bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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 &lt; .001), chemotherapy with anti-VEGF antibody, adjusted odds ratio = 3.45 (95% CI = 1.93 to 6.18, P &lt; .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

Abstract

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

AbstractStems 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&lt;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

Abstract

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

ABSTRACT
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

ABSTRACT
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

ABSTRACT
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

ABSTRACT
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

AbstractAndrogen 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

AbstractRecent 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

Abstract
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

Abstract
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

Abstract
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

AbstractGlyphosate 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.