bluuebunny/crossref_metadata_2025 huggingface dataset:
OsFD4 promotes the rice floral transition via florigen activation complex formation in the shoot apical meristem
Authors: Cerise Martina , Giaume Francesca , Galli Mary , Khahani Bahman , Lucas Jérémy , Podico Federico , Tavakol Elahe , Parcy François , Gallavotti Andrea , Brambilla Vittoria , Fornara Fabio
Published: August 2020

In rice, the florigens Heading Date 3a (Hd3a) and Rice Flowering Locus T 1 (RFT1), OsFD‐like basic leucine zipper (bZIP) transcription factors, and Gf14 proteins assemble into florigen activation/repressor complexes (FACs/FRCs), which regulate transition to flowering in leaves and apical meristem. Only OsFD1 has been described as part of complexes promoting flowering at the meristem, and little is known about the role of other bZIP transcription factors, the combinatorial complexity of FAC formation, and their DNA‐binding properties.

Here, we used mutant analysis, protein–protein interaction assays and DNA affinity purification (DAP) sequencing coupled to in silico prediction of binding syntaxes to study several bZIP proteins that assemble into FACs or FRCs.

We identified OsFD4 as a component of a FAC promoting flowering at the shoot apical meristem, downstream of OsFD1. The osfd4 mutants are late flowering and delay expression of genes promoting inflorescence development. Protein–protein interactions indicate an extensive network of contacts between several bZIPs and Gf14 proteins. Finally, we identified genomic regions bound by bZIPs with promotive and repressive effects on flowering.

We conclude that distinct bZIPs orchestrate floral induction at the meristem and that FAC formation is largely combinatorial. While binding to the same consensus motif, their DNA‐binding syntax is different, suggesting discriminatory functions.
The FUSED LEAVES1‐ADHERENT1 regulatory module is required for maize cuticle development and organ separation
Authors: Liu Xue , Bourgault Richard , Galli Mary , Strable Josh , Chen Zongliang , Feng Fan , Dong Jiaqiang , Molina Isabel , Gallavotti Andrea
Published: August 2020

All aerial epidermal cells in land plants are covered by the cuticle, an extracellular hydrophobic layer that provides protection against abiotic and biotic stresses and prevents organ fusion during development.

Genetic and morphological analysis of the classic maize adherent1 (ad1) mutant was combined with genome‐wide binding analysis of the maize MYB transcription factor FUSED LEAVES1 (FDL1), coupled with transcriptional profiling of fdl1 mutants.

We show that AD1 encodes an epidermally‐expressed 3‐KETOACYL‐CoA SYNTHASE (KCS) belonging to a functionally uncharacterized clade of KCS enzymes involved in cuticular wax biosynthesis. Wax analysis in ad1 mutants indicates that AD1 functions in the formation of very‐long‐chain wax components. We demonstrate that FDL1 directly binds to CCAACC core motifs present in AD1 regulatory regions to activate its expression. Over 2000 additional target genes of FDL1, including many involved in cuticle formation, drought response and cell wall organization, were also identified.

Our results identify a regulatory module of cuticle biosynthesis in maize that is conserved across monocots and eudicots, and highlight previously undescribed factors in lipid metabolism, transport and signaling that coordinate organ development and cuticle formation.
Screening for prevalence and abundance of Capnocytophaga spp by analyzing NGS data: A scoping review
Authors: Jolivet‐Gougeon Anne , Bonnaure‐Mallet Martine
Published: August 2020

Background

Capnocytophaga spp. are commensal bacteria of the oral cavity and constitute a genus of the core microbiome.

Objective

This genus is responsible for many local and systemic conditions in both the immunocompetent and immunocompromised patients, but its beneficial or deleterious role in the microbiota has been little explored.

Design

Online databases were used to identify papers published from 1999 to 2019 based on next‐generation sequencing (NGS) data to study comparative trials. Work using other identification methods, case reports, reviews, and non‐comparative clinical trials was excluded.

Results and conclusion

We selected 42 papers from among 668 publications. They showed a link between the abundance of Capnocytophaga spp. in the oral microbiota and various local pathologies (higher for gingivitis and halitosis; lower in active smokers, etc.) or systemic diseases (higher for cancer and carcinomas, IgA nephropathy, etc.). After discussing the limits inherent to the NGS techniques, we present several technical and biological hypotheses to explain the diversity of results observed between studies, as well as the links between the higher or lower abundance of Capnocytophaga spp and the appearance of local or systemic conditions and diseases.
Salvage surgery in head and neck cancer
Authors: van Weert Stijn , Leemans C. René
Published: August 2020

Salvage surgery after failed organ preservation treatment offers challenges for both the patient and the surgeon. The outcome is often uncertain and even today, 5‐year overall survival does not exceed 50 per cent. The chemoradiotherapy induced toxicity asks for meticulous discussion and planning in a multidisciplinary manner in a changing environment of increasing incidence of human papillomavirus induced oropharyngeal tumours, evolving surgical techniques and patient participation. Herein, we discuss the latest literature on salvage surgery and the need for identifying the proper prognosticators to ensure for an optimal treatment plan in potentially salvageable patients.
Adult congenital heart disease and anesthesia: An educational review
Authors: Lei Lei Emma , Heggie Jane
Published: August 2020

Prognosis has dramatically improved among children with congenital heart disease (CHD), and the median survival for severe CHD is currently 25 years (ie, into adulthood). However, additional cardiac surgeries are often necessary in adults with CHD, whose unique cardiovascular anatomy and physiology necessitate specialized management by experts in adult CHD (ACHD) during the perioperative period. ACHD is characterized by a combination of congenital cardiac lesions, intervention‐related anomalies that have developed over time, comorbidities caused by long‐standing CHD, and comorbidities related to various syndromes and lifestyle factors. The present educational review discusses the transition from pediatric to adult cardiac care, comorbidities that develop as a result of ACHD, the assessments necessary for patients with ACHD prior to both cardiac and noncardiac surgeries, and the key ACHD lesions relevant to perioperative management.
Long‐read sequencing reveals widespread intragenic structural variants in a recent allopolyploid crop plant
Authors: Chawla Harmeet Singh , Lee HueyTyng , Gabur Iulian , Vollrath Paul , Tamilselvan‐Nattar‐Amutha Suriya , Obermeier Christian , Schiessl Sarah V. , Song Jia‐Ming , Liu Kede , Guo Liang , Parkin Isobel A. P. , Snowdon Rod J.
Published: August 2020

Genome structural variation (SV) contributes strongly to trait variation in eukaryotic species and may have an even higher functional significance than single‐nucleotide polymorphism (SNP). In recent years, there have been a number of studies associating large chromosomal scale SV ranging from hundreds of kilobases all the way up to a few megabases to key agronomic traits in plant genomes. However, there have been little or no efforts towards cataloguing small‐ (30–10 000 bp) to mid‐scale (10 000–30 000 bp) SV and their impact on evolution and adaptation‐related traits in plants. This might be attributed to complex and highly duplicated nature of plant genomes, which makes them difficult to assess using high‐throughput genome screening methods. Here, we describe how long‐read sequencing technologies can overcome this problem, revealing a surprisingly high level of widespread, small‐ to mid‐scale SV in a major allopolyploid crop species, Brassica napus. We found that up to 10% of all genes were affected by small‐ to mid‐scale SV events. Nearly half of these SV events ranged between 100 bp and 1000 bp, which makes them challenging to detect using short‐read Illumina sequencing. Examples demonstrating the contribution of such SV towards eco‐geographical adaptation and disease resistance in oilseed rape suggest that revisiting complex plant genomes using medium‐coverage long‐read sequencing might reveal unexpected levels of functional gene variation, with major implications for trait regulation and crop improvement.
Development and Validation of the Japanese Version of Quality of Life Assessment of Spina Bifida in Children (QUALAS‐C‐J)
Authors: Kawahara Tae , Sugita Yoshifumi , Momose Hitoshi , Szymanski Konrad M. , Hida Eisuke , Yamazaki Akemi
Published: August 2020

Background

We previously developed the Japanese version of The Quality of Life Assessment of Spina Bifida in Teenagers, a health‐related quality‐of‐life instrument specific to children aged 13–17 years with spina bifida (SB). The Quality of Life Assessment of Spina Bifida in Children is a version of this questionnaire for children aged 8–12 years. The purpose of this study was to develop a Japanese version of the Quality of Life Assessment of Spina Bifida in Children (QUALAS‐C‐J) and verify its reliability and validity.

Methods

Three urologists specializing in SB, 2 nurses, and 1 statistician developed the QUALAS‐C‐J and conducted a pilot and main survey. Participants included children with SB and non‐disabled (ND) children. Participants completed the QUALAS‐C‐J and the Japanese version of KIDSCREEN‐27 (J‐KIDSCREEN) without parental help.

Results

Five children with SB participated in the pilot study and provided face and content validity. Sixty‐three children with SB and 40 age‐ and sex‐matched ND children participated in the main survey. The intraclass correlation coefficient in the retest was 0.80, and Cronbach's alpha in each domain was 0.73. The validity was verified by factor analysis, convergent / divergent validity, and known‐groups validity. Factor analysis converged to the same two‐factor structure as the original version. The correlation between QUALAS‐C‐J and J‐KIDSCREEN‐27 was weak (r=−0.06‐0.30). The scores of both groups for the two domains of the QUALAS‐C‐J were significantly lower in SB than ND children.

Conclusions

QUALAS‐C‐J is easy to answer, suitable for Japanese children with SB, reliable, and valid. It can be a communication tool for children with SB, medical staff, families, communities, and school teachers.
The effects of nutritional status and intervention on pulmonary functions in pediatric cystic fibrosis patients
Authors: Kilinc Ayse Ayzit , Beser Omer Faruk , Ugur Ebru Pelin , Cokugras Fugen Cullu , Cokugras Haluk
Published: August 2020

Background

Cystic fibrosis (CF) causes malabsorption of nutrients that exacerbate pulmonary problems. Nutritional interventions can improve pulmonary functions. We aimed to evaluate the effects of nutritional intervention in CF patients with malnutrition, and to determine if there is a correlation between nutritional status and pulmonary functions.

Methods

The study included 143 CF patients (67 females) with a mean 2 year follow‐up time. Patients’ sociodemographic data, presenting symptoms and history were recorded. Height‐for‐age, weight‐for‐age, weight‐for‐length/height (WFL/H), and body mass index (BMI) were calculated in all patients. Patients were grouped as well nourished, mild malnutrition, moderate malnutrition, and severe malnutrition. These four groups were compared in terms of pulmonary function test results, lung infections, and the hospitalization rate.

Results

Among the patients with a WFL/H or BMI z‐scores that decreased, the frequency of lung infection was 74.1% and the hospitalization rate was 40.7%, versus 34% and 12.3%, respectively among the patients with a WFL/H or BMI z‐scores that increased. The difference was significant (P = 0.02 and P = 0.01, respectively). The difference in bacterial lung infections differed significantly between the four nutritional status groups (P = 0.002). Patients in the well‐nourished group had significantly higher pulmonary function test scores than the other groups. The forced expiratory volume in the first second differed significantly between the patients with and without an increase in the WFL/H or BMI z‐scores (P = 0.001).

Conclusions

The appropriate nutritional intervention to pediatric CF patients with malnutrition, decrease the frequency of lung infections, and improve respiratory function.
Breast complaints in children and the effect of family history
Authors: Koksal Hande , Ates Dervis , Kara Buket
Published: August 2020

Background

To evaluate the correlation of physical examination, and radiological and pathological findings of children and adolescents with breast‐related complaints.

Methods

Children and adolescents with breast complaints between January 2016 and December 2019 were analyzed retrospectively.

Results

A total of 118 children and adolescent patients were included. Their ages ranged from 12 to 18 years (median, 16 years). Twenty‐one patients had a family history of breast cancer (17.8%). The most common complaints were pain, mass, and nipple discharge. Physical examination revealed mass (41.5%), tenderness (11%), and fullness (8.5%). Thirty‐nine patients were classified ultrasonographically with Breast Imaging Reporting and Data System (BIRADS) 3 (39.4%) and four patients were BIRADS 4 (4%). Excision was applied to all patients with BIRADS 4, and 13 of 39 patients with BIRADS 3. Pathological diagnoses of the patients with BIRADS 3 were fibroadenoma (n: 12, 92.3%) and benign phyllodes tumor (n: 1, 7.7%). In patients with BIRADS 4, three patients had fiboradenomas and one patient had a benign phyllodes tumor. No recurrence was observed in any patients who had an excision. Only six of the patients with positive family history had BIRADS 3 lesions, and the others were BIRADS 1. Excision was recommended in two patients and the pathological diagnoses were fibroadenoma.

Conclusion

In this age group, the most common complaints were pain and mass, while physical examination was normal in nearly half of the patients. All of the pathological diagnoses were benign. While evaluating the patients in this age range, the experience of the clinician and radiologist is important and we think that it is necessary to increase the awareness of the patient and family about physiological breast development and self‐breast examination.
Virus‐like particles expressing Plasmodium berghei MSP‐8 induce protection against P. berghei infection
Authors: Lee Su‐Hwa , Chu Ki‐Back , Kang Hae‐Ji , Basak Swarnendu , Kim Min‐Ju , Park Hyunwoo , Jin Hui , Moon Eun‐Kyung , Quan Fu‐Shi
Published: August 2020

Aims

Merozoite surface protein 8 (MSP‐8) of Plasmodium parasites plays an important role in erythrocyte invasion and is a potential malaria vaccine candidate.

Methods and Results

In this study, virus‐like particles (VLPs) expressing MSP‐8 of Plasmodium berghei on the surface of influenza virus matrix protein 1 (M1) core protein were generated for vaccine efficacy assessment. Mice were intramuscularly (IM) immunized with MSP‐8 VLPs twice and challenge‐infected with P. berghei. We found that VLP vaccination elicited higher levels of P. berghei‐specific IgG antibody response in the sera, along with blood CD4+ and CD8+ T‐cell response enhancement compared to the naïve control mice. CD4+ and CD8+ effector memory T‐cell and memory B‐cell responses in the spleen were found to be higher in VLP‐immunized mice compared to control mice. VLP vaccination significantly reduced inflammatory cytokine (IFN‐γ) response in the spleen and parasitemia levels in blood compared to naïve control mice.

Conclusions

These results indicate that MSP‐8 containing virus‐like particles could be a vaccine candidate for blood‐stage vaccine design.
RNA‐Seq analysis of the guppy immune response against Gyrodactylus bullatarudis infection
Authors: Konczal Mateusz , Ellison Amy R. , Phillips Karl P. , Radwan Jacek , Mohammed Ryan S. , Cable Joanne , Chadzinska Magdalena
Published: August 2020

Gyrodactylids are ubiquitous ectoparasites of teleost fish, but our understanding of the host immune response against them is fragmentary. Here, we used RNA‐Seq to investigate genes involved in the primary response to infection with Gyrodactylus bullatarudis on the skin of guppies, Poecilia reticulata, an important evolutionary model, but also one of the most common fish in the global ornamental trade. Analysis of differentially expressed genes identified several immune‐related categories, including IL‐17 signalling pathway and Th17 cell differentiation, cytokine‐cytokine receptor interaction, chemokine signalling pathway, NOD‐like receptor signalling pathway, natural killer cell‐mediated cytotoxicity and pathways involved in antigen recognition, processing and presentation. Components of both the innate and the adaptive immune responses play a role in response to gyrodactylid infection. Genes involved in IL‐17/Th17 response were particularly enriched among differentially expressed genes, suggesting a significant role for this pathway in fish responses to ectoparasites. Our results revealed a sizable list of genes potentially involved in the teleost‐gyrodactylid immune response.
Assessing recovery of alpine spoil heaps by vascular plant, bryophyte, and lichen functional traits
Authors: Sulavik Jan , Auestad Inger , Halvorsen Rune , Rydgren Knut
Published: August 2020

Functional traits are linked to ecosystem processes and services and therefore relevant in recovery assessment. However, traits of bryophytes and lichens, important components of many ecosystems, have received less attention than those of vascular plants. We explored the use of functional traits of multiple important organism groups in recovery assessment. We combined data on traits and species composition for vascular plants, bryophytes, and lichens from four alpine spoil heaps and their undisturbed surroundings in western Norway, collected at three time‐points spanning more than two decades. We studied changes in community‐weighted mean (CWM) trait values and distribution of trait‐category optima over time. We analyzed temporal variation in joint functional trait composition using the ordination regression‐based approach (ORBA) to predict time to recovery. We observed functional shifts along the successional gradient for all organism groups, e.g. from wind‐dispersed propagules shortly after disturbance to vegetative reproduction at later successional stages. Over time, the similarity between dispersal‐related traits of vascular plants and bryophytes on the spoil heaps and in their surroundings increased, indicating that propagule influx is important in alpine restoration. The joint functional trait composition of all spoil heaps converged towards that of their surroundings: one spoil heap had recovered 34 years after construction, while the predicted time to recovery for the other three was 59–74 years. Our results indicate that inclusion of multiple organism groups improves trait‐based recovery assessments and time‐to‐recovery predictions. Further development of trait databases is essential for future use of joint functional trait composition in recovery assessment.
A difference equation approach to Plancherel‐Rotach asymptotics for ‐orthogonal polynomials
Authors: Ismail Mourad , Law Chun‐Kong
Published: August 2020

In this paper, we employ a difference equation approach to study the Plancherel‐Rotach asymptotics of ‐orthogonal polynomials about their largest zeros. Our method for ‐difference equations is an analogue to the turning point problem for Hermite differential equations. It works well in the toy problems of Stieltjes‐Wigert polynomials and ‐Hermite polynomials.
Cold‐inducible RNA‐binding protein (CIRP) in inflammatory diseases: Molecular insights of its associated signalling pathways
Authors: Zhong Peng , Peng Jianye , Yuan Mingjie , Kong Bin , Huang He
Published: August 2020

Cold‐inducible RNA‐binding protein (CIRP) was previously identified as an intracellular stress‐response protein, which can respond to a variety of stress conditions by changing its expression and regulating mRNA stability through its binding site on the 3′‐UTR of its targeted mRNAs. Recently, extracellular CIRP (eCIRP) was discovered to be present in various inflammatory conditions and could act as a pro‐inflammatory factor. Genetic studies have demonstrated a key role for eCIRP in inflammatory conditions that led to the importance of targeting eCIRP in these diseases. Currently, the underlying mechanism of eCIRP‐induced inflammation is under intensive investigation and several signalling pathways are being explored. Here, we epitomized various signalling pathways that mediate the pro‐inflammatory effects of CIRP and also recapitulated all the CIRP‐derived peptides that can block the interaction between CIRP and its receptors in inflammatory setting.
Immunohistochemical characterization of immune cell infiltration in paediatric and adult Langerhans cell histiocytosis
Authors: Paredes Silvia Elena Yacarini , Almeida Luciana Yamamoto , Trevisan Glauce Lunardelli , Polanco Xiomara Beatriz Jimenez , Silveira Heitor Albergoni , Vilela Silva Evânio , Segato Raquel Assed Bezerra , da Silva Léa Assed Bezerra , Chahud Fernando , León Jorge Esquiche
Published: August 2020

Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasia commonly affecting children with frequent somatic mutations in MAPK pathway genes including BRAFV600E and MAP2K1. Some studies suggest that LCH cells can recruit and modulate inflammatory cells, which could provide reciprocal survival signals. To characterize the immune profile of infiltrating inflammatory cells, and to clarify their participation in LCH pathogenesis, a detailed immunohistochemical analysis was performed. Fifteen (10 children, 5 adults) LCH cases were assessed through macrophage (CD68 and CD163), mature dendritic cell (mDC; CD83 and CD208), regulatory T cell (Treg; CD4, CD25 and FOXP3) and cytotoxic lymphocyte (CL; CD56, CD57, perforin and granzyme B) immunomarkers. Moreover, lymphocytic and LCH markers were also analysed. All cases were S100, CD1a, CD207 and CD4‐positive. Bcl‐2 and cyclin D1 expression was observed in 13 of 15 cases. In the immune microenvironment, M2‐polarized macrophages and Tregs were the predominant cell populations, followed by significantly (P < .005) smaller levels of mDCs and CLs. Additionally, the number of CD3 + cells was significantly higher than that of CD20 + cells. In the CD3 + cell population, there were a significantly higher number of CD4 + cells than CD8 + cells. While there were no differences when comparing the paediatric and adult populations, FOXP3 + cells were significantly higher in patients with multisystem involvement and treated with chemotherapy, than single‐site cases and those without chemotherapy. Our results suggest that M2‐polarized macrophages and Treg infiltration can promote LCH development and survival, probably through pro‐tumoral, immunosuppressive and/or cytokine‐mediated mechanisms. This work highlights the need for further exploration of immune‐targeted therapy for LCH.
The interrater reliability of dynamic leap and balance test in healthy and chronic ankle instability
Authors: Jaffri Abbis H. , Amjad Muhammad , Saliba Susan
Published: August 2020

The primary aim of this study was to assess the interrater reliability of the Dynamic Leap and Balance Test (DLBT) in chronic ankle instability (CAI) and healthy groups. The secondary aim was to assess the differences in errors and time taken to complete the DLBT between the two groups for both raters and to identify cutoff scores to distinguish between patients with CAI and healthy controls. This was a controlled laboratory reliability analysis study. Fourteen healthy college‐aged subjects (9 women 5 men; weight = 62.10 ± 8.03; height = 168.35 ± 6.0) and sixteen with a history of CAI (9 women, 7 men; weight = 68.01 ± 10.74; height = 172.08 ± 11.37) participated. Interrater reliability was determined by independent raters for both total time taken to complete the task and errors made. The most optimal score to discriminate between two groups was determined by receiver operator curve analysis. Total time taken and errors made were also documented for group differences as secondary analysis. A strong agreement was found between the two raters for time and errors with intraclass correlation coefficient >0.80. Significantly (P < .05) higher number of errors were made and greater time taken by the CAI subjects when compared with healthy for both raters. The most optimal score to discriminate between CAI and healthy control was 43.28s and 4 errors. Excellent interrater reliability substantiates that it can be used confidently by different clinicians for testing dynamic balance. CAI group took more time and made more errors to complete the DLBT.
Ridge–mulch tillage and rotation with broad bean affect soil microbial community, diversity and crop yield in a long‐term potato continuous cropping field
Authors: Kang Yichen , Liu Yun , Qin Shuhao , Zhang Weina , Shi MingFu , Fan Yanling , Yang Xinyu
Published: August 2020

Soil microbial disorder caused by continuous cropping of potato is a major challenge in the semi‐arid region of northwest China. Crop rotation can enhance crop productivity and increase soil microbial diversity. However, the functional significance of changes in soil microbial communities in different ridge‐mulching patterns of potato continuous cropping soil is poorly understood. In view of this, a study was conducted in a 5‐year potato field, to determine the effect of three different tillage practices (nonfilm‐mulched flat plot‐CK, half‐mulched ridge cropping‐T1 and fully mulched ridge cropping‐T2) and two cropping systems (potato‐potato‐C and potato/broad bean‐R) on changes in the microbial community of the soil. The soil microbial community and diversity were examined using the high‐throughput sequencing methods. The dominant bacteria phylum found in the soil was Proteobacteria. The relative abundance of Proteobacteria in fully mulched ridge plots was greater than in half‐mulched ridge and nonfilm‐mulched flat plot. The dominant bacteria genus, Arthrobacter and Planctomyces, were found in the potato–broad bean rotation system, whereas Streptomyces, Steroidobacter and Lysobacter were foremost in the plots under continuous cropping of potato. The dominant phylum of fungi was Ascomycota, and the ratio was increased by film mulching under the continuous cropping system. The relative abundances of dominant genus Monographella, Humicola and Fusarium in the continuous cropping system were higher than that of the rotation system, while Mortierella and Acremonium were dominant in the rotation plots. Moreover, the relative abundance of Humicola and Mortierella was higher in fully mulched ridge plots, while Monographella and Acremonium were higher in the nonfilm‐mulched flat plots. Ridge–mulch tillage and rotation with broad bean could change the composition of soil microbial phylum and genus level, and ridge–mulch tillage may also effect on soil microbial diversity to some extent. Besides, the yields of potato and broad bean under mulched plots were enhanced by 58.03%–73.47% and 70.37%–80.19%, respectively. The yields were greater under fully mulched ridge plots.
Using integrated STEM as a stimulus to develop elementary students' statistical literacy
Authors: Hourigan Mairéad , Leavy Aisling M.
Published: August 2020

This paper presents insights from classroom practice where mathematical thinking, and in particular statistical literacy, are central to solving a STEM problem. We demonstrate that when an investigation sparks student interest and requires active participation, there are opportunities to experience the functionality of statistics.
A case‐control study to assess the role of polyomavirus in transplant complications: Where do we stand?
Authors: Garcia Urbán Julia , Gurrado Katia , Brea Rivas Paola C. , Abou Elrous Dina , Zubimendi Machain Mónica , Romero Gómez María , García Rodríguez Julio , Vicandi Plaza Blanca , Yébenes Gregorio Laura , García Fernández Eugenia , Jiménez Martín Carlos , López Oliva María‐Ovidia , González García Elena , Ledesma Sánchez Gabriel , Carreño Cornejo Gilda , Selgas Gutiérrez Rafael , Zarauza Santoveña Alejandro , Melgosa Hijosa Marta , Fernández Camblor Carlota , Mozo del Castillo Yasmina , Sisinni Luisa , Bueno Sánchez David , Pérez‐Martínez Antonio , Sánchez Zapardiel Elena , López Granados Eduardo , Monserrat Villatoro Jaime , Hernández Zabala Rafael , Borobia Alberto M. , Frías Jesús , Ramírez Elena
Published: August 2020

Purpose

The study's aim was to assess whether polyomavirus DNAemia screening was associated with different outcomes in patients with positive viremia compared with negative viremia.

Methods

Case‐control retrospective study of patients with polyomavirus DNAemia (viremia > 1000 copies/mL) matched 1:1 with controls. Control group consists of the patient who received a transplant immediately before or after each identified case and did have nil viremia.

Finding

Ultimately, 120 cases of BK polyomavirus (BKPyV) were detected and matched with 130 controls. Of these, 54 were adult kidney transplant recipients (KTRs), 43 were pediatric KTRs, and 23 were undergoing hemato‐oncologic therapy, of which 20 were undergoing hematopoietic stem cell transplantation. The odds ratio (OR) for overall risk of poorer outcomes in cases versus controls was 16.07 (95% CI: 5.55‐46.54). The unfavorable outcome of switching the immunosuppressive drug (ISD) (14/40,35%) was no different from that of those treated with reduced ISD doses (31/71, 43.6%, P = .250). Acute rejection or graft‐versus‐host disease, previous transplant, and intensity of immunosuppression (4 ISDs plus induction or conditioning) were risk factors for BKPyV‐DNAemia (OR: 13.96, 95% CI: 11.25‐15.18, P < .001; OR: 6.14, 95% CI: 3.91‐8.80, P < .001; OR: 5.53, 95% CI: 3.37‐7.30, P < .001, respectively).

Conclusions

Despite viremia screening, dose reduction, and change in therapeutic protocol, patients with positive BKPyV‐DNAemia present poorer outcomes and unfavorable results.
The potential for quality assurance systems to save costs and lives: the case of early infant diagnosis of HIV
Authors: Terris‐Prestholt F. , Boeras D. , Ong J. J. , Torres‐Rueda S. , Cassim N. , Mbengue M. A. S. , Mboup S. , Mwau M. , Munemo E. , Nyegenye W. , Odhiambo C. O. , Dabula P. , Sandstrom P. , Sarr M. , Simbi R. , Stevens W. , Tucker J. D. , Vickerman P. , Ciaranello A. , Peeling R. W.
Published: August 2020

Objectives

Scaling up of point‐of‐care testing (POCT) for early infant diagnosis of HIV (EID) could reduce the large gap in infant testing. However, suboptimal POCT EID could have limited impact and potentially high avoidable costs. This study models the cost‐effectiveness of a quality assurance system to address testing performance and screening interruptions, due to, for example, supply stockouts, in Kenya, Senegal, South Africa, Uganda and Zimbabwe, with varying HIV epidemics and different health systems.

Methods

We modelled a quality assurance system‐raised EID quality from suboptimal levels: that is, from misdiagnosis rates of 5%, 10% and 20% and EID testing interruptions in months, to uninterrupted optimal performance (98.5% sensitivity, 99.9% specificity). For each country, we estimated the 1‐year impact and cost‐effectiveness (US$/DALY averted) of improved scenarios in averting missed HIV infections and unneeded HIV treatment costs for false‐positive diagnoses.

Results

The modelled 1‐year costs of a national POCT quality assurance system range from US$ 69 359 in South Africa to US$ 334 341 in Zimbabwe. At the country level, quality assurance systems could potentially avert between 36 and 711 missed infections (i.e. false negatives) per year and unneeded treatment costs between US$ 5808 and US$ 739 030.

Conclusions

The model estimates adding effective quality assurance systems are cost‐saving in four of the five countries within the first year. Starting EQA requires an initial investment but will provide a positive return on investment within five years by averting the costs of misdiagnoses and would be even more efficient if implemented across multiple applications of POCT.
Sepsis from an apheresis platelet contaminated with Acinetobacter calcoaceticus/baumannii complex bacteria and Staphylococcus saprophyticus after pathogen reduction
Authors: Fridey Joy L. , Stramer Susan L. , Nambiar Ashok , Moayeri Morvarid , Bakkour Sonia , Langelier Charles , Crawford Emily , Lu Thea , Lanteri Marion C. , Kamm Jack , Miller Steve , Wagner Stephen J. , Benjamin Richard J. , Busch Michael P.
Published: August 2020

Background

Strategies to reduce platelet (PLT) bacterial contamination include donor screening, skin disinfection, sample diversion, bacterial culture, pathogen reduction (PR), and day‐of‐transfusion tests. We report bacterial sepsis following a pathogen‐reduced PLT transfusion.

Case Report

An adult male with relapsed acute lymphoblastic leukemia was successfully treated for central catheter–associated Staphylococcus aureus bacteremia. A peripherally inserted central catheter (PICC) was placed. Chills, rigors, and flushing developed immediately after PICC‐infused pathogen‐reduced PLTs, progressing to septic shock requiring intensive care management.

Methods

PICC and peripheral blood (PB), transfused bag saline flushes (TBFs), environmental samples, and the pathogen‐reduced untransfused co‐component (CC) were cultured. Plasma metagenomic and bacterial isolate whole‐genome sequencing; PLT mitochondrial DNA (mtDNA) testing of untransfused CC and TBF; CC testing for amotosalen (S‐59)/S‐59 photoproducts; isolate PR studies (INTERCEPT); and TBF polymerase chain reaction for recipient Y‐chromosome DNA were performed.

Results

PB and PICC cultures grew Acinetobacter calcoaceticus/baumannii complex (ACBC). TBF was gram‐positive; mass spectrometry identified ACBC and Staphylococcus saprophyticus (SS). CC Gram stain and cultures were negative. Environmental cultures, some done after decontamination, were ACBC/SS negative. Posttransfusion patient plasma and TBF ACBC sequences were genetically identical. No Y‐chromosome signal was detected in TBF. S‐59 photoproducts and evidence of mtDNA amplification inhibition were found in the CC. Spiking PR studies showed >5.9‐log inactivation for both isolates. Donor skin cultures for Acinetobacter were negative.

Conclusion

CC sterility, PR studies, residual S‐59 photoproducts, and mtDNA amplification inhibition suggest successful PR. Unidentified environmental sources and inherent or acquired bag defects may have contributed to postmanufacturing pathogen‐reduced PLT contamination.
Reference intervals for serum amyloid A, haptoglobin, ceruloplasmin, and fibrinogen in apparently healthy neonatal lambs
Authors: Dinler Ceren , Tuna Gulten Emek , Ay Erhan , Ulutas Bulent , Voyvoda Huseyin , Ulutas Pinar Alkim
Published: August 2020

Background

Acute‐phase proteins (APPs) are considered biomarkers for diagnoses, prognoses, and treatment and health status monitoring. Reference intervals (RIs) are an integral part of diagnostic laboratory testing and clinical decision‐making. The RIs for neonatal lambs are lacking.

Objective

This study aimed to determine the RIs of serum amyloid A (SAA), haptoglobin (Hp), ceruloplasmin (Cp), and fibrinogen (Fb) concentrations in neonatal cross‐bred Kivircik lambs.

Methods

The study consisted of 42 neonatal cross‐bred Kivircik lambs. Physical examinations were performed daily, and blood samples were collected at 0 (precolostrum), 1, 3, 7, 14, 21, and 28 days of age. The RIs of SAA, Hp, Cp, and Fb concentrations were calculated according to the recommendation of the American Society for Veterinary Clinical Pathology. Results were also evaluated for age‐ and sex‐related effects.

Results

The RI for serum Hp was 0‐0.4 g/L, and no apparent effect of age or sex was noted. Because of significant age‐ and sex‐related differences, the SAA (0.34‐55.12 µg/mL), Cp (2.4‐26.07 mg/mL), and Fb (218.86‐527.82 mg/mL) results were given as minimum and maximum values. Serum SAA on the 1st, 3rd, and 7th days of life, and Cp and Fb concentrations on the 14th and 21st days of life, were significantly higher than those on other study days.

Conclusions

This study is the first to establish RIs for neonatal lambs, and the values obtained could be useful for making clinical decisions regarding cross‐bred Kivircik lambs during this critical period.
Application of primary health care principles in national community health worker programs in low- and middle-income countries: a scoping review protocol
Authors: Perveen Shagufta , Mahmood Mohammad Afzal , Lassi Zohra S. , Perry Henry B. , Laurence Caroline
Published: August 2020

Objective:

This scoping review aims to map the available literature on the application of primary health care principles as reflected in the implementation of national-level community health worker programs in low- and middle-income countries.

Introduction:

There is extensive literature on how community health workers have been used to improve the health status of disadvantaged populations, especially in low- and middle-income countries. Established under the primary health care principles, national community health worker programs were expected to adopt and promote these principles to achieve improvements in health outcomes. However, there is limited evidence of the extent to which primary health care principles have been applied in the implementation of national community health worker programs.

Inclusion criteria:

The concept to be mapped is the application of primary health care principles in the implementation of national community health worker programs in low- and middle-income countries. Quantitative, qualitative, and mixed methods study designs will be included. Only English-language articles published from September 1978 to the present will be included. Study protocols, narrative reviews, systematic and scoping reviews, commentaries, text and opinion papers, viewpoints, editorials, and conference proceedings/abstracts and correspondences will be excluded. The programs operated by non-governmental organizations and articles not involving community health workers will also be excluded.

Methods:

Key information sources to be searched include MEDLINE, CINAHL, Embase, and Scopus. Two reviewers will independently screen the titles and abstracts against the inclusion criteria. The data charting will include specific details about the concept, context, study methods, and key findings relevant to the review question. Data will be presented in diagrammatic or tabular form accompanied by a narrative summary.
Emerging Antimicrobial-Resistant High-Risk Klebsiella pneumoniae Clones ST307 and ST147
Authors: Peirano Gisele , Chen Liang , Kreiswirth Barry N. , Pitout Johann D. D.
Published: August 2020

There is an enormous global public health burden due to antimicrobial-resistant (AMR)
Klebsiella pneumoniae
high-risk clones.
K. pneumoniae
ST307 and ST147 are recent additions to the family of successful clones in the species. Both clones likely emerged in Europe during the early to mid-1990s and, in a relatively short time, became prominent global pathogens, spreading to all continents (with the exception of Antarctica). ST307 and ST147 consist of multiple clades/clusters and are associated with various carbapenemases (i.
A Large-Class Undergraduate Microbiology Laboratory Activity on Microbial Diversity and Antimicrobial Resistance
Authors: Farkas Kata , McDonald James E.
Published: August 2020

The investigation of microbial diversity and adaptation is essential to comprehend biological processes. Yet, teaching basic microbiology techniques to large groups of students in limited time is challenging, as most approaches are time-consuming or require special equipment. In this activity, students performed three laboratory exercises in three hours involving the analysis of inoculated agar plates they prepared by swabbing samples from an environment of their choice, the examination of antimicrobial effects on growth, and the assessment of microbial enzymatic activity in soil. The activity was field tested in two classes (70 and 76 students, respectively) of first-year undergraduate biology and zoology students at the Bangor University (UK) using pre- and post-tests (
n
= 84). Based on the answers, learning gain scores (G) were calculated for each learning objective (LO). For all LOs, the mean post-test scores were higher than the mean pre-test scores. The activity significantly improved students’ understanding of microbial diversity (G = 0.36,
p
= 0.010) and microbial detection and quantification (G = 0.18 to 0.773, p ≤ 0.004). The lack of significant differences in scores for questions targeting microbial growth (G = 0.31,
p
= 0.292) and antimicrobial resistance (G = 0.38,
p
= 0.052) suggested some existing knowledge amongst undergraduates. However, the extent of knowledge showed great variation. The results may suggest that the activity is suitable to introduce microbiology-related laboratory work to students with limited laboratory skills and knowledge. Furthermore, the pre- and post-test approach used here is suitable for both course evaluation and monitoring attainment and can be used for program validation and quality control.
Increased Scaffolding and Inquiry in an Introductory Biology Lab Enhance Experimental Design Skills and Sense of Scientific Ability
Authors: Killpack Tess L. , Fulmer Sara M. , Roden Julie A. , Dolce Jocelyne L. , Skow Christa D.
Published: August 2020

We present a model for the process of redesigning the laboratory curriculum in Introductory Organismal Biology to increase opportunities for meaningful inquiry and increase student recognition of their scientific skill development. We created scaffolded modules and assignments to allow students to build and practice key skills in experimental design, data analysis, and scientific writing. Using the Tool for Interrelated Experimental Design, we showed significantly higher gains in experimental design scores in the redesigned course and a more consistent pattern of gains across a range of initial student scores compared with the original format. Students who completed the redesigned course rated themselves significantly higher in experimental design, data collection, and data analysis skills compared with students in the original format. Scores on the Laboratory Course Activity Survey were high for both formats and did not significantly differ. However, on written course evaluations, students in the redesigned course were more likely to report that they engaged in “real science” and their “own experiments.” They also had increased recognition of their specific analytical and writing skill development. Our results demonstrate that intentional, scaffolded instruction using inquiry modules can increase experimental design skills and sense of scientific ability in an introductory biology course.
Quantifying the Transmission of Foot-and-Mouth Disease Virus in Cattle via a Contaminated Environment
Authors: Colenutt Claire , Brown Emma , Nelson Noel , Paton David J. , Eblé Phaedra , Dekker Aldo , Gonzales José L. , Gubbins Simon
Published: August 2020

Effective control of a disease relies on comprehensive understanding of how transmission occurs, in order to design and apply effective control measures. Foot-and-mouth disease virus (FMDV) is primarily spread by direct contact between infected and naive individuals, although the high levels of virus shed by infected animals mean that virus can also be spread through contact with contaminated environments. Using a series of transmission experiments, we demonstrate that environmental transmission alone would be sufficient to sustain an outbreak. Key observations include that a risk of transmission exists before clinical signs of foot-and-mouth disease (FMD) are apparent in cattle and that survival of virus in the environment extends the transmission risk period. This study highlights the role a contaminated environment can play in the transmission of FMDV and presents approaches that can also be applied to study the transmission of other pathogens that are able to survive in the environment.
Subpopulations of Stressed Yersinia pseudotuberculosis Preferentially Survive Doxycycline Treatment within Host Tissues
Authors: Raneses Jasmine Ramirez , Ellison Alysha L. , Liu Bessie , Davis Kimberly M.
Published: August 2020

Bacterial infections are very difficult to treat when bacteria spread into the bloodstream and begin to replicate within deep tissues, such as the spleen. Subsets of bacteria can survive antibiotic treatment, but it remains unclear if this survival is because of limited drug diffusion into tissues, or if there are changes within the bacteria, promoting survival of some bacterial cells. Here, we have developed a fluorescent reporter to detect doxycycline (Dox) diffusion into host tissues, and we show that Dox impacts the bacterial population within hours of administration and inhibits bacterial growth for 48 h. However, bacterial growth resumes when antibiotic concentrations decrease. Subsets of bacteria, stressed by the host response to infection, survive Dox treatment at a higher rate. These results provide critical information about the dynamics that occur within deep tissues following antibiotic administration and suggest that subsets of bacteria are predisposed to survive inhibitory concentrations of antibiotic before exposure.
The Stringent Stress Response Controls Proteases and Global Regulators under Optimal Growth Conditions in Pseudomonas aeruginosa
Authors: Pletzer Daniel , Blimkie Travis M. , Wolfmeier Heidi , Li Yicong , Baghela Arjun , Lee Amy H. Y. , Falsafi Reza , Hancock Robert E. W.
Published: August 2020

Microorganisms need to adapt rapidly to survive harsh environmental changes. Here, we showed the broad influence of the highly studied bacterial stringent stress response under nonstressful conditions that indicate its general physiological importance and might reflect the readiness of bacteria to respond to and activate acute stress responses. Using RNA-Seq to investigate the transcriptional network of
Pseudomonas aeruginosa
cells revealed that >30% of all genes changed expression in a stringent response mutant under optimal growth conditions. This included genes regulated by global transcriptional regulators and novel downstream effectors. Our results help to understand the importance of this stress regulator in bacterial lifestyle under relatively unstressed conditions. As such, it draws attention to the consequences of targeting this ubiquitous bacterial signaling molecule.
Nonanadromous and anadromous Atlantic salmon differ in orientation responses to magnetic displacements
Authors: Minkoff David , Putman Nathan F. , Atema Jelle , Ardren William R.
Published: August 2020

Many animals undertaking long-distance migrations use Earth’s magnetic field as a “map” to assess their position for orientation. This phenomenon been particularly well-studied in salmonids using “magnetic displacement” experiments, in which animals are presented with magnetic field conditions that are characteristic of other geographic locations. However, whether use of magnetic map cues differs among populations of salmon has not been investigated. Here we show that nonanadromous and anadromous populations of Atlantic salmon (Salmo salar) raised under the same conditions within their native range differ in their response to magnetic displacements in the North Atlantic. The directions adopted by anadromous salmon juveniles to each of the magnetic displacements would support their migration from the eastern US to western Greenland, had the fish actually been at those locations. In contrast, nonanadromous salmon did not appear to respond to the magnetic displacements. The findings are consistent with the hypothesis that the innate magnetic map of anadromous salmon is adapted to guide their marine migration.