bluuebunny/crossref_metadata_2025 huggingface dataset:
Aspirin-Exacerbated Respiratory Disease With Allergic Fungal Rhinosinusitis: A Case Series of Overlapping Sinonasal Endotypes
Authors: Studer Matthew B. , Roland Lauren T. , Ochsner Matthew C. , Cox Daniel , DelGaudio John M. , Wise Sarah K. , Levy Joshua M.
Published: February 2020

Background

Chronic rhinosinusitis with nasal polyposis (CRSwNP) is a heterogeneous inflammatory disease with multiple underlying etiologies. Although several CRSwNP endotypes have been detailed, the current classification system does not adequately represent all patients with nasal polyps. We describe 2 patients meeting established diagnostic criteria for both aspirin-exacerbated respiratory disease (AERD) and allergic fungal rhinosinusitis (AFRS), which are considered distinct CRSwNP endotypes.

Objective

To describe patients meeting established diagnostic criteria for both AERD and AFRS in order to highlight deficits in the current CRSwNP endotype classification system as well as to expand awareness of the potential for aspirin desensitization as a treatment option in a subset of patients with AFRS.

Methods

Retrospective chart review with description of patient and diagnostic characteristics. AERD was diagnosed based on the presence of nasal polyps, asthma, and a documented history of sensitivity to nonsteroidal anti-inflammatory drugs. AFRS was diagnosed based on Bent and Kuhn criteria.

Results

Patients met established diagnostic criteria for both AERD and AFRS. Microscopic examination of sinus tissue revealed reactive bone, tissue eosinophilia (>10/high-powered field), and allergic mucin with noninvasive fungal elements. Subjects had an average of 4 endoscopic sinus surgeries and are currently maintained with adjunctive aspirin desensitization and/or anti-IL-5 biologic therapy.

Conclusions

This case series suggests that although they are treated as distinct CRSwNP endotypes, AERD and AFRS may have more overlap than was previously appreciated. Further research is needed to accurately identify discrete endotypes and associated treatment outcomes as we seek individualized patient care.
A Comprehensive Coronal and Axial Bone Dimension and Cartilage Thickness Evaluation of the Distal Humerus: Age and Sex Differences
Authors: Misir Abdulhamit , Gunay Ali Eray , Oguzkaya Sinan , Uzun Erdal , Kizkapan Turan Bilge , Yildiz Kadir Ilker , Ozcamdalli Mustafa
Published: February 2020

Objective

There are limited data on bone dimension and cartilage thickness of the distal humeral articular surface. This study aimed to evaluate sex- and age-related bone dimension and cartilage thickness differences and assess the effect of cartilage thickness on distal humeral shape.

Design

Elbow magnetic resonance images of 180 healthy participants were evaluated. Cartilage thicknesses of the trochlea and capitellum were measured at 19 points using coronal and axial images. In addition, bone diameters were measured from the flexion-extension axis to the 19 points on the coronal and axial magnetic resonance images. Sex differences were evaluated, and the correlation between age and measurement parameters was assessed.

Results

Significant sex differences regarding the diameters of the axial trochlear bone, coronal lateral trochlear bone, and medial capitellar bone, cartilage thickness at the apex of the lateral trochlear ridge in the axial and coronal plane and at the most lateral point of the capitellar articular surface in the axial plane were observed. A negative correlation was observed between age and axial plane trochlear bone dimensions and between age and coronal plane lateral trochlear and medial capitellar bone dimensions. No significant correlation was found between cartilage thickness and bone dimensions.

Conclusions

Bone dimension and cartilage thickness at the distal humerus vary according to sex and age. The data could be used in the donor site selection and graft preparation while osteochondral autograft transfer and allograft transplantation, and in the development of gender-compatible hemiarthroplasty implants.
Development and Validation of the Tertiary Student Locus of Control Scale
Authors: Santokhie Stefan , Lipps Garth E.
Published: February 2020

This study developed and validated a measure of Locus of Control in university students. Tertiary academic locus of control is the general expectancy that university students have regarding their ability to change their academic outcomes. Students who have an internal academic locus of control expect that their own efforts, skill, or luck will lead to academic success, while those with an external locus of control believe that academic outcomes are a result of luck, destiny, fate, or the behaviors of others. A series of steps were taken to develop the Tertiary Student Locus of Control (TSLOC) scale. These steps included defining the construct, developing a nomological network of the construct, and constructing an item pool of 66 items. Following the creation of the item pool, an item analysis was conducted on the 66-item measure to produce the 30-item TSLOC scale. The draft scale was administered to 100 participants (80 females and 20 males predominantly of Afro-Caribbean heritage from English-speaking Caribbean islands). The TSLOC scale had an internal consistency of .96 and had strong concurrent validity and moderate discriminant validity. A principal component analysis indicated that the TSLOC was a multidimensional scale composed of three underlying dimensions. The TSLOC scale was found to be valid and reliable for the current population of Caribbean tertiary students. The limitations and implications are discussed.
Clinical Outcomes After Medial Patellofemoral Ligament Reconstruction With Suture Fixation of the Gracilis Tendon via Transosseous Tunnels
Authors: Zhang Hangzhou , Ye Mao , Liang Qingwei
Published: February 2020

Background:

Several fixation methods have been introduced in medial patellofemoral ligament (MPFL) reconstruction. However, the optimal management of patients with recurrent patellar dislocation remains controversial.

Purpose:

To present a case series with a minimum 2-year follow-up of 29 patients with recurrent patellar dislocation who underwent a new transosseous suture fixation technique for MPFL reconstruction.

Study Design:

Case series; Level of evidence, 4.

Methods:

From January 2014 through February 2016, a total of 29 patients with recurrent patellar dislocation for which the MPFL was reconstructed with transosseous suture patellar fixation were studied. All patients were available for follow-up (mean, 37.52 months; range, 26-48 months). The patellar attachment was fixed by transosseous patellar sutures. The International Knee Documentation Committee (IKDC) subjective knee score, Kujala score, Tegner score, range of motion, congruence angle, patellar tilt angle, and complications were assessed both pre- and postoperatively.

Results:

No recurrent dislocation was observed in any of the 29 patients for a minimum of 2 years. All outcome scores improved significantly from preoperatively to postoperatively: the average IKDC subjective knee evaluation score from 53 to 87, Kujala from 54 to 90, Lysholm from 50 to 89, and Tegner from 3 to 5 ( P < .001 for all). The congruence angle significantly decreased from 22° preoperatively to –3° postoperatively, and the patellar tilt angle (Merchant) decreased from 23° preoperatively to 5° postoperatively ( P < .001 for both). In total, 25 patients (25/29; 86.21%) were completely pain-free when performing activities of daily living at the last follow-up, and 27 patients (93.1%) rated themselves as very satisfied or satisfied with the results.

Conclusion:

In patients with chronic recurrent patellar dislocation, transosseous patellar suture fixation for MPFL reconstruction can significantly improve patellar stability and achieve good results at short-term follow-up.
Clonal tracking in gene therapy patients reveals a diversity of human hematopoietic differentiation programs
Authors: Six Emmanuelle , Guilloux Agathe , Denis Adeline , Lecoules Arnaud , Magnani Alessandra , Vilette Romain , Male Frances , Cagnard Nicolas , Delville Marianne , Magrin Elisa , Caccavelli Laure , Roudaut Cécile , Plantier Clemence , Sobrino Steicy , Gregg John , Nobles Christopher L. , Everett John K. , Hacein-Bey-Abina Salima , Galy Anne , Fischer Alain , Thrasher Adrian J. , André Isabelle , Cavazzana Marina , Bushman Frederic D.
Published: February 2020

In gene therapy with human hematopoietic stem and progenitor cells (HSPCs), each gene-corrected cell and its progeny are marked in a unique way by the integrating vector. This feature enables lineages to be tracked by sampling blood cells and using DNA sequencing to identify the vector integration sites. Here, we studied 5 cell lineages (granulocytes, monocytes, T cells, B cells, and natural killer cells) in patients having undergone HSPC gene therapy for Wiskott-Aldrich syndrome or β hemoglobinopathies. We found that the estimated minimum number of active, repopulating HSPCs (which ranged from 2000 to 50 000) was correlated with the number of HSPCs per kilogram infused. We sought to quantify the lineage output and dynamics of gene-modified clones; this is usually challenging because of sparse sampling of the various cell types during the analytical procedure, contamination during cell isolation, and different levels of vector marking in the various lineages. We therefore measured the residual contamination and corrected our statistical models accordingly to provide a rigorous analysis of the HSPC lineage output. A cluster analysis of the HSPC lineage output highlighted the existence of several stable, distinct differentiation programs, including myeloid-dominant, lymphoid-dominant, and balanced cell subsets. Our study evidenced the heterogeneous nature of the cell lineage output from HSPCs and provided methods for analyzing these complex data.
Platelet glycoprotein VI promotes metastasis through interaction with cancer cell-derived Galectin-3
Authors: Mammadova-Bach Elmina , Gil-Pulido Jesus , Sarukhanyan Edita , Burkard Philipp , Shityakov Sergey , Schonhart Charlotte , Stegner David , Remer Katharina , Nurden Paquita , Nurden Alan T. , Dandekar Thomas , Nehez Laszlo , Dank Magdolna , Braun Attila , Mezzano Diego , Abrams Scott I , Nieswandt Bernhard
Published: February 2020

Increasing evidence suggests that platelets play a predominant role in colon and breast cancer metastasis but the underlying molecular mechanisms remain elusive. Glycoprotein VI (GPVI) is a platelet-specific receptor for collagen and fibrin that triggers platelet activation through immunoreceptor tyrosine-based activation motif (ITAM)-signaling and thereby regulates diverse functions including platelet adhesion, aggregation and procoagulant activity. GPVI has been proposed as a safe antithrombotic target as its inhibition is protective in models of arterial thrombosis with only minor effects on hemostasis. Here, we demonstrate that genetic deficiency of platelet GPVI in mice decreases experimental and spontaneous metastasis of colon and breast cancer cells. Similar results were obtained with mice lacking the spleen-tyrosine kinase Syk in platelets, an essential component of the ITAM-signaling cascade. In vitro and in vivo analyses show that mouse, as well as human GPVI, supports platelet adhesion to colon and breast cancer cells. Using a CRISPR/Cas9-based gene knock-out approach, we identified Galectin-3 as the major counter-receptor of GPVI on tumor cells. In vivo studies demonstrated that the interplay between platelet GPVI and tumor cell-expressed Galectin-3 utilizes ITAM-signaling components in platelets and favors the extravasation of tumor cells. Finally, we showed that JAQ1 F(ab)2-mediated inhibition of GPVI efficiently impairs platelet-tumor cell interaction and tumor metastasis. Our study reveals a new mechanism by which platelets promote the metastasis of colon and breast cancer cells and suggests that GPVI represents a promising target for antimetastatic therapies.
Hemopexin deficiency promotes acute kidney injury in sickle cell disease
Authors: Ofori-Acquah Solomon , Hazra Rimi , Orikogbo Oluwaseun O , Crosby Danielle , Flage Bethany , Ackah Ezekiel Bonwin , Lenhart Diane , Tan Roderick J , Vitturi Dario A , Paintsil Vivian , Owusu-Dabo Ellis , Ghosh Samit
Published: February 2020

Acute kidney injury (AKI) is a major clinical concern in sickle cell disease (SCD). Clinical evidence suggests that red cell alarmins may cause AKI in SCD however the sterile inflammatory process involved has hitherto not been defined. We discovered that hemopexin deficiency in SCD is associated with a compensatory increase in alpha-1-microglobulin (A1M) resulting in up to 10-fold higher A1M/hemopexin ratio in SCD compared to health controls. The A1M/hemopexin ratio is associated with markers of hemolysis and AKI in both humans and mice with SCD. Studies in mice showed that excess heme is directed to the kidneys in SCD in a process involving A1M causing AKI while excess heme in controls is transported to the liver as expected. Using genetic and bone marrow chimeric tools, we confirmed that hemopexin deficiency promotes AKI in sickle mice under hemolytic stress. However, AKI was blocked when hemopexin deficiency in sickle mice was corrected with infusions of purified hemopexin prior to the induction of hemolytic stress. This study identifies acquired hemopexin deficiency as a risk factor of AKI in SCD and hemopexin replacement as a potential therapy.
A T-cell–redirecting bispecific G-protein–coupled receptor class 5 member D x CD3 antibody to treat multiple myeloma
Authors: Pillarisetti Kodandaram , Edavettal Suzanne , Mendonça Mark , Li Yingzhe , Tornetta Mark , Babich Alexander , Majewski Nate , Husovsky Matt , Reeves Dara , Walsh Eileen , Chin Diana , Luistro Leopoldo , Joseph Jocelin , Chu Gerald , Packman Kathryn , Shetty Shoba , Elsayed Yusri , Attar Ricardo , Gaudet François
Published: February 2020

T-cell–mediated approaches have shown promise in myeloma treatment. However, there are currently a limited number of specific myeloma antigens that can be targeted, and multiple myeloma (MM) remains an incurable disease. G-protein–coupled receptor class 5 member D (GPRC5D) is expressed in MM and smoldering MM patient plasma cells. Here, we demonstrate that GPRC5D protein is present on the surface of MM cells and describe JNJ-64407564, a GPRC5DxCD3 bispecific antibody that recruits CD3+ T cells to GPRC5D+ MM cells and induces killing of GPRC5D+ cells. In vitro, JNJ-64407564 induced specific cytotoxicity of GPRC5D+ cells with concomitant T-cell activation and also killed plasma cells in MM patient samples ex vivo. JNJ-64407564 can recruit T cells and induce tumor regression in GPRC5D+ MM murine models, which coincide with T-cell infiltration at the tumor site. This antibody is also able to induce cytotoxicity of patient primary MM cells from bone marrow, which is the natural site of this disease. GPRC5D is a promising surface antigen for MM immunotherapy, and JNJ-64407564 is currently being evaluated in a phase 1 clinical trial in patients with relapsed or refractory MM (NCT03399799).
Mobile health application to support CPAP therapy in obstructive sleep apnoea: design, feasibility and perspectives
Authors: Suarez-Giron Monique , Garmendia Onintza , Lugo Vera , Ruiz Concepción , Salord Neus , Alsina Xavier , Farré Ramón , Montserrat Josep M. , Torres Marta
Published: February 2020

Background

Current continuous positive airway pressure (CPAP) devices can be monitored remotely; however, in-person visits are kept for clinical follow-up in order to promote CPAP use and resolve potential side-effects. Mobile health is a promising way to provide remote and easy clinical control for CPAP follow-up and support. We aimed to evaluate the feasibility and acceptance by obstructive sleep apnoea (OSA) patients and healthcare professionals of a newly designed mobile app (Appnea-Q) to promote clinical control through a self-monitoring tool for patients with CPAP supervised by sleep professionals.

Methods

Appnea-Q incorporates a simple follow-up questionnaire with automated responses, together with frequent problems and lifestyle recommendations sections. Feasibility, acceptance and usefulness were assessed. First, an internal validation was performed during outpatient CPAP follow-up visits with sleep professionals from various sleep units. Second, an external validation was performed in a subgroup of 15 patients at home.

Results

Most patients (n=75) considered the app useful and were willing to use it and recommend it (72–88%). Up to 64.87% agreed on its capacity to reduce hospital visits. Appnea-Q was rated as acceptable (79.37±19.29) by the system usability score. Sleep professionals (n=30) concurred on its usefulness for OSA patient follow-up, particularly during the first month of CPAP therapy. The external validation showed its feasibility among 11 out of 15 patients and their data were received accordingly on the professionals' web platform.

Conclusions

According to our validation process, and the viewpoints of the patients and professionals, our new mobile app is a feasible and well-received tool for personal OSA management. Future clinical trials should substantiate its performance and cost-effectiveness in the clinical arena.
Developing a core outcome set for children with protracted bacterial bronchitis
Authors: Gilchrist Francis J. , Ali Imran , Brodlie Malcolm , Carroll Will D. , Kemball Bridget , Walker James , Sinha Ian
Published: February 2020

Background

Protracted bacterial bronchitis (PBB) is a chronic endobrochial infection and a leading cause of chronic wet cough in children. There is an urgent need for a randomised controlled trial to investigate the optimal treatment but there is no core outcome set (COS) to inform choice of outcomes. A COS is a standardised set of outcomes representing the minimum that should be measured and reported in clinical trials of a specific condition. We have developed a COS for PBB.

Methods

Potential core outcomes were collated from a systematic review, interviews with parents and a clinician survey. A two-round Delphi survey of healthcare professionals identified which outcomes had consensus for inclusion. The final COS was agreed at a consensus meeting of parent representatives and clinicians.

Results

20 outcomes were identified for the Delphi survey. After two rounds, 10 reached consensus. These were combined and edited at the consensus meeting into the final six: 1) Resolution of cough assessed using a cough score/diary recorded daily by parent(s) during treatment; 2) relapse of chronic wet cough and/or cumulative antibiotic treatment during ≥12 months follow-up; 3) change in child's quality of life (parent-proxy reporting for young children); 4) emergence of antibiotic resistance; 5) development of bronchiectasis diagnosed on clinically indicated computed tomography scans; and 6) microbiological clearance of identified respiratory pathogen if samples readily available.

Conclusions

We have developed a COS for PBB which will reduce the outcome heterogeneity and bias of future clinical trials, as well as promoting comparison between studies.
Enhanced soil aggregate stability limits colloidal phosphorus loss potentials in agricultural systems
Authors: Li Fayong , Liang Xinqiang , Li Hua , Jin Yingbin , Jin Junwei , He Miaomiao , Klumpp Erwin , Bol Roland
Published: February 2020

Background

Colloid-facilitated phosphorus (P) transport is recognized as an important pathway for the loss of soil P in agricultural systems; however, information regarding soil aggregate-associated colloidal P (Pcoll) is lacking. To elucidate the effects of aggregate size on the potential loss of Pcoll in agricultural systems, soils (0–20 cm depth) from six land-use types were sampled in the Zhejiang Province in the Yangtze River Delta region, China. The aggregate size fractions (2–8 mm, 0.26–2 mm, 0.053–0.26 mm and < 0.053 mm) were separated using the wet sieving method. Colloidal P and other soil parameters in aggregates were analyzed.

Results

Our study demonstrated that 0.26–2 mm small macroaggregates had the highest total P (TP) content. In acidic soils, the highest Pcoll content was observed in the 0.26- to 2-mm-sized aggregates, while the lowest was reported in the < 0.053 mm (silt + clay)-sized particles, the opposite of that revealed in alkaline and neutral soils. Paddy soils contained less Pcoll than other land-use types. The proportion of Pcoll in total dissolved P (TDP) was dominated by < 0.053 mm (silt + clay)-sized particles. Aggregate size strongly influenced the loss potential of Pcoll in paddy soils, where Pcoll contributed up to 83% TDP in the silt + clay-sized particles. The Pcoll content was positively correlated with TP, Al, Fe, and the mean weight diameter. Aggregate-associated total carbon (TC), total nitrogen (TN), C/P, and C/N had significant negative effects on the contribution of Pcoll to potential soil P loss. The Pcoll content of the aggregates was controlled by the aggregate-associated TP and Al content, as well as the soil pH value. The potential loss of Pcoll from aggregates was controlled by its organic matter content.

Conclusion

We concluded that management practices that increase soil aggregate stability or its organic carbon content will limit Pcoll loss in agricultural systems.
A genome-wide scan study identifies a single nucleotide substitution in the tyrosinase gene associated with white coat colour in a red deer (Cervus elaphus) population
Authors: Reiner Gerald , Tramberend Kirsten , Nietfeld Florian , Volmer Klaus , Wurmser Christine , Fries Ruedi , Willems Hermann
Published: February 2020

Background

Red deer with very pale coat colour are observed sporadically. In the red deer (Cervus elaphus) population of Reinhardswald in Germany, about 5% of animals have a white coat colour that is not associated with albinism. In order to facilitate the conservation of the animals, it should be determined whether and to what extent brown animals carry the white gene. For this purpose, samples of one white hind and her brown calf were available for whole genome sequencing to identify the single nucleotide polymorphism(s) responsible for the white phenotype. Subsequently, samples from 194 brown and 11 white animals were genotyped.

Results

Based on a list of colour genes of the International Federation of Pigment Cell Societies, a non-synonymous mutation with exchange of a glycine residue at position 291 of the tyrosinase protein by arginine was identified as the cause of dilution of the coat colour. A gene test led to exactly matching genotypes in all examined animals. The study showed that 14% of the brown animals carry the white gene. This provides a simple and reliable way of conservation for the white animals. However, results could not be transferred to another, unrelated red deer population with white animals. Although no brown animals with a white tyrosinase genotype were detected, the cause for the white colouring in this population was different.

Conclusions

A gene test for the conservation of white red deer is available for the population of the Reinhardswald. While mutations in the tyrosinase are commonly associated with oculocutaneous albinism type 1, the amino acid exchange at position 291 was found to be associated with coat colour dilution in Cervus elaphus.
Comparative genomics applied to Mucor species with different lifestyles
Authors: Lebreton Annie , Corre Erwan , Jany Jean-Luc , Brillet-Guéguen Loraine , Pèrez-Arques Carlos , Garre Victoriano , Monsoor Misharl , Debuchy Robert , Le Meur Christophe , Coton Emmanuel , Barbier Georges , Meslet-Cladière Laurence
Published: February 2020

Background

Despite a growing number of investigations on early diverging fungi, the corresponding lineages have not been as extensively characterized as Ascomycota or Basidiomycota ones. The Mucor genus, pertaining to one of these lineages is not an exception. To this date, a restricted number of Mucor annotated genomes is publicly available and mainly correspond to the reference species, Mucor circinelloides, and to medically relevant species. However, the Mucor genus is composed of a large number of ubiquitous species as well as few species that have been reported to specifically occur in certain habitats. The present study aimed to expand the range of Mucor genomes available and identify potential genomic imprints of adaptation to different environments and lifestyles in the Mucor genus.

Results

In this study, we report four newly sequenced genomes of Mucor isolates collected from non-clinical environments pertaining to species with contrasted lifestyles, namely Mucor fuscus and Mucor lanceolatus, two species used in cheese production (during ripening), Mucor racemosus, a recurrent cheese spoiler sometimes described as an opportunistic animal and human pathogen, and Mucor endophyticus, a plant endophyte. Comparison of these new genomes with those previously available for six Mucor and two Rhizopus (formerly identified as M. racemosus) isolates allowed global structural and functional description such as their TE content, core and species-specific genes and specialized genes. We proposed gene candidates involved in iron metabolism; some of these genes being known to be involved in pathogenicity; and described patterns such as a reduced number of CAZymes in the species used for cheese ripening as well as in the endophytic isolate that might be related to adaptation to different environments and lifestyles within the Mucor genus.

Conclusions

This study extended the descriptive data set for Mucor genomes, pointed out the complexity of obtaining a robust phylogeny even with multiple genes families and allowed identifying contrasting potentially lifestyle-associated gene repertoires. The obtained data will allow investigating further the link between genetic and its biological data, especially in terms of adaptation to a given habitat.
In silico prediction and expression profile analysis of small non-coding RNAs in Herbaspirillum seropedicae SmR1
Authors: Dobrzanski Tatiane , Pobre Vânia , Moreno Leandro Ferreira , Barbosa Helba Cirino de Souza , Monteiro Rose Adele , de Oliveira Pedrosa Fábio , de Souza Emanuel Maltempi , Arraiano Cecília Maria , Steffens Maria Berenice Reynaud
Published: February 2020

Background

Herbaspirillum seropedicae is a diazotrophic bacterium from the β-proteobacteria class that colonizes endophytically important gramineous species, promotes their growth through phytohormone-dependent stimulation and can express nif genes and fix nitrogen inside plant tissues. Due to these properties this bacterium has great potential as a commercial inoculant for agriculture. The H. seropedicae SmR1 genome is completely sequenced and annotated but despite the availability of diverse structural and functional analysis of this genome, studies involving small non-coding RNAs (sRNAs) has not yet been done. We have conducted computational prediction and RNA-seq analysis to select and confirm the expression of sRNA genes in the H. seropedicae SmR1 genome, in the presence of two nitrogen independent sources and in presence of naringenin, a flavonoid secreted by some plants.

Results

This approach resulted in a set of 117 sRNAs distributed in riboswitch, cis-encoded and trans-encoded categories and among them 20 have Rfam homologs. The housekeeping sRNAs tmRNA, ssrS and 4.5S were found and we observed that a large number of sRNAs are more expressed in the nitrate condition rather than the control condition and in the presence of naringenin. Some sRNAs expression were confirmed in vitro and this work contributes to better understand the post transcriptional regulation in this bacterium.

Conclusions

H. seropedicae SmR1 express sRNAs in the presence of two nitrogen sources and/or in the presence of naringenin. The functions of most of these sRNAs remains unknown but their existence in this bacterium confirms the evidence that sRNAs are involved in many different cellular activities to adapt to nutritional and environmental changes.
QTL mapping of yield component traits on bin map generated from resequencing a RIL population of foxtail millet (Setaria italica)
Authors: Liu Tianpeng , He Jihong , Dong Kongjun , Wang Xuewen , Wang Wenwen , Yang Peng , Ren Ruiyu , Zhang Lei , Zhang Zhengsheng , Yang Tianyu
Published: February 2020

Background

Foxtail millet (Setaria italica) has been developed into a model genetical system for deciphering architectural evolution, C4 photosynthesis, nutritional properties, abiotic tolerance and bioenergy in cereal grasses because of its advantageous characters with the small genome size, self-fertilization, short growing cycle, small growth stature, efficient genetic transformation and abundant diverse germplasm resources. Therefore, excavating QTLs of yield component traits, which are closely related to aspects mentioned above, will further facilitate genetic research in foxtail millet and close cereal species.

Results

Here, 164 Recombinant inbreed lines from a cross between Longgu7 and Yugu1 were created and 1,047,978 SNPs were identified between both parents via resequencing. A total of 3413 bin markers developed from SNPs were used to construct a binary map, containing 3963 recombinant breakpoints and totaling 1222.26 cM with an average distance of 0.36 cM between adjacent markers. Forty-seven QTLs were identified for four traits of straw weight, panicle weight, grain weight per plant and 1000-grain weight. These QTLs explained 5.5–14.7% of phenotypic variance. Thirty-nine favorable QTL alleles were found to inherit from Yugu1. Three stable QTLs were detected in multi-environments, and nine QTL clusters were identified on Chromosome 3, 6, 7 and 9.

Conclusions

A high-density genetic map with 3413 bin markers was constructed and three stable QTLs and 9 QTL clusters for yield component traits were identified. The results laid a powerful foundation for fine mapping, identifying candidate genes, elaborating molecular mechanisms and application in foxtail millet breeding programs by marker-assisted selection.
Genome-wide association studies of Shigella spp. and Enteroinvasive Escherichia coli isolates demonstrate an absence of genetic markers for prediction of disease severity
Authors:   On behalf of the IBESS group, Hendriks Amber C. A. , Reubsaet Frans A. G. , Kooistra-Smid A. M. D. ( Mirjam) , Rossen John W. A. , Dutilh Bas E. , Zomer Aldert L. , van den Beld Maaike J. C.
Published: February 2020

Background

We investigated the association of symptoms and disease severity of shigellosis patients with genetic determinants of infecting Shigella and entero-invasive Escherichia coli (EIEC), because determinants that predict disease outcome per individual patient could be used to prioritize control measures. For this purpose, genome wide association studies (GWAS) were performed using presence or absence of single genes, combinations of genes, and k-mers. All genetic variants were derived from draft genome sequences of isolates from a multicenter cross-sectional study conducted in the Netherlands during 2016 and 2017. Clinical data of patients consisting of binary/dichotomous representation of symptoms and their calculated severity scores were also available from this study. To verify the suitability of the methods used, the genetic differences between the genera Shigella and Escherichia were used as control.

Results

The isolates obtained were representative of the population structure encountered in other Western European countries. No association was found between single genes or combinations of genes and separate symptoms or disease severity scores. Our benchmark characteristic, genus, resulted in eight associated genes and > 3,000,000 k-mers, indicating adequate performance of the algorithms used.

Conclusions

To conclude, using several microbial GWAS methods, genetic variants in Shigella spp. and EIEC that can predict specific symptoms or a more severe course of disease were not identified, suggesting that disease severity of shigellosis is dependent on other factors than the genetic variation of the infecting bacteria. Specific genes or gene fragments of isolates from patients are unsuitable to predict outcomes and cannot be used for development, prioritization and optimization of guidelines for control measures of shigellosis or infections with EIEC.
Circular RNA expression profile and its potential regulative role in human abdominal aortic aneurysm
Authors: Zhou Min , Shi Zhenyu , Cai Liang , Li Xu , Ding Yong , Xie Tianchen , Fu Weiguo
Published: February 2020

Background

This study aimed to identify the differentially expressed circular RNAs (circRNAs) between human abdominal aortic aneurysm (AAA) and the control group.

Methods

High-throughput sequencing was applied to determine the circRNA expression profiles of 4 paired aortic samples. Real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was carried out to testify 6 randomly selected dysregulated circRNAs. Kyoto Encyclopedia of Genes and Genomes and Gene ontology (GO) analysis were conducted for functional annotation of the parental genes. Additionally, interaction networks between circRNA and 5 putative microRNA (miRNA) partners were constructed.

Results

Finally, 411 differentially expressed circRNAs were discovered, including 266 downregulated and 145 upregulated circRNAs. Compared with the control group, the expression level of hsa (Homo sapiens) _circ_0005360 (LDLR) and hsa_circ_0002168 (TMEM189) were proved significantly lower in the AAA group by qRT-PCR. Regarding upregulated circRNAs, the most enriched GO molecular function, biological process and cellular component terms were poly(A) RNA binding, negative regulation of transcription from RNA polymerase II promoter and nucleoplasm, respectively. Moreover, circRNA/miRNA interaction networks showed that hsa_circ_0005360/miR-181b and hsa_circ_0002168/miR-15a axis might have a regulative role in human AAA.

Conclusions

This study revealed new circRNAs potentially related to the pathogenesis of AAA. Further experimental studies are warranted to clarify the potential molecular mechanisms.
Comparison of different rating scales for the use in Delphi studies: different scales lead to different consensus and show different test-retest reliability
Authors: Lange Toni , Kopkow Christian , Lützner Jörg , Günther Klaus-Peter , Gravius Sascha , Scharf Hanns-Peter , Stöve Johannes , Wagner Richard , Schmitt Jochen
Published: February 2020

Background

Consensus-orientated Delphi studies are increasingly used in various areas of medical research using a variety of different rating scales and criteria for reaching consensus. We explored the influence of using three different rating scales and different consensus criteria on the results for reaching consensus and assessed the test-retest reliability of these scales within a study aimed at identification of global treatment goals for total knee arthroplasty (TKA).

Methods

We conducted a two-stage study consisting of two surveys and consecutively included patients scheduled for TKA from five German hospitals. Patients were asked to rate 19 potential treatment goals on different rating scales (three-point, five-point, nine-point). Surveys were conducted within a 2 week period prior to TKA, order of questions (scales and treatment goals) was randomized.

Results

Eighty patients (mean age 68 ± 10 years; 70% females) completed both surveys. Different rating scales (three-point, five-point and nine-point rating scale) lead to different consensus despite moderate to high correlation between rating scales (r = 0.65 to 0.74). Final consensus was highly influenced by the choice of rating scale with 14 (three-point), 6 (five-point), 15 (nine-point) out of 19 treatment goals reaching the pre-defined 75% consensus threshold. The number of goals reaching consensus also highly varied between rating scales for other consensus thresholds. Overall, concordance differed between the three-point (percent agreement [p] = 88.5%, weighted kappa [k] = 0.63), five-point (p = 75.3%, k = 0.47) and nine-point scale (p = 67.8%, k = 0.78).

Conclusion

This study provides evidence that consensus depends on the rating scale and consensus threshold within one population. The test-retest reliability of the three rating scales investigated differs substantially between individual treatment goals. This variation in reliability can become a potential source of bias in consensus studies. In our setting aimed at capturing patients’ treatment goals for TKA, the three-point scale proves to be the most reasonable choice, as its translation into the clinical context is the most straightforward among the scales. Researchers conducting Delphi studies should be aware that final consensus is substantially influenced by the choice of rating scale and consensus criteria.
Hepatitis C screening, diagnosis, and cascade of care among people aged > 40 years in Brasilia, Brazil
Authors: Carvalho-Louro Daniela Mariano , Soares Eric Bassetti , Trevizoli Jose Eduardo , Marra Thayna Moreira Gomes , da Cunha Alexandre Lima Rodrigues , Rodrigues Marcelo Palmeira , Carvalho-Furtado Adriana Claudia Lopes , dos Santos Beatriz Taynara Araujo , de Assis da Rocha Neves Francisco
Published: February 2020

Background

Identifying patients with hepatitis C virus (HCV) infection and enhancing the cascade of care are essential for eliminating HCV infection. This study aimed to estimate the prevalence of positive anti-HCV serology in Brasilia, Brazil, and evaluate the efficiency of the cascade of care for HCV-positive individuals.

Methods

This cross-sectional study analyzed 57,697 rapid screening tests for hepatitis C in individuals aged > 40 years between June 2018 and June 2019. HCV-positive patients were contacted and scheduled to undergo the HCV RNA viral test, genotyping, and transient elastography.

Results

The prevalence of positive serology was 0.27%. Among 161 patients with positive anti-HCV serology, 124 (77%) were contacted, 109 (67.7%) were tested for HCV RNA viral load, and 69 (42.8%) had positive results. Genotype 1 (75%) was the most prevalent genotype. Among 65 patients (94.2%) who underwent transient elastography, 30 (46.2%) presented with advanced fibrosis. Additionally, of the 161 patients, 55 (34.1%) were referred for treatment, but only 39 (24.2%) complied, with 36 (22.4%) showing sustained virological response. By the end of the study, 16 patients were still awaiting to receive medication.

Conclusions

The prevalence of HCV-positive patients was low in Brasilia, and the gaps in the cascade of care for these patients were significantly below the targets of HCV infection elimination. This study opens new avenues for eliminating HCV infection and suggests that partnerships with clinical laboratories to conduct anti-HCV tests are a useful strategy to improve HCV diagnosis.

Trial registration

Research Ethics Committee of the Faculty of Health Sciences of the University of Brasília - UNB (CAAE number 77818317.2.0000.0030) and by the Ethics Committee of the Health Science Teaching and Research Foundation - FEPECS/SES/DF (CAAE number 77818317.2.3001.5553).
Hydroxychloroquine may reduce risk of Pneumocystis pneumonia in lupus patients: a Nationwide, population-based case-control study
Authors: Yeo Kai-Jieh , Chen Hsin-Hua , Chen Yi-Ming , Lin Ching-Heng , Chen Der-Yuan , Lai Chih-Ming , Chao Wen-Cheng
Published: February 2020

Background

Pneumocystis pneumonia (PCP) is increasingly being diagnosed in patients with systemic lupus erythematosus (SLE), and hydroxychloroquine (HCQ) has been found to possess antifungal activities. We hence aimed to investigate the association between HCQ and PCP risk among patients with SLE.

Methods

Using the 1997–2013 nationwide claim data, we identified 24,343 newly-diagnosed SLE patients. We then identified 58 PCP cases and selected 348 non-PCP controls matching (1:6) by age, sex, disease duration and the year of PCP diagnosis date. The risk of PCP was assessed by determing odds ratios (ORs) with 95% confidence intervals (CIs) by using multivariable conditional logistic regression.

Results

The risk of PCP was associated with moderate to severe renal disease (OR 6.73, 95% CI 1.98–22.92), higher doses of glucocorticoids (≤5 mg/day, reference; 5–10 mg/day, OR 25.88, 95% CI 2.97–225.33; > 10 mg/day, OR 286.58, 95% CI 28.58–> 999), higher 3-month cumulative dose of cyclophosphamide (not use, reference; ≤1.4 g, OR 0.64, 95% CI 0.14–3.01; > 1.4 g, OR 11.52, 95% CI 1.97–67.39) and use of mycophenolate mofetil/mycophenolic acid (OR 50.79, 95% CI 5.32–484.77), whereas 3-month cumulative dose of HCQ was associated with a reduced risk of PCP among patients with SLE (not use, reference; ≤14 g, OR 0.69, 95% CI 0.21–2.24; > 14 g, OR 0.20, 95% CI 0.05–0.71).

Conclusions

This study demonstrated incident PCP was associated with mycophenolate mofetil/mycophenolic acid use and higher doses of cyclophosphamide or glucocorticoid, whereas the use of a higher dose of HCQ was associated with a reduced risk of PCP in lupus patients.
Normothermic and hypothermic oxygenated perfusion for donation after circulatory death in kidney transplantation: do we pay higher risk of severe infection after transplantation?: a case report
Authors: Ravaioli Matteo , Corradetti Valeria , Renzulli Matteo , Germinario Giuliana , Maroni Lorenzo , Odaldi Federica , Fallani Guido , Pezzuto Anna Paola , Parlanti Daniele , Bova Raffaele , Bini Claudia , La Manna Gaetano , Comai Giorgia
Published: February 2020

Background

Normothermic and hypothermic oxygenated perfusion for donation after circulatory death in kidney transplantation are becoming popular in Italy, with the purpose of reducing the risk of primary non function and delayed graft function due to the prolonged warm ischemia time.

Potential complications related to these procedures are currently under investigation and are continuously emerging with the increasing experience. Post-operative infections - in particular graft arteritis - are a rare complication but determine high risk of mortality and of graft loss.

The acute onset of the arterial complications makes it very difficult to find an effective treatment, and early diagnosis is crucial for saving both patient and graft. Prevention of such infections in this particular setting are advisable.

Case presentation

We present a patient with an acute arterial rupture after transplantation of a DCD graft treated in-vivo hypothermic oxygenated perfusion. The cause was a severe arteritis of the renal artery caused by Candida krusei and Pseudomonas aeruginosa. We discussed our treatment and we compared it to the other reported series.

Conclusion

Fungal infections in DCD transplant may be treacherous and strategies to prevent them should be advocated.
Viscerotropic disease and acute uveitis following yellow fever vaccination: a case report
Authors: Volkov Lev , Grard Gilda , Bollaert Pierre-Edouard , Durand Guillaume A. , Cravoisy Aurélie , Conrad Marie , Nace Lionel , Courte Guilhem , Marnai Rémy , Leparc-Goffart Isabelle , Gibot Sébastien
Published: February 2020

Background

Yellow fever vaccine exists for over 80 years and is considered to be relatively safe. However, in rare cases it can produce serious neurotropic and viscerotropic complications. We report a case of a patient who presented both viscerotropic and neurological manifestations after yellow fever vaccination.

Case presentation

We describe the case of a 37 years old man who developed after the yellow fever vaccination a yellow fever vaccine-associated viscerotropic disease followed by acute uveitis. Prolonged detection of yellow fever RNA in blood and urine was consistent with yellow fever vaccine-associated adverse event. The final outcome was good, although with persistent fatigue over a few months.

Conclusions

Even if the yellow fever vaccine is relatively safe, physicians should be aware of its possible serious adverse effects.
Mutation Spectrum of Stickler Syndrome Type I and Genotype-phenotype Analysis in East Asian Population: a systematic review
Authors: Wang Dan-Dan , Gao Feng-Juan , Hu Fang-Yuan , Zhang Sheng-Hai , Xu Ping , Wu Ji-Hong
Published: February 2020

Background

Stickler syndrome is the most common genetic cause of rhegmatogenous retinal detachment (RRD) in children, and has a high risk of blindness. Type I (STL1) is the most common subtype, caused by COL2A1 mutations. This study aims to analyze the mutation spectrum of COL2A1 and further elucidate the genotype-phenotype relationships in the East Asian populations with STL1, which is poorly studied at present.

Methods

By searching MEDLINE, Web of Science, CNKI, Wanfang Data, HGMD and Clinvar, all publications associated with STL1 were collected. Then, they were carefully screened to obtain all reported STL1-related variants in COL2A1 and clinical features in East Asian patients with STL1.

Results

There were 274 COL2A1 variants identified in 999 patients with STL1 from 466 unrelated families, and more than half of them were truncation mutations. Of the 107 STL1 patients reported in the East Asian population, it was found that patients with truncation mutations had milder systemic phenotypes, whereas patients with splicing mutations had severer phenotypes. In addition, several recurrent variants (c.3106C > T, c.1833 + 1G > A, c.2710C > T and c.1693C > T) were found.

Conclusions

Genotype-phenotype correlations should certainly be studied carefully, contributed to making personalized follow-up plans and predicting prognosis of this disorder. Genome editing holds great potential for treating inherited diseases caused by pathogenic mutations. In this study, several recurrent variants were found, providing potential candidate targets for genetic manipulation in the future.
Validation of pre-operative risk scores of contrast-induced acute kidney injury in a Chinese cohort
Authors: Yin Wenjun , Zhou Ge , Zhou Lingyun , Liu Mancang , Xie Yueliang , Wang Jianglin , Zuo Shanru , Liu Kun , Hu Can , Chen Linhua , Yang Huiqin , Zuo Xiaocong
Published: February 2020

Background

Pre-operative risk scores are more valuable than post-procedure risk scores because of lacking effective treatment for contrast-induced acute kidney injury (CI-AKI). A number of pre-operative risk scores have been developed, but due to lack of effective external validation, most of them are also difficult to apply accurately in clinical practice. It is necessary to review and validate the published pre-operative risk scores for CI-AKI.

Materials and methods

We systematically searched PubMed and EMBASE databases for studies of CI-AKI pre-operative risk scores and assessed their calibration and discriminatory in a cohort of 2669 patients undergoing coronary angiography or percutaneous coronary intervention (PCI) from September 2007 to July 2017. The definitions of CI-AKI may affect the validation results, so three definition were included in this study, CI-AKI broad1 was defined as an increase in serum creatinine (Scr) of 44.2 μmol/L or 25%; CI-AKI broad2, an increase in Scr of 44.2 μmol/L or 50%; and CI-AKI-narrow, an increase in Scr of 44.2 μmol/L. The calibration of the model was assessed with the Hosmer-Lemeshow test and the discriminatory capacity was identified by C-statistic.

Results

Of the 8 pre-operative risk scores for CI-AKI identified, 7 were single-center study and only 1 was based on multi-center study. In addition, 7 of the scores were just validated internally and only Chen score was externally validated. In the validation cohort of 2669 patients, the incidence of CI-AKI ranged from 3.0%(Liu) to 16.4%(Chen) for these scores. Furthermore, the incidence of CI-AKI was 6.59% (178) for CI-AKI broad1, 1.44% (39) for CI-AKI broad2, and 0.67% (18) for CI-AKI-narrow. For CI-AKI broads, C-statistics varied from 0.44 to 0.57. For CI-AKI-narrow, the Maioli score had the best discrimination and calibration, what’s more, the C-statistics of Maioli, Chen, Liu and Ghani was ≥0.7.

Conclusion

Most pre-operative risk scores were established based on single-center studies and most of them lacked external validation. For CI-AKI broads, the prediction accuracy of all risk scores was low. The Maioli score had the best discrimination and calibration, when using the CI-AKI-narrow definition.