bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of a clinical decision support system for severity risk prediction and triage of COVID-19 patients at hospital admission: an international multicentre study
Authors: Wu Guangyao , Yang Pei , Xie Yuanliang , Woodruff Henry C. , Rao Xiangang , Guiot Julien , Frix Anne-Noelle , Louis Renaud , Moutschen Michel , Li Jiawei , Li Jing , Yan Chenggong , Du Dan , Zhao Shengchao , Ding Yi , Liu Bin , Sun Wenwu , Albarello Fabrizio , D'Abramo Alessandra , Schininà Vincenzo , Nicastri Emanuele , Occhipinti Mariaelena , Barisione Giovanni , Barisione Emanuela , Halilaj Iva , Lovinfosse Pierre , Wang Xiang , Wu Jianlin , Lambin Philippe
Published: July 2020

Background

The outbreak of coronavirus disease 2019 (COVID-19) has globally strained medical resources and caused significant mortality.

Objective

To develop and validate a machine-learning model based on clinical features for severity risk assessment and triage for COVID-19 patients at hospital admission.

Method

725 patients were used to train and validate the model. This included a retrospective cohort from Wuhan, China of 299 hospitalised COVID-19 patients from 23 December 2019 to 13 February 2020, and five cohorts with 426 patients from eight centres in China, Italy and Belgium from 20 February 2020 to 21 March 2020. The main outcome was the onset of severe or critical illness during hospitalisation. Model performances were quantified using the area under the receiver operating characteristic curve (AUC) and metrics derived from the confusion matrix.

Results

In the retrospective cohort, the median age was 50 years and 137 (45.8%) were male. In the five test cohorts, the median age was 62 years and 236 (55.4%) were male. The model was prospectively validated on five cohorts yielding AUCs ranging from 0.84 to 0.93, with accuracies ranging from 74.4% to 87.5%, sensitivities ranging from 75.0% to 96.9%, and specificities ranging from 55.0% to 88.0%, most of which performed better than the pneumonia severity index. The cut-off values of the low-, medium- and high-risk probabilities were 0.21 and 0.80. The online calculators can be found atwww.covid19risk.ai.

Conclusion

The machine-learning model, nomogram and online calculator might be useful to access the onset of severe and critical illness among COVID-19 patients and triage at hospital admission.
Osteogenesis of adipose-derived stem cells from patients with glucose metabolism disorders
Authors: Skubis-Sikora Aleksandra , Sikora Bartosz , Witkowska Agnieszka , Mazurek Urszula , Gola Joanna
Published: July 2020

Background

Adipose derived stem cells (ADSCs) are clinically widely used somatic stem cells obtained from white adipose tissue. They are characterized by ability to differentiate e.g. into osteoblasts and might successfully regenerate bone tissue in fracture repair. However, the main problem of somatic stem cells is a documented influence of various diseases, drugs or age which can inhibit cells activity. Therefore, in the present study, we investigated the influence of insulin resistance (IR) and type 2 diabetes (T2D) on the proliferation and differentiation potential of ADSCs.

Methods

The fat from subcutaneous abdominal adipose tissue was acquired by lipoaspiration from 23 voluntary participants, divided into three groups: with diabetes type 2, with insulin resistance and control healthy donors. The proliferative potential was analyzed by cell cytotoxicity assays and by mRNA expression of genes connected with proliferation. Flow cytometry was done for identifying proteins characteristic for mesenchymal stem cells and an analysis of osteogenic differentiation potential based on the assessment of osteogenic markers by real time RT-qPCR, and the evaluation of calcium deposition were also performed.

Results

The results showed that diabetes type 2 lowered the activity of ADSCs in proliferation assays and changed their phenotypical characteristics. Interestingly, we observed differences in the proliferation potential of ADSCs in patients with insulin resistance, which is often the first phase of diabetes, compared to the control. It might suggest that insulin resistance, early-stage T2D, alters the activity of cells. Moreover, expression of osteogenesis markers was higher in cells from T2D patients than in cells from patients with IR and control.

Conclusion

We conclude that type 2 diabetes changes the activity of stem cells, and insulin resistance influences on the proliferation of ADSCs.
The effects of cognitive-motor training interventions on executive functions in older people: a systematic review and meta-analysis
Authors: Wollesen Bettina , Wildbredt Alicia , van Schooten Kimberley S. , Lim Mei Ling , Delbaere Kim
Published: July 2020

Background

Ageing is associated with physical and cognitive decline, affecting independence and quality of life in older people. Recent studies show that in particular executive functions are important for daily-life function and mobility. This systematic review investigated the effectiveness of cognitive-motor training including exergaming on executive function (EF, set-shifting, working memory, inhibitory control) in healthy older people.

Methods

An electronic database search for randomised controlled trials (RCT), controlled clinical trials (CCT) and parallel group trials was performed using MEDLINE, EMBASE, and PsychINFO following PRISMA guidelines. Inclusion criteria were: (1) community-dwelling participants > 60 years without a medical condition or medical treatment, (2) reporting at least one cognitive-motor intervention while standing or walking, (3) use of dual-task interventions using traditional methods or modern technology to deliver a cognitive-motor task, (4) inclusion of at least one cognitive outcome. The PEDro scale was used for quality assessment.

Results

A total of 1557 studies were retrieved, of which 25 studies were included in this review. Eleven studies used a technology-based dual-task intervention, while 14 trials conducted a general cognitive-motor training. The age range of the cohort was 69 to 87 years. The interventions demonstrated positive effects on global cognitive function [mean difference 0.6, 95% CI 0.29–0.90] and inhibitory control [mean difference 0.61, 95% CI 0.28–0.94]. Effects were heterogeneous (I2 range: 60–95) and did not remain after a sensitivity analysis. Processing speed and dual-task costs also improved, but meta-analysis was not possible.

Conclusion

Cognitive-motor and technology-based interventions had a positive impact on some cognitive functions. Dual-task interventions led to improvements of domains related global cognitive functions and inhibitory control. Likewise, technology-based exergame interventions improved functions related to processing speed, attentional and inhibitory control. Training interventions with a certain level of exercise load such as progression in difficulty and task specificity were more effective to gain task-related adaptations on cognitive functions.
Re-Analysis of 16S Amplicon Sequencing Data Reveals Soil Microbial Population Shifts in Rice Fields under Drought Condition
Authors: Jang Seok-Won , Yoou Myeong-Hyun , Hong Woo-Jong , Kim Yeon-Ju , Lee Eun-Jin , Jung Ki-Hong
Published: July 2020

Rice (Oryza sativa. L) has been intensively studied to ensure a stable global supply of this commodity in the face of rapid global climate change. A critical factor that decreases crop yield is drought, which has been analyzed in various ways through many researches. Microbiome-based studies of rice investigate the symbiosis between rice and bacteria, which has been proposed as a way to overcome problems caused by drought. Several rice-associated metagenomic profiles obtained under drought conditions have been reported since the advent of next generation sequencing (NGS) technology. To elucidate the future diversity of plants and microorganisms and to promote sustainable agriculture, we reanalyzed 64 of the publicly available 16S amplicon sequencing data produced under drought condition. In the process of integrating data sets, however, we found an inconsistency that serves as a bottleneck for microbiome-based sustainability research. While this report provides clues about the composition of the microbiome under the drought conditions, the results are affected by differences in the location of the experiments, sampling conditions, and analysis protocols. Re-analysis of amplicon sequencing data of the soil microbiome in rice fields suggests that microbial composition shifts in response to drought condition and the presence of plants. Among the bacteria involved, the phylum Proteobacteria appears to play the most important role in the survival of rice under drought condition.
DiNeR: a Differential graphical model for analysis of co-regulation Network Rewiring
Authors: Zhang Jing , Liu Jason , Lee Donghoon , Lou Shaoke , Chen Zhanlin , Gürsoy Gamze , Gerstein Mark
Published: July 2020

Background

During transcription, numerous transcription factors (TFs) bind to targets in a highly coordinated manner to control the gene expression. Alterations in groups of TF-binding profiles (i.e. “co-binding changes”) can affect the co-regulating associations between TFs (i.e. “rewiring the co-regulator network”). This, in turn, can potentially drive downstream expression changes, phenotypic variation, and even disease. However, quantification of co-regulatory network rewiring has not been comprehensively studied.

Results

To address this, we propose DiNeR, a computational method to directly construct a differential TF co-regulation network from paired disease-to-normal ChIP-seq data. Specifically, DiNeR uses a graphical model to capture the gained and lost edges in the co-regulation network. Then, it adopts a stability-based, sparsity-tuning criterion -- by sub-sampling the complete binding profiles to remove spurious edges -- to report only significant co-regulation alterations. Finally, DiNeR highlights hubs in the resultant differential network as key TFs associated with disease. We assembled genome-wide binding profiles of 104 TFs in the K562 and GM12878 cell lines, which loosely model the transition between normal and cancerous states in chronic myeloid leukemia (CML). In total, we identified 351 significantly altered TF co-regulation pairs. In particular, we found that the co-binding of the tumor suppressor BRCA1 and RNA polymerase II, a well-known transcriptional pair in healthy cells, was disrupted in tumors. Thus, DiNeR successfully extracted hub regulators and discovered well-known risk genes.

Conclusions

Our method DiNeR makes it possible to quantify changes in co-regulatory networks and identify alterations to TF co-binding patterns, highlighting key disease regulators. Our method DiNeR makes it possible to quantify changes in co-regulatory networks and identify alterations to TF co-binding patterns, highlighting key disease regulators.
Genomic characterization of the most barotolerant Listeria monocytogenes RO15 strain compared to reference strains used to evaluate food high pressure processing
Authors: Duru Ilhan Cem , Andreevskaya Margarita , Laine Pia , Rode Tone Mari , Ylinen Anne , Løvdal Trond , Bar Nadav , Crauwels Peter , Riedel Christian U. , Bucur Florentina Ionela , Nicolau Anca Ioana , Auvinen Petri
Published: July 2020

Background

High pressure processing (HPP; i.e. 100–600 MPa pressure depending on product) is a non-thermal preservation technique adopted by the food industry to decrease significantly foodborne pathogens, includingListeria monocytogenes, from food.However, susceptibility towards pressure differs among diverse strains ofL. monocytogenesand it is unclear if this is due to their intrinsic characteristics related to genomic content. Here, we tested the barotolerance of 10 differentL. monocytogenesstrains, from food and food processing environments and widely used reference strains including clinical isolate, to pressure treatments with 400 and 600 MPa. Genome sequencing and genome comparison of the testedL. monocytogenesstrains were performed to investigate the relation between genomic profile and pressure tolerance.

Results

None of the tested strains were tolerant to 600 MPa. A reduction of more than 5 log10was observed for all strains after 1 min 600 MPa pressure treatment.L. monocytogenesstrain RO15 showed no significant reduction in viable cell counts after 400 MPa for 1 min and was therefore defined as barotolerant. Genome analysis of so far unsequencedL. monocytogenesstrain RO15, 2HF33, MB5, AB199, AB120, C7, and RO4 allowed us to compare the gene content of all strains tested. This revealed that the three most pressure tolerant strains had more than one CRISPR system with self-targeting spacers. Furthermore, several anti-CRISPR genes were detected in these strains. Pan-genome analysis showed that 10 prophage genes were significantly associated with the three most barotolerant strains.

Conclusions

L. monocytogenesstrain RO15 was the most pressure tolerant among the selected strains. Genome comparison suggests that there might be a relationship between prophages and pressure tolerance inL. monocytogenes.
Dual indexed library design enables compatibility of in-Drop single-cell RNA-sequencing with exAMP chemistry sequencing platforms
Authors: Southard-Smith Austin N. , Simmons Alan J. , Chen Bob , Jones Angela L. , Ramirez Solano Marisol A. , Vega Paige N. , Scurrah Cherie’ R. , Zhao Yue , Brenan Michael J. , Xuan Jiekun , Shrubsole Martha J. , Porter Ely B. , Chen Xi , Brenan Colin J. H. , Liu Qi , Quigley Lauren N. M. , Lau Ken S.
Published: July 2020

Background

The increasing demand of single-cell RNA-sequencing (scRNA-seq) experiments, such as the number of experiments and cells queried per experiment, necessitates higher sequencing depth coupled to high data quality. New high-throughput sequencers, such as the Illumina NovaSeq 6000, enables this demand to be filled in a cost-effective manner. However, current scRNA-seq library designs present compatibility challenges with newer sequencing technologies, such as index-hopping, and their ability to generate high quality data has yet to be systematically evaluated.

Results

Here, we engineered a dual-indexed library structure, called TruDrop, on top of the inDrop scRNA-seq platform to solve these compatibility challenges, such that TruDrop libraries and standard Illumina libraries can be sequenced alongside each other on the NovaSeq. On scRNA-seq libraries, we implemented a previously-documented countermeasure to the well-described problem of index-hopping, demonstrated significant improvements in base-calling accuracy on the NovaSeq, and provided an example of multiplexing twenty-four scRNA-seq libraries simultaneously. We showed favorable comparisons in transcriptional diversity of TruDrop compared with prior inDrop libraries.

Conclusions

Our approach enables cost-effective, high throughput generation of sequencing data with high quality, which should enable more routine use of scRNA-seq technologies.
Shedding light on cashmere goat hair follicle biology: from morphology analyses to transcriptomic landascape
Authors: Nocelli Cristina , Cappelli Katia , Capomaccio Stefano , Pascucci Luisa , Mercati Francesca , Pazzaglia Irene , Mecocci Samanta , Antonini Marco , Renieri Carlo
Published: July 2020

Background

Cashmere goat is known for its precious undercoat. Being photoperiod-dictated, cashmere growth has been studied focusing mainly on hair follicle cycle phases (anagen, catagen and telogen). An accurate molecular knowledge of the goat hair follicle cycle, disentangling gene expression changes during phases and recognizing timing boundaries, could be useful to improve cashmere goat management and ultimately cashmere production.

Results

To better describe goat’s hair follicle transcriptome we applied RNA-sequencing to isolated hair follicles from five Italian cashmere goats, during the anagen and catagen phase, identifying total of 214 differentially expressed genes (DEGs): 97 were up-regulated while 117 were down-regulated in catagen with respect to anagen. Gene Ontology and pathway analysis were performed. We detected 144 significant pathways spanning from estrogen, pluripotency of stem cells, thermogenesis and fatty acid metabolism that were strongly expressed during the hair follicle phases analysed. Finally, we validated promising DEGs by RT-qPCR in the same set of samples as well as in hair follicles and entire skin biopsies of another cashmere goats cohort accounting for early anagen, anagen, early catagen, and catagen phases.

Conclusions

As in the isolated hair follicles, some target genes were homogenously modulated during the four hair follicle phases. Ceruloplasmin (CP) and Keratin 4 (K4), confirmed their clear cut expression between growing and resting phase. In fact,K4was almost absent in catagen phases whileCPwas barely expressed in anagen phases. In particular, the strong expression ofK4in early anagen makes it an eligible marker to track the beginning of a new hair cycle, and therefore defining the optimum time for cashmere harvesting.
Pleiotropic effects of RsmA and RsmE proteins in Pseudomonas fluorescens 2P24
Authors: Zhang Yang , Zhang Bo , Wu Haiyan , Wu Xiaogang , Yan Qing , Zhang Li-Qun
Published: July 2020

Background

Pseudomonas fluorescens 2P24 is a rhizosphere bacterium that produces 2,4-diacetyphloroglucinol (2,4-DAPG) as the decisive secondary metabolite to suppress soilborne plant diseases. The biosynthesis of 2,4-DAPG is strictly regulated by the RsmA family proteins RsmA and RsmE. However, mutation of both of rsmA and rsmE genes results in reduced bacterial growth.

Results

In this study, we showed that overproduction of 2,4-DAPG in the rsmA rsmE double mutant influenced the growth of strain 2P24. This delay of growth could be partially reversal when the phlD gene was deleted or overexpression of the phlG gene encoding the 2,4-DAPG hydrolase in the rsmA rsmE double mutant. RNA-seq analysis of the rsmA rsmE double mutant revealed that a substantial portion of the P. fluorescens genome was regulated by RsmA family proteins. These genes are involved in the regulation of 2,4-DAPG production, cell motility, carbon metabolism, and type six secretion system.

Conclusions

These results suggest that RsmA and RsmE are the important regulators of genes involved in the plant-associated strain 2P24 ecologic fitness and operate a sophisticated mechanism for fine-tuning the concentration of 2,4-DAPG in the cells.
Postoperative supraventricular tachycardia and polymorphic ventricular tachycardia due to a novel SCN5A variant: a case report of a rare comorbidity that is difficult to diagnose
Authors: Kato Koichi , Ozawa Tomoya , Ohno Seiko , Nakagawa Yoshihisa , Horie Minoru
Published: July 2020

Background

Loss-of-function mutations of human cardiac sodium channel gene SCN5A induce a wide range of arrhythmic disorders. Mutation carriers with co-existing conditions such as congenital heart diseases and histories of cardiac surgeries, could develop complex arrhythmic events that are difficult to diagnose.

Case presentation

A 41-year-old Japanese male with a history of a surgical closure of an ASD presented impairment of consciousness by wide QRS tachycardia. Because the patient’s baseline ECG in sinus rhythm showed similar QRS axis with right bundle brunch block morphology, we suspected supraventricular tachycardia (SVT). During hospitalization, the patient developed polymorphic ventricular tachycardia that was induced by bradycardia. In an electrophysiological study, the SVT was identified as right atrial incisional tachycardia circulating around the scar in the right atrium.

The genetic analysis revealed a heterozygous SCN5A c.4037–4038 del TC, p. L1346HfsX38 variant. We diagnosed this patient as having progressive cardiac conduction disorder (PCCD) and polymorphic VT caused by the mutation. Incisional tachycardia with wide QRS morphology was a by-standing comorbidity related to the history of cardiac surgery which could miss lead the diagnosis.

The patient’s SVT was eliminated by radiofrequency catheter ablation. An implantable cardioverter defibrillator (ICD) was implanted for the secondary prevention of polymorphic VT. Cardiac pace-making therapy by the ICD to avoid bradycardia effectively suppressed the patient’s arrhythmic events.

Conclusions

We treated a patient with a sodium channel gene variant. Co-existing SVT originated by a scar in the right atrium made the diagnosis extremely difficult. A multilateral diagnostic approach using an ECG analysis, an electrophysiological study, and genetic screening enabled effective combination therapy comprised of catheter ablation and an ICD.
Directed acyclic graphs and causal thinking in clinical risk prediction modeling
Authors: Piccininni Marco , Konigorski Stefan , Rohmann Jessica L. , Kurth Tobias
Published: July 2020

Background

In epidemiology, causal inference and prediction modeling methodologies have been historically distinct. Directed Acyclic Graphs (DAGs) are used to model a priori causal assumptions and inform variable selection strategies for causal questions. Although tools originally designed for prediction are finding applications in causal inference, the counterpart has remained largely unexplored. The aim of this theoretical and simulation-based study is to assess the potential benefit of using DAGs in clinical risk prediction modeling.

Methods

We explore how incorporating knowledge about the underlying causal structure can provide insights about the transportability of diagnostic clinical risk prediction models to different settings. We further probe whether causal knowledge can be used to improve predictor selection in clinical risk prediction models.

Results

A single-predictor model in the causal direction is likely to have better transportability than one in the anticausal direction in some scenarios. We empirically show that the Markov Blanket, the set of variables including the parents, children, and parents of the children of the outcome node in a DAG, is the optimal set of predictors for that outcome.

Conclusions

Our findings provide a theoretical basis for the intuition that a diagnostic clinical risk prediction model including causes as predictors is likely to be more transportable. Furthermore, using DAGs to identify Markov Blanket variables may be a useful, efficient strategy to select predictors in clinical risk prediction models if strong knowledge of the underlying causal structure exists or can be learned.
Coronavirus disease 2019 (COVID-19): an evidence map of medical literature
Authors: Liu Nan , Chee Marcel Lucas , Niu Chenglin , Pek Pin Pin , Siddiqui Fahad Javaid , Ansah John Pastor , Matchar David Bruce , Lam Sean Shao Wei , Abdullah Hairil Rizal , Chan Angelique , Malhotra Rahul , Graves Nicholas , Koh Mariko Siyue , Yoon Sungwon , Ho Andrew Fu Wah , Ting Daniel Shu Wei , Low Jenny Guek Hong , Ong Marcus Eng Hock
Published: July 2020

Background

Since the beginning of the COVID-19 outbreak in December 2019, a substantial body of COVID-19 medical literature has been generated. As of June 2020, gaps and longitudinal trends in the COVID-19 medical literature remain unidentified, despite potential benefits for research prioritisation and policy setting in both the COVID-19 pandemic and future large-scale public health crises.

Methods

In this paper, we searched PubMed and Embase for medical literature on COVID-19 between 1 January and 24 March 2020. We characterised the growth of the early COVID-19 medical literature using evidence maps and bibliometric analyses to elicit cross-sectional and longitudinal trends and systematically identify gaps.

Results

The early COVID-19 medical literature originated primarily from Asia and focused mainly on clinical features and diagnosis of the disease. Many areas of potential research remain underexplored, such as mental health, the use of novel technologies and artificial intelligence, pathophysiology of COVID-19 within different body systems, and indirect effects of COVID-19 on the care of non-COVID-19 patients. Few articles involved research collaboration at the international level (24.7%). The median submission-to-publication duration was 8 days (interquartile range: 4–16).

Conclusions

Although in its early phase, COVID-19 research has generated a large volume of publications. However, there are still knowledge gaps yet to be filled and areas for improvement for the global research community. Our analysis of early COVID-19 research may be valuable in informing research prioritisation and policy planning both in the current COVID-19 pandemic and similar global health crises.
Sources of potential bias when combining routine data linkage and a national survey of secondary school-aged children: a record linkage study
Authors: Morgan Kelly , Page Nicholas , Brown Rachel , Long Sara , Hewitt Gillian , Del Pozo-Banos Marcos , John Ann , Murphy Simon , Moore Graham
Published: July 2020

Background

Linking survey data to administrative records requires informed participant consent. When linkage includes child data, this includes parental and child consent. Little is known of the potential impacts of introducing consent to data linkage on response rates and biases in school-based surveys. This paper assessed: i) the impact on overall parental consent rates and sample representativeness when consent for linkage was introduced and ii) the quality of identifiable data provided to facilitate linkage.

Methods

Including an option for data linkage was piloted in a sub-sample of schools participating in the Student Health and Wellbeing survey, a national survey of adolescents in Wales, UK. Schools agreeing to participate were randomized 2:1 to receive versus not receive the data linkage question. Survey responses from consenting students were anonymised and linked to routine datasets (e.g. general practice, inpatient, and outpatient records). Parental withdrawal rates were calculated for linkage and non-linkage samples. Multilevel logistic regression models were used to compare characteristics between: i) consenters and non-consenters; ii) successfully and unsuccessfully linked students; and iii) the linked cohort and peers within the general population, with additional comparisons of mental health diagnoses and health service contacts.

Results

The sub-sample comprised 64 eligible schools (out of 193), with data linkage piloted in 39. Parental consent was comparable across linkage and non-linkage schools. 48.7% (n = 9232) of students consented to data linkage. Modelling showed these students were more likely to be younger, more affluent, have higher positive mental wellbeing, and report fewer risk-related behaviours compared to non-consenters. Overall, 69.8% of consenting students were successfully linked, with higher rates of success among younger students. The linked cohort had lower rates of mental health diagnoses (5.8% vs. 8.8%) and specialist contacts (5.2% vs. 7.7%) than general population peers.

Conclusions

Introducing data linkage within a national survey of adolescents had no impact on study completion rates. However, students consenting to data linkage, and those successfully linked, differed from non-consenting students on several key characteristics, raising questions concerning the representativeness of linked cohorts. Further research is needed to better understand decision-making processes around providing consent to data linkage in adolescent populations.
Outbreak of KPC-2 Carbapenem-resistant Klebsiella pneumoniae ST76 and Carbapenem-resistant K2 Hypervirulent Klebsiella pneumoniae ST375 strains in Northeast China: molecular and virulent characteristics
Authors: Su Shanshan , Zhang Jisheng , Zhao Yongxin , Yu Lan , Wang Yong , Wang Yuchao , Bao Mingjia , Fu Yu , Li Chunjiang , Zhang Xiaoli
Published: July 2020

Background

Carbapenem-resistant hypervirulent Klebsiella pneumoniae strains have recently come into existence worldwide; however, researchers in northeast China are not aware of their clinical features and molecular characteristics.

Methods

Here, the molecular and virulent characteristics of 44 carbapenem-resistant K. pneumoniae (CRKP) isolates collected from January 2015 to December 2017 were studied. Multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE) were carried out to define the clonal relatedness among the isolates. PCR and capsular serotyping of the virulence-associated genes, as well as biofilm formation and serum complement-mediated killing assays, were employed to determine the virulent potential. The genomic features and associated mobile genetic elements of JmsCRE57 were detected by whole genome sequencing.

Results

The only positive isolate was JmsCRE57, which belonged to the ST375 serotype K2 that expressed uge, mrkD, fimH, kpn, aerobactin and rmpA virulence-associated genes and showed strong biofilm formation and serum sensitivity. Sequencing results showed that the JmsCRE57 genome mainly consisted of a circular chromosome, three antimicrobial resistant plasmids and a virulent plasmid. The antimicrobial resistant plasmid expressing blaKPC-2, blaCTX-M-15, aph(3″)-Ib, aph(6)-Id, qnrB1, aac(3)-IIa, aac(6′)-Ib-cr, blaOXA-1, blaTEM-1B, catB4, sul2, dfrA14 and blaSHV-99. The virulent plasmid belonged to the IncHI1B group, which is mainly composed of mucoid phenotype genes and siderophore-associated genes. The remaining CRKP strains that expressed uge, fimH, mrkD and kpn virulence-associated genes were not successfully typed.

Conclusion

Our results provide new insights on the epidemiology of carbapenem-resistant K2 hypervirulent K. pneumoniae ST375 and CRKP ST76 strains in northeast China, which may help control their future outbreaks.
Fatal outcome in a patient under immunosuppressant therapy infected with human T-lymphotropic virus type 1 (HTLV-1), cytomegalovirus (CMV) and Strongyloides stercoralis: a case report
Authors: Ashida Chisato , Kinoshita Koji , Nozaki Yuji , Funauchi Masanori
Published: July 2020

Background

Strongyloidiasis is a gastrointestinal parasitic infection caused by percutaneous infection with Strongyloides stercoralis. Digestive symptoms such as diarrhea and abdominal pain are the main manifestation, but serious infections such as septicemia, purulent meningitis, and bacterial pneumonia may occur in individuals harboring human T-lymphotropic virus type 1 (HTLV-1) or who are immunocompromised. Although coinfection with Strongyloides stercoralis and HTLV-1 can lead to chronic strongyloidiasis and a disseminated form of the disease, there is a high rate of response to the anthelmintic ivermectin.

Case presentation

We report a case of strongyloidiasis infection syndrome that was difficult to differentiate from immune reconstitution inflammatory syndrome (IRIS) for various reasons. The patient had been treated with the corticosteroids tacrolimus (Tac) and mycophenolate mofetil (MMF) for systemic lupus erythematosus (SLE) with lupus nephritis and pancytopenia. When the steroid was reduced, she developed cytomegalovirus (CMV) enteritis, and her respiratory status rapidly deteriorated immediately after the withdrawal of Tac and MMF. It was difficult to distinguish immune reconstitution inflammatory syndrome from strongyloidiasis infection syndrome because stool cultures were negative and eosinophils were not increased. Bronchoscopy revealed viable Strongyloides, leading to a diagnosis of strongyloidiasis infection syndrome, but the patient died despite treatment.

Conclusions

Both corticosteroid therapy and HTLV-1 infection can be associated with a decrease of eosinophils, despite the presence of parasitic infection. In conclusion, even if multiple culture tests are negative, the risk of parasitic infection should be assessed in patients receiving immunosuppressants and steroids even in non-endemic areas.
Neurologic alterations in an HIV adult patient with pertussis: a case report
Authors: Arango-Granados María Camila , Trompa Iván Mauricio
Published: July 2020

Background

Pertussis is a highly contagious disease of public health interest caused by the bacterium Bordetella pertussis. Although its incidence has decreased substantially after the introduction of a vaccination, the burden of the disease remains high. Although the paroxysmal phase is highly disabling, complications are uncommon and more prevalent in children than in adults. The most frequent neurological complication is encephalopathy, but seizures, paresis, paraplegia, ataxias, aphasias, and decerebration postures have also been described. The complication of decerebration postures has not been previously reported in adults.

Case presentation

We present a video case of an adult HIV patient with severe coughing paroxysms, post-tussive emesis and syncope, whose workup confirmed the diagnosis of a B. pertussis respiratory infection. During hospitalization, he had fluctuant encephalopathy and post-tussive decerebration postures following paroxysms. He was treated with antibiotic therapy and finally sent home without residual neurological deficits.

Conclusion

This case illustrates the biological plausibility of neurologic complications of pertussis in adults, which, albeit rare, can cause important morbidities. Future research should explore whether there are differences in the clinical presentation, risk factors and pathophysiology of the disease among adults or interventions aimed at preventing or treating pertussis encephalopathy.
Diffusion tensor imaging quantifying the severity of chronic hepatitis in rats
Authors: Huang Mengping , Lu Xin , Wang Xiaofeng , Shu Jian
Published: July 2020

Background

Diffusion tensor imaging (DTI) is mainly used for detecting white matter fiber in the brain. DTI was applied to assess fiber in liver disorders in previous studies. However, the data obtained have been insufficient in determining if DTI can be used to exactly stage chronic hepatitis. This study assessed the value of DTI for staging of liver fibrosis (F), necroinflammatory activity (A) and steatosis (S) with chronic hepatitis in rats.

Methods

Seventy male Sprague-Dawley rats were divided into a control group(n = 10) and an experimental group(n = 60). The rat models of chronic hepatitis were established by abdominal subcutaneous injections of 40% CCl4. All of the rats underwent 3.0 T MRI. Regions of interest (ROIs) were subjected to DTI to estimate the MR parameters (rADC value and FA value). Histopathology was used as the reference standard. Multiple linear regression was used to analyze the associations between the MR parameters and pathology. The differences in the MR parameters among the pathological stages were evaluated by MANOVA or ANOVA. The LSD test was used to test for differences between each pair of groups. ROC analysis was also performed.

Results

The count of each pathology was as follows: F0(n = 15), F1(n = 11), F2(n = 6), F3(n = 9), F4(n = 6); A0(n = 8), A1(n = 16), A2(n = 16), A3(n = 7); S0(n = 10), S1(n = 7), S2(n = 3), S3(n = 11), S4(n = 16). The rADC value had a negative correlation with liver fibrosis (r = − 0.392, P = 0.008) and inflammation (r = − 0.359, P = 0.015). The FA value had a positive correlation with fibrosis (r = 0.409, P = 0.005). Significant differences were found in the FA values between F4 and F0 ~ F3 (P = 0.03), while no significant differences among F0 ~ F3 were found (P > 0.05). The AUC of the FA value differentiating F4 from F0 ~ F3 was 0.909 (p < 0.001) with an 83.3% sensitivity and an 85.4% specificity when the FA value was at the cut-off of 588.089 (× 10− 6 mm2/s).

Conclusion

The FA value for DTI can distinguish early cirrhosis from normal, mild and moderate liver fibrosis, but the rADC value lacked the ability to differentiate among the fibrotic grades. Both the FA and rADC values were unable to discriminate the stages of necroinflammatory activity and steatosis.
Transplantation of a single kidney from pediatric donors less than 10 kg to children with poor access to transplantation: a two-year outcome analysis
Authors: Su Xiaojun , Shang Wenjun , Liu Longshan , Li Jun , Fu Qian , Feng Yonghua , Zhang Huanxi , Deng Ronghai , Wu Chenglin , Wang Zhigang , Pang Xinlu , Nashan Björn , Feng Guiwen , Wang Changxi
Published: July 2020

Background

Access to kidney transplantation by uremic children is very limited due to the lack of donors in many countries. We sought to explore small pediatric kidney donors as a strategy to provide transplant opportunities for uremic children.

Methods

A total of 56 cases of single pediatric kidney transplantation and 26 cases ofen blockidney transplantation from pediatric donors with body weight (BW) less than 10 kg were performed in two transplant centers in China and the transplant outcomes were retrospectively analyzed.

Results

The 1-year and 2-year death-censored graft survival in theen blockidney transplantation (KTx) group was inferior to that in the single KTx group. Subgroup analysis of the single KTx group found that the 1-year and 2-year death-censored graft survival in the group where the donor BW was between 5 and 10 kg was 97.7 and 90.0%, respectively. However, graft survival was significantly decreased when donor BW was ≤5 kg (p < 0.01), mainly because of the higher rate of thrombosis (p = 0.035). In the single KTx group, the graft length was increased from 6.7 cm at day 7 to 10.5 cm at 36 months posttransplant. The estimated glomerular filtration rate increased up to 24 months posttransplant. Delayed graft function and urethral complications were more common in the group with BW was ≤5 kg.

Conclusions

Our study suggests that single kidney transplantation from donors weighing over 5 kg to pediatric recipients is a feasible option for children with poor access to transplantation.
Acute kidney injury with extreme hyperuricemia after antithymocyte globulin treatment in a kidney transplant recipient with underlying aplastic anemia: a case report
Authors: Park Yohan , Chung Byung Ha , Park Cheol Whee , Kim Yong-Soo , Yang Chul Woo
Published: July 2020

Background

The occurrences of hyperuricemia and acute kidney injury after antithymocyte globulin treatment are unusual in kidney transplant recipients. Here, we report a unique case of acute kidney injury with extreme hyperuricemia after antithymocyte globulin treatment in a kidney transplant recipient with underlying aplastic anemia.

Case presentation

A 40-year-old woman with aplastic anemia who received a kidney transplant 5 years 6 months before presented to our emergency department with complaints of oliguria, generalized edema, and general weakness 6 days after receiving antithymocyte globulin treatment for acute T-cell-mediated rejection. Urinalysis revealed 100 uric acid crystal particles. The blood chemistry test results showed rapid increases in serum creatinine (from 2.86 mg/dL to 5.58 mg/dL) and uric acid levels (from 10.2 mg/dL to 32.7 mg/dL), which suggested acute uric acid nephropathy. Tumor lysis syndrome was suspected to be the cause of the acute uric acid nephropathy; hence, the patient was reevaluated for aplastic anemia. Human leukocyte antigen-DR15 was positive, and flow cytometry revealed a low percentage of glycophosphatidyl inositol-deficient granulocytes (2.9%), which suggested paroxysmal nocturnal hemoglobinuria clones. These findings indicate that the previously diagnosed aplastic anemia had either originally been hypocellular myelodysplastic syndrome (MDS) or later transformed into hypocellular MDS, which is a type of bone marrow failure syndrome.

Conclusions

Clinicians should consider unexpected tumor lysis syndrome to be the cause of complications after antithymocyte globulin treatment in kidney transplant recipients with underlying bone marrow failure syndrome.
The association between dyslipidemia and the incidence of chronic kidney disease in the general Zhejiang population: a retrospective study
Authors: Liang Xudong , Ye Meiyu , Tao Mei , Zheng Danna , Cai Ruyi , Zhu Yifan , Jin Juan , He Qiang
Published: July 2020

Background

According to the “lipid nephrotoxicity hypothesis”, there is now significant research being conducted in this area. By studying the role of hyperlipidemia in chronic kidney disease in the general Zhejiang population, we aimed to explore the correlation between changes in blood lipid levels and chronic kidney disease.

Methods

We collected and analyzed clinical data from ordinary residents who participated in the annual comprehensive physical examination with no overt kidney disease in Zhejiang Provincial People’s Hospital, China from January 2011 to December 2016. According to triglyceride, total cholesterol and low-density lipoprotein levels, participants were respectively divided into 4 groups. Statistical methods were used to evaluate the correlation between different blood lipid profiles and chronic kidney disease.

Results

Five thousand one hundred eighty-three participants were included in our study. During the six-year follow-up period, 227 participants (4.4%) developed chronic kidney disease. The odds ratio for incident chronic kidney disease was 3.14 (95%CI: 1.53–6.43) in Q3, 3.84 (95%CI: 1.90–7.76) in Q4 according to the total cholesterol group and 1.17 (95%CI: 1.04–1.32) in Q3, 1.40 (95%CI: 1.11–2.48) in Q4 according to the low-density lipoprotein group, respectively, after multivariable-adjusted analyses. According to the triglyceride grouping, the odds ratio for incident chronic kidney disease was 2.88 (95%CI: 1.29–6.43) in Q2, 2.92 (95%CI: 1.44–6.57) in Q3 and 3.08 (95%CI: 1.11–6.69) in Q4, after multivariable-adjusted analyses.

Conclusion

Increased triglycerides and high levels of total cholesterol and low-density lipoprotein were independently associated with an increased likelihood of estimated glomerular filtration rate (eGFR) decline and development of incident chronic kidney disease in the general Zhejiang population.
Synergisms of genome and metabolism stabilizing antitumor therapy (GMSAT) in human breast and colon cancer cell lines: a novel approach to screen for synergism
Authors: Ruhnau Jérôme , Parczyk Jonas , Danker Kerstin , Eickholt Britta , Klein Andreas
Published: July 2020

Background

Despite an improvement of prognosis in breast and colon cancer, the outcome of the metastatic disease is still severe. Microevolution of cancer cells often leads to drug resistance and tumor-recurrence. To target the driving forces of the tumor microevolution, we focused on synergistic drug combinations of selected compounds. The aim is to prevent the tumor from evolving in order to stabilize disease remission. To identify synergisms in a high number of compounds, we propose here a three-step concept that is cost efficient, independent of high-throughput machines and reliable in its predictions.

Methods

We created dose response curves using MTT- and SRB-assays with 14 different compounds in MCF-7, HT-29 and MDA-MB-231 cells. In order to efficiently screen for synergies, we developed a screening tool in which 14 drugs were combined (91 combinations) in MCF-7 and HT-29 using EC25 or less. The most promising combinations were verified by the method of Chou and Talalay.

Results

All 14 compounds exhibit antitumor effects on each of the three cell lines. The screening tool resulted in 19 potential synergisms detected in HT-29 (20.9%) and 27 in MCF-7 (29.7%). Seven of the top combinations were further verified over the whole dose response curve, and for five combinations a significant synergy could be confirmed. The combination Nutlin-3 (inhibition of MDM2) and PX-478 (inhibition of HIF-1α) could be confirmed for all three cell lines. The same accounts for the combination of Dichloroacetate (PDH activation) and NHI-2 (LDH-A inhibition). Our screening method proved to be an efficient tool that is reliable in its projections.

Conclusions

The presented three-step concept proved to be cost- and time-efficient with respect to the resulting data. The newly found combinations show promising results in MCF-7, HT-29 and MDA-MB231 cancer cells.
Etoposide-mediated interleukin-8 secretion from bone marrow stromal cells induces hematopoietic stem cell mobilization
Authors: Kang Ka-Won , Lee Seung-Jin , Kim Ji Hye , Lee Byung-Hyun , Kim Seok Jin , Park Yong , Kim Byung Soo
Published: July 2020

Background

We assessed the mechanism of hematopoietic stem cell (HSC) mobilization using etoposide with granulocyte-colony stimulating factor (G-CSF), and determined how this mechanism differs from that induced by cyclophosphamide with G-CSF or G-CSF alone.

Methods

We compared the clinical features of 173 non-Hodgkin’s lymphoma patients who underwent autologous peripheral blood stem cell transplantation (auto-PBSCT). Additionally, we performed in vitro experiments to assess the changes in human bone marrow stromal cells (hBMSCs), which support the HSCs in the bone marrow (BM) niche, following cyclophosphamide or etoposide exposure. We also performed animal studies under standardized conditions to ensure the following: exclude confounding factors, mimic the conditions in clinical practice, and identify the changes in the BM niche caused by etoposide-induced chemo-mobilization or other mobilization methods.

Results

Retrospective analysis of the clinical data revealed that the etoposide with G-CSF mobilization group showed the highest yield of CD34+ cells and the lowest change in white blood cell counts during mobilization. In in vitro experiments, etoposide triggered interleukin (IL)-8 secretion from the BMSCs and caused long-term BMSC toxicity. To investigate the manner in which the hBMSC-released IL-8 affects hHSCs in the BM niche, we cultured hHSCs with or without IL-8, and found that the number of total, CD34+, and CD34+/CD45- cells in IL-8-treated cells was significantly higher than the respective number in hHSCs cultured without IL-8 (p = 0.014, 0.020, and 0.039, respectively). Additionally, the relative expression ofCXCR2(an IL-8 receptor), andmTORandc-MYC(components of IL-8-related signaling pathways) increased 1 h after IL-8 treatment. In animal studies, the etoposide with G-CSF mobilization group presented higher IL-8-related cytokine and MMP9 expression and lower SDF-1 expression in the BM, compared to the groups not treated with etoposide.

Conclusion

Collectively, the unique mechanism of etoposide with G-CSF-induced mobilization is associated with IL-8 secretion from the BMSCs, which is responsible for the enhanced proliferation and mobilization of HSCs in the bone marrow; this was not observed with mobilization using cyclophosphamide with G-CSF or G-CSF alone. However, the long-term toxicity of etoposide toward BMSCs emphasizes the need for the development of more efficient and safe chemo-mobilization strategies.
Reduced anogenital distance, hematuria and left renal hypoplasia in a patient with 13q33.1–34 deletion: case report and literature review
Authors: He Xue , Shen Huijun , Fu Haidong , Feng Chunyue , Liu Zhixia , Jin Yanyan , Mao Jianhua
Published: July 2020

Background

13q33–q34 microdeletions are rare chromosomal aberrations associated with a high risk of developmental disability, facial dysmorphism, cardiac defects and other malformation of organs. It is necessary to collect and report evidence of this rare chromosome mutation to improve the prognosis of this rare disease.

Case presentation

We report a patient harboring an 11.56 Mb microdeletion at 13q33.1–34 region, which contains about 30 OMIM genes. Besides the common clinical manifestations such as facial dysmorphism, developmental delay, intellectual disability, epilepsy, and congenital heart disease, she also suffered from a reduced anogenital distance, hematuria and left renal hypoplasia. Most related cases were characterized by facial deformity and heart defects, but there were few reports on renal malformation, especially regarding renal hypoplasia with hematuria.

Conclusion

We have reported a patient suffering from a reduced anogenital distance, hematuria and left renal hypoplasia. A de novo 11.56 Mb deletion ranging from 13q33.1 to 13q34 (Chr13:103542220–115,106,996) was found by SNP-array analysis. It might be the first time for hematuria and renal hypoplasia to be reported as symptoms of 13q33-q34 deletion syndrome Neurodevelopmental disability, heart defects and urogenital/anorectal anomalies may be resulted from common or overlapping regions of deletion in chromosome bands 13q33.1-q34 and may share a common molecular mechanism.