bluuebunny/crossref_metadata_2025 huggingface dataset:
Aspergillus fumigatusacetate utilisation impacts virulence traits and pathogenicity
Authors: Ries Laure Nicolas Annick , de Castro Patricia Alves , Silva Lilian Pereira , Valero Clara , dos Reis Thaila Fernanda , Saborano Raquel , Duarte Iola F. , Persinoti Gabriela Felix , Steenwyk Jacob L. , Rokas Antonis , Almeida Fausto , Costa Jonas Henrique , Fill Taicia , Wong Sarah Sze Wah , Aimanianda Vishukumar , Rodrigues Fernando José Santos , Gonçales Relber A. , Duarte-Oliveira Cláudio , Carvalho Agostinho , Goldman Gustavo H.
Published: June 2021

Aspergillus fumigatusis a major opportunistic fungal pathogen of immunocompromised and immunocompetent hosts. To successfully establish an infection,A. fumigatusneeds to use host carbon sources, such as acetate, present in the body fluids and peripheral tissues. However, utilisation of acetate as a carbon source by fungi in the context of infection has not been investigated. This work shows that acetate is metabolised via different pathways inA. fumigatusand that acetate utilisation is under the regulatory control of a transcription factor (TF), FacB.A. fumigatusacetate utilisation is subject to carbon catabolite repression (CCR), although this is only partially dependent on the TF and main regulator of CCR CreA. The available extracellular carbon source, in this case glucose and acetate, significantly affectedA. fumigatusvirulence traits such as secondary metabolite secretion and cell wall composition, with the latter having consequences for resistance to oxidative stress, to anti-fungal drugs and to human neutrophil-mediated killing. Furthermore, deletion offacBsignificantly impaired thein vivovirulence ofA. fumigatusin both insect and mammalian models of invasive aspergillosis. This is the first report on acetate utilisation inA. fumigatusand this work further highlights the importance of available host-specific carbon sources in shaping fungal virulence traits and subsequent disease outcome, and a potential target for the development of anti-fungal strategies.

Importance

Aspergillus fumigatusis an opportunistic fungal pathogen in humans. During infection,A. fumigatusis predicted to use host carbon sources, such as acetate, present in body fluids and peripheral tissues, to sustain growth and promote colonisation and invasion. This work shows thatA. fumigatusmetabolises acetate via different pathways, a process that is dependent on the transcription factor FacB. Furthermore, the type and concentration of the extracellular available carbon source were determined to shapeA. fumigatusvirulence determinants such as secondary metabolite secretion and cell wall composition. Subsequently, interactions with immune cells are altered in a carbon source-specific manner. FacB is required forA. fumigatus in vivovirulence in both insect and mammalian models of invasive aspergillosis. This is the first report that characterises acetate utilisation inA. fumigatusand highlights the importance of available host-specific carbon sources in shaping virulence traits and potentially subsequent disease outcome.
Accuracy of somatic variant detection workflows for whole genome sequencing experiments
Authors: Jaksik Roman , Rosiak Jacek , Zawadzki Paweł , Sztromwasser Paweł
Published: June 2021

Whole genome sequencing (WGS) becomes increasingly important for advancing personalized cancer care, driving not only basic science studies but also entering into clinical applications. Translating raw WGS data into the right clinical decision requires high accuracy of somatic variant detection, therefore novel data analysis methods have to be carefully evaluated.

In this work we tested the performance of well-established somatic variant detection workflows: GATK, CPG-WGS, DRAGEN and Strelka2. By utilizing both real data, with well-defined mutations, and synthetic mutations spiked-in into real data, we were able to assess sensitivity and precision of each workflow, for various coverage and tumor purity levels.

Individual tools excelled in different evaluation approaches, however the results demonstrated that DRAGEN has the highest overall performance when sensitivity is preferred over precision, and the opposite is true for CGP-WGS. The differences in results obtained using synthetic and real datasets, indicate that benchmarks based only on a single reference set may provide an incomplete picture.
Epitome: Predicting epigenetic events in novel cell types with multi-cell deep ensemble learning
Authors: Morrow Alyssa Kramer , Hughes John Weston , Singh Jahnavi , Joseph Anthony Douglas , Yosef Nir
Published: June 2021

The accumulation of large epigenomics data consortiums provides us with the opportunity to extrapolate existing knowledge to new cell types and conditions. We propose Epitome, a deep neural network that learns similarities of chromatin accessibility between well characterized reference cell types and a query cellular context, and copies over signal of transcription factor binding and modification of histones from reference cell types when chromatin profiles are similar to the query. Epitome achieves state-of-the-art accuracy when predicting transcription factor binding sites on novel cellular contexts, and can further improve predictions as more epigenetic signals are collected from both reference cell types and the query cellular context of interest.
Geometric Network Analysis Provides Prognostic Information in Patients with High Grade Serous Carcinoma of the Ovary Treated with Immune Checkpoint Inhibitors
Authors: Elkin Rena , Oh Jung Hun , Liu Ying L. , Selenica Pier , Weigelt Britta , Reis-Filho Jorge S. , Zamarin Dmitriy , Deasy Joseph O. , Norton Larry , Levine Arnold J. , Tannenbaum Allen R.
Published: June 2021

Purpose

Network analysis methods can potentially quantify cancer disturbances in gene networks without introducing fitted parameters or variable selection. A new network curvature-based method is introduced to provide an integrated measure of variability within cancer gene networks. The method is applied to high grade serous ovarian cancers (HGSOCs) to predict response to immune checkpoint inhibitors (ICIs), and to rank key genes associated with prognosis.

Methods

Copy number alterations (CNAs) from targeted and whole exome sequencing data were extracted for HGSOC patients (n= 45) treated with ICIs. CNAs at a gene level were represented on a protein-protein interaction network to define patient-specific networks with a fixed topology. A version of Ollivier-Ricci curvature was used to identify genes that play a potentially key role in response to immunotherapy and further to stratify patients at high risk of mortality. Overall survival (OS) was defined as the time from the start of ICI treatment to either death or last follow-up. Kaplan-Meier analysis with log-rank test was performed to assess OS between the high and low curvature classified groups.

Results

The network curvature analysis stratified patients at high risk of mortality with p=0.00047 in Kaplan-Meier analysis. Genes with high curvature were in accordance with CNAs relevant to ovarian cancer.

Conclusion

Network curvature using CNAs has the potential to be a novel predictor for OS in HGSOC patients treated with immunotherapy.
Low numbers of cytokine transcripts drive inflammatory skin diseases by initiating amplification cascades in localized epidermal clusters
Authors: Schäbitz A. , Hillig C. , Farnoud A. , Jargosch M. , Scala E. , Pilz A.C. , Bhalla N. , Mubarak M. , Thomas J. , Stahle M. , Biedermann T. , Schmidt-Weber C.B. , Theis F. , Garzorz-Stark N. , Eyerich K K. , Menden M.P. , Eyerich S.
Published: June 2021

Abundant polyclonal T cells infiltrate chronic inflammatory diseases and characterization of these cells is needed to distinguish disease-driving from bystander immune cells. Here, we investigated 52,000 human cutaneous transcriptomes of non-communicable inflammatory skin diseases (ncISD) using spatial transcriptomics. Despite the expected T cell infiltration, we observed only 1-10 pathogenic T cell cytokine per skin section. Cytokine expression was limited to lesional skin and presented in a disease-specific pattern. In fact, we identified responder signatures in direct proximity of cytokines, and showed that single cytokine transcripts initiate amplification cascades of thousands of specific responder transcripts forming localized epidermal clusters. Thus, within the abundant and polyclonal T cell infiltrates of ncISD, only a few T cells drive disease by initiating an inflammatory amplification cascade in their local microenvironment.
Oxaliplatin kills cells via liquid-liquid demixing of nucleoli
Authors: Schmidt H. Broder , Jaafar Zane A. , Rodencal Jason J. , Leonetti Manuel D. , Dixon Scott J. , Rohatgi Rajat , Brandman Onn
Published: June 2021

Platinum (Pt) compounds such as oxaliplatin are amongst the most commonly prescribed anti-cancer drugs. Despite their considerable clinical impact, the molecular basis of platinum cytotoxicity and cancer specificity remain unclear. Here, we show that oxaliplatin, a backbone for the treatment of colorectal cancer, causes liquid-liquid demixing of nucleoli at clinically-relevant concentrations by interfering with the interaction networks that organize nucleoli. This biophysical defect leads to cell cycle arrest, impaired rRNA processing and shutdown of PolI-mediated transcription, ultimately resulting in cell death. We propose that the mechanism of action of oxaliplatin provides a blueprint for the therapeutic targeting of the increasing number of cellular processes being linked to biomolecular condensates.
Diverse routes of Club cell evolution in lung adenocarcinoma
Authors: Chen Yuanyuan , Toth Reka , Chocarro Sara , Weichenhan Dieter , Hey Joschka , Lutsik Pavlo , Sawall Stefan , Stathopoulos Georgios T. , Plass Christoph , Sotillo Rocio
Published: June 2021

The high plasticity of lung epithelial cells, has for many years, confounded the correct identification of the cell-of-origin of lung adenocarcinoma (LUAD), one of the deadliest malignancies worldwide. Here, we address the cell-of-origin of LUAD, by employing lineage-tracing mouse models combined with a CRISPR/Cas9 system to induce an oncogenic Eml4-Alk rearrangement in virtually all epithelial cell types of the lung. We find that Club cells give rise to lung tumours with a higher frequency than AT2 cells. Based on whole genome methylome, we identified that tumours retain an ‘epigenetic memory’ derived from their originating cell type but also develop a tumour-specific pattern regardless of their origin. Single-cell transcriptomic analyses identified two trajectories of Club cell evolution which are similar to the ones used during lung regeneration, providing a link between lung regeneration and cancer initiation. On both routes, tumours lose their Club cell identity and gain an AT2- like phenotype. Together, this study highlights the role of Club cells in LUAD initiation and unveils key mechanisms conferring LUAD heterogeneity.
MARCO+ lymphatic endothelial cells sequester arboviruses to limit viremia and viral dissemination
Authors: Carpentier Kathryn S. , Sheridan Ryan M. , Lucas Cormac J. , Davenport Bennett J. , Li Frances S. , Lucas Erin D. , McCarthy Mary K. , Reynoso Glennys V. , May Nicolas A. , Tamburini Beth A.J. , Hesselberth Jay R. , Hickman Heather D. , Morrison Thomas E.
Published: June 2021

While viremia in the vertebrate host is a major determinant of arboviral reservoir competency, transmission efficiency, and disease severity, immune mechanisms that control arboviral viremia are poorly defined. Here, we identify critical roles for the scavenger receptor MARCO in controlling viremia during arthritogenic alphavirus infections in mice. Following subcutaneous inoculation, alphavirus particles drain via the lymph and are rapidly captured by MARCO+ lymphatic endothelial cells (LECs) in the draining lymph node (dLN), limiting viral spread to the bloodstream. Upon reaching the bloodstream, alphavirus particles are cleared from the circulation by MARCO-expressing Kupffer cells in the liver, limiting viremia and further viral dissemination. MARCO-mediated accumulation of alphavirus particles in the dLN and liver is an important host defense mechanism as viremia and viral tissue burdens are elevated in MARCO-/- mice and disease is more severe. These findings uncover a previously unrecognized arbovirus scavenging role for LECs and improve our mechanistic understanding of viremia control during arboviral infections.
The model diatom Phaeodactylum tricornutum provides insights into the diversity and function of microeukaryotic DNA methyltransferases
Authors: Hoguin Antoine , Yang Feng , Groisillier Agnès , Bowler Chris , Genovesio Auguste , Ait-Mohamed Ouardia , Vieira Fabio Rocha Jimenez , Tirichine Leila
Published: June 2021

Cytosine methylation is an important epigenetic mark involved in the transcriptional control of transposable elements in mammals, plants and fungi. The Stramenopiles-Alveolate-Rhizaria (SAR) lineages are a major group of ecologically important marine microeukaryotes that include the main phytoplankton groups diatoms and dinoflagellates. However, little is known about their DNA methyltransferase diversity. Here, we performed anin-silicoanalysis of DNA methyltransferases found in marine microeukaryotes and showed that they encode divergent DNMT3, DNMT4, DNMT5 and DNMT6 enzymes. Furthermore, we found three classes of enzymes within the DNMT5 family. Using a CRISPR/Cas9 strategy we demonstrated that the loss of the DNMT5a gene correlates with a global depletion of DNA methylation and overexpression of young transposable elements in the model diatomPhaeodactylum tricornutum. The study provides a pioneering view of the structure and function of a DNMT family in the SAR supergroup using an attractive model species.
Maintaining and escaping feedback control in hierarchically organised tissue: a case study of the intestinal epithelium
Authors: Fischer Matthias M. , Herzel Hanspeter , Blüthgen Nils
Published: June 2021

The intestinal epithelium is one of the fastest renewing tissues in mammals. It shows a hierarchical organisation, where intestinal stem cells at the base of crypts give rise to rapidly dividing transit amplifying cells that in turn renew the pool of short-lived differentiated cells. Upon injury and stem-cell loss, cells can also dedifferentiate. Tissue homeostasis require a tightly regulated balance of differentiation and stem cell proliferation, and failure can lead to tissue extinction or to unbounded growth and cancerous lesions. Here, we present a two-compartment mathematical model of intestinal epithelium population dynamics that includes a known feedback inhibition of stem cell differentiation by differentiated cells. The model shows that feedback regulation stabilises the number of differentiated cells as these become invariant to changes in their apoptosis rate. Stability of the system is largely independent of feedback strength and shape, but specific thresholds exist after unbounded growth occurs. When dedifferentiation is added to the model, we find that the system can recover more gracefully after certain external perturbations. However, dedifferentiation makes the system more prone to loosing homoeostasis. Taken together, our mathematical model shows how a feedback-controlled hierarchical tissue can maintain homeostasis and can be robust to many external perturbations.
The biological underpinnings of therapeutic resistance in pancreatic cancer
Authors: Beatty Gregory L. , Werba Gregor , Lyssiotis Costas A. , Simeone Diane M.
Published: June 2021

Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer-related mortality in the United States and has only recently achieved a 5-yr survival rate of 10%. This dismal prognosis reflects the remarkable capacity of PDAC to effectively adapt to and resist therapeutic intervention. In this review, we discuss recent advances in our understanding of the biological underpinnings of PDAC and their implications as targetable vulnerabilities in this highly lethal disease.
Deletion of ERF and CIC causes abnormal skull morphology and global developmental delay
Authors: Singh Ram , Cohen Ana S.A. , Poulton Cathryn , Hjortshøj Tina Duelund , Akahira-Azuma Moe , Mendiratta Geetu , Khan Wahab A. , Azmanov Dimitar N. , Woodward Karen J. , Kirchhoff Maria , Shi Lisong , Edelmann Lisa , Baynam Gareth , Scott Stuart A. , Jabs Ethylin Wang
Published: June 2021

The ETS2 repressor factor (ERF) is a transcription factor in the RAS-MEK-ERK signal transduction cascade that regulates cell proliferation and differentiation, and pathogenic sequence variants in the ERF gene cause variable craniosynostosis inherited in an autosomal dominant pattern. The reported ERF variants are largely loss-of-function, implying haploinsufficiency as a primary disease mechanism; however, ERF gene deletions have not been reported previously. Here we describe three probands with macrocephaly, craniofacial dysmorphology, and global developmental delay. Clinical genetic testing for fragile X and other relevant sequencing panels were negative; however, chromosomal microarray identified heterozygous deletions (63.7–583.2 kb) on Chromosome 19q13.2 in each proband that together included five genes associated with Mendelian diseases (ATP1A3, ERF, CIC, MEGF8, and LIPE). Parental testing indicated that the aberrations were apparently de novo in two of the probands and were inherited in the one proband with the smallest deletion. Deletion of ERF is consistent with the reported loss-of-function ERF variants, prompting clinical copy-number-variant classifications of likely pathogenic. Moreover, the recent characterization of heterozygous loss-of-function CIC sequence variants as a cause of intellectual disability and neurodevelopmental disorders inherited in an autosomal dominant pattern is also consistent with the developmental delays and intellectual disabilities identified among the two probands with CIC deletions. Taken together, this case series adds to the previously reported patients with ERF and/or CIC sequence variants and supports haploinsufficiency of both genes as a mechanism for a variable syndromic cranial phenotype with developmental delays and intellectual disability inherited in an autosomal dominant pattern.
Incidental identification of inv(16)(p13.1q22)/CBFB–MYH11 variant transcript in a patient with therapy-related acute myeloid leukemia by routine leukemia translocation panel screen: implications for diagnosis and therapy
Authors: Quesada Andrés E. , Luthra Rajyalakshmi , Jabbour Elias , Patel Keyur P. , Khoury Joseph D. , Tang Zhenya , Alvarez Hector , Mallampati Saradhi , Garcia-Manero Guillermo , Montalban-Bravo Guillermo , Medeiros L. Jeffrey , Kanagal-Shamanna Rashmi
Published: June 2021

A 52-yr-old woman presented with therapy-related acute myeloid leukemia. A bone marrow biopsy showed 21% blasts with a myeloid phenotype and no other notable features such as abnormal eosinophils. Routine nanofluidics-based reverse transcriptase polymerase chain reaction (PCR) leukemia translocation panel designed to screen for recurrent genetic abnormalities in acute leukemia detected an inversion 16 transcript variant E. This prompted rereview of karyotype and fluorescence in situ hybridization studies, which confirmed inv(16), leading to appropriate prognostication and modification of treatment. This case underscores the utility of a powerful molecular screening method for the routine detection of recurrent genetic abnormalities of acute myeloid leukemia. It was especially useful in this case because of the lack of characteristic morphologic findings seen in inversion 16 and the difficulty in its detection by conventional karyotype analysis.
How GHRM is related to green creativity? A moderated mediation model of green transformational leadership and green perceived organizational support
Authors: Hameed Zahid , Naeem Rana Muhammad , Hassan Marria , Naeem Muhammad , Nazim Muhammad , Maqbool Adnan
Published: June 2021

Purpose

This study aims to examine the relationship between green human resource management (GHRM) practices and green transformational leadership toward inducing employees' green creativity. Specifically, drawing upon the ability, motivation and opportunity theory, the authors tested how green perceived organizational support (green POS) mediates the link between GHRM practices and employees' green creativity. Furthermore, based on the firm's resource-based view, the authors examine the moderating role of green transformational leadership on the relationship between GHRM practice and green POS.

Design/methodology/approach

Using a survey questionnaire, this research was conducted with a multi-source sample of 201 supervisors and their 428 subordinates from organizations working in grocery, food and personal care products in Pakistan.

Findings

The findings of structural equation modeling revealed that green POS plays a mediating role between GHRM and employees' green creativity. The study findings also highlighted that green transformational leadership moderates the positive relationship between GHRM practices and green POS.

Practical implications

Organizations need to implement GHRM practices to achieve environmental performance. Individuals are likely to recognize themselves with organizations that are engaged in green practices, and therefore, organizations can get benefits from implementing GHRM practices.

Originality/value

This research explores green POS and green transformational leadership as novel mechanisms through which GHRM practices influence employees' green creativity in organizations. In addition, the authors empirically examined our theorized relationships in the South Asian context.
Which social media posts generate the most buzz? Evidence from WeChat
Authors: She Jie , Zhang Tao , Chen Qun , Zhang Jianzhang , Fan Weiguo , Wang Hongwei , Chang Qingqing
Published: June 2021

Purpose

Following the hierarchy-of-effects model, this study aims to propose a two-step process framework to investigate social media post efficacy via attraction and likes.

Design/methodology/approach

The study analyzes 113,785 social media posts from 126 WeChat official accounts to explore how external (headline features and account type) and internal (content features and media type) features impact social media post attractions and likes, respectively.

Findings

The antecedents of post attraction differ from those of post likes. First, headline features (punctuation, length, sentiment and lexical density) and account type significantly influence social media post attraction. Second, content features (depth, tone, domain specificity, lexical density and readability) and media type affect social media post likes.

Originality/value

First, this study considers online user engagement as a two-step process regarding social media posts and explores different influencing factors. Second, the study constructs new variables (account type and domain specificity) in each stage of the two-step process model.
Impact of novel information technology on IT alignment and sustainable supply chain performance: evidence from Chinese manufacturing industry
Authors: Zhang Shushan , Sun Lei , Sun Qi , Dong Haiying
Published: June 2021

Purpose

This paper aims to explore how the novel information technology (NIT) [1] affects three dimensions of sustainable supply chain performance (economic performance, environmental performance and social performance) and how two dimensions of IT alignment (IT infrastructure alignment and IT human resources alignment) mediate the relationship between them.

Design/methodology/approach

NIT is defined, the dimension of IT alignment is expanded, the theoretical hypotheses are proposed and are tested using survey data from 394 manufacturing enterprises using NIT in China.

Findings

The results indicate that NIT plays a positive role in improving sustainable supply chain performance, and IT alignment mediates the impact of NIT on sustainable supply chain performance.

Originality/value

This study highlights the impact of NIT on sustainable supply chain performance and demonstrates IT alignment as a mediator between them, it also provides a deeper understanding of how different dimensions of IT alignment affect sustainable supply chain performance
BIM-enabled facilities management (FM): a scrutiny of risks resulting from cyber attacks
Authors: Ghadiminia Nikdokht , Mayouf Mohammad , Cox Sharon , Krasniewicz Jan
Published: June 2021

Purpose

Building information modelling (BIM) creates a golden thread of information of the facility, which proves useful to those with the malicious intent of breaching the security of the facility. A cyber-attack incurs adverse implications for the facility and its managing organisation. Hence, this paper aims to unravel the impact of a cybersecurity breach, by developing a BIM-facilities management (FM) cybersecurity-risk-matrix to portray what a cybersecurity attack means for various working areas of FM.

Design/methodology/approach

This study commenced with exploring cybersecurity within various stages of a BIM project. This showcased a heightened risk of cybersecurity at the post-occupancy phase. Hence, thematic analysis of two main domains of BIM-FM and cybersecurity in the built environment led to the development of a matrix that illustrated the impact of a cybersecurity attack on a BIM-FM organisation.

Findings

Findings show that the existing approaches to the management of cybersecurity in BIM-FM are technology-dependent, resulting in an over-reliance on technology and a lack of cybersecurity awareness of aspects related to people and processes. This study sheds light on the criticality of cyber-risk at the post-occupancy phase, highlighting the FM areas which will be compromised as a result of a cyber-attack.

Originality/value

This study seeks to shift focus to the people and process aspects of cybersecurity in BIM-FM. Through discussing the interconnections between the physical and digital assets of a built facility, this study develops a cyber-risk matrix, which acts as a foundation for empirical investigations of the matter in future research.
Teaching as a part of academics' professionalization: the case of Czech educational sciences
Authors: Poláchová Vašt'atková Jana , Dopita Miroslav
Published: June 2021

Purpose

The article explores the current as well as the future concepts of university teaching by the academics/the “leaders of educational sciences” in the context of the changes of the academia that have affected the academic professionalization.

Design/methodology/approach

The Delphi method was implemented to answer a research question dealing with the possible change in academics' concept of teaching as part of their current and future work. In this study, the experienced academics in the area of educational science are seen as the “leaders” since through their intensive teaching activities on all three levels (bachelor, master and doctoral) as well as through the high-quality research, they “lead” the concept of a particular science as well as the educational policy. Four rounds were used for consensus building among “leaders” based on a multiple interaction in an anonymous setting.

Findings

The research points out that academic professionalization in research is at its maximum. The currently perceived concept of teaching is content-oriented. However, the results also indicate the need for a gradual change in training Czech academics, should they accept their role also as university teachers in the future and be able to highlight the predicted change of teaching to support learning. Whether the strategy of a particular university will or will not accept all the academics' diverse roles seems to become the crucial factor.

Research limitations/implications

Several rounds with the same group of experts, which is the principle of Delphi method, is at the same time a limitation of the study, as in most of the research based on this method. The participation in the expert panel dropped throughout the rounds; however, geographic (in terms of university) dispersion of participating experts remained. The final fourth round confirmed the collective judgments of academics.

Practical implications

The article broadens the understanding of changes in the content of academics' professionalization with respect to changes in the academia. It emphasizes the role of an academic as an educator and concludes with the need of institutional reform in the context of a single university in a decentralized system.

Social implications

The article questions the trends of (national) educational policy in the sense that academics at universities are not only scientists but also teachers. However, the study also shows that the acceptance of their teaching abilities remains mainly on the organizational level.

Originality/value

A less common method of data collection among rather rarely involved group of experts in educational sciences brings a different view of the profession of academics, who (not only in the Czech context) are seen mainly as researchers and not as teachers. Humboldt's ideal regarding the unity of diverse roles is, thus, threatened due to narrower focus on academics' professionalization.
Employee performance appraisal system development in the National Library and Archives of Iran (NLAI): soft operational research approach
Authors: Zendehdel Nobari Babak , Gholipour Aryan , Ebrahimi Elham , Shoja Ali
Published: June 2021

Purpose

The performance evaluation process is a key step in any management system and constitutes the basis for continuous improvement. Resistance to change is considered as a critical factor in any change management project; so, development of employee performance appraisal systems like all of the change management projects has always faced many challenges. This study seeks to illustrate the two-year experience (2018–2020) and lessons learned by developing an employee performance appraisal system in the National Library and Archives of Iran (NLAI) as a cultural public sector organization.

Design/methodology/approach

This study was carried out by using soft operational research (OR) approaches, using a novel combination of two methods, soft system methodology (SSM) and importance performance analysis (IPA). For this purpose, at the beginning, with the help of the SSM approach, the challenges of implementation was identified, then, using the opinions and experiences of the system's stakeholders, improvement actions were defined and prioritized using the IPA method.

Findings

The research findings showed that “coaching development,” “optimizing the forced distribution rating system (FDRS)” and “customizing the system” are the most important improvement actions.

Originality/value

The research has bridged the gap between research and practice in the field of employee performance appraisal system in national libraries.
Lipid transfer protein syndrome due to wild grape juice and various vegetables: A life‐threatening food allergen
Authors: Hanada Miho , Nakagawa Michiyo , Hamabata Akemi , Amano Hiroo
Published: June 2021

We report a 16‐year‐old Japanese male with mugwort pollinosis in whom ingestion of wild grape juice and various vegetables caused recurrent general urticaria, abdominal pain, dyspnea, and loss of consciousness. A skin prick test demonstrated positive reactions to a wide variety of both non‐heated and heated vegetables and fruits such as wild grape, bell pepper, onion, Chinese cabbage, tomato, eggplant, and broccoli. The serum immunoglobulin E levels (ImmunoCAP ISAC®) for Art v 3, Pla a 3, Pru p 3, and Jug r 3, which are lipid transfer protein (LTP) homologs, were positive but those for Bet v 1 and Bet v 2 were negative. We diagnosed the patient as having LTP syndrome, a condition in which additional factors such as exercise, non‐steroidal anti‐inflammatory drugs, or alcohol may trigger an allergic reaction. Wild grapes contain a large amount of salicylic acid, and in our patient ingestion of wild grape juice led to immediate loss of consciousness in the absence of exercise. This suggests that salicylic acid contained in fruits and vegetables may act as an important cofactor in LTP syndrome. Although sensitization to LTP is rarely reported in Asia, LTP are considered to be potentially life‐threatening food allergens, and therefore warrant attention.
Seasonal hydrologic and geologic forcing drive hot spring geochemistry and microbial biodiversity
Authors: Colman Daniel R. , Lindsay Melody R. , Harnish Annette , Bilbrey Evan M. , Amenabar Maximiliano J. , Selensky Matthew J. , Fecteau Kristopher M. , Debes Randall V. , Stott Matthew B. , Shock Everett L. , Boyd Eric S.
Published: June 2021

Hot springs integrate hydrologic and geologic processes that vary over short‐ and long‐term time scales. However, the influence of temporal hydrologic and geologic change on hot spring biodiversity is unknown. Here, we coordinated near‐weekly, cross‐seasonal (~140 days) geochemical and microbial community analyses of three widely studied hot springs with local precipitation data in Yellowstone National Park. One spring (‘HFS’) exhibited statistically significant, coupled microbial and geochemical variation across seasons that was associated with recent precipitation patterns. Two other spring communities, ‘CP’ and ‘DS’, exhibited minimal to no variation across seasons. Variability in the seasonal response of springs is attributed to differences in the timing and extent of aquifer recharge with oxidized near‐surface water from precipitation. This influx of oxidized water is associated with changes in community composition, and in particular, the abundances of aerobic sulfide‐/sulfur‐oxidizers that can acidify waters. During sampling, a new spring formed after a period of heavy precipitation and its successional dynamics were also influenced by surface water recharge. Collectively, these results indicate that changes in short‐term hydrology associated with precipitation can impact hot spring geochemistry and microbial biodiversity. These results point to potential susceptibility of certain hot springs and their biodiversity to sustained, longer‐term hydrologic changes.
A novel multiplex of 12 multicopy Y‐STRs for forensic application
Authors: Shang Lei , Ding Guangshu , Mo Xiaoting , Sun Jing , Sun Hui , Yu Zhengliang , Li Wanshui
Published: June 2021

Y chromosomal short tandem repeats (Y‐STRs) have been applied overwhelmingly in forensic areas for solving paternity identification and sexual assault cases. Yet the widely used Y‐STR kits contain mostly single‐copy markers, which may restrict the discrimination power. Here, a novel Y‐STR multiplex was developed and validated in order to complement the currently available Y‐STR kits, especially on differentiating male relatives. The assay includes twelve multicopy Y‐STR loci (DYF371, DYF383S1, DYS385, DYF387S1, DYS389I/II, DYF399S1, DYF404S1, DYF409S1, DYF411S1, DYS464, DYS526, DYS527; four of them are rapidly mutating ones), 1 single‐copy Y‐STR (DYS391), and Amelogenin, and was optimized to amplify at annealing temperature of 59°C and 28 cycles. Validation studies show that full profiles are obtained with 0.125 ng of male DNA. The system is capable of overcoming high concentrations of inhibitors such as hematin, EDTA, and humic acid. Besides, the results demonstrate good sizing precision and the ability to detect male‐specific profiles in male/female DNA mixtures at a ratio of 1:800. Excellent species specificity was also observed in microorganisms and non‐primates, while detectable peaks were found in some primates. Based on published genetic data, gene diversity values were above 0.7 for most of the loci in our multiplex, inferring a high capacity in discriminating unrelated and related male individuals. The kit is of great potential for forensic application.
A phase 3, open‐label, single‐arm study of vadadustat for anemia in chronic kidney disease for Japanese patients on hemodialysis not receiving erythropoiesis‐stimulating agents
Authors: Nangaku Masaomi , Kondo Kazuoki , Takabe Souichirou , Ueta Kiichiro , Tandai Tsubasa , Kawaguchi Yutaka , Komatsu Yasuhiro
Published: June 2021

Vadadustat is an oral hypoxia‐inducible factor prolyl hydroxylase inhibitor approved in Japan for the treatment of anemia in patients with chronic kidney disease (CKD). This phase 3, open‐label, single‐arm study evaluated the efficacy and safety of vadadustat in 24 Japanese patients with CKD‐associated anemia on hemodialysis who were not receiving erythropoiesis‐stimulating agents (ESAs). Patients received vadadustat for 24 weeks; the starting dose was 300 mg/day and doses were adjusted to achieve the target hemoglobin (Hb) range of 10.0–12.0 g/dL. The least squares mean of average Hb at Weeks 20 and 24 (95% confidence interval) was 10.75 g/dL (10.35, 11.14). The most common adverse event was shunt stenosis (25.0%). Adverse drug reactions (diarrhea and vomiting) occurred in two patients (8.3%) and the severity was mild. Vadadustat increased and maintained Hb levels within the target range and was generally well‐tolerated in Japanese patients with anemia on hemodialysis not receiving ESAs.
Effective doses and associated age‐related risks for common paediatric diagnostic nuclear medicine and PET procedures at a large Australian paediatric hospital
Authors: Earl Victoria J , Baker Luke J , Perdomo Amanda A
Published: June 2021

Introduction

Effective dose alone cannot be used to specify and communicate the radiation risk for an individual as risks are dependent on many factors including age and gender. There are limited published data regarding age‐specific effective doses and the associated lifetime risk of developing cancers for paediatrics. In this study, we have estimated the typical effective doses for six commonly performed paediatric nuclear medicine and positron emission tomography (PET) studies at the Royal Children’s Hospital, Melbourne, Australia. Effective doses were used to estimate and categorise associated stochastic risks with commonly used risk terminology.

Methods

Paediatric protocols for common nuclear medicine and PET studies and the World Health Organization (WHO) 50th percentile weight‐for‐age data for females and males aged up to 18 years were used to estimate typical organ and effective doses using ICRP dosimetric tables for radiopharmaceuticals and lifetime risk of cancer incidence using BEIR VII Phase 2 report data. Results were used to determine standardised levels of risk.

Results

Organ doses, effective doses, corresponding lifetime risk of cancer incidence and level of risk category from six common nuclear medicine and PET studies for paediatric patients were calculated and presented for ease of communication.

Conclusion

Typical effective doses from common paediatric nuclear medicine and PET studies and the associated lifetime risk of cancer incidence and level of risk have been established for our institution. This can be used to convey risks to health professionals, patients and carers in ways that are easy to understand and compare with other everyday risks.
RUBIC (ReproUnion Biobank and Infertility Cohort): A binational clinical foundation to study risk factors, life course, and treatment of infertility and infertility‐related morbidity
Authors: Priskorn Lærke , Tøttenborg Sandra Søgaard , Almstrup Kristian , Andersson Anna‐Maria , Axelsson Jonatan , Bräuner Elvira Vaclavik , Elenkov Angel , Freiesleben Nina la Cour , Giwercman Yvonne Lundberg , Grøndahl Marie Louise , Hansen Ann Holm , Hansen Laura Smidt , Henic Emir , Kitlinski Margareta Laczna , Landersoe Selma Kloeve , Lindh Christian , Løkkegaard Ellen Leth , Malm Johan , Olsen Kristina Wendelboe , Petersen Kajsa Uglevig , Schmidt Lone , Stormlund Sacha , Svendsen Pernille Fog , Vassard Ditte , Wang Nathalie Friis , Zedeler Anne , Bhasin Shalender , Chavarro Jorge , Eisenberg Michael L. , Hauser Russ , Huhtaniemi Ilpo , Krawetz Stephen A. , Marko‐Varga György , Salonia Andrea , Toppari Jorma , Juul Anders , Jørgensen Niels , Nielsen Henriette Svarre , Pinborg Anja , Rylander Lars , Giwercman Aleksander
Published: June 2021

Background

Infertility affects 15%–25% of all couples during their reproductive life span. It is a significant societal and public health problem with potential psychological, social, and economic consequences. Furthermore, infertility has been linked to adverse long‐term health outcomes. Despite the advanced diagnostic and therapeutic techniques available, approximately 30% of infertile couples do not obtain a live birth after fertility treatment. For these couples, there are no further options to increase their chances of a successful pregnancy and live birth.

Objectives

Three overall questions will be studied: (1) What are the risk factors and natural life courses of infertility, early embryonic loss, and adverse pregnancy outcomes? (2) Can we develop new diagnostic and prognostic biomarkers for fecundity and treatment success? And (3) what are the health characteristics of women and men in infertile couples at the time of fertility treatment and during long‐term follow‐up?

Material and Methods

ReproUnion Biobank and Infertility Cohort (RUBIC) is established as an add‐on to the routine fertility management at Copenhagen University Hospital Departments in the Capital Region of Denmark and Reproductive Medicine Centre at Skåne University Hospital in Sweden. The aim is to include a total of 5000 couples equally distributed between Denmark and Sweden. The first patients were enrolled in June 2020. All eligible infertile couples are prospectively asked to participate in the project. Participants complete an extensive questionnaire and undergo a physical examination and collection of biospecimens (blood, urine, hair, saliva, rectal swabs, feces, semen, endometrial biopsies, and vaginal swabs). After the cohort is established, the couples will be linked to the Danish and Swedish national registers to obtain information on parental, perinatal, childhood, and adult life histories, including disease and medication history. This will enable us to understand the causes of infertility and identify novel therapeutic options for this important societal problem.
Testicular torsion–detorsion causes dysfunction of mitochondrial oxidative phosphorylation
Authors: Shih Hung‐Jen , Chang Chao‐Yuan , Huang I‐Tao , Tsai Pei‐Shan , Han Chia‐Li , Huang Chun‐Jen
Published: June 2021

Background: Semen quality impairment is a serious consequence of testicular torsion–detorsion. Adequate germ‐cell mitochondrial oxidative phosphorylation plays a crucial role in male fertility. Changes in cellular oxidative phosphorylation in testicular tissues after testicular torsion–detorsion remain unclear.

Objectives: This study investigated whether testicular torsion–detorsion induces alternations of mitochondrial oxidative phosphorylation in testicular tissues.

Materials and Methods: BALB/c male mice were divided into a Sham group and a testicular torsion–detorsion group. At the end of the procedure, the mice were euthanized, and their bilateral testicles were removed. Mitochondria morphology was evaluated through transmission electron microscopy. The cellular respiratory functions of germ cells were evaluated using a Seahorse analyzer assay. The proteome profiles in testicular tissues were analyzed using liquid chromatography–tandem mass spectrometry. The differences in the expression levels of each component in the oxidative phosphorylation were revealed using Ingenuity Pathways Analysis.

Results: Inner mitochondrial membrane disruption was found in ipsilateral twisted testicular mitochondria in the torsion–detorsion group but not in contralateral untwisted testes. The cellular respiratory function in germ cells was significantly decreased after testicular torsion–detorsion in ipsilateral twisted testes but not in contralateral untwisted testes. Liquid chromatography–tandem mass spectrometry analysis of ipsilateral twisted testicular tissue revealed that mitochondrial proteins were differentially expressed after testicular torsion–detorsion. Testicular torsion–detorsion induced downregulation of oxidative phosphorylation and revealed alternations of specific proteins in the oxidative phosphorylation complexes.

Discussion and Conclusion: Testicular torsion–detorsion produced mitochondria injury and dysregulation of mitochondrial oxidative phosphorylation in ipsilateral twisted testes. Different protein expressions were identified in the mitochondrial oxidative phosphorylation complexes with testicular torsion–detorsion; new therapeutic targets may be identified to restore the oxidative phosphorylation function of germ cells.
Early repolarization pattern in adult females with eating disorders
Authors: Frederiksen Tanja Charlotte , Krogh Christiansen Morten , Clausen Loa , Kjærulf Jensen Henrik
Published: June 2021

Introduction

The risk of cardiovascular death is increased in patients with eating disorders (ED), but the background for this is unknown. Early repolarization pattern (ERP) on the electrocardiogram (ECG) has been associated with increased risk of sudden cardiac death.

Methods

We investigated the prevalence of ERP in 233 female patients with anorexia nervosa (AN) and bulimia nervosa (BN) (age 18–35 years) compared with 123 healthy female controls.

Results

Early repolarization pattern was present in 52 (22%) of ED patients (16 (15%) AN patients and 36 (29%) BN patients) and 17 (14%) of healthy controls. When adjusting for age, BMI, heart rate, use of selective serotonin reuptake inhibitors (SSRI), and potassium level, the odds ratio (OR) for ERP was 2.1 (95% CI 1.1–4.2, p = .03). There was an increased prevalence of inferolateral ERP in patients with ED compared with healthy controls (OR = 4.3, 95% CI 1.7–11.3, p = .003) as well as ERP with a downward/horizontal sloping ST segment (OR = 3.1, 95% CI 1.3–7.6, p = .01). Additionally, J‐point elevation >0.2 mV was more prevalent in patients with ED (OR = 3.3, 95% CI 1.1–9.7, p = .03).

Conclusion

The prevalence of ERP was increased in patients with ED compared with healthy controls. This finding may provide a possible explanation for the increased cardiovascular mortality in ED patients.
Comparison of viscocanalostomy plus suture‐assisted near‐360‐degree trabeculotomy and viscocanalostomy plus rigid probe trabeculotomy in primary congenital glaucoma
Authors: Yu Qiuli , Liang Ya , Ji Fangfang , Sun Hong , Zhang Xiaojun , Zhou Qing , Chen Zhijun , Gu Hongwei , Yuan Zhilan
Published: June 2021

Purpose

To compare the efficacy and safety of viscocanalostomy plus near‐360‐degree suture trabeculotomy (VST) with viscocanalostomy plus rigid probe trabeculotomy (VT) in treating primary congenital glaucoma (PCG) over a one‐year follow‐up.

Methods

This consecutive retrospective study included patients with PCG confirmed within 3 years of age from March 2017 to October 2019. Efficacy was evaluated by comparing the postoperative intraocular pressure (IOP) curve and the success rate at one year after surgery. Safety was assessed by comparing the postoperative complications. The number of anti‐glaucoma agents, horizontal corneal diameter (HCD) and cup‐to‐disc ratio (C/D) of the two surgical methods were also compared.

Results

Data of 90 eyes from 61 patients were analysed. The baseline parameters of the two groups were similar. The IOP at 12 months after surgery in the VST group was 12.7 ± 4.8 mmHg, while that in the VT group was 15.8 ± 6.5 mmHg. The IOP at 6, 9 and 12 months postoperatively in the VST group was significantly lower than in the VT group (p < 0.05). Viscocanalostomy plus near‐360‐degree suture trabeculotomy (VST) remained a significant favourable factor for complete one‐year success (93.6% versus 74.4%, p = 0.005) but not qualified one‐year success (97.9% versus 88.4%, p = 0.06). The number of anti‐glaucoma agents, HCD and C/D were reduced in both groups. Postoperative complications were not significantly different between the two groups.

Conclusions

In children with PCG, VST provides a more durable IOP control than VT over the one‐year follow‐up, with a similar safety profile.