Thuy Ngoc , Gonzalez Cleotilde
Published: June 2021

A major challenge for research in artificial intelligence is to develop systems that can infer the goals, beliefs, and intentions of others (i.e., systems that have theory of mind, ToM). In this research, we propose a cognitive ToM framework that uses a well‐known theory of decisions from experience to construct a computational representation of ToM. Instance‐based learning theory (IBLT) is used to construct a cognitive model that generates ToM from the observation of other agents' behavior. The IBL model of the observer distinguishes itself from previous models of ToM that make unreasonable assumptions about human cognition, are hand‐crafted for particular settings, complex, or unable to explain a cognitive development of ToM compared to human's ToM. The IBL model learns from the observation of goal‐directed agents' behavior in a gridworld navigation task, and it infers and predicts the behaviors of the agents in new gridworlds across different degrees of decision complexity in similar ways to the way human observers do. We provide evidence for the alignment of the IBL observer's predictions under various levels of decision complexity. We also advance the demonstration of the IBL predictions using a classic test of false beliefs (the Sally–Anne test), which is commonly used to test ToM in humans. We discuss our results and the potential of the IBL observer model to improve human–machine interactions.
Meta‐analysis of transcriptomic studies of cytokinin‐treated rice roots defines a core set of cytokinin response genes
Authors: Polko Joanna K. , Potter Kevin C. , Burr Christian A. , Schaller G. Eric , Kieber Joseph J.
Published: June 2021

Cytokinins regulate diverse aspects of plant growth and development, primarily through modulation of gene expression. The cytokinin‐responsive transcriptome has been thoroughly described in dicots, especially Arabidopsis, but much less so in monocots. Here, we present a meta‐analysis of five different transcriptomic analyses of rice (Oryza sativa) roots treated with cytokinin, including three previously unpublished experiments. We developed a treatment method in which hormone is added to the media of rice seedlings grown in sterile hydroponic culture under a continuous airflow, which resulted in minimal perturbation of the seedlings, thus greatly reducing changes in gene expression in the absence of exogenous hormone. We defined a core set of 205 upregulated and 86 downregulated genes that were differentially expressed in at least three of the transcriptomic datasets. This core set includes genes encoding the type‐A response regulators (RRs) and cytokinin oxidases/dehydrogenases, which have been shown to be primary cytokinin response genes. GO analysis revealed that the upregulated genes were enriched for terms related to cytokinin/hormone signaling and metabolism, while the downregulated genes were significantly enriched for genes encoding transporters. Variations of type‐B RR binding motifs were significantly enriched in the promoters of the upregulated genes, as were binding sites for other potential partner transcription factors. The promoters of the downregulated genes were generally enriched for distinct cis‐acting motifs and did not include the type‐B RR binding motif. This analysis provides insight into the molecular mechanisms underlying cytokinin action in a monocot and provides a useful foundation for future studies of this hormone in rice and other cereals.
Has the trend of declining blood transfusions in the United States ended? Findings of the 2019 National Blood Collection and Utilization Survey
Authors: Jones Jefferson M. , Sapiano Mathew R. P. , Mowla Sanjida , Bota Dorothy , Berger James J. , Basavaraju Sridhar V.
Published: June 2021

Introduction

Previous iterations of National Blood Collection and Utilization Survey (NBCUS) have demonstrated declines in blood collection and transfusion in the United States since 2008, including declines of 3.0% and 6.1% in red blood cell (RBC) collections and transfusions between 2015 and 2017, respectively. This study describes results of the 2019 NBCUS.

Methods

The survey was distributed to all US blood collection centers, all hospitals performing ≥1000 surgeries annually, and a 40% random sample of hospitals performing 100–999 surgeries annually. Weighting and imputation were used to generate national estimates for units of blood and components collected, distributed, transfused, and outdated.

Results

In 2019, 11,590,000 RBC units were collected (95% confidence interval [CI], 11,151,000–12,029,000 units), a 5.1% decrease compared with 2017, while 10,852,000 RBC units were transfused (95% CI, 10,444–11,259 units), a 2.5% increase from 2017. Between 2017 and 2019, platelet distributions (2,508,000 units; 95% CI, 2,375,000–2,641,000 units) decreased by 2.0%, and plasma distributions (2,679,000 units; 95% CI, 2,525,000–2,833,000 units) decreased by 16.5%. During the same time period, platelet transfusions (2,243,000 units; 95% CI, 1,846,000–2,147,000 units) increased by 15.8% and plasma transfusions (2,185,000 units; 95% CI, 2,068,000–2,301,000 units) decreased by 8.0%.

Conclusion

Utilization of RBC in the United States might have reached a nadir. Between 2017 and 2019, RBC collections declined while RBC transfusions did not significantly change, suggesting a narrowing between blood supply and demand. Monitoring national blood collection and utilization data is integral to understanding trends in blood supply safety and availability.
T cells mediate cell non‐autonomous arterial ageing in mice
Authors: Trott Daniel W. , Machin Daniel R. , Phuong Tam T. T. , Adeyemo AdeLola O. , Bloom Samuel I. , Bramwell R. Colton , Sorensen Eric S. , Lesniewski Lisa A. , Donato Anthony J.
Published: June 2021

Key points

Increased large artery stiffness and impaired endothelium‐dependent dilatation occur with advanced age.

We sought to determine whether T cells mechanistically contribute to age‐related arterial dysfunction.

We found that old mice exhibited greater proinflammatory T cell accumulation around both the aorta and mesenteric arteries.

Pharmacologic depletion or genetic deletion of T cells in old mice resulted in ameliorated large artery stiffness and greater endothelium‐dependent dilatation compared with mice with T cells intact.

Ageing of the arteries is characterized by increased large artery stiffness and impaired endothelium‐dependent dilatation. T cells contribute to hypertension in acute rodent models but whether they contribute to chronic age‐related arterial dysfunction is unknown. To determine whether T cells directly mediate age‐related arterial dysfunction, we examined large elastic artery and resistance artery function in young (4–6 months) and old (22–24 months) wild‐type mice treated with anti‐CD3 F(ab’2) fragments to deplete T cells (150 μg, i.p. every 7 days for 28 days) or isotype control fragments. Old mice exhibited greater numbers of T cells in both aorta and mesenteric vasculature when compared with young mice. Old mice treated with anti‐CD3 fragments exhibited depletion of T cells in blood, spleen, aorta and mesenteric vasculature. Old mice also exhibited greater numbers of aortic and mesenteric IFN‐γ and TNF‐α‐producing T cells when compared with young mice. Old control mice exhibited greater large artery stiffness and impaired resistance artery endothelium‐dependent dilatation in comparison with young mice. In old mice, large artery stiffness was ameliorated with anti‐CD3 treatment. Anti‐CD3‐treated old mice also exhibited greater endothelium‐dependent dilatation than age‐matched controls. We also examined arterial function in young and old Rag‐1–/– mice, which lack lymphocytes. Rag‐1–/– mice exhibited blunted increases in large artery stiffness with age compared with wild‐type mice. Old Rag‐1–/– mice also exhibited greater endothelium‐dependent dilatation compared with old wild‐type mice. Collectively, these results demonstrate that T cells play an important role in age‐related arterial dysfunction.
Hybrid molecular beam epitaxy growth of BaTiO3 films
Authors: Nunn William , Sandlass Sara , Wegner Maike , Haislmaier Ryan , Kumar Abinash , Tangi Malleswararao , LeBeau James , Quandt Eckhard , James Richard D. , Jalan Bharat
Published: June 2021

The ability to reproducibly synthesize thin films with precise composition and controlled structure is essential for fundamental study and mass production. Here, we demonstrate the hybrid molecular beam epitaxy (MBE) growth of epitaxial, single crystalline BaTiO3 films with different thicknesses on Nb-doped SrTiO3 substrates with atomically smooth surfaces. By combining scanning transmission electron microscopy, temperature-dependent high-resolution x-ray diffraction, reflection high-energy electron diffraction, and atomic force microscopy, we study the effect of growth conditions and the interplay between stoichiometry and epitaxial strain on the resulting structure. Furthermore, we demonstrate a close to bulk-like ferroelectric phase transition in thicker films and highlight the effect of strain on the phase transition temperature. This work establishes the hybrid MBE approach for the growth of heteroepitaxial BaTiO3 films on conducting substrates with scalable thickness and controlled stoichiometry.
The DNA binding arm of lambda repressor: critical contacts from a flexible region
Authors: Clarke ND , Beamer LJ , Goldberg HR , Berkower C , Pabo CO
Published: June 2021

Segments of protein that do not adopt a well-ordered conformation in the absence of DNA can still contribute to site-specific recognition of DNA. The first six residues (NH2-Ser1-Thr2-Lys3-Lys4-Lys5-Pro6-) of phage lambda repressor are flexible but are important for site-specific binding. Low-temperature x-ray crystallography and codondirected saturation mutagenesis were used to study the role of this segment. All of the functional sequences have the form [X]1-[X]2-[Lys or Arg]3-[Lys]4-[Lys or Arg]5-[X]6. A high-resolution (1.8 angstrom) crystal structure shows that Lys3 and Lys4 each make multiple hydrogen bonds with guanines and that Lys5 interacts with the phosphate backbone. The symmetry of the complex breaks down near the center of the site, and these results suggest a revision in the traditional alignment of the six lambda operator sites.
Long-term high-titer neutralizing activity induced by octameric synthetic HIV-1 antigen
Authors: Wang CY , Looney DJ , Li ML , Walfield AM , Ye J , Hosein B , Tam JP , Wong-Staal F
Published: June 2021

A titer for homologous viral neutralization activity (greater than 1:19,683) was observed after a 3.5-year immunization period with an octameric, branching peptide representing the principal neutralizing determinant (PND) of the human immunodeficiency virus-1IIIB envelope protein. Booster immunizations elicited persistent and potent antibodies in guinea pigs, exceeding responses produced by a conventional bovine serum albumin conjugate by 100-fold. Peptide length, central presentation of a conserved sequence, and inclusion of an upstream sequence contributed to immunogenicity. Titers (greater than 1:1,000) of heterotypic neutralizing antibodies also developed. Octameric PND peptides are a promising approach for an acquired immunodeficiency syndrome (AIDS) vaccine.
Structural basis for enhanced infectivity and immune evasion of SARS-CoV-2 variants
Authors: Cai Yongfei , Zhang Jun , Xiao Tianshu , Lavine Christy L. , Rawson Shaun , Peng Hanqin , Zhu Haisun , Anand Krishna , Tong Pei , Gautam Avneesh , Lu Shen , Sterling Sarah M. , Walsh Richard M. , Rits-Volloch Sophia , Lu Jianming , Wesemann Duane R. , Yang Wei , Seaman Michael S. , Chen Bing
Published: June 2021

SARS-CoV-2 from alpha to epsilon

As battles to contain the COVID-19 pandemic continue, attention is focused on emerging variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus that have been deemed variants of concern because they are resistant to antibodies elicited by infection or vaccination or they increase transmissibility or disease severity. Three papers used functional and structural studies to explore how mutations in the viral spike protein affect its ability to infect host cells and to evade host immunity. Gobeil
et al
. looked at a variant spike protein involved in transmission between minks and humans, as well as the B1.1.7 (alpha), B.1.351 (beta), and P1 (gamma) spike variants; Cai
et al
. focused on the alpha and beta variants; and McCallum
et al
. discuss the properties of the spike protein from the B1.1.427/B.1.429 (epsilon) variant. Together, these papers show a balance among mutations that enhance stability, those that increase binding to the human receptor ACE2, and those that confer resistance to neutralizing antibodies. —VV
Complete Genome Sequences of Six Staphylococcus pseudintermedius Strains from Dogs with Superficial Pyoderma in Georgia, USA
Authors: Byukusenge Maurice , Banovic Frane , Li Lingling , Kuchipudi Suresh V. , Jayarao Bhushan M. , Watson Cynthia K. , Naikare Hemant K.
Published: June 2021

Staphylococcus pseudintermediusis a pathogen of veterinary importance, as it is the major causative agent of superficial pyoderma in dogs. We present the complete genome sequences of six strains ofS. pseudintermediusderived from dogs affected with epidermal collarettes and superficial bacterial folliculitis, which are two variants of superficial pyoderma.
High-Quality Draft Genome Sequence of the Siderophilic and Thermophilic
Leptolyngbyaceae
Cyanobacterium JSC-12
Authors: Brown Igor , Tringe Susannah G. , Ivanova Natalia , Goodwin Lynne , Shapiro Nicole , Alcorta Jaime , Pan Donald , Chistoserdov Andrei , Sarkisova Svetlana , Woyke Tanja
Published: June 2021

The siderophilic, thermophilic
Leptolyngbyaceae
cyanobacterium JSC-12 was isolated from a microbial mat in an iron-depositing hot spring. Here, we report the high-quality draft genome sequence of JSC-12, which may help elucidate the mechanisms of resistance to extreme iron concentrations in siderophilic cyanobacteria and lead to new remediation biotechnologies.
Seismic fault weakening via CO2 pressurization enhanced by mechanical deformation of dolomite fault gouges
Authors: Kim Hyun Na , So Byung-Dal , Kim Min Sik , Han Kee Sung , Oh Sol Bi
Published: June 2021

Carbon dioxide emissions from dolomite decarbonation play an essential role in the weakening of carbonate faults by lowering the effective normal stress, which is thermally activated at temperatures above 600–700 °C. However, the mechanochemical effect of low-crystalline ultrafine fault gouge on the decarbonation and slip behavior of dolomite-bearing faults remains unclear. In this study, we obtained a series of artificial dolomite fault gouges with systematically varying particle sizes and dolomite crystallinities using a high-energy ball mill. The laboratory-scale pulverization of dolomite yielded MgO at temperatures below 50 °C, indicating that mechanical decarbonation without significant heating occurred due to the collapse of the crystalline structure, as revealed by X-ray diffraction and solid-state nuclear magnetic resonance results. Furthermore, the onset temperature of thermal decarbonation decreased to ∼400 °C. Numerical modeling reproduced this two-stage decarbonation, where the pore pressure increased due to low-temperature thermal decarbonation, leading to slip weakening on the fault plane even at 400–500 °C; i.e., 200–300 °C lower than previously reported temperatures. Thus, the presence of small amounts of low-crystalline dolomite in a fault plane may lead to a severely reduced shear strength due to thermal decomposition at ∼400 °C with a small slip weakening distance.
Prior oil and gas production can limit the occurrence of injection-induced seismicity: A case study in the Delaware Basin of western Texas and southeastern New Mexico, USA
Authors: Dvory Noam Z. , Zoback Mark D.
Published: June 2021

We demonstrate that pore pressure and stress changes resulting from several decades of oil and gas production significantly affect the likelihood of injection-related induced seismicity. We illustrate this process in the Delaware Basin (western Texas and southeastern New Mexico, USA), in which hydraulic fracturing and waste-water injection have been inducing numerous earthquakes in the southernmost part of the basin where there has been no prior oil and gas production from the formations in which the earthquakes are now occurring. In the seismically quiescent part of the basin, we show that pore-pressure and poroelastic-stress changes associated with prior oil and gas production make induced seismicity less likely. The findings of this study have important implications for the feasibility of large-scale carbon storage in depleted oil and gas reservoirs.
Igneous rock area and age in continental crust
Authors: Peters Shanan E. , Walton Craig R. , Husson Jon M. , Quinn Daven P. , Shorttle Oliver , Keller C. Brenhin , Gaines Robert R.
Published: June 2021

Rock quantity and age are fundamental features of Earth's crust that pertain to many problems in geoscience. Here we combine new estimates of igneous rock area in continental crust from the Macrostrat database (https://macrostrat.org/) with a compilation of detrital zircon ages in order to investigate rock cycling and crustal growth. We find that there is little or no decrease in igneous rock area with increasing rock age. Instead, igneous rock area in North America exhibits four distinct Precambrian peaks, remains low through the Neoproterozoic, and then increases only modestly toward the recent. Peaks in Precambrian detrital zircon age frequency distributions align broadly with peaks in igneous rock area, regardless of grain depositional age. However, detrital zircon ages do underrepresent a Neoarchean peak in igneous rock area; young grains and ca. 1.1 Ga grains are also overrepresented relative to igneous area. Together, these results suggest that detrital zircon age distributions contain signatures of continental denudation and sedimentary cycling that are decoupled from the cycling of igneous source rocks. Models of continental crustal evolution that incorporate significant early increase in volume and increased sedimentation in the Phanerozoic are well supported by these data.
Supplemental Material: Skarn fluid sources as indicators of timing of Cordilleran arc emergence and paleogeography in the southwestern United States
Authors: Gevedon Michelle , al. et
Published: June 2021

A complete description of analytical methods used in this study and tables of all isotopic data.
Supplemental Material: Extreme fractionation of selenium isotopes and possible deep biospheric origin of platinum nuggets from Minas Gerais, Brazil
Authors: Cabral Alexandre R. , al. et
Published: June 2021

Methods and data tables.
Physicochemical Interaction Processes in the Carbon (Diamond)–Silicon System
Authors: Shevchenko V. Ya. , Perevislov S. N. , Ugolkov V. L.
Published: June 2021

The chemical processes occurring during the interaction of carbon (diamond) with silicon are experimentally investigated. Thermal analysis of the interaction of diamond with silicon is carried out. This made it possible to determine the mechanism of the synthesis of silicon carbide and subsequent reaction sintering of diamond particles based on Turing’s reaction-diffusion process and the formation of a microstructure consisting of triple periodic surfaces of the minimal energy.
Atypical presentation of allergic interstitial nephritis likely induced by ciprofloxacin
Authors: Valdez Imbert Ronald , Sekulic Miroslav , Saad Pir , Jim Belinda
Published: June 2021

Though the prevalence of drug induced allergic interstitial nephritis (AIN) appears to be increasing, the diagnostic and treatment strategies still remain vague. We present a 56-year-old man with a history of hypertension, chronic kidney disease stage IIIa, recent exposure to ciprofloxacin who presented with acute kidney injury. Though the suspicion of AIN was high, his urinary sediment was bland, that is, no leucocytes or leucocyte casts. A renal biopsy subsequently showed features of AIN correlating with a resolving phase of inflammation. Given the resolving nature of the pathology, we chose not to complete a course of corticosteroids despite his need for temporary haemodialysis. He was able to fully recover his renal function. In this report, we emphasise the unreliable nature of the urinary sediment in the diagnosis of AIN, the utility of a renal biopsy in helping to guide treatment, and the controversial data in corticosteroid treatment.
Saccular aneurysm of the iliofemoral vein: an uncommon mimic of an occult inguinal hernia
Authors: Metzger Gregory , Doughton John
Published: June 2021

A 72-year-old man presented to clinic with a 1-week history of worsening groin pain. He had a normal hip examination and tenderness worsened with valsalva, but no mass palpated in the inguinal region. He was found to have a large saccular aneurysm of the iliofemoral vein on ultrasound and subsequently started on anticoagulation and referred to vascular surgery.
Morphological characteristics preceding exudative neovascularisation secondary to macular telangiectasia type 2
Authors: Hess Kristina , Charbel Issa Peter , Holz Frank G , Tzaridis Simone
Published: June 2021

Aims

To identify morphological characteristics preceding the development of exudative neovascularisation secondary to Macular Telangiectasia type 2 (MacTel) using multimodal retinal imaging.

Methods

In this retrospective study, eyes with a minimum observation period of 6 months prior to the de novo diagnosis of an exudative neovascularisation secondary to MacTel were analysed. Morphological changes preceding the formation of neovascularisation were evaluated using colour fundus photography, infrared imaging, fluorescein angiography, macular pigment measurement and optical coherence tomography (OCT). OCT-angiography (OCT-A) images were additionally available in a subset of patients.

Results

Twenty eyes from 20 patients were examined over a median period of 17 months (range: 6–100 months). Eyes were characterised by an accelerated progression of ellipsoid zone loss (median of 0.013 mm2/month), increased thickness of the temporal parafovea and hyper-reflective lesions on OCT. The latter underwent morphological changes preceding the development of exudative neovascularisation, including an increase in size and density, and expansion to outer retinal layers and the retinal pigment epithelium. All eyes showed a foveal depletion of macular pigment. On OCT-A, a focal increase in blood flow was observed at the level of the outer retina/choriocapillaris, and retinal–retinal and retinal–choroidal anastomoses preceded the formation of exudative neovascularisation.

Conclusions

Multimodal imaging allows the identification of prognostic morphological features preceding the formation of exudative neovascularisation in MacTel. Eyes exhibiting these characteristics should be monitored closely and patients should be alert for emergent symptoms in order to detect and treat neovascularisation early and, thereby, prevent irreversible visual loss.
Saliva 1,5-anhydroglucitol is associated with early-phase insulin secretion in Chinese patients with type 2 diabetes
Authors: Ying Lingwen , Jian Chaohui , Ma Xiaojing , Ge Kun , Zhu Wei , Wang Yufei , Zhao Aihua , Zhou Jian , Jia Wei , Bao Yuqian
Published: June 2021

Introduction

Saliva collection is a non-invasive test and is convenient. 1,5-anhydroglucitol (1,5-AG) is a new indicator reflecting short-term blood glucose levels. This study aimed to explore the relationship between saliva 1,5-AG and insulin secretion function and insulin sensitivity.

Research design and methods

Adult patients with type 2 diabetes who were hospitalized were enrolled. Based on blood glucose and C-peptide, homeostasis model assessment 2 for β cell secretion function, C-peptidogenic index (CGI), △2-hour C-peptide (2hCP)/△2-hour postprandial glucose (2hPG), ratio of 0–30 min area under the curve for C-peptide and area under the curve for glucose (AUCCP30/AUCPG30), and AUC2hCP/AUC2hPGwere calculated to evaluate insulin secretion function, while indicators such as homeostasis model assessment 2 for insulin resistance were used to assess insulin sensitivity.

Results

We included 284 subjects (178 men and 106 women) with type 2 diabetes aged 20–70 years. The saliva 1,5-AG level was 0.133 (0.089–0.204) µg/mL. Spearman’s correlation analysis revealed a significantly negative correlation between saliva 1,5-AG and 0, 30, and 120 min blood glucose, glycated hemoglobin A1c, and glycated albumin (all p<0.05), and a significantly positive association between saliva 1,5-AG and CGI (r=0.171, p=0.004) and AUCCP30/AUCPG30(r=0.174, p=0.003). The above correlations still existed after adjusting for age, sex, body mass index, and diabetes duration. In multiple linear regression, saliva 1,5-AG was an independent factor of CGI (standardizedβ=0.135, p=0.015) and AUCCP30/AUCPG30(standardizedβ=0.110, p=0.020).

Conclusions

Saliva 1,5-AG was related to CGI and AUCCP30/AUCPG30in patients with type 2 diabetes.

Trial registration number

ChiCTR-SOC-17011356.
BASAN index (Body mass index, Age, Sex, Arterial hypertension and Neck circumference) predicts severe apnoea in adults living at high altitude
Authors: Oliveros Henry , Lobelo Rafael , Giraldo-Cadavid Luis Fernando , Bastidas Alirio , Ballesteros Constanza , Bernal Rafael , Patiño Lilian , Herrera Karen , Gozal David
Published: June 2021

Objectives

Obstructive sleep apnoea (OSA)/hypopnoea syndrome is associated with serious and major multiorgan morbidities, particularly in its most severe forms. However, no severe OSA screening instruments are available for high altitude residents that enable adequate identification and clinical prioritisation of such patients. We aimed at developing a severe OSA prediction tool based on the clinical characteristics and anthropometric measurements of a clinical referral cohort living at 2640 m.a.s.l.

Design

Cohort-nested cross-sectional study.

Setting

Sleep laboratory for standard polysomnography (PSG) in Colombia.

Participants

A predictive model was generated from 8718 participants referred to the PSG laboratory. Results were subsequently validated in a second cohort of 1898 participants.

Primary outcome

To identify clinical and anthropometric variables associated with severe OSA (>30 events/hour) and to include them in a binary logistic regression model.

Results

The significant variables that were retained with the presence of severe OSA included Body mass index (BMI), Age, Sex, Arterial hypertension and Neck circumference (BASAN). The area under the receiver operating characteristic curvefor the BASAN index was 0.69 (95% CI: 0.68 to 0.70) in the derivation cohort and 0.67 (95% CI: 0.65 to 0.69) in the validation cohort, whereby a BASAN index ≥2 had a sensitivity of 95% and a specificity of 17% to detect severe OSA.

Conclusion

An objectively based approach to screen for the presence of severe OSA, the BASAN index, exhibits favourable sensitivity characteristics that should enable its operational use as a screening tool in a Hispanic population with a clinical suspicion of OSA and living at high altitude.
Associations between daily screen time and sleep in a racially and socioeconomically diverse sample of US infants: a prospective cohort study
Authors: Emond Jennifer A , O'Malley A James , Neelon Brian , Kravitz Richard M , Ostbye Truls , Benjamin-Neelon Sara E
Published: June 2021

Objective

To determine the associations between screen media use and sleep throughout infancy (3–12 months).

Design

Prospective Nurture birth cohort.

Setting

North Carolina, USA, 2013–2015.

Participants

Women enrolled in their second to third trimester, completed a phone interview after birth, and completed home visits at 3, 6, 9 and 12 months post partum.

Primary and secondary outcome measures

Women reported the usual hours their infants slept during the day and night and their infants’ usual use of five screen media activities at 3, 6, 9 and 12 months post partum. Adjusted mixed-effects regression analyses modelled the associations between infant screen time and sleep outcomes while disaggregating the between-infant and within-infant effects.

Results

Among 558 mother–infant dyads, 374 (67.0%) infants were black and 304 (54.5%) households earned <$20 000 per year. Half (254, 50.2%) of the infants engaged with screens at 3 months of age, while 326 (72.9%) engaged at 12 months. The median value of the average daily screen time over the study period was 50 (IQR: 10–141) min. Infant screen time was inversely associated with night-time sleep duration only when considering between-infant effects (adjusted beta: −2.9; 95% CI −5.9 to 0.0; p=0.054 for log-transformed screen time). Effects were stronger for television+DVD viewing specifically (adjusted beta: −5.2; 95% CI −9.1 to −1.4; p<0.01 for log-transformed television+DVD time). For example, an infant who averaged 1 hour of television+DVD viewing over the study period slept, on average, 9.20 (95% CI 9.02 to 9.37) hours per night by 12 months compared with 9.60 (95% CI 9.41 to 9.80) hours per night for an infant with no screen time over the study period. There were no significant within-infant effects between screen time and night-time sleep, and screen time was not associated with daytime sleep or night-time awakenings.

Conclusions

Screen time during infancy was inversely associated with night-time sleep duration; however, causal associations remain uncertain.

Trial registration number

NCT01788644.
Methodological review to develop a list of bias items used to assess reviews incorporating network meta-analysis: protocol and rationale
Authors: Lunny Carole , Tricco Andrea C , Veroniki Areti-Angeliki , Dias Sofia , Hutton Brian , Salanti Georgia , Wright James M , White Ian , Whiting Penny
Published: June 2021

Introduction

Systematic reviews with network meta-analysis (NMA; ie, multiple treatment comparisons, indirect comparisons) have gained popularity and grown in number due to their ability to provide comparative effectiveness of multiple treatments for the same condition. The methodological review aims to develop a list of items relating to biases in reviews with NMA. Such a list will inform a new tool to assess the risk of bias in NMAs, and potentially other reporting or quality checklists for NMAs which are being updated.

Methods and analysis

We will include articles that present items related to bias, reporting or methodological quality, articles assessing the methodological quality of reviews with NMA, or papers presenting methods for NMAs. We will search Ovid MEDLINE, the Cochrane library and difficult to locate/unpublished literature. Once all items have been extracted, we will combine conceptually similar items, classifying them as referring to bias or to other aspects of quality (eg, reporting). When relevant, reporting items will be reworded into items related to bias in NMA review conclusions, and then reworded as signalling questions.

Ethics and dissemination

No ethics approval was required. We plan to publish the full study open access in a peer-reviewed journal, and disseminate the findings via social media (Twitter, Facebook and author affiliated websites). Patients, healthcare providers and policy-makers need the highest quality evidence to make decisions about which treatments should be used in healthcare practice. Being able to critically appraise the findings of systematic reviews that include NMA is central to informed decision-making in patient care.
Low-grade oncocytic tumour expands the spectrum of renal oncocytic tumours and deserves separate classification: a review of 23 cases from a single tertiary institute
Authors: Akgul Mahmut , Al-Obaidy Khaleel I , Cheng Liang , Idrees Muhammad T
Published: June 2021

Aims

Low-grade oncocytic tumour (LOT) has recently been introduced as a potential distinct entity.

Methods

At the Indiana University department of pathology, primary renal epithelial neoplasms between 2005 and 2020 were searched after appropriate institutional review board permissions.

Results

Twenty-three cases (male/female ratio 14/9) with a median age of 66 (23–84 years) were identified. The majority of patients underwent partial nephrectomy (15/23, 65%), with a median tumour size of 4.0 cm (2.2–10.5 cm). Only one case had infiltration beyond the kidney (perinephric fat). Solid/diffuse proliferation of tightly packed oncocytic tumour cells and occasional tubule formations, with an abrupt edematous change in the stroma with loosely connected small clusters of tumour cells. Along with diffuse CK7 expression with lack of CD117 in all cases, vimentin was positive in 8/23 cases (35%, 5 focal). CD10 was expressed in 6/13 (46%, 4 focal). Alpha-Methylacyl-CoA Racemase (AMACR) was positive in 5/8 (63%) cases. Focal but intense cytoplasmic colloidal iron stain was present in 3/20 (15%) cases. Luminal or cytoplasmic/perinuclear precipitation was observed in 8/20 (40%) cases. Succinate Dehydrogenase B (SDHB) was performed in 6 cases, with all retained expression.

Conclusions

LOT is a clinically indolent and potentially benign entity with distinguishable morphology and immunohistochemical profile that can be performed and be easily interpreted in most of surgical pathology settings. Additional studies with larger cohorts, comprehensive molecular evaluation and longer follow-up are needed to definitively recognise these tumours as a separate entity and to further address the possibility of active surveillance options in eligible patients.
Ethnic disparities in preventable hospitalisation in England: an analysis of 916 375 emergency admissions
Authors: Petersen Jakob , Kandt Jens , Longley Paul
Published: June 2021

Objectives

To study ethnic inequalities in ambulatory care sensitive conditions (ACSC) in England.

Design

Observational study of inpatient hospital admission database enhanced with ethnicity coding of patient surnames. The primary diagnosis of the first episode in spells with emergency admission were coded with definitions for acute ACSC, chronic ACSC and vaccine-preventable diseases.

Setting

National Health Service England.

Participants

916 375 ACSC emergency admissions in 7 39 618 patients were identified between April 2011 and March 2012.

Main outcome measures

ORs of ACSC for each ethnic group relative to the White British majority group adjusted for age, sex and area deprivation.

Results

Acute ACSC admission risk adjusted for age and sex was particularly high among Other (OR 1.73; 95% CI 1.69 to 1.77) and Pakistani (1.51; 95% CI 1.48 to 1.54) compared with White British patients. For chronic ACSC, high risk was found among Other (2.02; 95% CI 1.97 to 2.08), Pakistani (2.07; 95% CI 2.02 to 2.12) and Bangladeshi (1.36; 95% CI 1.30 to 1.42). For vaccine-preventable diseases, other (2.42; 95% CI 2.31 to 2.54), Pakistani (1.94; 95% CI 1.85 to 2.04), Bangladeshi (1.48; 95% CI 1.36 to 1.62), Black African (1.45; 95% CI 1.36 to 1.54) and white other (1.38; 95% CI 1.33 to 1.43) groups. Elevated risk was only partly explained in analyses also adjusting for area deprivation.

Conclusions

ACSC admission was especially high among individuals of Bangladeshi, Pakistani, Black African, white other or other background with up to twofold differences compared with the white British group. This suggests that these ethnic groups are not receiving optimal primary care.
Overview of Severe Asthma, with Emphasis on Pediatric Patients: A Review for Practitioners
Authors: Abellard Arabelle , Pappalardo Andrea A
Published: June 2021

Asthma is the most common life-threatening chronic disease in children. Although guidelines exist for the diagnosis and treatment of asthma, treatment of severe, pediatric asthma remains difficult. Limited studies in the pediatric population on new asthma therapies, complex issues with adolescence and adherence, health disparities, and unequal access to guideline-based care complicate the care of children with severe, persistent asthma. The purpose of this review is to provide an overview of asthma, including asthma subtypes, comorbidities, and risk factors, to discuss diagnostic considerations and pitfalls and existing treatments, and then present existing and emerging therapeutic approaches to asthma management. An improved understanding of asthma heterogeneity, clinical characteristics, inflammatory patterns, and pathobiology can help further guide the management of severe asthma in children. More studies are needed in the pediatric population to understand emerging therapeutics application in children. Effective multimodal strategies tailored to individual characteristics and a commitment to address risk factors, modifiers, and health disparities may help reduce the burden of asthma in the USA.
Genotype-associated cerebellar profiles in ALS: focal cerebellar pathology and cerebro-cerebellar connectivity alterations
Authors: Bede Peter , Chipika Rangariroyashe H. , Christidi Foteini , Hengeveld Jennifer C. , Karavasilis Efstratios , Argyropoulos Georgios D. , Lope Jasmin , Li Hi Shing Stacey , Velonakis Georgios , Dupuis Léonie , Doherty Mark A. , Vajda Alice , McLaughlin Russell L. , Hardiman Orla
Published: June 2021

Objective

Cerebellar disease burden and cerebro-cerebellar connectivity alterations are poorly characterised in amyotrophic lateral sclerosis (ALS) despite the likely contribution of cerebellar pathology to the clinical heterogeneity of the condition.

Methods

A prospective imaging study has been undertaken with 271 participants to systematically evaluate cerebellar grey and white matter alterations, cerebellar peduncle integrity and cerebro-cerebellar connectivity in ALS. Participants were stratified into four groups: (1) patients testing positive for GGGGCC repeat expansions inC9orf72, (2) patients carrying an intermediate-length repeat expansion inATXN2, (3) patients without established ALS-associated mutations and (4) healthy controls. Additionally, the cerebellar profile of a single patient with ALS who had anATXN2allele length of 62 was evaluated. Cortical thickness, grey matter and white matter volumes were calculated in each cerebellar lobule complemented by morphometric analyses to characterise genotype-associated atrophy patterns. A Bayesian segmentation algorithm was used for superior cerebellar peduncle volumetry. White matter diffusivity parameters were appraised both within the cerebellum and in the cerebellar peduncles. Cerebro-cerebellar connectivity was assessed using deterministic tractography.

Results

Cerebellar pathology was confined to lobules I–V of the anterior lobe in patients with sporadic ALS in contrast to the considerable posterior lobe and vermis disease burden identified inC9orf72mutation carriers. Patients with intermediateATXN2expansions did not exhibit significant cerebellar pathology.

Conclusions

Focal rather than global cerebellar degeneration characterises ALS. Pathognomonic ALS symptoms which are typically attributed to other anatomical regions, such as dysarthria, dysphagia, pseudobulbar affect, eye movement abnormalities and cognitive deficits, may be modulated, exacerbated or partially driven by cerebellar changes in ALS.
Biochemical and biophysical investigation of the HalM2 lanthipeptide synthetase using mass spectrometry
Authors: Hamry Sally R. , Thibodeaux Christopher J.
Published: June 2021

The rapid emergence of antimicrobial resistance in clinical settings has called for renewed efforts to discover and develop new antimicrobial compounds. Lanthipeptides present a promising, genetically encoded molecular scaffold for the engineering of structurally complex, biologically active peptides. These peptide natural products are constructed by enzymes (lanthipeptide synthetases) with relaxed substrate specificity that iteratively modify the precursor lanthipeptide to generate structures with defined sets of thioether macrocycles. The mechanistic features that guide the maturation of lanthipeptides into their proper, fully modified forms are obscured by the complexity of the multistep maturation and the large size and dynamic structures of the synthetases and precursor peptides. Over the past several years, our lab has been developing a suite of mass spectrometry-based techniques that are ideally suited to untangling the complex reaction sequences and molecular interactions that define lanthipeptide biosynthesis. This review focuses on our development and application of these mass spectrometry-based techniques to investigate the biochemical, kinetic, and biophysical properties of the haloduracin β class II lanthipeptide synthetase, HalM2.
A method to improve quantum state fidelity in circuits executed on IBM’s quantum computers
Authors: Sisodia Mitali , Shukla Abhishek , de Almeida Alexandre A.A. , Dueck Gerhard W. , Pathak Anirban
Published: June 2021

Recently, various quantum computing and communication tasks have been implemented using IBM’s superconductivity-based quantum computers. Here, we show that the circuits used in most of those works were not optimized and obtain the corresponding optimized circuits. Optimized circuits implementable in IBM quantum computers are also obtained for a set of reversible benchmark circuits. With a clear example, it is shown that the reduction in circuit cost enhances the fidelity of the output state (with respect to the theoretically expected state in the absence of noise) as fewer gates and less circuit depth introduce fewer errors during evolution of the state. Further, considering Mermin inequality as an example, it is shown that the violation of the classical limit is enhanced when we use optimized circuits. Thus, the present approach can be used to identify a relatively weaker signature of quantumness and to establish quantum supremacy in a stronger manner.
Vulnerability to global warming of the critically endangered Añelo Sand Dunes Lizard (Liolaemus cuyumhue) from the Monte Desert, Patagonia Argentina
Authors: Brizio M. Victoria , Cabezas-Cartes Facundo , Fernández Jimena B. , Gómez Alés Rodrigo , Avila Luciano J.
Published: June 2021

The body temperature of lizards is strongly influenced by the thermal quality of microhabitats, exploiting the favourable environmental temperatures, and avoiding exposure to extreme thermal conditions. For these reasons, reptile populations are considered to be especially vulnerable to changes in environmental temperatures produced by climate change. Here, we study the thermal physiology of the critically endangered Añelo Sand Dunes Lizard (Liolaemus cuyumhue Avila, Morando, Perez and Sites, 2009). We hypothesise that (i) there is a thermal coadaptation between optimal temperature for locomotor performance of L. cuyumhue and its thermal preference; (ii) L. cuyumhue lives in an environment with low thermal quality; and (iii) a rise in environmental temperatures due to global warming will impose a decrement in locomotor speed represented by lower warming tolerance and narrower thermal safety margins, increasing their already high vulnerability. We recorded field body temperatures (T b), preferred body temperatures (T pref), the operative temperature (T e), and the thermal sensitivity of locomotion at different body temperatures. Our results indicate that this lizard is not currently under environmental stress or exceeding its thermal limits, but that it is thermoregulating below T pref to avoid overheating, and that an increase in environmental temperature higher than 3.5 °C will strongly affect the use of microhabitats with direct sun exposure.
The biodiversity crisis in Canada: failures and challenges of federal and sub-national strategic and legal frameworks
Authors: Ray Justina C. , Grimm Jaime , Olive Andrea
Published: June 2021

Negative biodiversity trends are evident in Canada, in spite of its ecological and economic wealth and high governance capacity. We examined the current implementation of Canada’s national biodiversity strategy—the planning instrument to the United Nations Convention on Biological Diversity—through its existing legal framework. We did this by evaluating biodiversity-related strategies and plans and 201 federal, provincial, and territorial laws. We found that while most jurisdictions claim dedicated attention to biodiversity, there is little evidence of an integrated approach within provinces and territories and across the federation. Biodiversity conservation led by governments underscores the need for considerations of species and ecosystem services to be mainstreamed into economic and development decision-making. Key challenges to this include Canada’s unusual degree of decentralized constitutionally ascribed authority over natural assets and its historical and continued economic emphasis on extraction of natural resources—a conflict of interest for jurisdictions. Transitioning to scale-appropriate planning and integrated decision-making that can address the pressures and causes of biodiversity conservation in Canada will require transformative change. Law reform, while necessary, will not succeed unless accompanied by a whole-of-government approach, a shift to a bio-centric mindset, innovative governance (particularly Indigenous-led conservation), and federal leadership with strong levels of financial investment.