bluuebunny/crossref_metadata_2025 huggingface dataset:
Results from the Survey of Antibiotic Resistance (SOAR) 2015–17 in Pakistan: data based on CLSI, EUCAST (dose-specific) and pharmacokinetic/pharmacodynamic (PK/PD) breakpoints
Authors: Torumkuney D , Anwar S , Nizamuddin S , Malik N , Morrissey I
Published: March 2020

Objectives

To determine antibiotic susceptibility of community-acquired respiratory tract infection (CA-RTI) isolates of Streptococcus pneumoniae and Haemophilus influenzae collected in 2015–17 from Pakistan.

Methods

MICs were determined by CLSI broth microdilution and susceptibility was assessed using CLSI, EUCAST (dose-specific) and pharmacokinetic/pharmacodynamic (PK/PD) breakpoints.

Results

A total of 94 S. pneumoniae and 122 H. influenzae isolates were collected. Susceptibility to penicillin was noted in 23.4% of the S. pneumoniae isolates by CLSI oral/EUCAST low-dose IV breakpoints, although by CLSI IV and EUCAST high-dose breakpoints all isolates were characterized as susceptible. Susceptibility to trimethoprim/sulfamethoxazole (10.6%), macrolides (33%) and cefaclor (28.7%) was low but higher susceptibility was observed to ceftriaxone (100%), amoxicillin and amoxicillin/clavulanic acid (98.9%), cefuroxime (oral, 97.9%), cefpodoxime (96.8%), fluoroquinolones (93.6%–96.8%) and cefdinir (76.6%) by CLSI breakpoints. However, using EUCAST breakpoints, susceptibility to cefpodoxime (70.2%) and cefuroxime (oral, 61.7%) was reduced. H. influenzae isolates were almost all β-lactamase negative (96.7%). Using CLSI breakpoints, ≥93.4% of isolates were susceptible to all antibiotics tested except fluoroquinolones (75.4%–77.1%) and trimethoprim/sulfamethoxazole (41%). The proportion of isolates susceptible using EUCAST breakpoints was similar or identical for penicillins, trimethoprim/sulfamethoxazole and the cephalosporins that have EUCAST breakpoints; the proportion of isolates susceptible using EUCAST breakpoints was similar or identical to that using CSLI breakpoints except for cefuroxime (oral), where only 1.6% of isolates were considered susceptible. Susceptibility of H. influenzae to fluoroquinolones was also lower by EUCAST breakpoints (33.6%–34.4%). The application of different EUCAST breakpoints for low and higher doses for some of the antibiotics (amoxicillin, amoxicillin/clavulanic acid, ampicillin, penicillin, ceftriaxone, clarithromycin, erythromycin, levofloxacin and trimethoprim/sulfamethoxazole) allowed, for the first time in a SOAR study, the effect of raising the dosage on susceptibility to be quantified.

Conclusions

Antibiotic susceptibility in these important respiratory tract pathogens varied in Pakistan based on different breakpoints. These data are important for empirical therapy choices in the treatment of CA-RTIs.
Threshold Change in CEA as a Predictor of Non-Progression to First-Line Systemic Therapy in Metastatic Colorectal Cancer Patients With Elevated CEA
Authors: Gulhati Pat , Yin Jun , Pederson Levi , Schmoll Hans-Joachim , Hoff Paulo , Douillard Jean-Yves , Hecht J Randolph , Tournigand Christophe , Tebbut Niall , Chibaudel Benoist , Gramont Aimery De , Shi Qian , Overman Michael James
Published: March 2020

Background

Carcinoembryonic antigen (CEA) levels are used in conjunction with imaging to monitor response to systemic therapy in metastatic colorectal cancer (mCRC). We sought to identify a threshold for CEA change from baseline to predict progressive disease (PD) in mCRC patients receiving first-line therapy.

Methods

Patients from trials collected in the ARCAD database were included if baseline CEA was at least 10 ng/mL and repeat CEA was available within 14 days of first restaging scan. Optimal cutoffs for CEA change were identified by receiver operating characteristic analysis. Prediction performance of cutoffs was evaluated by sensitivity, specificity, and negative predictive value. Analyses were conducted by treatment class: chemotherapy alone, chemotherapy with anti-VEGF antibody, and chemotherapy with anti-EGFR antibody.

Results

A total of 2643 mCRC patients treated with systemic therapy were included. Median percent change of CEA from baseline to first restaging for patients with complete response, partial response, or stable disease (non-PD) and PD was −53.1% and +23.6% for chemotherapy alone (n = 957) and −71.7% and −45.3% for chemotherapy with anti-VEGF antibody (n = 1355). The optimal area under the curve cutoff for differentiating PD from non-PD on first restaging was −7.5% for chemotherapy alone and −62.0% for chemotherapy with anti-VEGF antibody; chemotherapy alone, adjusted odds ratio = 6.51 (95% CI = 3.31 to 12.83, P < .001), chemotherapy with anti-VEGF antibody, adjusted odds ratio = 3.45 (95% CI = 1.93 to 6.18, P < .001). A 99% negative predictive value clinical cutoff for prediction of non-PD would avoid CT scan at first restaging in 21.0% of chemotherapy alone and 16.2% of chemotherapy with anti-VEGF antibody–treated patients. Among patients with stable disease on first restaging, those with decreased CEA from baseline had statistically significantly improved progression-free and overall survival.

Conclusions

Change in CEA from baseline to first restaging can accurately predict non-progression and correlates with long-term outcomes in patients receiving systemic chemotherapy.
Latino STYLE: Preliminary Findings From an HIV Prevention RCT Among Latino Youth
Authors: Lescano Celia M , Castillo Humberto López , Calcano Ercilia , Mayor Manuel , Porter Milagro , Rivera-Torgerson Yairí , Dion Charles , Marhefka Stephanie L , Barker David , Brown Larry K ,   The Latino STYLE Research Group
Published: March 2020

Objective

Latino STYLE is a family-centered, HIV-focused intervention (HIV) emphasizing cultural factors and parent-adolescent communication. We hypothesized that, compared with a general health promotion (HP) intervention, the HIV arm would improve caregiver and adolescent HIV knowledge, attitudes, parental monitoring, sexual communication, and family relationships after a 3-month postintervention period. This article reports on the short-term findings of the longer trial.

Methods

A single-site, two-arm, parallel, family-based, randomized, controlled trial was conducted; eligible participants were Latino adolescents aged 14–17 and their primary caregiver. The study was conducted at the University of South Florida with 227 adolescent-caregiver dyads allocated to the HIV (n = 117) or HP (n = 110) intervention after completing a baseline assessment. Interim measures at 3-month follow-up included demographics, HIV knowledge, self-efficacy, parental monitoring, sexual communication, family relationships, and adolescent sexual behavior.

Results

Adolescents in the HIV group reported small effects in parental permissiveness and the HP group reported small effects for family support. Caregivers in both groups reported decreases in all outcomes. Incidence of past 90-day sexual intercourse decreased in both treatment arms. Among those who were sexually active over the past 90 days, the number of sex acts decreased from baseline, particularly in the HIV group. The percentage of condom-protected sex acts increased in the HIV group and decreased in the HP group, but did not reach statistical significance.

Conclusions

The HIV Latino STYLE intervention was not efficacious in improving hypothesized outcomes over a 3-month period. However, exploratory analyses revealed moderate effects for decreases in adolescent sexual risk behavior, particularly in the HIV group.
Tomato SD1, encoding a kinase-interacting protein, is a major locus controlling stem development
Authors: Ye Jie , Tian Ranwen , Meng Xiangfei , Tao Peiwen , Li Changxing , Liu Genzhong , Chen Weifang , Wang Ying , Li Hanxia , Ye Zhibiao , Zhang Yuyang
Published: March 2020

Stems serve as key determinants of plant development by connecting and supporting parts of the plant body, transporting nutrients important for long-distance communication that affect crop yield, and producing new organs. Nonetheless, studies on the regulation of stem development in crops are rather limited. Here, we found a significant correlation (P<0.001) between stem diameter (SD) and fruit size in tomato (Solanum lycopersicum). We performed a genome-wide association study and identified a novel quantitative trait locus (QTL), SDR9 (stem diameter regulator on CHROMOSOME 9), that co-localized with a gene encoding a kinase-interacting family protein (KIP), which is the most likely candidate gene related to SD (hereafter referred to as SD1). Overexpression of SD1 in thin-stem accessions resulted in increased SD. In contrast, suppressed expression of SD1 in thick-stem accessions using RNA interference exhibited the opposite effect. Further microscopic analyses showed that SD1 affected the stem diameter by controlling the size and number of secondary phloem cells. An 11-bp indel in the promoter region of SD1 that disrupts a gibberellin-responsive cis-element was linked to SD. Expression analysis revealed that SD1 was mainly expressed at the cambium of the stem and positively regulates stem development. Evolutionary analysis revealed that the thick-stem allele of SD1 was selected during the recent process of tomato improvement. Our results provide novel genetic and molecular insight into natural variation of SD in tomato and may accelerate the breeding of high yield tomato.
Functional Evaluation of a Shock Absorbing Insole During Military Training in a Group of Soldiers: A Pilot Study
Authors: Lullini Giada , Giangrande Alessia , Caravaggi Paolo , Leardini Alberto , Berti Lisa
Published: March 2020

Objective

Soldiers’ lower limbs and feet are frequently affected by overload- and overuse-related injuries. In order to prevent or limit the incidence of these injuries, the use of foot orthoses is often recommended. The aim of this study is to assess the effects of shock-absorbing insoles on in-shoe plantar pressure magnitude and distribution in a group of professional infantry soldiers wearing military boots during standard indoor military training.

Methods

Twenty male professional soldiers of the Italian Army (age 35.1 ± 6.1 years; BMI 25.2 ± 2.3 kg/m2) were recruited for this study. Each subject underwent clinical examination to assess possible overuse-related diseases of the lower limb and trunk. Subjects with altered foot morphology according to the Foot Posture Index (FPI) were excluded from this study. Twelve subjects were considered eligible and therefore underwent an indoor training routine comprised of marching, running, jumping inside parallel bars and jumping from different heights. Soldiers repeated the training session twice wearing standard military boots along with two types of insoles: the standard prefabricated insole within the boots (STI), and a special shock-absorbing insole (SAI) featuring an elastic medial arch support. A 99-capacitive sensor insole system was used to record plantar pressure distribution in both feet. Analysis of in-shoe pressure parameters at rearfoot, midfoot and forefoot and in the total foot was performed via a custom-software application developed in MATLAB. Perceived foot comfort (VAS 0–15) was also assessed.

Results

Pressure parameters recorded during walking and running were considered suitable for statistical analysis. In the whole foot region, pressure parameters were 18–22% lower in military boots fitted with the SAI during walking and 14–18% lower during running. SAI resulted in better comfort (+25%) with respect to the prefabricated boot orthotics (median comfort: SAI = 15/15; STI = 12/15; p = 0.0039) both during walking and running.

Conclusions

Shock-absorbing insoles can be an effective solution when fitted inside military boots. The present functional evaluation shows that wearing a prefabricated shock-absorbing insole can provide a significant amelioration of perceived foot comfort and plantar pressure parameters. Further studies are now needed with a larger population and more demanding exercises.
On the red supergiant problem
Authors: Kochanek C S
Published: March 2020

We examine the problem of estimating the mass range corresponding to the observed red supergiant (RSG) progenitors of Type IIP supernovae. Using Monte Carlo simulations designed to reproduce the properties of the observations, we find that the approach of Davies & Beasor significantly overestimates the maximum mass, yielding an upper limit of Mh/M⊙ = 20.5 ± 2.6 for an input population with Mh/M⊙ = 18. Our preferred Bayesian approach does better, with Mh/M⊙ = 18.6 ± 2.1 for the same input populations, but also tends to overestimate Mh. For the actual progenitor sample and a Salpeter initial mass function, we find $M_{\rm h}/\mathrm{M}_\odot = 19.01_{-2.04}^{+4.04}$ for the Eldridge & Tout mass–luminosity relation used by Smartt and Davies & Beasor, and $M_{\rm h}/\mathrm{M}_\odot = 21.28_{-2.28}^{+4.52}$ for the Sukhbold, Woosley & Heger mass–luminosity relation. Based on the Monte Carlo simulations, we estimate that these are overestimated by $(3.3\pm 0.8)\, \mathrm{M}_\odot$. The red supergiant problem remains.
xGASS: the role of bulges along and across the local star-forming main sequence
Authors: Cook Robin H W , Cortese Luca , Catinella Barbara , Robotham Aaron
Published: March 2020

We use our catalogue of structural decomposition measurements for the extended GALEX Arecibo SDSS Survey (xGASS) to study the role of bulges both along and across the galaxy star-forming main sequence (SFMS). We show that the slope in the sSFR–M⋆ relation flattens by ∼0.1 dex per decade in M⋆ when re-normalizing specifice star formation rate (sSFR) by disc stellar mass instead of total stellar mass. However, recasting the sSFR–M⋆ relation into the framework of only disc-specific quantities shows that a residual trend remains against disc stellar mass with equivalent slope and comparable scatter to that of the total galaxy relation. This suggests that the residual declining slope of the SFMS is intrinsic to the disc components of galaxies. We further investigate the distribution of bulge-to-total ratios (B/T) as a function of distance from the SFMS (ΔSFRMS). At all stellar masses, the average B/T of local galaxies decreases monotonically with increasing ΔSFRMS. Contrary to previous works, we find that the upper envelope of the SFMS is not dominated by objects with a significant bulge component. This rules out a scenario in which, in the local Universe, objects with increased star formation activity are simultaneously experiencing a significant bulge growth. We suggest that much of the discrepancies between different works studying the role of bulges originate from differences in the methodology of structurally decomposing galaxies.
Measuring limb darkening of stars in high-magnification microlensing events by the Finite Element Method
Authors: Golchin L , Rahvar S
Published: March 2020

The finite-size effect in gravitational microlensing provides a possibility to measure the limb darkening of distant stars. We use the Finite Element Method (FEM) as an inversion tool for discretization and inversion of the magnification–limb darkening integral equation. This method makes no explicit assumption about the shape of the brightness profile more than the flatness of the profile near the centre of the stellar disc. From the simulation, we investigate the accuracy and stability of this method and we use regularization techniques to stabilize it. Finally, we apply this method to the single lens, high-magnification transit events of OGLE-2004-BLG-254 (SAAO-I), MOA-2007-BLG-233/OGLE-2007-BLG-302 (OGLE-I, MOA-R), MOA-2010-BLG-436 (MOA-R), MOA-2011-BLG-93 (Canopus-V), MOA-2011-BLG-300/OGLE-2011-BLG-0990 (Pico-I), and MOA-2011-BLG-325/OGLE-2011-BLG-1101 (LT-I) in which light curves have been observed with a high cadence near the peak (Choi et al. 2012). The recovered intensity profile of stars from our analysis for five light curves is consistent with the linear and square-root limb darkening profiles and two events with the square-root profile. The advantage of FEM is to extract limb darkening of stars without any assumption about the limb darkening model.
Detection of neutral atomic species in the ultra-hot Jupiter WASP-121b
Authors: Cabot Samuel H C , Madhusudhan Nikku , Welbanks Luis , Piette Anjali , Gandhi Siddharth
Published: March 2020

The class of ultra-hot Jupiters comprises giant exoplanets undergoing intense irradiation from their host stars. They have proved to be a particularly interesting population for their orbital and atmospheric properties. One such planet, WASP-121b, is in a highly misaligned orbit close to its Roche limit, and its atmosphere exhibits a thermal inversion. These properties make WASP-121b an interesting target for additional atmospheric characterization. In this paper, we present analyses of archival high-resolution optical spectra obtained during transits of WASP-121b. We model the Rossiter-McLaughlin effect and the Centre-to-Limb Variation and find that they do not significantly affect the transmission spectrum in this case. However, we discuss scenarios where these effects warrant more careful treatment by modelling the WASP-121 system and varying its properties. We report a new detection of atmospheric absorption from H α in the planet with a transit depth of $1.87\pm 0.11{{\ \rm per\ cent}}$. We further confirm a previous detection of the Na i doublet, and report a new detection of Fe i via cross-correlation with a model template. We attribute the H α absorption to an extended Hydrogen atmosphere, potentially undergoing escape, and the Fe i to equilibrium chemistry at the planetary photosphere. These detections help to constrain the composition and chemical processes in the atmosphere of WASP-121b.
Differential modulation of the androgen receptor for prostate cancer therapy depends on the DNA response element
Authors: Kregel Steven , Bagamasbad Pia , He Shihan , LaPensee Elizabeth , Raji Yemi , Brogley Michele , Chinnaiyan Arul , Cieslik Marcin , Robins Diane M
Published: March 2020

Androgen receptor (AR) action is a hallmark of prostate cancer (PCa) with androgen deprivation being standard therapy. Yet, resistance arises and aberrant AR signaling promotes disease. We sought compounds that inhibited genes driving cancer but not normal growth and hypothesized that genes with consensus androgen response elements (cAREs) drive proliferation but genes with selective elements (sAREs) promote differentiation. In a high-throughput promoter-dependent drug screen, doxorubicin (dox) exhibited this ability, acting on DNA rather than AR. This dox effect was observed at low doses for multiple AR target genes in multiple PCa cell lines and also occurred in vivo. Transcriptomic analyses revealed that low dox downregulated cell cycle genes while high dox upregulated DNA damage response genes. In chromatin immunoprecipitation (ChIP) assays with low dox, AR binding to sARE-containing enhancers increased, whereas AR was lost from cAREs. Further, ChIP-seq analysis revealed a subset of genes for which AR binding in low dox increased at pre-existing sites that included sites for prostate-specific factors such as FOXA1. AR dependence on cofactors at sAREs may be the basis for differential modulation by dox that preserves expression of genes for survival but not cancer progression. Repurposing of dox may provide unique opportunities for PCa treatment.
Uncovering the key dimensions of high-throughput biomolecular data using deep learning
Authors: Zhang Shixiong , Li Xiangtao , Lin Qiuzhen , Lin Jiecong , Wong Ka-Chun
Published: March 2020

Recent advances in high-throughput single-cell RNA-seq have enabled us to measure thousands of gene expression levels at single-cell resolution. However, the transcriptomic profiles are high-dimensional and sparse in nature. To address it, a deep learning framework based on auto-encoder, termed DeepAE, is proposed to elucidate high-dimensional transcriptomic profiling data in an encode–decode manner. Comparative experiments were conducted on nine transcriptomic profiling datasets to compare DeepAE with four benchmark methods. The results demonstrate that the proposed DeepAE outperforms the benchmark methods with robust performance on uncovering the key dimensions of single-cell RNA-seq data. In addition, we also investigate the performance of DeepAE in other contexts and platforms such as mass cytometry and metabolic profiling in a comprehensive manner. Gene ontology enrichment and pathology analysis are conducted to reveal the mechanisms behind the robust performance of DeepAE by uncovering its key dimensions.
Isolation and analysis of rereplicated DNA by Rerep-Seq
Authors: Menzel Johannes , Tatman Philip , Black Joshua C
Published: March 2020

Changes in gene copy number contribute to genomic instability, the onset and progression of cancer, developmental abnormalities and adaptive potential. The origins of gene amplifications have remained elusive; however, DNA rereplication has been implicated as a source of gene amplifications. The inability to determine which sequences are rereplicated and under what conditions have made it difficult to determine the validity of the proposed models. Here we present Rerep-Seq, a technique that selectively enriches for rereplicated DNA in preparation for analysis by DNA sequencing that can be applied to any species. We validated Rerep-Seq by simulating DNA rereplication in yeast and human cells. Using Rerep-Seq, we demonstrate that rereplication induced in Saccharomyces cerevisiae by deregulated origin licensing is non-random and defined by broad domains that span multiple replication origins and topological boundaries.
Type II and type IV toxin–antitoxin systems show different evolutionary patterns in the global Klebsiella pneumoniae population
Authors: Horesh Gal , Fino Cinzia , Harms Alexander , Dorman Matthew J , Parts Leopold , Gerdes Kenn , Heinz Eva , Thomson Nicholas R
Published: March 2020

The Klebsiella pneumoniae species complex includes important opportunistic pathogens which have become public health priorities linked to major hospital outbreaks and the recent emergence of multidrug-resistant hypervirulent strains. Bacterial virulence and the spread of multidrug resistance have previously been linked to toxin–antitoxin (TA) systems. TA systems encode a toxin that disrupts essential cellular processes, and a cognate antitoxin which counteracts this activity. Whilst associated with the maintenance of plasmids, they also act in bacterial immunity and antibiotic tolerance. However, the evolutionary dynamics and distribution of TA systems in clinical pathogens are not well understood. Here, we present a comprehensive survey and description of the diversity of TA systems in 259 clinically relevant genomes of K. pneumoniae. We show that TA systems are highly prevalent with a median of 20 loci per strain. Importantly, these toxins differ substantially in their distribution patterns and in their range of cognate antitoxins. Classification along these properties suggests different roles of TA systems and highlights the association and co-evolution of toxins and antitoxins.
Multidisciplinary patient-centered management of brain metastases and future directions
Authors: Palmer Joshua D , Trifiletti Daniel M , Gondi Vinai , Chan Michael , Minniti Giuseppe , Rusthoven Chad G , Schild Steven E , Mishra Mark V , Bovi Joseph , Williams Nicole , Lustberg Maryam , Brown Paul D , Rao Ganesh , Roberge David
Published: March 2020

The incidence of brain metastasis is increasing as improvements in systemic therapy lead to increased survival. This provides new and challenging clinical decisions for patients who are trying to balance the risk of recurrence or progression with treatment-related side effects, and it requires appropriate management strategies from multidisciplinary teams. Improvements in prognostic assessment and systemic therapy with increasing activity in the brain allow for individualized care to better guide the use of local therapies and/or systemic therapy. Here, we review the current landscape of brain-directed therapy for the treatment of brain metastasis in the context of recent improved systemic treatment options. We also discuss emerging treatment strategies including targeted therapies for patients with actionable mutations, immunotherapy, modern whole-brain radiation therapy, radiosurgery, surgery, and clinical trials.
Accounting for Multiple Comparisons in Statistical Analysis of the Extensive Bioassay Data on Glyphosate
Authors: Crump Kenny , Crouch Edmund , Zelterman Daniel , Crump Casey , Haseman Joseph
Published: March 2020

Glyphosate is a widely used herbicide worldwide. In 2015, the International Agency for Research on Cancer (IARC) reviewed glyphosate cancer bioassays and human studies and declared that the evidence for carcinogenicity of glyphosate is sufficient in experimental animals. We analyzed 10 glyphosate rodent bioassays, including those in which IARC found evidence of carcinogenicity, using a multiresponse permutation procedure that adjusts for the large number of tumors eligible for statistical testing and provides valid false-positive probabilities. The test statistics for these permutation tests are functions of p values from a standard test for dose-response trend applied to each specific type of tumor. We evaluated 3 permutation tests, using as test statistics the smallest p value from a standard statistical test for dose-response trend and the number of such tests for which the p value is less than or equal to .05 or .01. The false-positive probabilities obtained from 2 implementations of these 3 permutation tests are: smallest p value: .26, .17; p values ≤ .05: .08, .12; and p values ≤ .01: .06, .08. In addition, we found more evidence for negative dose-response trends than positive. Thus, we found no strong evidence that glyphosate is an animal carcinogen. The main cause for the discrepancy between IARC’s finding and ours appears to be that IARC did not account for the large number of tumor responses analyzed and the increased likelihood that several of these would show statistical significance simply by chance. This work provides a more comprehensive analysis of the animal carcinogenicity data for this important herbicide than previously available.
Soil moisture heterogeneity regulates water use in Populus nigra L. by altering root and xylem sap phytohormone concentrations
Authors: Puértolas Jaime , Pardos Marta , de Ollas Carlos , Albacete Alfonso , Dodd Ian C
Published: March 2020

Soil moisture heterogeneity in the root zone is common both during the establishment of tree seedlings and in experiments aiming to impose semi-constant soil moisture deficits, but its effects on regulating plant water use compared with homogenous soil drying are not well known in trees. Pronounced vertical soil moisture heterogeneity was imposed on black poplar (Populus nigra L.) grown in soil columns by altering irrigation frequency, to test whether plant water use, hydraulic responses, root phytohormone concentrations and root xylem sap chemical composition differed between wet (well-watered, WW), and homogeneously (infrequent deficit irrigation, IDI) and heterogeneously dry soil (frequent deficit irrigation, FDI). At the same bulk soil water content, FDI plants had greater water use than IDI plants, probably because root abscisic acid (ABA) concentration was low in the upper wetter layer of FDI plants, which maintained root xylem sap ABA concentration at basal levels in contrast with IDI. Soil drying did not increase root xylem concentration of any other hormone. Nevertheless, plant-to-plant variation in xylem jasmonic acid (JA) concentration was negatively related to leaf stomatal conductance within WW and FDI plants. However, feeding detached leaves with high (1200 nM) JA concentrations via the transpiration stream decreased transpiration only marginally. Xylem pH and sulphate concentration decreased in FDI plants compared with well-watered plants. Frequent deficit irrigation increased root accumulation of the cytokinin trans-zeatin (tZ), especially in the dry lower layer, and of the ethylene precursor 1-aminocyclopropane-1-carboxylic acid (ACC), in the wet upper soil layer. Root hormone accumulation might explain the maintenance of high root hydraulic conductance and water use in FDI plants (similar to well-watered plants) compared with IDI plants. In irrigated tree crops, growers could vary irrigation scheduling to control water use by altering the hormone balance.
Atrial arrhythmias in heart failure with a reduced ejection fraction
Authors: Dewland Thomas A. , Nazer Babak
Published: March 2020

Purpose of review

Atrial arrhythmias are common among individuals with heart failure with a reduced ejection fraction (HFrEF). This review describes management options for these arrhythmias and discusses emerging clinical data supporting catheter ablation.

Recent findings

Several recent clinical trials indicate that catheter ablation is superior to pharmacologic therapy for management of symptomatic atrial fibrillation in the setting of HFrEF. Restoration and maintenance of sinus rhythm appears to have the greatest benefit with regard to ejection fraction improvement among individuals with a nonischemic heart failure etiology and minimal left ventricular fibrosis.

A rhythm control strategy should be strongly considered in patients with HFrEF, especially when the atrial arrhythmia is symptomatic or is present at the time of a heart failure diagnosis. Catheter ablation may be the preferred strategy for maintenance of sinus rhythm in this patient population.
Inhibiting Glycogen Synthase Kinase-3 Mitigates the Hematopoietic Acute Radiation Syndrome in a Sex- and Strain-dependent Manner in Mice
Authors: Daniel Andrea R. , Lee Chang-Lung , Oh Patrick , Luo Lixia , Ma Yan , Kirsch David G.
Published: March 2020

The Radiation and Nuclear Countermeasures Program at the National Institute of Allergy and Infectious Diseases (NIAID) mandated that medical countermeasures for treating Acute Radiation Syndrome (ARS) must have efficacy when administered at least 24 h after radiation exposure. At this time point, many cells within key target tissues, such as the hematopoietic system and the gastrointestinal (GI) tract, will already be dead. Therefore, drugs that promote the regeneration of surviving cells may improve outcomes. The serine/threonine kinase glycogen synthase kinase-3 (GSK-3) regulates stem and progenitor cell self-renewal and regeneration in the hematopoietic and GI compartments. We tested inhibition of GSK-3β by SB216763 24 h after total body irradiation (TBI) and sub-total body irradiation (SBI). Here, we show that subcutaneous administration of SB216763 promotes the regeneration of surviving hematopoietic stem/progenitor cells (HSPCs), including myeloid progenitor cells, and improves survival of C57Bl/6 male mice when administered 24 h after TBI. However, these results were not recapitulated in female C57Bl/6 animals, suggesting a sex difference in GSK-3β signaling in HSPCs. Subcutaneous administration of SB216763 in male mice stimulated activation of Sox2 transcription but failed to induce Sox2 transcription in female C57Bl/6 mice. Using TCF/lef-GFP reporter mice, we examined Wnt signaling in HSPCs of irradiated male and female mice treated with SB216763. GSK-3 inhibition elevated Wnt reporter activity in HSPCs isolated from male but not female mice. SB216763 did not mitigate hematopoietic ARS in males or females of a second strain of wild-type mice, C3H. In addition, administration of SB216763 did not mitigate hematopoietic ARS beyond the currently available standard approved therapy of ciprofloxacin and granulocyte-colony stimulating factor (G-CSF) in male C57Bl/6 mice. Further, SB216763 did not mitigate GI-ARS after SBI in C57Bl/6 male mice. The lack of efficacy in both sexes and multiple strains of mice indicate that SB216763 is not suitable for further drug development as a mitigator of ARS. Our studies demonstrate that activation of Wnt signaling in HSPCs promotes hematopoietic regeneration following radiation exposure, and targeting this pathway downstream of GSK-3β may mitigate ARS in a sex- and strain-independent manner.
Complications of vitreoretinal surgery
Authors: Belin Peter J. , Parke D. Wilkin
Published: March 2020

Purpose of review

The present article reviews the most common and most serious vision-threatening and life-threatening complications of vitreoretinal surgery.

Recent findings

Serious complications after vitreroretinal surgery are rare. Endophthalmitis for example has recently been estimated to occur in 0.08% of small gague vitrectomy. Other complications such as cataract are almost unavoidable, becoming visually significant in up to 80% of patients. The introduction of smaller gauge vitrectomy systems has reduced surgical times, conjunctival scarring and inflammation, and the rate of some complications such as retinal tears. Ocular venous air embolism is an exceedingly rare complication that is potentially life threating and therefore important for all vitreoretinal surgeons to be aware of.

Though vitreoretinal surgery is well tolerated and effective, it is inevitable that all surgeons will experience complications and are therefore best served by understanding the potential complications, strategies to reduce the likelihood of them occurring, and ways to address them when they do happen.
Echocardiographic Follow-up of Perinatally HIV-infected Children and Adolescents
Authors: Vallilo Nathália Gaspar , Durigon Giuliana Stravinskas , Lianza Alessandro Cavalcanti , de Fátima Rodrigues Diniz Maria , Shiraishi Sawamura Karen Saori , Brito Carolina Rocha , de Souza Marques Heloisa Helena , Ferraro Alexandre Archanjo , Leal Gabriela Nunes
Published: March 2020

Background:

The effects of HIV and antiretroviral therapy on cardiovascular system of perinatally infected children throughout their development are not fully understood.

Objectives:

To determine the prevalence of cardiac abnormalities in a retrospective cohort of perinatally HIV-infected patients and to investigate associations between echocardiographic and clinical data during their follow-up.

Methods:

Review of medical records and echocardiogram reports of 148 perinatally HIV-infected patients between January 1991 and December 2015.

Results:

Four hundred and eighty echocardiograms were analyzed and 46 (31%) patients showed cardiac abnormalities, frequently subclinical and transient. Nadir CD4 count was higher in patients with consistently normal echocardiogram: 263 (4–1480) versus 202 (5–1746) cells/μL, P = 0.021. Right ventricular (RV) dilation was detected in 18.9%, left ventricular (LV) dilation in 21.6%, septal hypertrophy in 12.2%, LV posterior wall hypertrophy in 6%, LV systolic dysfunction in 8% and pulmonary hypertension in 8.7% of patients. Opportunistic infections were associated with RV dilation [odds ratio (OR = 4.34; 1.78–10.53; P < 0.01)], pulmonary hypertension (OR = 8.78; 2.80–27.51; P < 0.01) and LV systolic dysfunction (OR = 5.38; 1.55–18.71; P < 0.01). Longer duration of highly active antiretroviral therapy was associated with reduced risk of LV dilation (OR = 0.91; 0.85–0.97; P < 0.01) and systolic dysfunction (OR = 0.71; 0.59–0.85; P < 0.01). Protease inhibitors use was associated with reduced risk of RV dilation (OR = 0.54; 0.30–0.97; P < 0.05), LV dilation (OR = 0.35; 0.21–0.60; P < 0.01) and LV systolic dysfunction (OR = 0.07; 0.02–0.31; P < 0.01). Higher CD4 count was associated with lower risk of LV systolic dysfunction (OR = 0.82; 0.69–0.98; P < 0.05).

Conclusions:

Echocardiograms identified cardiac abnormalities among children with perinatally acquired HIV infection, and data suggest that immunologic status and therapeutic strategies throughout development can influence cardiac disease burden in this population.
Intraoperative aberrometry vs modern preoperative formulas in predicting intraocular lens power
Authors: Raufi Nikolas , James Charlene , Kuo Anthony , Vann Robin
Published: March 2020

Purpose:

To compare the outcomes of an intraoperative aberrometer (ORA) to the Barrett Universal II (Barrett II) and Hill-RBF 2.0 (Hill-RBF) intraocular lens (IOL) power calculation formulas.

Setting:

Duke University Eye Center, Durham, North Carolina, USA.

Design:

Retrospective study.

Methods:

Patients without history of refractive corneal surgery who had an uneventful cataract surgery from April 2016 to June 2018 were enrolled. Refractive prediction error was calculated with the Barrett II formula, the Hill-RBF formula, and the ORA intraoperative aberrometer (OIA) and was stratified by axial length, IOL type, and the percentage of eyes within a diopteric range of target refraction.

Results:

Nine-hundred forty-nine eyes were included. The mean and median absolute predictive errors were 0.29 diopters (D) and 0.23 D (Barrett II), 0.31 D and 0.24 D (Hill-RBF), and 0.31 D and 0.25 D (intraoperative aberrometry), respectively (P > .05). Axial length stratification did not influence statistical difference in the IOL prediction methods. Barrett II outperformed the OIA toric multifocal (P = .011) group. Postoperative refraction was within 0.50 D of target in 84% (Barrett II), 83% (Hill-RBF), and 82% (OIA) of eyes (P > .05).

Conclusions:

Comparing the OIA to the Barrett II and Hill-RBF calculators, there was minimal clinical difference in the toric multifocal group. Regarding postoperative predicted spherical equivalent, for patients without a history of refractive surgery and good potential visual acuity, refractive outcome was not improved by utilizing the OIA.
Long-term follow-up of a custom-made prosthetic iris device in patients with congenital aniridia
Authors: Figueiredo Gabriel B. , Snyder Michael E.
Published: March 2020

Purpose:

To investigate the effectiveness and safety of a custom-made iris prosthetic device used to reduce photic symptoms in patients with congenital aniridia.

Setting:

Cincinnati Eye Institute, Cincinnati, Ohio, USA.

Design:

Retrospective single-surgeon case series.

Methods:

The charts of all eyes of patients diagnosed with congenital aniridia syndrome who underwent implantation of the custom-made iris prosthesis at the setting institution between 2008 and 2018 were reviewed. Eyes with more than 6 months of follow-up were included in evaluation. Charts were carefully reviewed for comorbid conditions, interventions, and outcomes.

Results:

Ninety-six eyes of 50 patients were included in the study. Subjective reduction in photophobia and glare was reported in 95.7% and 95.2% of cases, respectively. The incidence of aniridia fibrosis syndrome (AFS) in this study (3.1%; 95% confidence interval, 0.6%-8.9%) was similar to previous studies in the literature.

Conclusions:

The custom-made iris prosthesis was an effective and safe option to reduce photic symptoms in patients with congenital aniridia. The custom, flexible iris implant does not appear to alter the risk for AFS. These highly complex eyes with significant comorbid pathologies demand an individualized approach and careful long-term follow-up.
Black Acral Nodule
Authors: Kearns Donovan , Dodd Christina , Jacob Sharon E.
Published: March 2020

Teledermatology is a term to describe the provision of dermatologic medical services through telecommunication technology. This is a teledermatology case of black acral nodule.
Caregivers of Patients With Brain Metastases: A Description of Caregiving Responsibilities and Psychosocial Well-being
Authors: Ketcher Dana , Otto Amy K. , Reblin Maija
Published: March 2020

BACKGROUND

There are increasing numbers of cancer patients with brain metastases, and there is a high potential for caregiving burden. Little work has explored caregiving responsibilities and psychosocial well-being in informal family caregivers (FCGs) of cancer patients with brain metastases. This study aimed to address this gap in the literature.

METHODS

Data were drawn from baseline pilot study data. Caregivers completed demographic information and provided a self-report of their caring responsibilities and psychosocial well-being via questionnaire.

RESULTS

Participants were 21 FCGs of patients with brain metastases. Many caregivers are devoting extensive time to providing care; there was high variability in the number and types of caregiving activities reported. Although many caregivers report feeling well supported, other aspects of psychosocial well-being were less robust, including anxiety, depression, burden, and coping self-efficacy.

CONCLUSION

Although FCGs reported mitigating factors such as social support, they still experience significant distress. Findings support previous work suggesting that neuro-oncology caregiving is burdensome, with adverse effects on health and well-being. Foundational work, such as this, will set the stage to identify areas for future intervention.
The Quality of Life as a Predictor of Social Support for Multiple Sclerosis Patients and Caregivers
Authors: Dębska Grażyna , Milaniak Irena , Skorupska-Król Agnieszka
Published: March 2020

BACKGROUND: Coping with a diagnosis of multiple sclerosis (MS) is challenging. MS is one of the most common causes of nontraumatic disability in young adults, and patients may need assistance with daily life activities. This article explores the relation between quality of life (QOL) and the perceived available social support among patients with MS and their families. METHODS: The study included 120 subjects (60 patient-caregiver dyads). The average age of the patients was 53.95 ± 10.19 years, and for caregivers, it was 50.8 ± 13.3 years. The study used 2 subscales of the Berlin Social Support Scale (perceived availability of social support and need for social support) and the World Health Organization Quality of Life questionnaire for the assessment of QOL. RESULTS: QOL in MS is lower compared with that of their caregivers in all dimensions except the social domain (P < .001, r = 0.54–0.64). A higher need for social support was experienced by caregivers. The need for support in this group is affected by 3 predictors: QOL in the environmental domain and in the physical domain as well as their subjective health. An improvement in QOL in all the domains is related to an increase of perceived available support, in both the group of patients and that of their caregivers (P < .05, ρ = 0.28–0.59). CONCLUSIONS: Perceived available support is of great importance for both patients and their caregivers to enable them to function better in the physical, mental, social, and environmental domains of their QOL, where social relationships play a predictive role.
Minimally Invasive Cochlear Implantation Assisted by Intraoperative CT Scan Combined to Neuronavigation
Authors: Duret Sonia , Guigou Caroline , Grelat Mickael , Bozorg-Grayeli Alexis
Published: March 2020

Objective:

The objective of this work was to study the feasibility of minimally invasive cochlear implantation under intraoperative computerized tomography-scan coupled to navigation.

Materials and Methods:

Five human resin temporal bones (two adults and three children) were used. Initially, a temporal bone imaging was obtained by the intraoperative CT-scan coupled to the navigation (O-ARM). The navigation-assisted drilling began at the mastoid surface creating a conical tunnel (4–2 mm in diameter) through the facial recess and down to the round window. A cochleostomy was performed based on the navigation. A sham electrode array was inserted in the drilled tunnel and into the cochlea.

Postoperative CT-scan and dissection were performed to evaluate the trajectory, and possible injury to the external auditory canal, ossicles, or facial nerve.

Results:

The mean duration of the procedure was 24.4 ± 3.79 minutes (range, 15–35). Cochleostomy was possible in all cases without injury to other structures. The sham array was inside the cochlea in all cases. The mean distance between the drilled canal and the mastoid portion of the facial nerve was 1.2 ± 0.07 mm (range, 1.08–1.38). The mean tracking error was 0.6 ± 0.26 mm (range, 0.20–0.72) at the entry point, 0.6 ± 0.33 mm (range, 0.2–1.02) at the facial nerve and 0.4 ± 0.07 mm (range, 0.36–0.51) at the cochleostomy.

Conclusion:

Cochlear implantation through a minimally invasive approach assisted by intraoperative imaging combined with navigation was feasible in operating room environment and experimental conditions.
Comparison of a Mid Scala and a Perimodiolar Electrode in Adults: Performance, Impedances, and Psychophysics
Authors: Battmer Rolf-Dieter , Scholz Sandra , Gazibegovic Dzemal , Ernst Arne , Seidl Rainer O.
Published: March 2020

Objectives:

The HiFocus Mid-Scala electrode array (HFms) is designed to sit within the scala tympani without touching either the lateral wall or the modiolus. The aim of this study was to compare the HFms to the Helix perimodiolar electrode array.

Method:

Two groups of recipients with Helix (n = 22 ears) and HFms (n = 29 ears) electrode arrays were retrospectively identified and matched by age at implantation and duration of severe to profound deafness. Most comfortable listening levels (M), impedances, Freiburger Monosyllables in quiet, and Oldenburg sentences in adaptive noise were compared at 3, 6, and 12 months postimplant.

Results:

Median scores for monosyllables in quiet for the HFms group were significantly better than the Helix group at each test interval (p < 0.05). Speech perception in quiet also significantly improved from 3 to 12 months for both groups (p < 0.001). There was no significant difference between the groups for speech in noise. Impedances were significantly lower for the HFms group at 12 months (p < 0.05) except at the basal end and M levels were generally higher.

Conclusions:

The HFms group had better median performance for monosyllables in quiet than the Helix group at each test interval, although performance in noise was similar. For speech in noise, the HFms group appear to reach optimum performance quicker than the Helix group. Impedances were lower in the HFms group across the array, other than at the most basal end, and support our hypothesis that the HFms assumes a more lateral position within the cochlea than the Helix electrode, although our article did not include imaging data.
Prevalence and correlation of anxiety and depression on the prognosis of postoperative non-small-cell lung cancer patients in North China
Authors: Huang Xuan , Zhang Tian-Ze , Li Guang-Hua , Liu Lei , Xu Guang-Quan
Published: March 2020

Identify the prevalence of postoperative anxiety and depression as well as their correlations with clinical features and survival profiles in non-small-cell lung cancer (NSCLC) patients who underwent resection.

Four hundred NSCLC patients who underwent resection were recruited, and their anxiety and depression were assessed by hospital anxiety and depression scale (HADS) at discharge after surgery. Besides, 480 healthy controls (HCs) were also enrolled and assessed by HADS.

The HADS-Anxiety score of NSCLC patients (7.8 ± 3.9) was greatly higher than that of HCs (4.8 ± 2.7), and the anxiety prevalence of NSCLC patients (49.6%) were dramatically increased compared with HCs (13.8%). Furthermore, the HADS-Depression score (7.2 ± 3.6) of NSCLC patients was considerably increased compared with HCs (4.2 ± 2.6), and the depression prevalence of NSCLC patients (38.3%) was significantly raised compared with HCs (10.0%). Besides, anxiety correlated with gender, marital status, hypertension, diabetes, pathological differentiation, tumor size, lymph node metastasis, TNM stage and carcinoembryonic antigen level, meanwhile, depression correlated with marital status, employment status before surgery, diabetes, pathological differentiation, and TNM stage in NSCLC patients. Additionally, the anxiety and depression predicted shorter disease-free survival in NSCLC patients. And the anxiety predicted worse overall survival (OS), while no association of depression with OS was observed in NSCLC patients.

Post-operative anxiety and depression are highly prevalent and implicated in the ongoing care and prognosis prediction in NSCLC patients who underwent resection.