bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional seed traits and germination patterns predict species coexistence in Northeast Mediterranean foredune communities
Authors: Del Vecchio Silvia , Mattana Efisio , Ulian Tiziana , Buffa Gabriella
Published: October 2020

Background and Aims

The structure of plant communities, which is based on species abundance ratios, is closely linked to ecosystem functionality. Seed germination niche plays a major role in shaping plant communities, although it has often been neglected when explaining species coexistence. The aim of this work is to link the seed germination niche to community ecology, investigating how functional seed traits contribute to species coexistence.

Methods

Species selection was based on a database of 504 vegetation surveys from the Veneto coast (Italy). Through cluster analysis we identified the foredune community and selected all of its 19 plant species. By using the ‘Phi coefficient’ and frequency values, species were pooled in different categories (foundation species, accidental species of the semi-fixed dune and aliens), then the 19 species were grouped according to their germination responses to temperature and photoperiod through cluster analyses. For each germination cluster, we investigated germination trends against temperature and photoperiod by using generalized linear mixed models.

Key Results

We identified four germination strategies: (1) high germination under all tested conditions (‘high-germinating’); (2) high germination at warm temperatures in the dark (‘dark warm-cued’); (3) high germination at warm temperatures in the light (‘light warm-cued’); and (4) low germination, regardless of conditions (‘low-germinating’). Foredune foundation species showed a narrow germination niche, being ‘low-germinating’ or ‘dark warm-cued’. Annual species of semi-fixed dunes were ‘high-germinating’, while alien species were the only members of the ‘light warm-cued’ cluster.

Conclusions

Our research suggests that different categories of species have dissimilar seed germination niches, which contributes to explaining their coexistence. Climatic events, such as rising temperature, could alter germination patterns, favouring seed regeneration of certain categories (i.e. alien and semi-fixed dune species) at the expense of others (i.e. foundation species, pivotal to ecosystem functioning), and hence potentially altering the plant community structure.
Percu-Ax aortic valve implantation with a double arm approach: a case report
Authors: Trani Carlo , Aurigemma Cristina , Romagnoli Enrico , Burzotta Francesco
Published: October 2020

Background

Transaxillary route for structural and coronary percutaneous interventions represents a valid alternative access in patients with obstructive peripheral disease. Nevertheless, its widespread use is limited by a less manageable haemostasis procedure.

Case summary

In this case, we describe a minimalistic high-risk transcatheter aortic valve implantation (TAVI) procedure (TAVI Score 6.42%) conducted with a double arm approach (radial and axillary accesses) in an 88-year-old patient with severe aortic stenosis and multiple co-morbidities preventing both surgical (Society of Thoracic Surgeons mortality 7.9%) and percutaneous transfemoral approach (extensive peripheral artery disease). We also described the successful management of a complicated transaxillary haemostasis with this technique.

Discussion

In our cases, a minimalist double-arm approach was successfully used for TAVI procedure as an alternative to transfemoral approach assuring effective and safe management of vascular access haemostasis.
Novel antisense therapy targeting microRNA-132 in patients with heart failure: results of a first-in-human Phase 1b randomized, double-blind, placebo-controlled study
Authors: Täubel Jörg , Hauke Wilfried , Rump Steffen , Viereck Janika , Batkai Sandor , Poetzsch Jenny , Rode Laura , Weigt Henning , Genschel Celina , Lorch Ulrike , Theek Carmen , Levin Arthur A , Bauersachs Johann , Solomon Scott D , Thum Thomas
Published: October 2020

Aims

Cardiac microRNA-132-3p (miR-132) levels are increased in patients with heart failure (HF) and mechanistically drive cardiac remodelling processes. CDR132L, a specific antisense oligonucleotide, is a first-in-class miR-132 inhibitor that attenuates and even reverses HF in preclinical models. The aim of the current clinical Phase 1b study was to assess safety, pharmacokinetics, target engagement, and exploratory pharmacodynamic effects of CDR132L in patients on standard-of-care therapy for chronic ischaemic HF in a randomized, placebo-controlled, double-blind, dose-escalation study (NCT04045405).

Methods and results

Patients had left ventricular ejection fraction between ≥30% and <50% or amino terminal fragment of pro-brain natriuretic peptide (NT-proBNP) >125 ng/L at screening. Twenty-eight patients were randomized to receive CDR132L (0.32, 1, 3, and 10 mg/kg body weight) or placebo (0.9% saline) in two intravenous infusions, 4 weeks apart in four cohorts of seven (five verum and two placebo) patients each. CDR132L was safe and well tolerated, without apparent dose-limiting toxicity. A pharmacokinetic/pharmacodynamic dose modelling approach suggested an effective dose level at ≥1 mg/kg CDR132L. CDR132L treatment resulted in a dose-dependent, sustained miR-132 reduction in plasma. Patients given CDR132L ≥1 mg/kg displayed a median 23.3% NT-proBNP reduction, vs. a 0.9% median increase in the control group. CDR132L treatment induced significant QRS narrowing and encouraging positive trends for relevant cardiac fibrosis biomarkers.

Conclusion

This study is the first clinical trial of an antisense drug in HF patients. CDR132L was safe and well tolerated, confirmed linear plasma pharmacokinetics with no signs of accumulation, and suggests cardiac functional improvements. Although this study is limited by the small patient numbers, the indicative efficacy of this drug is very encouraging justifying additional clinical studies to confirm the beneficial CDR132L pharmacodynamic effects for the treatment of HF.
Differences in Influenza-Specific CD4 T-Cell Mediated Immunity Following Acute Infection Versus Inactivated Vaccination in Children
Authors: Shannon Ian , White Chantelle L , Yang Hongmei , Nayak Jennifer L
Published: October 2020

Background

Early childhood influenza infections imprint influenza-specific immune memory, with most studies evaluating antibody specificity. In this study, we examined how infection versus inactivated influenza vaccination (IIV) establish pediatric CD4 T-cell mediated immunity to influenza and whether this poises the immune system to respond differently to IIV the following year.

Methods

We tracked influenza-specific CD4 T-cell responses in 16 H3N2 infected and 28 IIV immunized children following both initial exposure and after cohorts were revaccinated with IIV the following fall. PBMCs were stimulated with peptide pools encompassing the translated regions of the H3 HA and NP proteins and were then stained to assess CD4 T-cell specificity and function.

Results

Compared to IIV, infection primed a greater magnitude CD4 T-cell response specific for the infecting HA and NP proteins, with more robust NP-specific immunity persisting through year 2. Post infection, CD4 T cells preferentially produced combinations of cytokines that included interferon-γ. Interestingly, age-specific patterns in CD4 T-cell reactivity demonstrated the impact of multiple influenza exposures over time.

Conclusions

These data indicate that infection and vaccination differentially prime influenza-specific CD4 T-cell responses in early childhood, with these differences contributing to the lasting immunologic imprinting established following early influenza infection.

Clinical Trials Registration

NCT02559505.
Quality Risk Management-Based AQbD Approach to Development of VEER Chromatography Method for the Estimation of Multiple Combined Formulations of Anti-Hypertensive Drugs
Authors: Prajapati Pintu B , Thakor Mukti A , Bodiwala Kunjan B , Shah Shailesh A
Published: October 2020

Background

A number of chromatography methods for estimating combined dosage forms of telmisartan have been published in the literature, but each combined dosage form needs separate chromatography conditions for analysis.

Objective

The versatile, economical, eco-friendly, and robust chromatographic method has been developed for simultaneous estimation of multiple combined pharmaceutical dosage forms of anti-hypertensive drugs using the analytical quality by design approach based on principles of quality risk management (QRM) and design of experiment (DoE).

Method

Analytical QRM was performed by identifying probable method risk parameters and risk assessment for the development of the method. DoE was performed by Taguchi Orthogonal Array (OA)  screening design and Box-Behnken response surface design using Design-Expert software (trial version). Chromatographic separation was performed using silica gel 60 GF254 as stationary phase and toluene–ethyl acetate–methanol–glacial acetic acid (5.5 + 2 + 1 + 0.2, v/v/v/v) as a mobile phase keeping saturation time of 15 min. The developed method was applied for the assay of six combined pharmaceutical dosage forms of anti-hypertensive drugs.

Results

The developed method was found to be validated for accuracy, precision, specificity, linearity, LOD, LOQ, and robustness as per ICH guideline. The results of the assay were found in good agreement with the labelled claim.

Conclusions

The developed method can be applied for analysis and quality control of multiple combined dosage forms of telmisartan.

Highlights

A QRM and DoE-based AQbD approach was applied for development of chromatography method for simultaneous estimation of multiple combined dosage forms of telmisartan. The developed method was successfully applied for simultaneous estimation of six different multiple combined dosage forms of temisrtan.
Influence of Trap Color, Type, and Placement on Capture Efficacy forProtaetia brevitarsis(Coleoptera: Scarabaeidae)
Authors: Cai Huanhuan , Zhang Tao , Su Yinghua , Wang Zhongyue , Zhang Xiaofang , Wang Shaoshan , Liu Yongqiang
Published: October 2020

In recent years, Protaetia brevitarsis Lewis has gradually become an important pest of several crops including grape (Vitis vinifera L.) and peach (Amygdalus persica L.) in Xinjiang, China. Toward improving trapping efficacy as part of a management program, various colors, types, and placement of traps and the use of an attractant were evaluated in field and laboratory studies. Laboratory color-choice tests and field tests indicated that P. brevitarsis adults preferred red. In trap placement tests, more adults were captured on traps placed 1 or 1.5 m above the ground and on top of the horizontal grape canopy. Before grape ripening, more adults were captured in traps placed in a 0.5-m border around the outside edge of the vineyard; during grape ripening, more were caught within the vineyard. Newly designed traps that were red, with a triangular baffle and a landing plate, were more efficient than traditional bucket-shaped traps. When P. brevitarsis adults were trapped and killed from June to July 2018, the population of P. brevitarsis adults in August to early September 2018 was significantly lower than in August to early September 2017, when adults had not been trapped and killed in the prior 2 mo.
Bayesian Selection of Asset Pricing Factors Using Individual Stocks
Authors: Hwang Soosung , Rubesam Alexandre
Published: October 2020

We apply Bayesian variable selection to investigate linear factor asset pricing models for a large set of candidate factors identified in the literature. We extract model and factor posterior probabilities from thousands of individual stocks via Markov Chain Monte Carlo estimation together with the exact distribution of pricing statistics. Our results show that only a small number of factors are relevant and, except for the market and size factors, these are not the factors in widely used linear factor models such as Fama and French (2015, Journal of Financial Economics 116, 1–22) or Hou et al. (2015, The Review of Financial Studies 28, 650–705). Moreover, many different linear factor models achieve similar empirical performance, suggesting that the search for a single linear factor model is unlikely to yield a definitive answer.
Adaptor protein APPL1 links neuronal activity to chromatin remodeling in cultured hippocampal neurons
Authors: Wu Yu , Lv Xinyou , Wang Haiting , Qian Kai , Ding Jinjun , Wang Jiejie , Hua Shushan , Sun Tiancheng , Zhou Yiting , Yu Lina , Qiu Shuang
Published: October 2020

Local signaling events at synapses or axon terminals are communicated to the nucleus to elicit transcriptional responses, and thereby translate information about the external environment into internal neuronal representations. This retrograde signaling is critical to dendritic growth, synapse development, and neuronal plasticity. Here, we demonstrate that neuronal activity induces retrograde translocation and nuclear accumulation of endosomal adaptor APPL1. Disrupting the interaction of APPL1 with Importin α1 abolishes nuclear accumulation of APPL1, which in turn decreases the levels of histone acetylation. We further demonstrate that retrograde translocation of APPL1 is required for the regulation of gene transcription and then maintenance of hippocampal late-phase long-term potentiation. Thus, these results illustrate an APPL1-mediated pathway that contributes to the modulation of synaptic plasticity via coupling neuronal activity with chromatin remodeling.
Presentation, Management, and Outcomes Across the Rural-Urban Continuum for Hepatocellular Carcinoma
Authors: Zhou Kali , Pickering Trevor A , Gainey Christina S , Cockburn Myles , Stern Mariana C , Liu Lihua , Unger Jennifer B , El-Khoueiry Anthony B , Terrault Norah A
Published: October 2020

Background

Hepatocellular carcinoma is 1 of few cancers with rising incidence and mortality in the United States. Little is known about disease presentation and outcomes across the rural-urban continuum.

Methods

Using the population-based Surveillance, Epidemiology, and End Results registry, we identified adults with incident hepatocellular carcinoma between 2000 and 2016. Urban, suburban, and rural residence at time of cancer diagnosis were categorized by the Census Bureau’s percent of the population living in nonurban areas. We examined association between place of residence and overall survival. Secondary outcomes were late tumor stage and receipt of therapy.

Results

Of 83 368 incident cases of hepatocellular carcinoma, 75.8%, 20.4%, and 3.8% lived in urban, suburban, and rural communities, respectively. Median survival was 7 months (interquartile range = 2-24). All stage and stage-specific survival differed by place of residence, except for distant stage. In adjusted models, rural and suburban residents had a respective 1.09-fold (95% confidence interval [CI] = 1.04 to 1.14; P < .001) and 1.08-fold (95% CI = 1.05 to 1.10; P < .001) increased hazard of overall mortality as compared with urban residents. Furthermore, rural and suburban residents had 18% (odds ratio [OR] = 1.18, 95% CI = 1.10 to 1.27; P < .001) and 5% (OR = 1.05, 95% CI = 1.02 to 1.09; P = .003) higher odds of diagnosis at late stage and were 12% (OR = 0.88, 95% CI = 0.80 to 0.94; P < .001) and 8% (OR = 0.92, 95% CI = 0.88 to 0.95; P < .001) less likely to receive treatment, respectively, compared with urban residents.

Conclusions

Residence in a suburban and rural community at time of diagnosis was independently associated with worse indicators across the cancer continuum for liver cancer. Further research is needed to elucidate the primary drivers of these rural-urban disparities.
The completed SDSS-IV extended Baryon Oscillation Spectroscopic Survey: BAO and RSD measurements from anisotropic clustering analysis of the quasar sample in configuration space between redshift 0.8 and 2.2
Authors: Hou Jiamin , Sánchez Ariel G , Ross Ashley J , Smith Alex , Neveux Richard , Bautista Julian , Burtin Etienne , Zhao Cheng , Scoccimarro Román , Dawson Kyle S , de Mattia Arnaud , de la Macorra Axel , du Mas des Bourboux Hélion , Eisenstein Daniel J , Gil-Marín Héctor , Lyke Brad W , Mohammad Faizan G , Mueller Eva-Maria , Percival Will J , Rossi Graziano , Vargas Magaña Mariana , Zarrouk Pauline , Zhao Gong-Bo , Brinkmann Jonathan , Brownstein Joel R , Chuang Chia-Hsun , Myers Adam D , Newman Jeffrey A , Schneider Donald P , Vivek M
Published: October 2020

We measure the anisotropic clustering of the quasar sample from Data Release 16 (DR16) of the Sloan Digital Sky Survey IV extended Baryon Oscillation Spectroscopic Survey (eBOSS). A sample of 343 708 spectroscopically confirmed quasars between redshift 0.8 < z < 2.2 are used as tracers of the underlying dark matter field. In comparison with DR14 sample, the final sample doubles the number of objects as well as the survey area. In this paper, we present the analysis in configuration space by measuring the two-point correlation function and decomposing it using the Legendre polynomials. For the full-shape analysis of the Legendre multipole moments, we measure the baryon acoustic oscillation (BAO) distance and the growth rate of the cosmic structure. At an effective redshift of zeff = 1.48, we measure the comoving angular diameter distance DM(zeff)/rdrag = 30.66 ± 0.88, the Hubble distance DH(zeff)/rdrag = 13.11 ± 0.52, and the product of the linear growth rate and the rms linear mass fluctuation on scales of $8 \, h^{-1}\, {\rm Mpc}$, fσ8(zeff) = 0.439 ± 0.048. The accuracy of these measurements is confirmed using an extensive set of mock simulations developed for the quasar sample. The uncertainties on the distance and growth rate measurements have been reduced substantially (∼45 and ∼30 per cent) with respect to the DR14 results. We also perform a BAO-only analysis to cross check the robustness of the methodology of the full-shape analysis. Combining our analysis with the Fourier-space analysis, we arrive at $D^{{\bf c}}_{\rm M}(z_{\rm eff})/r_{\rm drag} = 30.21 \pm 0.79$, $D^{{\bf c}}_{\rm H}(z_{\rm eff})/r_{\rm drag} = 13.23 \pm 0.47$, and $f\sigma _8^{{\bf c}}(z_{\rm eff}) = 0.462 \pm 0.045$.
Hubble Space Telescope observations of [O iii] emission in nearby QSO2s: physical properties of the ionized outflows
Authors: Trindade Falcão Anna , Kraemer S B , Fischer T C , Crenshaw D M , Revalski M , Schmitt H R , Vestergaard M , Elvis M , Gaskell C M , Hamann F , Ho L C , Hutchings J , Mushotzky R , Netzer H , Storchi-Bergmann T , Turner T J , Ward M J
Published: October 2020

We use Hubble Space Telescope/Space Telescope Imaging Spectrograph long-slit G430M and G750M spectra to analyse the extended [O iii] λ5007 emission in a sample of 12 nearby (z < 0.12) luminous (Lbol > 1.6 × 1045 erg s−1) QSO2s. The purpose of the study is to determine the properties of the mass outflows of ionized gas and their role in active galactic nucleus feedback. We measure fluxes and velocities as functions of radial distances. Using cloudy models and ionizing luminosities derived from [O iii] λ5007, we are able to estimate the densities for the emission-line gas. From these results, we derive masses of [O iii]-emitting gas, mass outflow rates, kinetic energies, kinetic luminosities, momenta, and momentum flow rates as a function of radial distance for each of the targets. For the sample, masses are several times $10^{3}$–$10^{7}\, {\rm M_{\odot }}$ and peak outflow rates are from 9.3 × 10−3 to $10.3\, {\rm M_{\odot }}\, {\rm yr^{-1}}$. The peak kinetic luminosities are (3.4 × 10−8)–(4.9 × 10−4) of the bolometric luminosity, which does not approach the (5.0 × 10−3)–(5.0 × 10−2) range required by some models for efficient feedback. For Mrk 34, which has the largest kinetic luminosity of our sample, in order to produce efficient feedback there would have to be 10 times more [O iii]-emitting gas than that we detected at its position of maximum kinetic luminosity. Three targets show extended [O iii] emission, but compact outflow regions. This may be due to different mass profiles or different evolutionary histories.
From lenticulars to blue compact dwarfs: the stellar mass fraction is regulated by disc gravitational instability
Authors: Romeo Alessandro B , Agertz Oscar , Renaud Florent
Published: October 2020

The stellar-to-halo mass relation (SHMR) is not only one of the main sources of information we have on the connection between galaxies and their dark matter haloes, but also an important indicator of the performance of galaxy formation models. Here, we use one of the largest sample of galaxies with both high-quality rotation curves and near-infrared surface photometry, and perform a detailed comparative analysis of the SHMR. Our analysis shows that there are significant statistical differences between popular forms of the SHMR, and illustrates the predictive power of a new physically motivated scaling relation, which connects the stellar mass fraction (M⋆/Mh) to the stellar specific angular momentum (j⋆) and the stellar radial velocity dispersion (σ⋆) via disc gravitational instability. Making use of such a relation, we demonstrate (i) how challenging it is to reproduce the efficiency of galaxy formation even for state-of-the-art cosmological hydrodynamical simulations, and (ii) that the evolution of the stellar mass fraction is regulated by disc gravitational instability: when M⋆/Mh varies, j⋆ and σ⋆ also vary as predicted by our scaling relation, thus erasing the memory of such evolution. This implies that the process of disc gravitational instability is intriguingly uniform across disc galaxies of all morphological types: from lenticulars to blue compact dwarfs. In particular, the cosmic variance of Toomre’s Q is 0.2 dex, a universal value for both stars and atomic gas.
Extracting galaxy merger time-scales II: a new fitting formula
Authors: Poulton R J J , Power C , Robotham A S G , Elahi P J , Lagos C D P
Published: October 2020

Predicting the merger time-scale (τmerge) of merging dark matter haloes, based on their orbital parameters and the structural properties of their hosts, is a fundamental problem in gravitational dynamics that has important consequences for our understanding of cosmological structure formation and galaxy formation. Previous models predicting τmerge have shown varying degrees of success when compared to the results of cosmological N-body simulations. We build on this previous work and propose a new model for τmerge that draws on insights derived from these simulations. We find that published predictions can provide reasonable estimates for τmerge based on orbital properties at infall, but tend to underpredict τmerge inside the host virial radius (R200) because tidal stripping is neglected, and overpredict it outside R200 because the host mass is underestimated. Furthermore, we find that models that account for orbital angular momentum via the circular radius Rcirc underpredict (overpredict) τmerge for bound (unbound) systems. By fitting for the dependence of τmerge on various orbital and host halo properties, we derive an improved model for τmerge that can be applied to a merging halo at any point in its orbit. Finally, we discuss briefly the implications of our new model for τmerge for semi-analytical galaxy formation modelling.
RNAi technology targeting the FGFR3-TACC3 fusion breakpoint: an opportunity for precision medicine
Authors: Parker Kerrigan Brittany C , Ledbetter Daniel , Kronowitz Matthew , Phillips Lynette , Gumin Joy , Hossain Anwar , Yang Jing , Mendt Mayela , Singh Sanjay , Cogdell David , Ene Chibawanye , Shpall Elizabeth , Lang Frederick F
Published: October 2020

Background

Fusion genes form as a result of abnormal chromosomal rearrangements linking previously separate genes into one transcript. The FGFR3-TACC3 fusion gene (F3-T3) has been shown to drive gliomagenesis in glioblastoma (GBM), a cancer that is notoriously resistant to therapy. However, successful targeting of F3-T3 via small molecular inhibitors has not revealed robust therapeutic responses, and specific targeting of F3-T3 has not been achieved heretofore. Here, we demonstrate that depleting F3-T3 using custom siRNA to the fusion breakpoint junction results in successful inhibition of F3-T3+ GBMs, and that exosomes can successfully deliver these siRNAs.

Methods

We engineered 10 unique siRNAs (iF3T3) that specifically spanned the most common F3-T3 breakpoint with varying degrees of overlap, and assayed depletion by qPCR and immunoblotting. Cell viability assays were performed. Mesenchymal stem cell–derived exosomes (UC-MSC) were electroporated with iF3T3, added to cells, and F3-T3 depletion measured by qPCR.

Results

We verified that depleting F3-T3 using shRNA to FGFR3 resulted in decreased cell viability and improved survival in glioma-bearing mice. We then demonstrated that 7/10 iF3T3 depleted F3-T3, and importantly, did not affect levels of wild-type (WT) FGFR3 or TACC3. iF3T3 decreased cell viability in both F3T3+ GBM and bladder cancer cell lines. UC-MSC exosomes successfully delivered iF3T3 in vitro, resulting in F3-T3 depletion.

Conclusion

Targeting F3-T3 using siRNAs specific to the fusion breakpoint is capable of eradicating F3T3+ cancers without toxicity related to inhibition of WT FGFR3 or TACC3, and UC-MSC exosomes may be a plausible vehicle to deliver iF3T3.
Mechanistic connotations of restriction of intramolecular motions (RIM)
Authors: Tu Yujie , Zhao Zheng , Lam Jacky W Y , Tang Ben Zhong
Published: October 2020

Restriction of intramolecular motion (RIM) is the widely-accpeted mechanism of aggregation-induced emission (AIE). In this concise and comprehensive perspective, four mechanistic models related to different nonradiative pathways are summarized with examples to disclose the connotation of RIM, and meaningful mechanistic topics for future researches are advised.
Genome-Wide Association Study Identifies Novel Colony Stimulating Factor 1 Locus Conferring Susceptibility to Cryptococcosis in Human Immunodeficiency Virus-Infected South Africans
Authors: Kannambath Shichina , Jarvis Joseph N , Wake Rachel M , Longley Nicky , Loyse Angela , Matzaraki Vicky , Aguirre-Gamboa Raúl , Wijmenga Cisca , Doyle Ronan , Paximadis Maria , Tiemessen Caroline T , Kumar Vinod , Pittman Alan , Meintjes Graeme , Harrison Thomas S , Netea Mihai G , Bicanic Tihana
Published: October 2020

Background

Cryptococcus is the most common cause of meningitis in human immunodeficiency virus (HIV)-infected Africans. Despite universal exposure, only 5%–10% of patients with HIV/acquired immune deficiency syndrome and profound CD4+ T-cell depletion develop disseminated cryptococcosis: host genetic factors may play a role. Prior targeted immunogenetic studies in cryptococcosis have comprised few Africans.

Methods

We analyzed genome-wide single-nucleotide polymorphism (SNP) genotype data from 524 patients of African descent: 243 cases (advanced HIV with cryptococcal antigenemia and/or cryptococcal meningitis) and 281 controls (advanced HIV, no history of cryptococcosis, negative serum cryptococcal antigen).

Results

Six loci upstream of the colony-stimulating factor 1 (CSF1) gene, encoding macrophage colony-stimulating factor (M-CSF) were associated with susceptibility to cryptococcosis at P < 10–6 and remained significantly associated in a second South African cohort (83 cases; 128 controls). Meta-analysis of the genotyped CSF1 SNP rs1999713 showed an odds ratio for cryptococcosis susceptibility of 0.53 (95% confidence interval, 0.42–0.66; P = 5.96 × 10−8). Ex vivo functional validation and transcriptomic studies confirmed the importance of macrophage activation by M-CSF in host defence against Cryptococcus in HIV-infected patients and healthy, ethnically matched controls.

Conclusions

This first genome-wide association study of susceptibility to cryptococcosis has identified novel and immunologically relevant susceptibility loci, which may help define novel strategies for prevention or immunotherapy of HIV-associated cryptococcal meningitis.
One-Relator Maximal Pro-p Galois Groups and the Koszulity Conjectures
Authors: Quadrelli Claudio
Published: October 2020

Let p be a prime number and let ${\mathbb{K}}$ be a field containing a root of 1 of order p. If the absolute Galois group $G_{\mathbb{K}}$ satisfies $\dim\, H^1(G_{\mathbb{K}},\mathbb{F}_p)\lt\infty$ and $\dim\, H^{\,2}(G_{\mathbb{K}},\mathbb{F}_p)=1$, we show that L. Positselski’s and T. Weigel’s Koszulity conjectures are true for ${\mathbb{K}}$. Also, under the above hypothesis, we show that the $\mathbb{F}_p$-cohomology algebra of $G_{\mathbb{K}}$ is the quadratic dual of the graded algebra ${\rm gr}_\bullet\mathbb{F}_p[G_{\mathbb{K}}]$, induced by the powers of the augmentation ideal of the group algebra $\mathbb{F}_p[G_{\mathbb{K}}]$, and these two algebras decompose as products of elementary quadratic algebras. Finally, we propose a refinement of the Koszulity conjectures, analogous to I. Efrat’s elementary type conjecture.
Restricted Mean Value Theorems and the Metric Theory of Restricted Weyl Sums
Authors: Chen Changhao , Shparlinski Igor E
Published: October 2020

We study the behaviour of Weyl sums on a subset ${\mathcal X}\subseteq [0,1)^d$ with a natural measure µ on ${\mathcal X}$. For certain measure spaces $({\mathcal X}, \mu),$ we obtain non-trivial bounds for the mean values of the Weyl sums, and for µ-almost all points of ${\mathcal X}$ the Weyl sums satisfy the square root cancellation law. Moreover, we characterize the size of the exceptional sets in terms of Hausdorff dimension.

Finally, we derive variants of the Vinogradov mean value theorem averaging over measure spaces $({\mathcal X}, \mu)$. We obtain general results, which we refine for some special spaces ${\mathcal X}$ such as spheres, moment curves and line segments.
Orbitofrontal-Striatal Structural Alterations Linked to Negative Symptoms at Different Stages of the Schizophrenia Spectrum
Authors: Kirschner Matthias , Schmidt André , Hodzic-Santor Benazir , Burrer Achim , Manoliu Andrei , Zeighami Yashar , Yau Yvonne , Abbasi Nooshin , Maatz Anke , Habermeyer Benedikt , Abivardi Aslan , Avram Mihai , Brandl Felix , Sorg Christian , Homan Philipp , Riecher-Rössler Anita , Borgwardt Stefan , Seifritz Erich , Dagher Alain , Kaiser Stefan
Published: October 2020

Negative symptoms such as anhedonia and apathy are among the most debilitating manifestations of schizophrenia (SZ). Imaging studies have linked these symptoms to morphometric abnormalities in 2 brain regions implicated in reward and motivation: the orbitofrontal cortex (OFC) and striatum. Higher negative symptoms are generally associated with reduced OFC thickness, while higher apathy specifically maps to reduced striatal volume. However, it remains unclear whether these tissue losses are a consequence of chronic illness and its treatment or an underlying phenotypic trait. Here, we use multicentre magnetic resonance imaging data to investigate orbitofrontal-striatal abnormalities across the SZ spectrum from healthy populations with high schizotypy to unmedicated and medicated first-episode psychosis (FEP), and patients with chronic SZ. Putamen, caudate, accumbens volume, and OFC thickness were estimated from T1-weighted images acquired in all 3 diagnostic groups and controls from 4 sites (n = 337). Results were first established in 1 discovery dataset and replicated in 3 independent samples. There was a negative correlation between apathy and putamen/accumbens volume only in healthy individuals with schizotypy; however, medicated patients exhibited larger putamen volume, which appears to be a consequence of antipsychotic medications. The negative association between reduced OFC thickness and total negative symptoms also appeared to vary along the SZ spectrum, being significant only in FEP patients. In schizotypy, there was increased OFC thickness relative to controls. Our findings suggest that negative symptoms are associated with a temporal continuum of orbitofrontal-striatal abnormalities that may predate the occurrence of SZ. Thicker OFC in schizotypy may represent either compensatory or pathological mechanisms prior to the disease onset.
Cloning, high-level gene expression and bioinformatics analysis of SP15 and LeIF fromLeishmania majorand IranianPhlebotomus papatasisaliva as single and novel fusion proteins: a potential vaccine candidate against leishmaniasis
Authors: Bordbar Ali , Amanlou Massoud , Pooshang Bagheri Kamran , Ready Paul Donald , Ebrahimi Sahar , Shahbaz Mohammadi Hamid , Ghafari Seyedeh Maryam , Parvizi Parviz
Published: October 2020

Background

Early exacerbation of cutaneous leishmaniasis is mainly affected by both the salivary and Leishmania parasite components. Little is known of the vaccine combination made by immunogenic proteins of sandfly saliva (SP15) with Leishmania parasites (LeIF) as a single prophylactic vaccine, namely SaLeish. Also, there are no data available to determine the species-specific sequence of SP15 isolated from the Iranian Phlebotomus papatasi.

Methods

Integrated bioinformatics and genetic engineering methods were employed to design, optimize and obtain a vector–parasite-based vaccine formulation in a whole-length fusion form of LeIF-SP15 against leishmaniasis. Holistic gene optimization was initially performed to obtain a high yield of pure ‘whole-SaLeish’ expression using bioinformatics analyses. Genomic and salivary gland RNAs of wild-caught P. papatasi were extracted and their complementary DNA was amplified and cloned into pJET vector.

Results

The new chimeric protein of whole-SaLeish and randomly selected transcripts of native PpIRSP15 (GenBank accession nos. MT025054 and MN938854, MN938855 and MN938856) were successfully expressed, purified and validated by immunoblotting assay. Furthermore, despite the single amino acid polymorphisms of PpIRSP15 found at positions Y23 and E73 within the population of wild Iranian sandflies, antigenicity and conservancy of PpIRSP15 epitopes remained constant to activate T cells.

Conclusions

The SaLeish vaccine strategy takes advantage of a plethora of vector–parasite immunogenic proteins with potential protective efficacy to stimulate both the innate and specific cellular immune responses against Leishmania parasites.
Usefulness of Trabecular CT Attenuation Measurement of Lumbar Spine in Predicting Osteoporotic Compression Fracture
Authors: Lee Byung-Jou , Koo Hae-Won , Yoon Sang Won , Sohn Moon-Jun
Published: October 2020

Study Design.

Retrospective study

Objective.

The aim of this study was to evaluate the usefulness of computed tomography (CT) attenuation in defining trabecular region-of-interest (t-ROI) at lumbar vertebral body in the assessment of osteoporotic compression fracture (OCF) compared to spinal dual x-ray absorptiometry (DXA).

Summary of Background Data.

Even though osteoporosis was not diagnosed in the bone mineral density measurement using DXA, we often experienced cases where the screw was weakly inserted due to low bone quality during screw insertion.

Methods.

A total of 188 patients who met the inclusion criteria were enrolled. We determined best cutoff value of the simple t-ROI attenuation at the most relevant level for predicting OCF. We assessed correlations between the simple t-ROI attenuation at the most relevant level and OCF rate, and investigate the association between the number of compression fracture and simple t-ROI attenuation at the most relevant level.

Results.

L4 ROI attenuation is the most accurate measurement for predicting osteoporotic compression fracture with an area under the curve of 0.798. The optimal cutoff point of L4 ROI attenuation was measured at 90.5 HU with 88.8% and 60.6% sensitivity and specificity, respectively. L4 ROI attenuation was significantly correlated with the osteoporotic compression fracture rate (r = −0.545, P < 0.001). The number of compression fracture (coefficient of determination R2 = 0.286; P < 0.001) was independently correlated with L4 ROI attenuation.

Conclusion.

Simple t-ROI computed tomography attenuation is an accurate measurement tool in predicting OCF compared to DXA T-score. The value of L4 t-ROI attenuation is the most relevant measurement for predicting osteoporotic compression fracture, is an alternative to DXA, and can predict the number and rate of compression fractures. Spine surgeons should be aware of L4 t-ROI attenuation to make successful fusion in spine surgery for elderly patients group.

Level of Evidence: 3
Safety and Efficacy of Early Ambulation on an Alternative Oxygen Delivery Device for Patients Receiving Bedside Heated Humidified High-Flow Nasal Cannula Therapy
Authors: Bassett Shane M. , Jordan Jennifer L. , Weeks Douglas L.
Published: October 2020

Purpose:

Patients in the intensive care unit (ICU) receiving heated humidified high-flow nasal cannula (HHFNC) therapy for acute respiratory failure have limited ambulation distance due to restrictions in supplying HHFNC away from bedside. This study investigated the safety and efficacy of transitioning patients requiring HHFNC to a portable high-flow oxygen (HFO2) device for ambulation.

Methods:

Twenty-three patients with acute respiratory failure participated in this prospective longitudinal observational study. Three diagnostic groups were formed (cardiac n = 8; pulmonary n = 11; and other n = 4). Initial aerobic tolerance was established through bedside marching on HHFNC, then participants transitioned to HFO2 for ambulation. During each phase, vital signs were monitored.

Results:

No differences were found among diagnostic groups or sexes during ambulation for blood pressure, heart rate (HR), respiratory rate (RR), oxygen saturation (SpO2), or the Borg dyspnea scale (BDS) (all P > .05). Outcomes during marching and ambulation differed from outcomes at rest and during recovery for HR, RR, SpO2, and BDS (all P < .001). Transitory adverse events during ambulation included anxiety (n = 2), hypotension (n = 1), and arrhythmia (n = 2).

Conclusions:

Results indicate it is safe and efficacious for patients in the ICU with acute respiratory failure requiring HHFNC to ambulate on HFO2 under the supervision of a physical therapist.
Case Series of Urrets-Zavalia Syndrome After Descemet Membrane Endothelial Keratoplasty
Authors: Bhullar Paramjit K. , Venkateswaran Nandini , Kim Terry
Published: October 2020

Purpose:

To present a case series of Urrets-Zavalia syndrome (UZS) that developed after Descemet membrane endothelial keratoplasty (DMEK).

Methods:

A retrospective chart review was performed to identify patients who underwent DMEK by a single surgeon at the Duke Eye Center from 2017 to 2019 and subsequently developed UZS. Demographic data, preoperative history, operative notes, and postoperative course were reviewed.

Results:

We describe 5 cases of UZS after DMEK (ages 19–74 years; 3 men and 2 women). Onset of UZS was noted at postoperative week 1 (n = 1), 2 (n =3), or 4 (n = 1). Four patients had an underlying diagnosis of Fuchs endothelial dystrophy and 1 had posterior polymorphous corneal dystrophy. Sixty percent (n = 3) of patients had an elevated intraocular pressure on postoperative day 0 or 1, and 40% (n = 2) of patients also had a pupillary block. One patient developed UZS after a rebubbling procedure for partial graft detachment and another developed UZS after repeat DMEK transplantation. Of the 3 patients who underwent bilateral combined DMEK and cataract surgery, 1 developed UZS in the second eye, whereas 2 developed UZS in the first eye. Most patients experienced monocular diplopia or had cosmetic concerns because of their mydriatic pupils. Two patients had spontaneous improvement in mydriasis.

Conclusions:

UZS after DMEK is rare, with only 2 cases in the literature: Holtmann et al and Isac et al. We present the largest case series of UZS after DMEK to date. Postoperative elevation in intraocular pressure is a common contributing factor. Evaluation of more patients may elucidate additional risk factors for this condition.
The Association of Intraocular Pressure With Obesity and Cardiometabolic Risk in a Young Farmworker Population
Authors: Reddy Aditya , Halenda Kevin , Cromer Pamela , Chen Li , Butler Julian , Raed Anas , Bhagatwala Jigar , Sponseller Tracie , Bollinger Kathryn , Zhu Haidong , Young Lufei , Layman Debbie , Dong Yanbin
Published: October 2020

Précis:

Intraocular pressure (IOP) was found to be significantly correlated with body mass index (BMI), waist circumference, and diastolic blood pressure (DBP) in a farmworker population located in the southeast Georgia, USA. BMI was correlated with IOP, independent of systemic blood pressures.

Purpose:

Elevated IOP is a known risk factor for glaucomatous optic neuropathy and is believed to be associated with obesity and cardiometabolic diseases. The high prevalence of these conditions in the United States necessitates an evaluation of the relationship among obesity, cardiometabolic risks, and IOP among understudied younger populations.

Materials and Methods:

Farmworker data were collected from the annual Costa-Layman Health Fair between 2013 and 2017. Correlations of IOP with demographic factors, obesity, and cardiometabolic risks were analyzed using analysis of covariance, partial Pearson correlations, and linear regressions.

Results:

In the farmworker population (n=346), the mean IOP was 15.5 mm Hg and the prevalence of ocular hypertension (IOP>21 mm Hg) was 5.5%. BMI, waist circumference, and DBP were significantly correlated (r=0.192, P=0.001; r=0.128, P=0.017; r=0.142, P=0.007, respectively) with IOP when adjusted for age, sex, and ethnicity. Each 10 mm Hg increase in DBP corresponded with a 0.51 mm Hg increase in IOP. With adjustment for age, sex, ethnicity, systolic blood pressure, and DBP, BMI remained significantly correlated with IOP (r=0.166, P=0.002).

Conclusions:

Higher IOP is associated with obesity measures including BMI and waist circumference and is correlated with DBP. These findings suggest that BMI is an independent risk factor for elevated IOP.
Comfort With Touch and Influencing Factors Among Chinese Midwives
Authors: Qin Fang , Meng Guihua , Luo Chenling , Wei Huiqiang , Zhang Lili , Shi Lei
Published: October 2020

The aim of this study was to identify comfort with touch (CT) and influencing factors among Chinese midwives. Midwives (N = 252) from 7 hospitals in Guangdong, China, were asked to complete a self-report questionnaire between November 2018 and April 2019. The questionnaire included the Nurses' Comfort with Touch Scale (NCTS), the Nurses' Perceived Professional Benefits (NPPB) Scale, the Maslach Burnout Inventory–General Survey (MBI-GS), and a self-designed demographic questionnaire. Multivariate linear regression was used to identify influencing factors for CT. Mean NCTS total score was 88.90 ± 14.40, and the mean item score was 5.23 ± 0.91, which indicated a respectable score. Within the NCTS, CT was highest in the comfort support category (5.32 ± 0.29) whereas CT was lowest in the physical comfort category (4.28 ± 0.28). Multivariate regression analysis demonstrated that CT among Chinese midwives was associated with positive experiences or feelings surrounding the patient-nurse relationship (B = 3.239, P < .001), perceived professional benefit (PPB, positive professional identity) (B = 0.240, P < .001), emotional exhaustion (B = −0.414, P < .001), depersonalization (negative attitude toward the work setting) (B = −0.773, P < .001), and personal accomplishment (evaluation of self-worth) (B = 0.170, P = .015). Touch training and educational programs are recommended for Chinese midwives to enhance awareness and acceptance of touch care. In addition, promoting positive patient-nurse relationships, improving PPB, and reducing burnout are recommended to enhance CT among Chinese midwives. Because of the size and racial homogeneity of the sample, further studies are recommended to identify CT and influencing factors in a larger, more diverse population of midwives worldwide.
Prenatal Glucocorticoid Treatment Completeness and Steroid Hormonal Levels as Related to Infant and Maternal Health
Authors: Cho June , Chien Lung-Chang , Holditch-Davis Diane
Published: October 2020

This study was conducted to confirm the negative associations between testosterone and cortisol levels and health and developmental outcomes in very low-birth weight (VLBW) infants after controlling for prenatal glucocorticoid (GC) treatment. Seventy-four VLBW infant-mother pairs were recruited from a neonatal intensive care unit in the Southeastern United States. We divided the pairs into the complete (n = 58) and incomplete (n = 16) GC treatment groups. Data on infants and mothers were obtained at birth, 40 weeksʼ postmenstrual age, and 3 and 6 monthsʼ corrected age. Salivary testosterone and cortisol levels of the pairs were determined at 40 weeksʼ postmenstrual age using enzyme immunoassay. Log-linear and general linear mixed models showed that gestational age and birth weight were lower when testosterone was 1 pg/mL higher. When cortisol was 1 μg/dL higher, technology dependence at discharge was higher and motor development at 6 months was lower. Mothers with complete GC treatment had greater parity and gravida, more prenatal visits, and more medical complications. The study outcomes supported our hypothesis that steroid hormonal levels are more predictive of infant health and development than GC treatment completeness. Single dose of GC treatment might be just as effective as 2 doses, although further study with more subjects would be needed to confirm. As the associations with steroid hormonal levels lasted longer than the GC treatment associations, we recommend confirming the predictive effects of testosterone and cortisol levels after 6 months.
Outcomes Following Left Ventricular Assist Device Exchange: Focus on the Impacts of Device Infection
Authors: Yost Gardner , Coyle Laura , Gallagher Colleen , Cotts William , Pappas Patroklos , Tatooles Antone
Published: October 2020

Hemodynamic support with continuous-flow left ventricular assist device (CF-LVAD) therapy has proven a reliable treatment for advanced heart failure. Although modern LVADs are highly durable, device failure and infection can be resolved with surgical exchange of pump components. In this study, we investigated the incidence and outcomes of LVAD exchange with the HeartMate II and HeartWare HVAD. Data were obtained from 677 patients who underwent CF-LVAD implantation between 2005 and 2016. Patients who underwent a device exchanged were included. The primary outcomes were length of hospital stay and mortality. Of the 677 patients included in this study, 72 (10.6%) required LVAD exchange. Thirty-day and 1-year mortality rates were comparable to primary LVAD implantation: 4.3% vs. 3.49%, p = 0.727 and 20.3% vs. 20.7%, p = 0.989, respectively. Thirty-one patients (4.5%) underwent exchange with ongoing infection. Kaplan–Meier analysis indicated significant differences in survival between groups based on indication for exchange. Patients who underwent exchange after more than 150 days of active infection suffered worse postexchange survival than those who underwent exchanged earlier (P = 0.007). While exchange was required only in 10.6% of patients undergoing LVAD implantation, our results show device exchange may be executed safely and effectively, with long-term outcomes similar to primary LVAD implantation. The indication for device exchange impacts postexchange outcomes, and those exchanged with LVAD infection tend to fare worse than those exchanged for device malfunction or thrombus. Patients who are exchanged with active infection have better postoperative survival if the exchange is performed expeditiously after medical management has failed.