bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cutaneous manifestations in Costello syndrome: HRAS p.Gly12Ser affects RIN1-mediated integrin trafficking in immortalized epidermal keratinocytes
Authors: Nauth Theresa , Bazgir Farhad , Voß Hannah , Brandenstein Laura I , Mosaddeghzadeh Niloufar , Rickassel Verena , Deden Sophia , Gorzelanny Christian , Schlüter Hartmut , Ahmadian Mohammad R , Rosenberger Georg 
Published: August 2022

Abstract
Heterozygous germline missense variants in the HRAS gene underlie Costello syndrome (CS). The molecular basis for cutaneous manifestations in CS is largely unknown. We used an immortalized human cell line, HaCaT keratinocytes, stably expressing wild-type or CS-associated (p.Gly12Ser) HRAS and defined RIN1 as quantitatively most prominent, high-affinity effector of active HRAS in these cells. As an exchange factor for RAB5 GTPases, RIN1 is involved in endosomal sorting of cell-adhesion integrins. RIN1-dependent RAB5A activation was strongly increased by HRASGly12Ser, and HRAS-RIN1-ABL1/2 signaling was induced in HRASWT- and HRASGly12Ser-expressing cells. Along with that, HRASGly12Ser expression decreased total integrin levels and enriched β1 integrin in RAB5- and EEA1-positive early endosomes. The intracellular level of active β1 integrin was increased in HRASGly12Ser HaCaT keratinocytes due to impaired recycling, whereas RIN1 disruption raised β1 integrin cell surface distribution. HRASGly12Ser induced co-localization of β1 integrin with SNX17 and RAB7 in early/sorting and late endosomes, respectively. Thus, by retaining β1 integrin in intracellular endosomal compartments, HRAS-RIN1 signaling affects the subcellular availability of β1 integrin. This may interfere with integrin-dependent processes as we detected for HRASGly12Ser cells spreading on fibronectin. We conclude that dysregulation of receptor trafficking and integrin-dependent processes such as cell adhesion are relevant in the pathobiology of CS.
Dynamic Immune Profile in French Toxoplasmosis Patients
Authors: Denis Julie , Gommenginger Chloé , Strechie Teodora , Filisetti Denis , Beal Laetitia , Pfaff Alexander W , Villard Odile 
Published: August 2022

AbstractBackgroundToxoplasma gondii infection is usually benign in Europe due to the strong predominance of type II strains. Few studies have been conducted to examine the immunological course of infection in humans and have yielded conflicting results, maybe influenced by heterogeneous parasite strains.MethodsWe measured 23 immune mediators in 39, 40, and 29 sera of French noninfected, acutely infected, and chronically infected immunocompetent pregnant women, respectively.ResultsFour different cytokine patterns were identified regarding their dynamics through infection phases. For 11 of the cytokines (IFN-β, IFN-γ, IL-4, IL5, IL-6, IL-10, IL-12, IL-15, CXCL9, CCL2, and CSF2) the serum levels were significantly elevated during acute infection. The inflammatory mediators IL-1β, IL-17A, IL-18, TNF-α, and CSF3 remained unchanged during acute infection, while they were significantly lower in chronically infected compared to noninfected patients. As for the anti-inflammatory cytokines TGF-β and CCL5, their levels remained significantly elevated during chronic infection. We also observed a significant negative correlation of several cytokine concentrations with IgG levels, indicating a rapid decline of serum concentrations during the acute phase.ConclusionsThese results indicate an anti-inflammatory pattern in chronically infected patients in a type II dominated setting and demonstrate the highly dynamic immune situation during acute infection.
Rapid detection of CTX-M-type ESBLs and carbapenemases directly from biological samples using the BL-DetecTool
Authors: Volland Hervé , Ballesté-Delpierre Clara , Szabó Dóra , Gonzalez Camille , Takissian Julie , Aszalos Albert Zoltan , Ostorhazi Eszter , Farkas Szilvia , Kamotsay Katalin , Rosenmoller Magda , Stankov-Pugès Milovan , Francius Laura , Boutigny Laure , Sivan Virginie , Simon Stéphanie , Gelhaye Stéphanie , Bosch Jordi , Vila Jordi , Naas Thierry 
Published: August 2022

Abstract

Background
Lateral flow immunoassays (LFIA) have shown their usefulness for detecting CTX-M- and carbapenemase-producing Enterobacterales (CPEs) in bacterial cultures. Here, we have developed and validated the BL-DetecTool to detect CTX-M enzymes and carbapenemases directly from clinical samples.

Methods
The BL-DetecTool is an LFIA that integrates an easy sample preparation device named SPID (Sampling, Processing, Incubation and Detection). It was evaluated in three University hospitals on urine, blood culture (BC) and rectal swab (RS) specimens either of clinical origin or on spiked samples. RS evaluation was done directly and after a 24 h enrichment step.

Results
The CTX-M BL-DetecTool was tested on 485 samples (154 BC, 150 urines, and 181 RS) and revealed a sensitivity and specificity of 97.04% (95% CI 92.59%–99.19%) and 99.43% (95% CI 97.95%–99.93%), respectively. Similarly, the Carba5 BL-DetecTool was tested on 382 samples (145 BC, 116 urines, and 121 RS) and revealed a sensitivity and specificity of 95.3% (95% CI 89.43%–98.47%) and 100% (95% CI 98.67%–100%), respectively. While with the Carba5 BL-DetecTool five false negatives were observed, mostly in RS samples, with the CTX-M BL-DetecTool, in addition to four false-negatives, two false-positives were also observed. Direct testing of RS samples revealed a sensitivity of 78% and 86% for CTX-M and carbapenemase detection, respectively.

Conclusions
BL-DetecTool showed excellent biological performance, was easy-to-use, rapid, and could be implemented in any microbiology laboratory around the world, without additional equipment, no need for electricity, nor trained personnel. It offers an attractive alternative to costly molecular methods.
Challenges of in vitro propagation and antimicrobial susceptibility testing of Mycoplasma genitalium
Authors: Pitt Rachel , Boampong Dolcibella , Day Michaela , Jensen Jorgen Skov , Cole Michelle 
Published: August 2022

Abstract
The sexually transmitted bacterial pathogen Mycoplasma genitalium has proved a complex organism to work with in the laboratory setting. Exhibiting an extremely fastidious nature, successful in vitro propagation of M. genitalium has remained elusive for many researchers. Antimicrobial resistance to both first- and second-line recommended therapies (macrolides and fluoroquinolones, respectively) is commonly reported. However, phenotypic susceptibility testing is not routinely performed, due to the difficulties of in vitro growth. Instead, molecular detection of known resistance determinants is used to infer susceptibility/resistance. However, associations between determinant detection and clinical treatment failure are not always clear. Furthermore, molecular assays have limited use for detection of emerging resistance mechanisms. The present review collates and discusses the development of successful culture systems for initial isolation of this organism and current methodologies employed for phenotypic susceptibility testing to aid researchers in this field. As with Neisseria gonorrhoeae, future treatment options are extremely limited for M. genitalium and, if this sexually transmitted infection is to remain treatable, phenotypic susceptibility testing will play an invaluable role in evaluation of potential therapeutics. As such, retainment of these techniques is imperative.
A DNA Metabarcoding Workflow to Identify Species in Spices and Herbs
Authors: Cottenet Geoffrey , Cavin Christophe , Blancpain Carine , Chuah Poh Fong , Pellesi Roberta , Suman Michele , Nogueira Sofia , Gadanho Mario 
Published: August 2022

Abstract

Background
Spices and herbs are food categories regularly cited as highly susceptible to be adulterated. To detect potential adulteration with undeclared species, DNA-based methods are considered the most suitable tools.

Objective
In this study, the performance of the ready-to-use Thermo Scientific™ NGS Food Authenticity Workflow (Thermo Fisher Scientific)—a commercial DNA metabarcoding approach—is described. The tool was further applied to analyze 272 commercial samples of spices and herbs.

Method
Pure samples of spices and herbs were analyzed with the Thermo Scientific NGS Food Authenticity Workflow to assess its specificity, and spikings down to 1% (w/w) allowed evaluation of its sensitivity. Commercial samples, 62 and 210, were collected in Asian and European markets, respectively.

Results
All tested species were correctly identified often down to the species level, while spikings at 1% (w/w) confirmed a limit of detection at this level, including in complex mixtures composed of five different spices and/or herbs. The analysis of 272 commercial samples showed that 78% were compliant with the declared content, whereas the rest were shown to contain undeclared species that were in a few cases allergenic or potentially toxic.

Conclusions
The Thermo Scientific NGS Food Authenticity Workflow was found to be suitable to identify food plant species in herbs and spices, not only when tested on pure samples, but also in mixtures down to 1% (w/w). The overall workflow is user-friendly and straightforward, which makes it simple to use and facilitates data interpretation.

Highlights
The Thermo Scientific NGS Food Authenticity Workflow was found to be suitable for species identification in herbs and spices, and it allowed the detection of undeclared species in commercial samples. Its ease of use facilitates its implementation in testing laboratories.
Characterization of Feeding Behavior and its Relationship With the Longevity of Wild and Peridomestic Triatoma dimidiata, Latreille 1811 (Hemiptera, Reduviidae) Under Laboratory Conditions
Authors: Marín-Ortiz Juan Carlos , Parra-Henao Gabriel , Altamiranda-Saavedra Mariano , Jaramillo-O Nicolás 
Published: August 2022

Abstract
Triatoma dimidiata (Latreille 1811) is considered the second most important vector of the Trypanosa cruzi etiological agent of Chagas disease in Colombia. It has a life cycle that involves a domiciled, peridomiciled, and wild distribution. The study of feeding behavior and its influence on the survival of sylvatic and peridomestic populations can help identify a possible differential risk in the transmission of Chagas disease to humans, mainly in northwestern and east-central Colombia. We characterize the main parameters of feeding behavior and their influence on the longevity and survival of two rat-fed populations of T. dimidiata from Colombia, one in the north-west (from palms in a tropical dry forest area) and the other in the center-east (peridomiciliated), under controlled environmental conditions. The palm population took considerably longer than the peridomestic population to complete its life cycle under experimental laboratory conditions, being both populations univoltine since they have only one life cycle per year. Statistically significant differences were evidenced using Box-Cox model between the survival rates of T. dimidiata populations when the parameters related to blood intake and behavior were incorporated, in contrast to the survival models in which the origin only was considered as a factor. Our results could be used to generate recommendations to guide prevention strategies in communities near sylvatic and peridomiciliated populations of T. dimidiata.
Social Vulnerability and Risk of Nonrelapse Mortality After Allogeneic Hematopoietic Cell Transplantation
Authors: Bhandari Rusha , Teh Jennifer Berano , He Tianhui , Nakamura Ryotaro , Artz Andrew S , Jankowska Marta M , Forman Stephen J , Wong F Lennie , Armenian Saro H 
Published: August 2022

Abstract

Background
Risk of nonrelapse mortality (NRM) after hematopoietic cell transplantation (HCT) is high. Patient-level clinical prediction models such as the HCT–comorbidity index (HCT-CI) help identify those at increased risk for NRM, but the independent contribution of social determinants of health on HCT outcomes is not well characterized.

Methods
This study included 1602 patients who underwent allogeneic HCT between 2013 and 2019 at City of Hope. Census tract–level social vulnerability was measured using the social vulnerability index (SVI). Fine-Gray multivariable regression evaluated the association between SVI and 1-year NRM. Subgroup analysis examined risk of NRM across combined SVI and HCT-CI categories and by race and ethnicity.

Results
Cumulative incidence of 1-year NRM after HCT was 15.3% (95% confidence interval [CI] = 13.6% to 17.1%). In multivariable analysis, patients in the highest SVI tertile (highest social vulnerability) had a 1.4-fold risk (subdistribution hazard ratio [sHR] = 1.36, 95% CI = 1.04 to 1.78) of NRM compared with individuals in the lower tertiles; patients in the highest SVI tertile who also had elevated (≥3) HCT-CI scores had the highest risk (sHR = 1.81, 95% CI = 1.26 to 2.58) of 1-year NRM (reference: lower SVI tertiles and HCT-CI &lt; 3). High social vulnerability was associated with risk of 1-year NRM in Asian (sHR = 2.03, 95% CI = 1.09 to 3.78) and Hispanic (sHR = 1.63, 95% CI = 1.04 to 2.55) but not non-Hispanic White patients.

Conclusions
High social vulnerability independently associated with 1-year NRM after HCT, specifically among minority populations and those with a high comorbidity burden at HCT. These findings may inform targeted approaches for needs assessment during and after HCT, allowing for timely interventions to improve health outcomes in at-risk patients.
Internalizing Symptoms in Adolescents With Sickle Cell Disease
Authors: Heitzer Andrew M , Longoria Jennifer , Porter Jerlym S , MacArthur Erin , Potter Brian , Ding Juan , Gossett Jeffrey , Kang Guolian , Hankins Jane S 
Published: August 2022

Abstract

Objective
Sickle cell disease (SCD) is a genetic blood disorder that may affect patients’ mood and behavior. However, measuring the prevalence of internalizing symptoms (anxiety and depression) in patients with SCD has been elusive. We assessed internalizing symptoms in adolescents with SCD to evaluate prevalence and to test whether neurocognitive performance and frequency of pain-related episodes were associated with internalizing concerns.

Methods
One hundred eighty-five patients (57% HbSS/HbSß0-thalassemia, 43% HbSC/HbSß+-thalassemia), ages 12–18 years, received a neuropsychological evaluation as a part of a larger cohort study. Internalizing symptoms were measured using the Behavior Assessment System for Children, Second or Third Edition. Scores on the depression and anxiety scales were compared to normative values using Wilcoxon signed rank test. Spearman correlations examined associations between neurocognitive performances and internalizing symptoms. Robust multivariable regression models measured associations between internalizing symptoms and age, sex, sickle genotype, total hemoglobin, fetal hemoglobin, socioeconomic status, and frequency of pain episodes.

Results
Parent- and self-reported ratings of internalizing symptoms were not elevated compared to normative expectations. Overall, 1.8% and 6.3% of the sample displayed clinically elevated symptoms of anxiety and depression based on self-report, respectively. There were no associations between internalizing symptoms and neurocognitive performance (all p &gt; .05). In multivariable analyses, the frequency of pain episodes was positively associated with self-reported anxiety (p = .006) and parent-reported depressive symptoms (p = .017).

Conclusions
Adolescents with SCD do not report elevated internalizing symptoms compared to normative expectations. Further research is needed to examine the trajectory of internalizing symptoms and the bidirectional relationship between pain and psychosocial functioning in SCD.
Modelling the persistent low-state γ-ray emission of the PKS 1510−089 blazar with electromagnetic cascades initiated in hadronuclear interactions
Authors: Dzhatdoev T A , Khalikov E V , Latypova V S , Podlesnyi E I , Vaiman I A 
Published: August 2022

ABSTRACT
Blazars may accelerate protons and/or nuclei as well as electrons. The hadronic component of accelerated particles in blazars may constitute the bulk of their high-energy budget; nevertheless, this component is elusive because of the high value of the energy threshold of proton interactions with photon fields inside the source. However, the broad line regions (BLRs) of some flat spectrum radio quasars (FSRQs) may contain a sufficient amount of matter to render primary protons ‘visible’ in γ-rays via hadronuclear interactions. In this paper, we study the persistent γ-ray emission of the FSRQ PKS 1510−089 in its low state, utilizing the publicly available Fermi-LAT data, as well as using the spectrum measured with the Major Atmospheric Gamma Imaging Cherenkov (MAGIC) telescopes. We find an indication that there is an excess of γ-rays at the energy range ≳ 20 GeV with respect to a simple baseline log-parabolic intrinsic spectral model. This excess could be explained in a scenario invoking hadronuclear interactions of primary protons on the BLR material with the subsequent development of electromagnetic cascades in photon fields. We present a Monte Carlo calculation of the spectrum of this cascade component, taking as input the BLR photon field spectrum calculated with the cloudy code. To our knowledge, this is the first calculation of an electromagnetic cascade spectrum inside a blazar based on a direct calculation of the photon field spectrum with a spectral synthesis code.
Dust grain size evolution in local galaxies: a comparison between observations and simulations
Authors: Relaño M , De Looze I , Saintonge A , Hou K-C , Romano L E C , Nagamine K , Hirashita H , Aoyama S , Lamperti I , Lisenfeld U , Smith M W L , Chastenet J , Xiao T , Gao Y , Sargent M , van der Giessen S A 
Published: August 2022

ABSTRACT
The evolution of the dust grain size distribution has been studied in recent years with great detail in cosmological hydrodynamical simulations taking into account all the channels under which dust evolves in the interstellar medium. We present a systematic analysis of the observed spectral energy distribution of a large sample of galaxies in the local Universe in order to derive not only the total dust masses but also the relative mass fraction between small and large dust grains (DS/DL). Simulations reproduce fairly well the observations except for the high-stellar mass regime where dust masses tend to be overestimated. We find that ∼45 per cent of galaxies exhibit DS/DL consistent with the expectations of simulations, while there is a subsample of massive galaxies presenting high DS/DL (log (DS/DL) ∼ −0.5), and deviating from the prediction in simulations. For these galaxies which also have high-molecular gas mass fractions and metallicities, coagulation is not an important mechanism affecting the dust evolution. Including diffusion, transporting large grains from dense regions to a more diffuse medium where they can be easily shattered, would explain the observed high DS/DL values in these galaxies. With this study, we reinforce the use of the small-to-large grain mass ratio to study the relative importance of the different mechanisms in the dust life cycle. Multiphase hydrodynamical simulations with detailed feedback prescriptions and more realistic subgrid models for the dense phase could help to reproduce the evolution of the dust grain size distribution traced by observations.
The Neurodevelopmental Gene MSANTD2 Belongs to a Gene Family Formed by Recurrent Molecular Domestication of Harbinger Transposons at the Base of Vertebrates
Authors: Etchegaray Ema , Baas Dominique , Naville Magali , Haftek-Terreau Zofia , Volff Jean Nicolas 
Published: August 2022

Abstract
The formation of new genes is a major source of organism evolutionary innovation. Beyond their mutational effects, transposable elements can be co-opted by host genomes to form different types of sequences including novel genes, through a mechanism named molecular domestication. We report the formation of four genes through molecular domestication of Harbinger transposons, three in a common ancestor of jawed vertebrates about 500 million years ago and one in sarcopterygians approx. 430 million years ago. Additionally, one processed pseudogene arose approx. 60 million years ago in simians. In zebrafish, Harbinger-derived genes are expressed during early development but also in adult tissues, and predominantly co-expressed in male brain. In human, expression was detected in multiple organs, with major expression in the brain particularly during fetal development. We used CRISPR/Cas9 with direct gene knock-out in the F0 generation and the morpholino antisense oligonucleotide knock-down technique to study in zebrafish the function of one of these genes called MSANTD2, which has been suggested to be associated to neuro-developmental diseases such as autism spectrum disorders and schizophrenia in human. MSANTD2 inactivation led to developmental delays including tail and nervous system malformation at one day post fertilization. Affected embryos showed dead cell accumulation, major anatomical defects characterized by impaired brain ventricle formation and alterations in expression of some characteristic genes involved in vertebrate nervous system development. Hence, the characterization of MSANTD2 and other Harbinger-derived genes might contribute to a better understanding of the genetic innovations having driven the early evolution of the vertebrate nervous system.
Metagenomics versus total RNA sequencing: most accurate data-processing tools, microbial identification accuracy and perspectives for ecological assessments
Authors: Hempel Christopher A , Wright Natalie , Harvie Julia , Hleap Jose S , Adamowicz Sarah J , Steinke Dirk 
Published: August 2022

Abstract
Metagenomics and total RNA sequencing (total RNA-Seq) have the potential to improve the taxonomic identification of diverse microbial communities, which could allow for the incorporation of microbes into routine ecological assessments. However, these target-PCR-free techniques require more testing and optimization. In this study, we processed metagenomics and total RNA-Seq data from a commercially available microbial mock community using 672 data-processing workflows, identified the most accurate data-processing tools, and compared their microbial identification accuracy at equal and increasing sequencing depths. The accuracy of data-processing tools substantially varied among replicates. Total RNA-Seq was more accurate than metagenomics at equal sequencing depths and even at sequencing depths almost one order of magnitude lower than those of metagenomics. We show that while data-processing tools require further exploration, total RNA-Seq might be a favorable alternative to metagenomics for target-PCR-free taxonomic identifications of microbial communities and might enable a substantial reduction in sequencing costs while maintaining accuracy. This could be particularly an advantage for routine ecological assessments, which require cost-effective yet accurate methods, and might allow for the incorporation of microbes into ecological assessments.
In-Person Versus Tele-Infectious Disease (Tele-ID) Care: Is One Better?
Authors: Gupta Nupur , Bariola J Ryan , Mellors John W , Abdel-Massih Rima C 
Published: August 2022

Abstract
We compared outcomes at 3 community hospitals before and after switching from in-person to a Tele-ID group from an academic medical center. Compared to in-person, Tele-ID received significantly more consultations with similar outcomes for length of hospital stay, transfers, readmission, and mortality. Tele-ID is a suitable alternative for community settings.