bluuebunny/crossref_metadata_2025 huggingface dataset:
Safety and Immunogenicity of a Quadrivalent Meningococcal Conjugate Vaccine in Healthy Meningococcal-Naïve Children 2–9 Years of Age: A Phase III, Randomized Study
Authors: Baccarini Carmen I. , Simon Michael W. , Brandon Donald , Christensen Shane , Jordanov Emilia , Dhingra Mandeep S.
Published: August 2020

Background:

Invasive meningococcal disease is a major cause of meningitis in children. An investigational meningococcal (serogroups A, C, Y, and W) tetanus toxoid conjugate vaccine (MenACYW-TT) could offer protection against invasive meningococcal disease in this population. This phase III study assessed the immunogenicity and safety of MenACYW-TT in children compared with a licensed quadrivalent meningococcal vaccine conjugated with diphtheria protein CRM197 (MenACWY-CRM).

Methods:

Healthy children 2–9 years of age in the United States, including Puerto Rico, were randomized (1:1) to receive MenACYW-TT (n = 499) or MenACWY-CRM (n = 501) (NCT03077438). Meningococcal antibody titers to the 4 vaccine serogroups were measured using a serum bactericidal antibody assay with human complement (hSBA) before and at day 30 after vaccination. Noninferiority between the vaccine groups was assessed by comparing seroresponse rates (postvaccination titers ≥1:16 when prevaccination titers were <1:8, or ≥4-fold increase if prevaccination titers were ≥1:8) to the 4 serogroups at day 30. Safety was monitored.

Results:

The proportion of participants achieving seroresponse at day 30 in the MenACYW-TT group was noninferior to the MenACWY-CRM group (A: 55.4% vs. 47.8%; C: 95.2% vs. 47.8%; W: 78.8% vs. 64.1%; Y: 91.5% vs. 79.3%, respectively). Geometric mean titers for serogroups C, W, and Y were higher with MenACYW-TT than for MenACWY-CRM. Both vaccines were well-tolerated and had similar safety profiles.

Conclusions:

MenACYW-TT was well-tolerated in children and achieved noninferior immune responses to MenACWY-CRM against each of the 4 vaccine serogroups.
Transient Pancytopenia Subsequently Diagnosed With Acute Leukemia: A Report of 4 Cases of Acute Lymphoblastic Leukemia and Acute Myeloid Leukemia
Authors: Kirk Susan E. , Young Elizabeth , Ray Anish , Dzurik Yvette , Elghetany Tarek , Sasa Ghadir
Published: August 2020

A transient pancytopenic phase has been described in pediatric leukemia. The characteristic complete recovery of peripheral counts can obscure a clinician’s suspicion for malignancy and may impact subsequent follow-up care. The authors describe 4 pediatric patients that had transient pancytopenia with an initial abnormal marrow finding. These patients were subsequently diagnosed with acute leukemia within 5 months of presentation. Awareness of this phenomenon by the provider and education of families may help with the appropriate and timely diagnosis of subsequent leukemia.
Does Age Impact the Clinical Presentation of Adult Women Seeking Specialty Eating Disorder Treatment?
Authors: Henriksen Christine A. , Mackenzie Corey S. , Fergusson Patricia , Bouchard Danielle R.
Published: August 2020

Recent evidence suggests that eating disorders (EDs) are becoming increasingly common in older women. Previous research examining differences between younger and older women with EDs has been mixed, making it unclear whether older women with EDs represent a distinct group. We sought to determine whether there are age differences in the clinical presentation of women seeking specialty treatment for an ED. We examined the linear relationship between age and clinical constructs among adult women (N = 436) diagnosed with a Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, ED. Across analyses, there was no impact of age on most measures of ED symptoms, comorbid psychopathology, self-esteem, quality of life, and motivation to change. However, older age was associated with fewer interoceptive awareness difficulties, maturity fears, anxiety symptoms, and body image concerns. These findings suggest that the clinical presentation of older ED cases is largely similar, although somewhat less severe than in younger women. The implications of this research for future research and treatment are discussed.
Brief Report: Cessation of Long-Term Cotrimoxazole Prophylaxis in HIV-Infected Children Does Not Alter the Carriage of Antimicrobial Resistance Genes
Authors: Francis Freddy , Gough Ethan K. , Edens Thaddeus J. , Berejena Chipo , Bwakura-Dangarembizi Mutsawashe , Shonhai Annie , Nathoo Kusum J. , Glass Magdalena , Gibb Diana M. , Prendergast Andrew J. , Manges Amee R.
Published: August 2020

Background:

Cotrimoxazole (CTX) is a broad-spectrum antimicrobial, combining trimethoprim and sulfamethoxazole. CTX prophylaxis reduces mortality and morbidity among people living with HIV in regions with high prevalence of bacterial infections and malaria. The Antiretroviral research for Watoto trial evaluated the effect of stopping versus continuing CTX prophylaxis in sub-Saharan Africa.

Methods:

In this study, 72 HIV-infected Zimbabwean children, on antiretroviral therapy, provided fecal samples at 84 and 96 weeks after randomization to continue or stop CTX. DNA was extracted for whole metagenome shotgun sequencing, with sequencing reads mapped to the Comprehensive Antibiotic Resistance Database to identify CTX and other antimicrobial resistance genes.

Results:

There were minimal differences in the carriage of CTX resistance genes between groups. The dfrA1 gene, conferring trimethoprim resistance, was significantly higher in the continue group (P = 0.039) and the tetA(P) gene conferring resistance to tetracycline was significantly higher in the stop group (P = 0.013). CTX prophylaxis has a role in shaping the resistome; however, stopping prophylaxis does not decrease resistance gene abundance.

Conclusions:

No differences were observed in resistance gene carriage between the stop and continue groups. The previously shown multi-faceted protective effects of CTX in antiretroviral research for Watoto trial clinical outcomes are not outweighed by the risk of multi-drug resistance gene selection due to prophylaxis. These findings are reassuring, given current recommendations for long-term CTX prophylaxis among children living with HIV in sub-Saharan Africa to decrease mortality and morbidity.
Molecular dynamics reveals complex compensatory effects of ionic strength on the SARS-CoV-2 Spike/hACE-2 interaction
Authors: Souza Anacleto Silva de , Rivera Jose D. , Medeiros Vitor , Ge Pingju , Souza Robson Francisco de , Farah Chuck Shaker , Ulrich Henning , Marana Sandro Roberto , Kopke Salinas Roberto , Guzzo Cristiane Rodrigues
Published: August 2020

The SARS-CoV-2 pandemic has already killed more than 800,000 people worldwide. To gain entry, the virus uses its spike protein to bind to host hACE-2 receptors on the host cell surface and mediate fusion between viral and cell membranes. As initial steps leading to virus entry involves significant changes in protein conformation as well as in the electrostatic environment in the vicinity of the spike-hACE-2 complex, we explored the sensitivity of the interaction to changes in ionic strength through computational simulations and surface plasmon resonance. We identified two regions in the receptor-binding domain (RBD), E1 and E2, which interact differently with hACE-2. At high salt concentration, E2-mediated interactions are weakened but are compensated by strengthening E1-mediated hydrophobic interactions. These results provide a detailed molecular understanding of spike RBD/hACE-2 complex formation and stability under a wide range of ionic strengths.
Chronic hyperglycaemia drives functional impairment of lymphocytes in diabeticINSC94Ytransgenic pigs
Authors: Giese Isabella-Maria , Renner Simone , Wolf Eckhard , Hauck Stefanie M. , Deeg Cornelia A.
Published: August 2020

People with diabetes mellitus have an increased risk for infections, however, there is still a critical gap in precise knowledge about altered immune mechanisms in this disease. Since diabeticINSC94Ytransgenic pigs exhibit elevated blood glucose and a stable diabetic phenotype soon after birth, they provide a favourable model to explore functional alterations of immune cells in an early stage of diabetes mellitusin vivo. Hence, we investigated peripheral blood mononuclear cells (PBMC) of these diabetic pigs compared to non-transgenic wild-type littermates. We found a 5-fold decreased proliferative response of T cells inINSC94Ytg pigs to polyclonal T cell mitogen phytohaemagglutinin (PHA). Using label-free LC-MS/MS, a total of 2,704 proteins were quantified, and distinct changes in protein abundances in CD4+T cells of early-stage diabetic pigs were detectable. Additionally, we found significant increases in mitochondrial oxygen consumption rate (OCR) and higher basal glycolytic activity in PBMC of diabeticINSC94Ytg pigs, indicating an altered metabolic immune cell phenotype in diabetics. Thus, our study provides new insights into molecular mechanisms of dysregulated immune cells triggered by permanent hyperglycaemia.
Adolescent-onset and adult-onset schizophrenia: reduced ribosomal protein expression via mTOR signalling in patient-derived olfactory cells
Authors: Li Yichen , Föcking Melanie , Cristino Alexandre S. , English Jane , Cagney Gerard , James Anthony , Cotter David , Szele Francis G. , Mackay-Sim Alan
Published: August 2020

Schizophrenia is a heterogeneous disorder associated with many genetic and environmental risk factors that could affect brain development. It is unknown whether adolescent-onset and adult-onset schizophrenia have similar aetiology. To address this we used discovery-based proteomics to find proteins differentially expressed in olfactory neurosphere-derived cells from adolescents with schizophrenia compared to age- and gender-matched healthy controls. Of 1638 proteins identified, 241 were differentially expressed in patient cells, with significant down-regulation of ribosomal and cytoskeletal proteins, and dysregulation of protein synthesis pathways. We then re-analysed our previous adult-onset proteomic data to compare directly with adolescent-onset protein expression. Schizophrenia-associated protein expression in adult-onset patients was remarkably similar to adolescent-onset patients. To increase sample size and power we combined the two datasets for a bioinformatic meta-analysis. Schizophrenia-associated protein expression indicated significant downregulation of the mTOR signalling pathway, which regulates protein synthesis, indicated by the reduced expression of all ribosomal proteins and other mTOR-dependent proteins: RPS6, VIM, LDHB and PPP2R1A. A protein-protein interaction network built from differentially expressed proteins in the combined dataset was significantly associated with schizophrenia-associated risk genes and with proteins regulating neural stem cell differentiation, cell adhesion and growth cones in the developing brain. This study demonstrates that despite the divergent age of onset, the proteomes of olfactory neural stem cells of adolescent- and adult-onset patients are remarkably similar. The dysregulated proteins in patient cells form a tightly interconnected protein-protein interaction network associated with mTOR signalling, protein translation, neurogenesis and axon growth - all key components of brain development.
Resistance levels to the cassava green mite,Mononychellus tanajoa, in cassava germplasm (Manihot esculenta)
Authors: Marín Jaime , Carabali Arturo , Lerma James Montoya
Published: August 2020

The cassava green mite (CGM),Mononychellus tanajoa(Acari: Tetranychidae), is one of the main pests of cassava, causing direct damage by sucking the plant’s sap. Although the mite has a wide distribution in Latin America and Africa and a high potential to expand to Asia, limited information is available onM. tanajoabiology and life history parameters on its primary host. In this study, we quantified the levels of resistance of 10 cassava genotypes (i.e., NAT-31, ALT-12, ALT-6, COL-1505, ECU-72, ECU-160, PER-182, PER-335, 60444, CMC-40) based on the mite’s oviposition preference and development time in no-choice and choice bioassays. The genotype NAT-31 significantly differed from other genotypes forM. tanajoadevelopment time and oviposition rate: each stage of the CGM life cycle appeared to be delayed in NAT-31, suggesting that NAT-31 resistance is mediated through a general reduction of CGM fitness on this genotype. Resistance in the remaining genotypes was variable in comparison to a susceptible (control) genotype. ECU-72, a parental line of NAT-31, present a difference related to oviposition preference, development time and sex ratio. These parameters allow the identification of different levels of resistance (antixenotic and antibiosis) when compared to the susceptible genotype. CGM displayed significantly different oviposition preference from the susceptible genotypes. Identification and characterization of resistance to CGM in cassava germplasm might be key to further advance knowledge about natural resistance mechanisms and develop strategies to introgress resistance to CGM in farmer- and industry-preferred cassava varieties.
Disentangling intrinsic and extrinsic gene expression noise in growing cells
Authors: Lin Jie , Amir Ariel
Published: August 2020

Gene expression is a stochastic process. Despite the increase of protein numbers in growing cells, the protein concentrations are often found to be confined within small ranges throughout the cell cycle. Considering the time trajectory of protein concentration as a random walker in the concentration space, an effective restoring force (with a corresponding “spring constant”) must exist to prevent the divergence of concentration due to random uctuations. In this work, we prove that the magnitude of the effective spring constant is directly related to the fraction of intrinsic noise in the total protein concentration noise. We show that one can infer the magnitude of intrinsic, extrinsic, and measurement noises of gene expression solely based on time-resolved data of protein concentration, without any a priori knowledge of the underlying gene expression dynamics. We apply this method to experimental data of single-cell bacterial gene expression. The results allow us to estimate the average protein number and the translation burst parameter.
Visual literacy in consumption: consumers, brand aesthetics and the curated self
Authors: Lynch Leonie , Patterson Maurice , Ní Bheacháin Caoilfhionn
Published: August 2020

Purpose

This paper aims to consider the visual literacy mobilized by consumers in their use of brand aesthetics to construct and communicate a curated self.

Design/methodology/approach

The research surveyed a range of visual material from Instagram. Specifically, the goal was to use “compositional interpretation”, an approach to visual analysis that is not methodologically explicit but which, in itself, draws upon the visual literacy of the researcher to provide a descriptive analysis of the formal visual quality of images as distinct from their symbolic resonances. The research also incorporates 10 phenomenological-type interviews with consumers. Consistent with a phenomenological approach, informants were selected because they have “lived” the experience under investigation, in this case requiring them to be keen consumers of the Orla Kiely brand.

Findings

Findings indicate that consumers deploy their visual literacy in strategic visualization (imaginatively planning and coordinating artifacts with other objects in their collection, positioning and using them as part of an overall visual repertoire), composition (becoming active producers of images) and emergent design (turning design objects into display pieces, repurposing design objects or simply borrowing brand aesthetics to create designed objects of their own).

Research limitations/implications

This research has implications for the understanding of visual literacy within consumer culture. Engaging comprehensively with the visual compositions of consumers, this research moves beyond brand symbolism, semiotics or concepts of social status to examine the self-conscious creation of a curated self. The achievement of such a curated self depends on visual literacy and the deployment of abstract design language by consumers in the pursuit of both aesthetic satisfaction and social communication.

Practical implications

This research has implications for brand designers and managers in terms of how they might control or manage the use of brand aesthetics by consumers.

Originality/value

To date, there has been very little consumer research that explores the nature of visual literacy and even less that offers an empirical investigation of this concept within the context of brand aesthetics. The research moves beyond brand symbolism, semiotics and social status to consider the deployment of abstract visual language in communicating the curated self.
Marketing dashboards, resource allocation and performance
Authors: Clark Bruce
Published: August 2020

Purpose

This study aims to examine the effects of marketing dashboards on resource allocation between exploratory and exploitative activities. It proposes that tactical dashboards will lead managers to place less emphasis on exploratory activities and more emphasis on exploitative activities – with performance consequences – but that these effects will be contingent on the information and decision-making environment.

Design/methodology/approach

Study hypotheses were tested using an experiment tracking objective decisions over five periods in the Markstrat simulation. A total of 105 firms, each managed by a team of Master of Business Administration students, were divided into 2 dashboard conditions and a control condition.

Findings

Teams given a tactical dashboard were less likely to engage in exploratory activities when information load was high. Tactical dashboards also suppressed exploration early in the simulation. Dashboards were associated with negative firm performance overall.

Research implications/limitations

The research suggests that dashboards can bias resource allocation, but the effects are contingent on the information and decision-making environment. Dashboards demonstrated a negative relationship with performance. The research lacked cognitive process measures and was limited to a single simulated industry type.

Practical implications

Dashboards are not a panacea for decision-making and performance and will need to change under changing conditions. Executives should build flexibility into the design and use of their dashboards and periodically audit the value the dashboard produces.

Originality/value

While widespread in marketing practice, dashboards have received little study and none involving decision-making over time and changing conditions. This research advances on limited existing work by examining objective causal effects.
Balancing benefits: evidence-based guidelines for school-banking programmes
Authors: Jackson Michaela , Parker Lukas , Brennan Linda , Robinson Jenny
Published: August 2020

Purpose

After comprehensive review of discourse surrounding school-banking programmes and marketing to children, the authors develop evidence-based guidelines for such programmes. Guidance for organisations is provided to ensure they understand these products' impact on children and other vulnerable consumers.

Design/methodology/approach

A comprehensive, systematised review of literature related to school-banking programmes was undertaken during 2019, 22 Boolean searches were collated, appraised using a five-step quality appraisal framework and analysed against selection criteria. To accommodate literature across disciplines, quality appraisal combined two existing hierarchies of evidence and peer-review status.

Findings

Searches returned over 375,000 articles; 149 were relevant and met quality thresholds. Evidence supports the role of financial education in producing positive financial outcomes. However, education should involve communities and families to enhance consumer socialisation and limit negative consequences. From this, guidelines are presented accounting for students' and parents' ability to understand marketing messages and the impact of in-school marketing on students – including on longer-term perceptions, attitudes and behaviours.

Practical implications

Guidelines are to assist financial institutions, policymakers and schools balance the benefits of financial literacy and education with potentially negative consequences of school-banking programmes. Classifying programmes as marketing rather than CSR also benefits organisations contributing corporate resources and voluntarily engaging practices underpinned by commitment to community well-being.

Originality/value

Avoiding moral panic, the authors instead outline evidence-based guidelines on school-banking programmes. The quality appraisal process used in this review offers a new approach to synthesising inter-disciplinary evidence.
Driving acquisition performance: how much integration is enough?
Authors: Pangarkar Nitin
Published: August 2020

Purpose

This paper aims to develop a generalizable framework for acquisition performance.

Design/methodology/approach

This paper attempts to simulate a controlled experiment by examining the strategies and performance of the same acquired company under different acquirers. The inductive methodology is used to derive a generalizable framework about the key factors impacting the performance of the acquired firm.

Findings

This study finds that the acquired firm’s performance is better when the environment is munificent and the acquirer uses an appropriate level of integration. Several antecedents of each of these dimensions were identified.

Research limitations/implications

Because the inferences are based on a small sample, the study’s framework needs to be tested in other settings and possibly empirically tested in larger samples to improve its generalizability.

Practical implications

Every year, corporations around the world spend large sums of capital on acquisitions and significant managerial resources on integrating the acquired firms, with decidedly mixed results. The framework proposed in the paper can help managers to improve the performance of their acquisitions.

Originality/value

Unlike prior studies that have quantitatively analysed mixed samples of acquisitions and often arrived at inconclusive results, this study uses the inductive approach based on a few case studies to derive a framework that can be applied across industries. The framework accounts for the key industry and transaction-related contingent factors that can influence the performance of acquisitions under varied circumstances.
Understanding the impact of lifestyle on sustainable consumption behavior: a sharing economy perspective
Authors: Matharu Manita , Jain Ruchi , Kamboj Shampy
Published: August 2020

Purpose

The purpose of this study is to investigate the potential determinants of sustainable consumption behavior. This study describes lifestyle of health and sustainability (LOHAS) tendency and the effects of such lifestyles on the behavioral intentions for sustainable consumption in sharing economy.

Design/methodology/approach

This research adapts LOHAS tendency, consumer attitude, subjective norm, perceived behavioral control and consumers' behavioral intention for sustainable consumption scale in Indian context to describe the sustainable consumption behavior by extending the theory of planned behavior (TPB). Data of 627 individuals collected through a questionnaire, after the scales validation process and thereafter a structural equation analysis has been performed.

Findings

The findings confirm the extended TPB, wherein LOHAS tendency has emerged as an antecedent to consumer attitudes for taking part in sustainable consumption. Results highlight that consumer attitudes, subjective norms and perceived behavioral control are significant determining factors of consumers' sustainable consumption behavior.

Research limitations/implications

This study has examined the sustainable consumption behavior by considering the lifestyle tendency. A few other limitations are also discussed.

Originality/value

Consumer behavior in sharing economy is surely one of the emerging research areas; there is dearth of research to understand Indian consumers' sustainable consumption, particularly from lifestyle perspective. This research establishes relationship between LOHAS tendency and sustainable consumption, which may serve as a contributor to sharing economy in terms of LOHAS consumer's lifestyle and their sustainable consumption behavior.
Writing through theoretical frameworks in the doctoral classroom
Authors: Baird Stephanie Borgert , Kearney Kerri S. , Nephew Alissa
Published: August 2020

Purpose

Many doctoral students apply theoretical frameworks to writing assignments as part of their academic coursework and, later, in the practice of analyzing and reporting research. However, students often struggle to effectively apply theoretical frameworks to their writing processes. Thus, as one way of contributing to the writing pedagogies of doctoral-level instructors, the purpose of this study is to explore doctoral students’ learning experiences with analyzing and reporting organizational data using theoretical frameworks.

Design/methodology/approach

This study examines the perspectives of 29 doctoral students through analytical papers and reflections, letters and interviews.

Findings

Five themes within the context of current literature on writing were identified. These included students experiencing discomfort, even fear, about writing; students needing to write and receive honest feedback to learn how to write; the need for an instructional process that moves from conceptual to detailed instructions; understanding that writing has conceptual and skills implications that cannot be achieved in a single class; and the analytical writing process contributes to an understanding of the complexity of holding a doctoral degree.

Practical implications

The findings demonstrate the importance of helping doctoral students gain confidence and improve writing with theoretical frameworks, which can be accomplished with structured formats, through repetition and from instructor feedback.

Originality/value

This study offers unique insights into the challenges that doctoral students face when writing through theoretical frameworks and how instructors can interact with and potentially improve students’ writing skills and abilities.
Securing a furan‐based biorefinery: disclosing the genetic basis of the degradation of hydroxymethylfurfural and its derivatives in the model fungus Aspergillus nidulans
Authors: Martins Celso , Hartmann Diego O. , Varela Adélia , Coelho Jaime A. S. , Lamosa Pedro , Afonso Carlos A. M. , Silva Pereira Cristina
Published: August 2020

Hydroxymethylfurfural (HMF) is a promising lignocellulosic‐derived source for the generation of diverse chemical building blocks constituting an alternative to fossil fuels. However, it remains unanswered if ubiquitous fungi can ensure their efficient decay, similar to that observed in highly specialised fungi. To disclose the genetic basis of HMF degradation in aspergilli, we performed a comprehensive analysis of Aspergillus nidulans ability to tolerate and to degrade HMF and its derivatives (including an HMF‐dimer). We identified the degradation pathway using a suite of metabolomics methods and showed that HMF was modified throughout sequential reactions, ultimately yielding derivatives subsequently channelled to the TCA cycle. Based on the previously revealed hmfFGH gene cluster of Cupriavidus basilensis, we combined gene expression of homologous genes in Aspergillus nidulans and functional analyses in single‐deletion mutants. Results were complemented with orthology analyses across the genomes of twenty‐five fungal species. Our results support high functional redundancy for the initial steps of the HMF degradation pathway in the majority of the analysed fungal genomes and the assignment of a single‐copy furan‐2,5‐dicarboxylic acid decarboxylase gene in A. nidulans. Collectively our data made apparent the superior capacity of aspergilli to mineralise HMF, furthering the environmental sustainability of a furan‐based chemistry.
Genomics of natural history collections for understanding evolution in the wild
Authors: Lopez Lua , Turner Kathryn G. , Bellis Emily S. , Lasky Jesse R.
Published: August 2020

A long‐standing question in biology is how organisms change through time and space in response to their environment. This knowledge is of particular relevance to predicting how organisms might respond to future environmental changes caused by human‐induced global change. Usually researchers make inferences about past events based on an understanding of current static genetic patterns, but these are limited in their capacity to inform on underlying past processes. Natural history collections (NHCs) represent a unique and critical source of information to provide temporally deep and spatially broad time‐series of samples. By using NHC samples, researchers can directly observe genetic changes over time and space and link those changes with specific ecological/evolutionary events. Until recently, such genetic studies were hindered by the intrinsic challenges of NHC samples (i.e. low yield of highly fragmented DNA). However, recent methodological and technological developments have revolutionized the possibilities in the novel field of NHC genomics. In this Special Feature, we compile a range of studies spanning from methodological aspects to particular case studies which demonstrate the enormous potential of NHC samples for accessing large genomic data sets from the past to advance our knowledge on how populations and species respond to global change at multiple spatial–temporal scales. We also highlight possible limitations, recommendations and a few opportunities for future researchers aiming to study NHC genomics.
Lamin A safeguards the m6A methylase METTL14 nuclear speckle reservoir to prevent cellular senescence
Authors: Zhang Jie , Ao Ying , Zhang Zhen , Mo Yanzhen , Peng Linyuan , Jiang Yue , Wang Zimei , Liu Baohua
Published: August 2020

Mutations in LMNA gene are frequently identified in patients suffering from a genetic disorder known as Hutchison–Gilford progeria syndrome (HGPS), providing an ideal model for the understanding of the mechanisms of aging. Lamin A, encoded by LMNA, is an essential component of the subnuclear domain‒nuclear speckles; however, the functional significance in aging is unclear. Here, we show that Lamin A interacts with the m6A methyltransferases, METTL3 and METTL14 in nuclear speckles. Lamin A deficiency compromises the nuclear speckle METTL3/14 reservoir and renders these methylases susceptible to proteasome‐mediated degradation. Moreover, METTL3/14 levels progressively decline in cells undergoing replicative senescence. Overexpression of METTL14 attenuates both replicative senescence and premature senescence. The data reveal an essential role for Lamin A in safeguarding the nuclear speckle reservoir of the m6A methylase METTL14 to antagonize cellular senescence.
Adjuvant therapy for high‐risk renal cell carcinoma after nephrectomy how many trials are positive? Only one or more than one
Authors: Ravaud A.
Published: August 2020

Adjuvant treatment with VEGFR tyrosine kinase inhibitor in renal cell carcinoma after nephrectomy has been reported through four clinical trials: S‐TRAC, ASSURE, PROTECT and ATLAS. Only S‐TRAC has been significantly positive on primary endpoint DFS under sunitinib compared to placebo, whereas ASSURE, PROTECT and ATLAS did not show any gain under sunitinib, sorafenib, pazopanib or axitinib, respectively. Nevertheless, there are arguments for a trend for the impact of anti‐angiogenic therapy on outcome of patients with high‐risk renal cell carcinoma cancer following nephrectomy, allowing for a fair discussion with patients to decide for or against an adjuvant treatment.
Diagnostic performance of discontinuous density gradient centrifugation for estimating human semen quality
Authors: Zhang Yanan , Cheng Juan , Ou Jianping , Liu Zhuojie , Liu Yonghui , Zang Zhi‐Jun
Published: August 2020

Background

Semen analysis plays an important role in the diagnosis of male infertility. However, many studies have demonstrated that the current methods of semen analysis are inefficient for assessing male fertility.

Objective

To test whether prior discontinuous density gradient centrifugation (DDCG) improves the performance of semen analysis in diagnosing male infertility.

Materials and methods

Infertile men and fertile men were recruited from the clinic. Pre‐ and post‐DDGC values for the semen parameters of sperm concentration, total sperm number, percent total motility, percent progressive motility, percent normal sperm morphology, and sperm DNA fragmentation rate were compared.

Results

A total of 528 men (252 infertile men and 276 fertile men) were enrolled in the present study. After DDGC, sensitivity was significantly increased for sperm concentration, total sperm number, and sperm morphology (P < .01); specificity was significantly increased for progressive motility and sperm morphology (P < .01); and diagnostic accuracy was significantly improved for all of these parameters (area under the curve (AUC): P < .01). Total motility and sperm DNA fragmentation rate exhibited no obvious change in sensitivity, specificity or accuracy after DDGC (all P > .01). For the combination of all these semen parameters, diagnostic accuracy improved significantly after DDGC (AUC: P < .01). In a multiple regression analysis, only sperm morphology and sperm DNA fragmentation rate had P values less than 0.05 before DDGC, whereas all parameters except total sperm number contributed to the equation after DDGC.

Discussion

DDGC is a mature, standardized procedure for clinical commonly used to optimize spermatozoa. The diagnostic accuracy of semen analysis was significantly improved after DDGC, which indicated that assessing “functional spermatozoa” might be a more suitable method for semen analysis than the WHO 2010 criteria.

Conclusion

Assessing semen parameters after DDGC might improve their diagnostic accuracy for male infertility.
Variables affecting long‐term usage rate of sperm samples cryopreserved for fertility preservation in cancer patients
Authors: Ferrari Stefania , Paffoni Alessio , Reschini Marco , Noli Stefania , Dallagiovanna Chiara , Guarneri Cristina , Filippi Francesca , Somigliana Edgardo
Published: August 2020

Background

Previous evidence highlighted that only a minority of men who banked their semen before cancer therapies subsequently used their frozen samples. This may question the economical validity of sperm cryopreservation programmes. However, in most contributions, the duration of follow‐up was insufficient to draw robust information on the real rate of use.

Objectives

To shed more light on the potential benefits of cryopreservation programmes.

Materials and methods

Men who cryopreserved their semen in a public hospital for a diagnosis of cancer between 1986 and 2009 were retrospectively reviewed. The rate of use as well as the possible determinants was investigated.

Results

The median time of follow‐up was 12 [IQR: 7‐16] years. One hundred forty‐four patients out of 1,524 (9.4%, 95%CI: 8.1%‐11.0%) used their frozen samples of whom 64% were azoospermic. The rate of men achieving parenthood with frozen semen was 46%. Predictive factors of use were older age at the time of storage, lower sperm count at the time of storage and a diagnosis of testicular cancer. The impact of this latter factor was also supported by the lower frequency of azoospermia after cancer treatment in these patients.

Discussion

Cost‐beneficial studies are warranted to assess and possibly improve the economical validity of sperm banking.

Conclusion

The usage rate of frozen sperm in cancer patient is low, even extending the duration of follow‐up.
Redundancy among risk predictors derived from heart rate variability and dynamics: ALLSTAR big data analysis
Authors: Yuda Emi , Ueda Norihiro , Kisohara Masaya , Hayano Junichiro
Published: August 2020

Background

Many indices of heart rate variability (HRV) and heart rate dynamics have been proposed as cardiovascular mortality risk predictors, but the redundancy between their predictive powers is unknown.

Methods

From the Allostatic State Mapping by Ambulatory ECG Repository project database, 24‐hr ECG data showing continuous sinus rhythm were extracted and SD of normal‐to‐normal R‐R interval (SDNN), very‐low‐frequency power (VLF), scaling exponent α1, deceleration capacity (DC), and non‐Gaussianity λ25s were calculated. The values were dichotomized into high‐risk and low‐risk values using the cutoffs reported in previous studies to predict mortality after acute myocardial infarction. The rate of multiple high‐risk predictors accumulating in the same person was examined and was compared with the rate expected under the assumption that these predictors are independent of each other.

Results

Among 265,291 ECG data from the ALLSTAR database, the rates of subjects with high‐risk SDNN, DC, VLF, α1, and λ25s values were 2.95, 2.75, 5.89, 15.75, and 18.82%, respectively. The observed rate of subjects without any high‐risk value was 66.68%, which was 1.10 times the expected rate (60.74%). The ratios of observed rate to the expected rate at which one, two, three, four, and five high‐risk values accumulate in the same person were 0.73 times (24.10 and 32.82%), 1.10 times (6.56 and 5.99%), 4.26 times (1.87 and 0.44%), 47.66 times (0.63 and 0.013%), and 1,140.66 times (0.16 and 0.00014%), respectively.

Conclusions

High‐risk predictors of HRV and heart rate dynamics tend to cluster in the same person, indicating a high degree of redundancy between them.
Innovative approaches and recent advances in the study of ontogeny of drug metabolism and transport
Authors: van Groen Bianca D. , Allegaert Karel , Tibboel Dick , de Wildt Saskia N.
Published: August 2020

The disposition of a drug is driven by various processes, such as drug metabolism, drug transport, glomerular filtration and body composition. These processes are subject to developmental changes reflecting growth and maturation along the paediatric continuum. However, knowledge gaps exist on these changes and their clinical impact. Filling these gaps may aid better prediction of drug disposition and creation of age‐appropriate dosing guidelines. We present innovative approaches to study these developmental changes in relation to drug metabolism and transport. First, analytical methods such as including liquid chromatography–mass spectrometry for proteomic analyses allow quantitation of the expressions of a wide variety of proteins, e.g. membrane transporters, in a small piece of organ tissue. The latter is specifically important for paediatric research, where tissues are scarcely available. Second, innovative study designs using radioactive labelled microtracers allowed study—without risk for the child—of the oral bioavailability of compounds used as markers for certain drug metabolism pathways. Third, the use of modelling and simulation to support dosing recommendations for children is supported by both the European Medicines Agency and the US Food and Drug Administration. This may even do away with the need for a paediatric trial. Physiologically based pharmacokinetics models, which include age‐specific physiological information are, therefore, increasingly being used, not only to aid paediatric drug development but also to improve existing drug therapies.
Activation of AT2 receptors prevents diabetic complications in female db/db mice by NO‐mediated mechanisms
Authors: Dominici Fernando P. , Veiras Luciana C. , Shen Justin Z.Y. , Bernstein Ellen A. , Quiroga Diego T. , Steckelings Ulrike M. , Bernstein Kenneth E. , Giani Jorge F.
Published: August 2020

Background and Purpose

The AT2 receptor plays a role in metabolism by opposing the actions triggered by the AT1 receptors. Activation of AT2 receptors has been shown to enhance insulin sensitivity in both normal and insulin resistance animal models. In this study, we investigated the mechanism by which AT2 receptors activation improves metabolism in diabetic mice.

Experimental Approach

Female diabetic (db/db) and non‐diabetic (db/+) mice were treated for 1 month with the selective AT2 agonist, compound 21 (C21, 0.3 mg·kg−1·day−1, s.c.). To evaluate whether the effects of C21 depend on NO production, a subgroup of mice was treated with C21 plus a sub‐pressor dose of the NOS inhibitor l‐NAME (0.1 mg·ml−1, drinking water).

Key Results

C21‐treated db/db mice displayed improved glucose and pyruvate tolerance compared with saline‐treated db/db mice. Also, C21‐treated db/db mice showed reduced liver weight and decreased hepatic lipid accumulation compared with saline‐treated db/db mice. Insulin signalling analysis showed increased phosphorylation of the insulin receptor, Akt and FOXO1 in the livers of C21‐treated db/db mice compared with saline‐treated counterparts. These findings were associated with increased adiponectin levels in plasma and adipose tissue and reduced adipocyte size in inguinal fat. The beneficial effects of AT2 receptors activation were associated with increased eNOS phosphorylation and higher levels of NO metabolites and were abolished by l‐NAME.

Conclusion and Implications

Chronic C21 infusion exerts beneficial metabolic effects in female diabetic db/db mice, alleviating type 2 diabetes complications, through a mechanism that involves NO production.
Manuka honey versus saline sinus irrigation in the treatment of cystic fibrosis‐associated chronic rhinosinusitis: A randomised pilot trial
Authors: Lee Victoria S. , Humphreys Ian M. , Purcell Patricia L. , Davis Greg E.
Published: August 2020

Objectives

Manuka honey attacks biofilms, which contribute to bacterial persistence in cystic fibrosis sinusitis. The primary objective was to determine feasibility of investigating manuka honey as an irrigation treatment for cystic fibrosis sinusitis and secondarily to assess the treatment's preliminary effectiveness.

Design

Prospective, single‐blinded (clinician only), randomised, parallel two‐arm pilot trial.

Setting

Tertiary rhinology clinic.

Participants

Subjects had recalcitrant cystic fibrosis sinusitis and previous sinus surgery. They received manuka honey or saline sinus irrigations twice daily for 30 days.

Main Outcome Measures

Main outcomes were recruitment/retention rates and tolerability. Preliminary effectiveness was assessed based on quality‐of‐life Sinonasal Outcome Test‐22 and Lund‐Kennedy endoscopic change scores and post‐treatment culture negativity.

Results

Over 10 months, 13 subjects were enrolled, and 77% (10/13) were included in the analysis. Manuka honey irrigations were well‐tolerated. The quality‐of‐life change score was clinically significant for manuka honey (−9 [−14,−6]) but not saline (−5 [−9,−1]), although the difference was not statistically significant (P = .29). Lund‐Kennedy endoscopic change score was significantly better for manuka honey (−3 [−5,−3]) versus saline (0 [0,0]) (P = .006). There was no difference in post‐treatment culture negativity between manuka honey (1/5, 20%) and saline (0/5, 0%) (P = 1.00).

Conclusions

Manuka honey irrigations were well tolerated, and retention rates were high. Preliminary data showed that manuka honey achieved a clinically important difference in quality‐of‐life score and a significantly better endoscopic outcome. Microbiological control was difficult to achieve. A future definitive trial would require multi‐institutional recruitment.
Physicians' political party affiliation and clinical management of obesity
Authors: Zatz Laura Y. , Hersh Eitan , Gudzune Kimberly A. , Thorndike Anne N. , N. Goldenberg Matthew , Bleich Sara N.
Published: August 2020

Studies have documented that few patients with obesity receive evidence‐based care. One provider characteristic that may impact clinical obesity care, but that has been under studied to date, is political party affiliation. This study sought to evaluate how primary care physicians (PCPs) report managing patients with obesity and assess whether there are differences between Democratic and Republican PCPs. This was a secondary analysis of a cross‐sectional survey of 225 PCPs registered to vote as Democrats or Republicans in 29 US States. After reading a patient vignette, the PCPs reported the following outcomes: likelihood of documenting obesity in the medical record; likelihood of discussing obesity with the patient; and likelihood of engaging in eight different obesity management options. Almost all PCPs reported they would document obesity in the medical record (Republican = 97.6%, Democrat = 94.3%) and discuss it further (Republican = 95.2%, Democrat = 92.2%). Among eight obesity management options, PCPs were least likely to say they would prescribe medication (3.9%) or refer the patient to counselling (24.0%), regardless of political affiliation. Republicans were more likely to report that they would inquire about the time course of obesity (73.4% v. 56.2%, P = 0.012) and discuss health risks of obesity (91.0% vs 78.3%, P = .018). Republican and Democratic PCPs report some differences in managing patients with obesity, suggesting that political beliefs may play a role in some clinical care.
Alcohol industry arguments for putting profit before health in the midst of a pandemic: The Western Australian experience
Authors: Keric Danica , Stafford Julia
Published: August 2020

In an effort to limit the impact of alcohol on the Western Australian (WA) health system during the coronavirus disease (COVID‐19) pandemic, the WA Government introduced temporary restrictions on takeaway alcohol purchases for several weeks in March and April 2020. In response, alcohol industry representatives encouraged the WA Government to remove the restrictions and replace them with a voluntary alcohol industry initiative. We looked at alcohol industry representatives' comments in media and online publications during this period. We found that the industry framed alcohol as an essential product, focused on the impact of the restrictions on WA businesses and framed the restrictions as complex and ineffective. The themes and arguments we identified are commonly used by the alcohol industry and are not unique to the pandemic. The alcohol industry's response to the COVID‐19 restrictions in Australia provides a unique case study of how the alcohol industry attempts to interfere in public health policy.
Factors associated with spoken language comprehension in children with cerebral palsy: a systematic review
Authors: Vaillant Emma , Geytenbeek Johanna J M , Jansma Elise P , Oostrom Kim J , Vermeulen R Jeroen , Buizer Annemieke I
Published: August 2020

Aim

To identify factors that are relevant for spoken language comprehension in children with cerebral palsy (CP), following the International Classification of Functioning, Disability and Health – Children and Youth (ICF‐CY) framework.

Method

A systematic literature search was conducted using the electronic literature databases PubMed, Embase, PsycInfo, and Cochrane Library, from January 1967 to December 2019. Included studies involved children with CP, results regarding spoken language comprehension, and analysis of at least one associated factor. Factors were classified within ICF‐CY domains.

Results

Twenty‐one studies met inclusion criteria. Factors in the ICF‐CY domains of body functions and structure were most frequently reported. White brain matter abnormalities, motor type, functional mobility, and intellectual functioning appear to be relevant factors in spoken language comprehension in CP. Factors in the domain of activities and participation, as well as contextual factors, have rarely been studied in the context of spoken language comprehension in CP.

Interpretation

Most factors known to be important for spoken language comprehension in typically developing children and/or known to be susceptible to change by interventions are understudied in CP.

What this paper adds

Factors related to spoken language comprehension are understudied in cerebral palsy.

Factors in the ICF‐CY ‘body functions and structures’ domain are investigated most.

Structural brain abnormalities, motor type, functional mobility, and intellectual functions are relevant