bluuebunny/crossref_metadata_2025_split huggingface dataset:
Involvement of a FAD-Linked Oxidase RSc0454 for Expression of the Type III Secretion System and Pathogenicity in Ralstonia solanacearum
Authors: Chen Min , Chen Nan , Wang Jiwu , Zhou YuJian , Han Liangliang , Shi Xiaojun , Hikichi Yasufumi , Ohnishi Kouhei , Li Jing , Zhang Yong 
Published: August 2021

Ralstonia solanacearum RSc0454 is predicted as a FAD-linked oxidase based on protein homologies, while it contains distinct domains of lactate dehydrogenase and succinate dehydrogenase. A previous study demonstrated that RSc0454 exhibits lactate dehydrogenase activity using pyruvate and NADH as substrates, and is essential for pathogenicity of R. solanacearum. Here, we genetically characterized involvement of RSc0454 on bacterial growth and expression of genes for the type III secretion system (T3SS, a pathogenicity determinant) in R. solanacearum. The RSc0454 mutant grew normally in rich medium but grew faintly in host plants, and failed to grow in minimal medium. Supplementary succinate but not lactate could substantially restore some phenotypes of RSc0454 mutants, including faint growth in host plants, diminished growth in the minimal medium, and lost pathogenicity toward host plants. Expression of T3SS genes is directly controlled by a master regulator, HrpB, and hrpB expression is positively regulated by HrpG and PrhG in parallel ways. Deletion of RSc0454 substantially reduced expression levels of hrpB and T3SS both in vitro and in planta. Moreover, RSc0454 is revealed to be required for the T3SS expression via HrpG and PrhG, although through some novel pathway, and impaired expression of these genes was not due to growth deficiency of RSc0454 mutants. RSc0454 is suggested to be important for redox balance inside cells, and supplementary NADH partially restored diminished growth of the RSc0454 mutant in the minimal medium only in the presence of succinate at some moderate concentrations, indicating that the unbalanced redox in the RSc0454 mutant might be responsible for its diminished growth in the minimal medium. Taken together, these results provide novel insights into the understanding of various biological functions of this FAD-linked oxidase RSc0454 and involvement of the redox balance on expression of the T3SS in R. solanacearum. [Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Basophil activation test in food allergy: is it ready for real-time?
Authors: Keswani Tarun , Patil Sarita U. 
Published: August 2021

Purpose of review
Utilization of basophil activation in the diagnosis and monitoring of food allergy has gained increasing recognition. An ex-vivo functional assay, basophil activation reflects clinical reactivity, thereby providing clinically relevant insights. Moreover, as a biomarker of reactivity and tolerance, basophil activation testing (BAT) may provide a useful tool for management of food allergies. Despite its utility, significant limitations of BAT have prevented widespread use. Addressing these limitations will increase the future application and adoption of BAT in food allergy.

Recent findings
A number of clinical trials in the past few years have demonstrated the use of BAT in the diagnosis and treatment of food allergy. Specifically, BAT has been found to be a biomarker of tolerance.

Summary
Basophil activation testing is an effective biomarker for diagnosis and monitoring of food allergy.
Use of xenografts and allografts in scalp reconstruction
Authors: Poonia Seerat K. , Harris Brianna N. 
Published: August 2021

Purpose of review
Scalp reconstruction requires a full array of reconstructive options given the complex anatomy and protection of vital structures. Not all patients qualify for advanced reconstructive options and therefore rely on short, effective procedures with minimal morbidity. This review aims to focus on xenografts and allografts to achieve an adequate reconstruction while minimizing morbidity.

Recent findings
Although bovine xenografts have been used for many decades, there have been recent advances in porcine xenografts to aid in scalp defects. Similarly, new allogenic materials have emerged as additional tools in the armamentarium to promote wound healing.

Summary
Both xenografts and allografts offer viable options for complex scalp reconstruction.
Use of advanced cardiac imaging in congenital heart disease: growth, indications and innovations
Authors: Steele Jeremy M. , Moore Ryan A. , Lang Sean M. 
Published: August 2021

Purpose of review
Significant improvements in the diagnosis and management of patients with congenital heart disease (CHD) have led to improved survival. These patients require life-long noninvasive evaluation. The use of advanced imaging such as cardiac magnetic resonance imaging (CMR) and cardiac computed tomography (CCT) has increased to support this need. The purpose of this review is to discuss the basics of advanced cardiac imaging, indications and review the recent innovations.

Recent findings
Recent literature has demonstrated the increasing reliance of advanced imaging for CHD patients. In addition, research is focusing on CMR techniques to shorten scan time and address previous limitations that made imaging younger and sicker patients more challenging. CCT research has involved demonstrating high-quality images with low radiation exposure. Advances in digital technology have impacted the interactivity of 3D imaging through the use of virtual and augmented reality platforms. With the increased reliance of advanced imaging, appropriate use criteria have been developed to address possible under or over utilization.

Summary
The utilization of advanced cardiac imaging continues to increase. As CMR and CCT continue to grow, increased knowledge of these modalities and their usage will be necessary for clinicians caring for CHD patients.
Age disparities in transplantation
Authors: Melandro Fabio , Del Turco Serena , Ghinolfi Davide 
Published: August 2021

Purpose of review
The aim of this review is to outline disparities in liver and kidney transplantation across age spectrum. Disparities do not involve only recipients whose age may severely affect the possibility to access to a potentially life-saving procedure, but donors as well. The attitude of transplant centers to use older donors reflects on waiting list mortality and drop-out. This review examines which age categories are currently harmed and how different allocation systems may minimize disparities.

Recent findings
Specific age categories suffer disparities in the access to transplantation. A better understanding of how properly evaluate graft quality, a continuous re-evaluation of the most favorable donor-to-recipient match and most equitable allocation system are the three key points to promote ‘justice and equality’ among transplant recipients.

Summary
The duty to protect younger patients waiting for transplantation and the request of older patients to have access to potentially life-saving treatment urge the transplant community to use older organs thus increasing the number of available grafts, to evaluate new allocation systems with the aim to maximize ‘utility’ while respecting ‘equity’ and to avoid ‘futility’ thus minimizing waiting list mortality and drop-out, and improving the survival benefits for all patients requiring a transplant.

Video abstract

http://links.lww.com/COOT/A9
Mental Health Impact in Latin American Pediatric Rheumatologists During the COVID-19 Pandemic
Authors: Kozu Kátia T. , Casella Caio B. , Strabelli Claudia A.A. , Aikawa Nadia E. , Campos Lucia M.A. , Elias Adriana M. , Miguel Eurípedes C. , Polanczyk Guilherme V. , Silva Clovis A. 
Published: August 2021

Objective
The aim of this study was to assess mental health in Latin American pediatric rheumatologists (LAPRs) during the COVID-19 pandemic.

Methods
A cross-sectional study was performed with 318 LAPRs based on an online, self-rated survey about clinical practice/mental health impacts during the COVID-19 pandemic. Validated self-reported scales for anxiety (Generalized Anxiety Disorder [GAD-7]) and depression (Patient Health Questionnaire [PHQ-9]) were evaluated.

Results
The response rate was 126 of 318 (40%), including 13 of 20 (65%) Latin American countries. Working on the COVID-19 frontline was reported by 27% of LAPRs. Anxiety and moderate/severe depression were observed in 49% and 25%, respectively. No LAPRs reported previous mental health disorders. Deaths of childhood-onset systemic lupus erythematosus and juvenile idiopathic arthritis patients with confirmed/suspected COVID-19 were reported by 8% and 2% of LAPRs, respectively. Further analysis of LAPRs revealed that the median current age was significantly lower in LAPRs with anxiety than in those without anxiety (39 [29–43] vs 45 [30–70] years, p = 0.029). Working on the frontline of COVID-19 (37% vs 17%, p = 0.015), feeling helpless (39% vs 17%, p = 0.009), and experiencing burnout (39% vs 11%, p = 0.0001) were factors significantly higher in LAPRs with anxiety. Median nighttime sleep abnormalities measured by the visual analog scale (VAS) (8 [0–10] vs 4 [0–10], p = 0.009) were significantly higher in the anxiety group, whereas the physical activity VAS was lower (0.5 [0–10] vs 3 [0–10], p = 0.005). A positive Spearman correlation was shown between the GAD-7 score and nighttime sleep abnormality VAS score (r = +0.348, p < 0.001), and a negative correlation was shown between the GAD-7score and physical activity VAS score (r = −0.192, p = 0.031).

Conclusions
Anxiety and depression were relevant to the experience of LAPRs during the COVID-19 pandemic, impacting their mental health. Reporting information about mental health is essential to planning future preventive and health promotion strategies.
IGF-1 Differentially Modulates Glutamate-Induced Toxicity and Stress in Cells of the Neurogliovascular Unit
Authors: Hayes Cellas A. , Ashmore Brandon G. , Vijayasankar Akshaya , Marshall Jessica P. , Ashpole Nicole M. 
Published: August 2021

ABSTRACTThe age-related reduction in circulating levels of insulin-like growth factor-1 (IGF-1) is associated with increased risk of stroke and neurodegenerative diseases in advanced age. Numerous reports highlight behavioral and physiological deficits in blood-brain barrier function and neurovascular communication when IGF-1 levels are low. Administration of exogenous IGF-1 reduces the extent of tissue damage and sensorimotor deficits in animal models of ischemic stroke, highlighting the critical role of IGF-1 as a regulator of neurovascular health. The beneficial effects of IGF-1 in the nervous system are often attributed to direct actions on neurons; however, glial cells and the cerebrovasculature are also modulated by IGF-1, and systemic reductions in circulating IGF-1 likely influence the viability and function of the entire neuro-glio-vascular unit. We recently observed that reduced IGF-1 led to impaired glutamate handling in astrocytes. Considering glutamate excitotoxicity is one of the main drivers of neurodegeneration following ischemic stroke, the age-related loss of IGF-1 may also compromise neural function indirectly by altering the function of supporting glia and vasculature. In this study, we assess and compare the effects of IGF-1 signaling on glutamate-induced toxicity and reactive oxygen species (ROS)-produced oxidative stress in primary neuron, astrocyte, and brain microvascular endothelial cell cultures. Our findings verify that neurons are highly susceptible to excitotoxicity, in comparison to astrocytes or endothelial cells, and that a prolonged reduction in IGFR activation increases the extent of toxicity. Moreover, prolonged IGFR inhibition increased the susceptibility of astrocytes to glutamate-induced toxicity and lessened their ability to protect neurons from excitotoxicity. Thus, IGF-1 promotes neuronal survival by acting directly on neurons and indirectly on astrocytes. Despite increased resistance to excitotoxic death, both astrocytes and cerebrovascular endothelial cells exhibit acute increases in glutamate-induced ROS production and mitochondrial dysfunction when IGFR is inhibited at the time of glutamate stimulation. Together these data highlight that each cell type within the neuro-glio-vascular unit differentially responds to stress when IGF-1 signaling was impaired. Therefore, the reductions in circulating IGF-1 observed in advanced age are likely detrimental to the health and function of the entire neuro-glio-vascular unit.
Immune enhancement to prevent infected pancreatic necrosis: A double-blind randomized controlled trial
Authors: Ke Lu , Zhou Jing , Mao Wenjian , Chen Tao , Zhu Yin , Pan Xinting , Mei Hong , Singh Vikesh , Buxbaum James , Doig Gordon , He Chengjian , Gu Weili , Lu Weihua , Tu Shumin , Ni Haibin , Zhang Guoxiu , Zhao Xiangyang , Sun Junli , Chen Weiwei , Song Jingchun , Shao Min , Tu Jianfeng , Xia Liang , He Wenhua , Zhu Qingyun , Li Kang , Yao Hongyi , Wu Jingyi , Fu Long , Jiang Wendi , Zhang He , Lin Jiajia , Li Baiqiang , Tong Zhihui , Windsor John , Liu Yuxiu , Li Weiqin ,   Chinese Acute Pancreatitis Clinical Trials Group (CAPCTG)
Published: August 2021

AbstractBACKGROUND&AIMSInfected pancreatic necrosis (IPN) is a highly morbid complication of acute pancreatitis (AP). Since there is evidence of immunosuppression in the early phase of AP, immune enhancement using Thymosin alpha 1 (Tα1), which stimulates both innate and adaptive immunity, may be a therapeutic strategy to prevent IPN. Our aim was to assess the efficacy of early Tα1 treatment on the development of IPN.METHODSWe conducted a multicenter, randomized, double-blind, placebo-controlled trial in patients with predicted severe acute necrotizing pancreatitis (ANP). ANP patients with an APACHE II score≥8 admitted within seven days of the advent of symptoms were considered eligible. Enrolled patients were assigned to receive a subcutaneous injection of Tα1 1.6 mg, every 12 hours for the first 7 days and 1.6 mg once a day for the subsequent 7 days or matching placebo (normal saline). The primary outcome was the development of IPN during the index admission.RESULTSFrom Mar 2017 through Dec 2020, 508 patients were randomized at 16 hospitals, of whom 254 were assigned to receive Tα1 and 254 placebo. During the index admission, 40/254 (15.7%) patients in the Tα1 group developed IPN compared with 46/254 patients (18.1%) in the placebo group (difference -2.4% [95%CI -7.4% to 5.0%]; p=0.47). The results were similar in four predefined subgroups. There was no difference in other major complications, including new-onset organ failure (10.6% vs. 15.0%; p=0.15), bleeding (6.3% vs. 3.5%; p=0.15), and gastrointestinal fistula (2.0% vs. 2.4%; p=0.75) during the index admission.CONCLUSIONSThe immune-enhancing Tα1 treatment of patients with predicted severe ANP did not reduce the incidence of IPN during the index admission.Trial registrationClinicaltrials.gov registry: NCT02473406.
Schwann cells contribute to keloid formation
Authors: Direder Martin , Weiss Tamara , Copic Dragan , Vorstandlechner Vera , Laggner Maria , Mildner Caterina Selina , Klas Katharina , Bormann Daniel , Haslik Werner , Radtke Christine , Farlik Matthias , Shaw Lisa , Golabi Bahar , Tschachler Erwin , Hötzenecker Konrad , Ankersmit Hendrik Jan , Mildner Michael 
Published: August 2021

AbstractKeloids are disfiguring, hypertrophic scars with yet poorly understood pathomechanisms, which could lead to severe functional impairments. Here we analyzed the characteristics of keloidal cells by single cell sequencing and discovered the presence of an abundant population of Schwann cells that persisted in the hypertrophic scar tissue after wound healing. In contrast to normal skin, keloidal Schwann cells possess a repair-like phenotype and high cellular plasticity. Our data support the hypothesis that keloidal Schwann cells contribute to the formation of the extracellular matrix and are able to affect M2 polarization of macrophages. Indeed, we show that macrophages in keloids predominantly display a M2 polarization and produce factors that inhibit Schwann cell differentiation. Our data suggest a contribution of this cross-talk to the continuous expansion of keloids, and that targeting Schwann cells might represent an interesting novel treatment option for keloids.
Symptoms that predict positive COVID-19 testing and hospitalization: an analysis of 9,000 patients
Authors: Jalalizadeh Mehrsa , Leme Patricia A. F. , Buosi Keini , Dionato Franciele A. V. , Giacomelli Cristiane F. , Col Luciana S.B. Dal , Ferrari Karen L. , Pagliarone Ana Carolina , Gon Lucas M. , Cezar Douglas F.O. , Esfahani Akbar A. , Reis Leonardo O. 
Published: August 2021

ABSTRACTPurposeTo develop a reliable tool that predicts which patients are most likely to be COVID-19 positive and which ones have an increased risk of hospitalization.MethodsFrom February 2020 to April 2021, trained nurses recorded age, gender, and symptoms in an outpatient COVID-19 testing center. All positive patients were followed up by phone for 14 days or until symptom-free. We calculated the symptoms odds ratio for positive results and hospitalization and proposed a “random forest” machine-learning model to predict positive testing.ResultsA total of 8,998 patients over 16 years old underwent COVID-19 RT-PCR, with 1,914 (21.3%) positives. Fifty patients needed hospitalization (2.6% of positives), and three died (0.15%). Most common symptoms were: cough, headache, sore throat, coryza, fever, myalgia (57%, 51%, 44%, 36%, 35%, 27%, respectively). Cough, fever, and myalgia predicted positive COVID-19 test, while others behaved as protective factors. The best predictors of positivity were fever plus anosmia/ageusia (OR=6.31), and cough plus anosmia/ageusia (OR=5.82), both p<0.0001. Our random forest model had an ROC-AUC of 0.72 (specificity=0.70, sensitivity=0.61, PPV=0.38, NPV=0.86). Having steady fever during the first days of infection and persistent dyspnea increased the risk of hospitalization (OR=6.66, p<0.0001 and OR=3.13, p=0.003, respectively), while anosmia-ageusia (OR=0.36, p=0.009) and coryza (OR=0.31, p=0.014) were protective.ConclusionPresent study and algorithm may help identify patients at higher risk of having SARS-COV-2 (online calculator http://wdchealth.covid-map.com/shiny/calculator/), and also disease severity and hospitalization based on symptoms presence, pattern, and duration, which can help physicians and health care providers.
Marine gregarine genomes reveal the breadth of apicomplexan diversity and provide new insights on gliding motility
Authors: Boisard Julie , Duvernois-Berthet Evelyne , Duval Linda , Schrével Joseph , Guillou Laure , Labat Amandine , Le Panse Sophie , Prensier Gérard , Ponger Loïc , Florent Isabelle 
Published: August 2021

ABSTRACTOur current view of the evolutionary history, coding and adaptive capacities of Apicomplexa, protozoan parasites of a wide range of metazoan, is currently strongly biased toward species infecting humans, as data on early diverging apicomplexan lineages infecting invertebrates is extremely limited. Here, we characterized the genome of the marine eugregarinePorospora gigantea, intestinal parasite of Lobsters, remarkable for the macroscopic size of its vegetative feeding forms (trophozoites) and its gliding speed, the fastest so far recorded for Apicomplexa. Two highly syntenic genomes named A and B were assembled. Similar in size (~9 Mb) and coding capacity (~5300 genes), A and B genomes are 10.8% divergent at the nucleotide level, corresponding to 16-38 My in divergent time. Orthogroup analysis across 25 (proto)Apicomplexa species, includingGregarina niphandrodes, showed that A and B are highly divergent from all other known apicomplexan species, revealing an unexpected breadth of diversity. Phylogenetically these two species branch sister to Cephaloidophoroidea, and thus expand the known crustacean gregarine superfamily. The genomes were mined for genes encoding proteins necessary for gliding, a key feature of apicomplexans parasites, currently studied through the molecular model called glideosome. Sequence analysis shows that actin-related proteins and regulatory factors are strongly conserved within apicomplexans. In contrast, the predicted protein sequences of core glideosome proteins and adhesion proteins are highly variable among apicomplexan lineages, especially in gregarines. These results confirm the importance of studying gregarines to widen our biological and evolutionary view of apicomplexan species diversity, and to deepen our understanding of the molecular bases of key functions enabling parasitism, such as the glideosome.
Increasing temporal variance leads to stable species range limits
Authors: Benning John W. , Hufbauer Ruth A. , Weiss-Lehman Christopher 
Published: August 2021

AbstractWhat prevents populations of a species from adapting to the novel environments outside the species’ geographic distribution? Previous models highlighted how gene flow across spatial environmental gradients determines species expansion vs. extinction and the location of species range limits. However, space is only one of two axes of environmental variation — environments also vary in time, and we know temporal environmental variation has important consequences for population demography and evolution. We used analytical and individual-based evolutionary models to explore how temporal variation in environmental conditions influences the spread of populations across a spatial environmental gradient. We find that temporal variation greatly alters our predictions for range dynamics compared to temporally static environments. When temporal variance is equal across the landscape, the fate of species (expansion vs. extinction) is determined by the interaction between the degree of temporal autocorrelation in environmental fluctuations and the steepness of the spatial environmental gradient. When the magnitude of temporal variance changes across the landscape, stable range limits form where this variance increases maladaptation sufficiently to prevent local persistence. These results illustrate the pivotal influence of temporal variation on the likelihood of populations colonizing novel habitats and the location of species range limits.
Phased Mutations and Complex Rearrangements in Human Prostate Cancer Cell Lines through Linked-Read Whole Genome Sequencing
Authors: Pham Minh-Tam , Gupta Harshath , Gupta Anuj , Vaghasia Ajay , Skaist Alyza , Garrison McKinzie A. , Coulter Jonathan B. , Haffner Michael C. , Isaacs William B. , Wheelan Sarah J. , Nelson William G. , Yegnasubramanian Srinivasan 
Published: August 2021

ABSTRACTA limited number of cell lines have fueled the majority of preclinical Prostate cancer (PCa) research. Despite tremendous effort in characterizing their molecular profiles, comprehensive whole genome sequencing with allelic phasing of somatic genome alterations has not been undertaken to date. Here, we utilized whole genome Linked-read sequencing to obtain haplotype information from the seven most commonly used PCa cell lines (PC3, LNCaP, DU145, CWR22Rv1, VCaP, LAPC4, MDA-PCa-2b), four castrate resistant (CR) subclones (LNCaP_Abl, LNCaP_C42b, VCaP-CR, LAPC4-CR), and an immortalized prostate epithelial line RWPE-1. Phasing of mutations allowed derivation of “Gene-level Haplotype” to assess whether a gene harbored heterozygous mutations in one or both alleles, providing a comprehensive catalogue of mono or bi-allelically inactivated genes. Phased structural variant analysis allowed identification of complex rearrangement chains consistent with chromothripsis and chromoplexy, with breakpoints occurred across a single allele, providing further evidence that complex SVs occurred in a concerted event, rather than through accumulation of multiple independent rearrangements. Additionally, comparison of parental and CR subclones revealed previously known and novel genomic alterations associated with the CR clones. This study therefore comprehensively characterized phased genomic alterations in the commonly used PCa cell lines and provided a useful resource for future cancer research.