bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Disease Severity on Respiratory Impedance in Parkinson’s Disease
Authors: Sampath Meghashree , Srivastava Achal Kumar , Goyal Vinay , Jaryal Ashok Kumar , Deepak Kishore Kumar , Talwar Anjana
Published: November 2020

Background:

Parkinson’s disease (PD) is a progressive neurodegenerative disorder. PD has been traditionally perceived as a motor disorder. However, it is frequently associated with pulmonary dysfunction which has been assessed by Spirometry, an effort-dependent technique.

Purpose:

To evaluate in patients with PD the effect of disease severity on respiratory impedance using Impulse Oscillometry (IOS) and to correlate with Spirometry.

Methods:

The study was conducted on 30 patients diagnosed with PD. Pulmonary function was assessed by IOS and spirometer. IOS is an effort-independent technique that uses sound waves of different frequencies to measure airway resistance. Spirometer measures the lung volume and generates flow–volume and volume–time relationship.

Results:

The mean age of patients was 60.1±9.45. Resistance at 5 Hz (R5) was found to be negatively correlated with forced expiratory volume in the first second of the FVC manoeuver (FEV1) ( r = –0.628, P = .002), FEV1/FVC (forced vital capacity) ( r = –0.487, P = .025), and PEF ( r = –0.599, P = .004), and resistance at 20 Hz (R20) with FEV1 ( r = –0.474, P = .029) and PEF ( r = –0.522, P = .015). There was significant increase in R5 (0.32(0.36–0.28) vs 0.47(0.60–0.36); P = .04) and R20 (0.25(0.28–0.20) vs 0.30(0.40–0.25); P = .04) in stage II as compared to stage I of Hoehn–Yahr scale.

Conclusion:

IOS might be a promising tool for diagnosis of respiratory dysfunction in addition to Spirometry, especially in cases where patients are not able to perform forced manoeuvers.
Myocarditis caused by naturally acquired canine distemper virus infection in 4 dogs
Authors: Kim Dae Young , Zinn Michael M. , Odemuyiwa Solomon O. , Mitchell William J. , Johnson Gayle C.
Published: November 2020

Canine distemper virus (CDV) has long been recognized as a cause of myocarditis; however, cases of myocarditis caused by naturally acquired CDV infection have been reported only rarely in dogs. We describe here our retrospective study of naturally acquired systemic CDV infection in 4 dogs, 4–7 wk old, that had myocarditis, with myocardial necrosis and fibrosis. One of the 4 dogs had intracytoplasmic eosinophilic inclusion bodies in cardiomyocytes. Other lesions included bronchointerstitial pneumonia (4 of 4), necrotizing hepatitis (2 of 4), splenic lymphoid necrosis (2 of 4), encephalitis (1 of 3; brain was not submitted in 1 case), and necrotizing gastroenteritis (1 of 4). The presence of CDV in the heart was confirmed by immunohistochemistry in all 4 dogs.
Species-Specific Immunoassay Aids Identification of Pathogen and Tracks Infectivity in Foot Infection
Authors: Hao Stephanie P. , Masters Elysia A. , Ninomiya Mark J. , Beck Christopher A. , Schwarz Edward M. , Daiss John L. , Oh Irvin
Published: November 2020

Background:

Conventional bacterial cultures frequently fail to identify the dominant pathogen in polymicrobial foot infections, in which Staphylococcus aureus is the most common infecting pathogen. Previous work has shown that species-specific immunoassays may be able to identify the main pathogen in musculoskeletal infections. We sought to investigate the clinical applicability of a S. aureus immunoassay to accurately identify the infecting pathogen and monitor its infectivity longitudinally in foot infection. We hypothesized that this species-specific immunoassay could aid in the diagnosis of S. aureus and track the therapeutic response in foot infections.

Methods:

From July 2015 to July 2019, 83 infected foot ulcer patients undergoing surgical intervention (debridement or amputation) were recruited and blood was drawn at 0, 4, 8, and 12 weeks. Whole blood was analyzed for S. aureus–specific serum antibodies (mix of historic and new antibodies) and plasmablasts were isolated and cultured to quantify titers of newly synthesized antibodies (NSAs). Anti– S. aureus antibody titers were compared with culture results to assess their concordance in identifying S. aureus as the pathogen. The NSA titer changes at follow-ups were compared with wound healing status to evaluate concordance between evolving host immune response and clinically resolving or relapsing infection.

Results:

Analysis of serum for anti– S. aureus antibodies showed significantly increased titers of 3 different anti– S. aureus antibodies, IsdH ( P = .037), ClfB ( P = .025), and SCIN ( P = .005), in S. aureus culture-positive patients compared with culture-negative patients. Comparative analysis of combining antigens for S. aureus infection diagnosis increased the concordance further. During follow-up, changes of NSA titers against a single or combination of S. aureus antigens significantly correlated with clinically resolving or recurring infection represented by wound healing status.

Conclusion:

In the management of foot infection, the use of S. aureus–specific immunoassay may aid in diagnosis of the dominant pathogen and monitoring of the host immune response against a specific pathogen in response to treatment. Importantly, this immunoassay could detect recurrent foot infection, which may guide a surgeon’s decision to intervene.

Level of Evidence:

Level II, prospective comparative study.
A Diffractive Story
Authors: Coulter Cathy
Published: November 2020

Magical realism is a literary genre that offers possibilities as a posthumanist narrative research project. Magical realism employs literary tools such as a nonlinear aspect of time, a subjective sense of causality, and a conflation of the magical and the ordinary. Such tools offer possibilities in narrative research to create ontological sense-events that exist within assemblages that entangle the reader, the narrator, the place, the writer, and the participants temporally, spatially, and sensually within a flattened event. This article explores the possibilities of magical realism, offering a fleeting assemblage and a subsequent diffractive analysis. It employs a magical realist narrative construction based on a collaborative partnership between an Alaska Native village and a public university in which language revitalization efforts are sought through various school-based projects, including a teacher-training program, creation of subsistence-based native language curriculum, and other projects.
Black lives matter: Organization recommits to racial justice
Authors: Mir Raza , Zanoni Patrizia
Published: November 2020

We at Organization are committed to “Black Lives Matter,” three simple words that represent a complex and powerful set of truths about the ongoing struggles of the Black community against the structural interests that beset them. We share many of the values that guide this global social movement. As a journal, we pledge to carry the ethical and political momentum generated by this mobilization for justice forward in the organization studies community and beyond. This brief note is both a reminder of what we have stood for as critical scholars since our early days, and an admission that we have not done nearly enough. Most importantly, it is a commitment to foregrounding and addressing anti-Black racism in our analyses, our actions, and our institutions.
A calculation method of sliding friction coefficient on tooth surface for helical gear pair based on loaded tooth contact analysis and elastohydrodynamic lubrication theory
Authors: Wang Cheng , Ken Mao
Published: November 2020

The sliding friction coefficient on tooth surface is related to power loss, carry capacity and transmission performance of gear. Reasonable transmission analysis of gear pair is the premise of accurate calculation of sliding friction coefficient on tooth surface. However, for helical gear pair, the line contact without considering machining error/installation error/modification of gear is usually adopted to replace the major axis of ellipse caused by contact load. Therefore, in this paper, contact path on tooth surface, length of contact line, load distribution on tooth surface and loaded transmission errors are accurately calculated by loaded tooth contact analysis (LTCA). Combing with elastohydrodynamic lubrication (EHL) theory, a calculation method of sliding friction coefficient on tooth surface for helical gear pair is proposed.
Increased risk of 2-year death in patients who discontinued their use of statins
Authors: Seaman Karla , Sanfilippo Frank , Bulsara Max , Roughead Elizabeth , Kemp-Casey Anna , Bulsara Caroline , Watts Gerald F , Preen David
Published: November 2020

Objective

This study examined the association between statin usage (discontinued, reduced or continued) and two-year death following a 21% increase in the Pharmaceutical Benefits Scheme (PBS) consumer co-payment in Western Australia.

Methods

A retrospective observational study in Western Australia using linked administrative Commonwealth PBS data and State hospital inpatient and death data (n = 207,066) was undertaken. We explored the two-year all-cause and ischemic heart disease(IHD)/stroke-specific-death in individuals who discontinued, reduced or continued statin medication following the January 2005 PBS co-payment increase, overall, by beneficiary status (general population vs. social security recipients) and by a history of admission for ischemic heart disease or stroke. Non-cardiovascular (CVD)-related death was also considered.

Results

In the first six months of 2005, 3.3% discontinued, 12.5% reduced and 84.2% continued statin therapy. We found those who discontinued statins were also likely to discontinue at least two other medicines compared to those who continued therapy. There were 4,607 all-cause deaths. For IHD/stroke-specific death, there were 1,317. For all non-CVD-related death, there were 2,808 deaths during the 2-year follow-up period. Cox regression models, adjusted for demographic and clinical characteristics, showed a 39%-61% increase in the risk of all-cause death for individuals who reduced or discontinued statin medication compared to those who continued their statin medication (Discontinued: Adj HR = 1.61, 95% CI 1.40–1.85; Reduced: Adj HR = 1.39, 95% CI 1.28–1.51). For IHD/stroke-specific death, there was an increased risk of death by 28–76% (Discontinued: Adj sHR = 1.76, 95% CI 1.37–2.27; Reduced: Adj sHR = 1.28, 95% CI 1.10–1.49), and for non-CVD-related death, there was an increased risk of death by 44–57% (Discontinued: Adj sHR = 1.57, 95% CI 1.31–1.88; Reduced: Adj sHR = 1.44, 95% CI 1.30–1.60), for individuals who discontinued or reduced their statin medication compared to those who continued.

Conclusions

Patients who discontinued their statin therapy had a significantly increased risk of IHD and stroke death. Health professionals should be aware that large co-payment changes may be associated with patients discontinuing or reducing medicines to their health detriment. Factors that lead to such changes in patient medication-taking behaviour need to be considered and addressed at the clinical and policy levels.
Beliefs about causal factors for suicide in rural Alaska Native communities and recommendations for prevention
Authors: Skewes Monica C. , Gameon Julie A. , Grubin Fiona , DeCou Christopher R. , Whitcomb Lindsey
Published: November 2020

Rural Indigenous communities in Alaska suffer staggeringly high rates of suicide. In close-knit Alaska Native villages, each suicide leaves a trail of affected family and community members in its wake. This research aimed to understand community perceptions of what causes suicide in rural Alaska Native villages and generate recommendations for prevention strategies. In-depth interviews were conducted with 25 Alaska Native university students who moved from rural villages to an urban area to attend college. All had been profoundly affected by others’ suicides and shared their beliefs about causal factors and recommendations for prevention efforts. Perceived causes included resistance to seeking help or discussing personal problems, loss of culture, traumatic experiences, geographical and social isolation, lack of opportunity, substance abuse, and exposure to others’ suicides. Participants believed that suicide is preventable and recommended multi-level approaches to address suicide disparities. They provided recommendations for potentially effective and culturally appropriate prevention strategies, including increasing cultural and social connections, educating community members about mental health, and increasing accessibility of counseling services/reducing barriers to mental health services utilization.
Brexit’s implications for EU-NATO cooperation: Transatlantic bridge no more?
Authors: Ewers-Peters Nele Marianne
Published: November 2020

Since its accession to the European Union, the United Kingdom has played an important role in the design and development of the European Union’s foreign, security and defence policy. While it is among the founding members of North Atlantic Treaty Organization, it is also one of the main contributors to European security and played an active part in developing the relationship between both organisations. With the United Kingdom’s decision to leave the European Union, questions concerning the implications of Brexit on European Union–North Atlantic Treaty Organization cooperation arise. As the transatlantic bridge between the two organisations, Britain also faces an uncertain position within the European security architecture. It therefore needs to redefine its relations with the European Union and its own position among other member states. Taking into account the development of national security interests and recent political events, this article develops three possible scenarios that may occur for the European Union–North Atlantic Treaty Organization relationship depending on the outcome of the Brexit negotiations.
Machines as manifestations of global systems: Steps toward a sociometabolic ontology of technology
Authors: Hornborg Alf
Published: November 2020

Anthropologists have generally found it reasonable to understand the Industrial Revolution in Britain as a product of global historical processes including colonialism and the structure of world trade. The extent to which the industrialization of British textile production was contingent on global processes has been illuminated in detail by historians such as Joseph Inikori. Andre Gunder Frank proposed that we should reconceptualize technological development as a ‘world economic process, which took place in and because of the structure of the world economy’. Yet the theoretical implications of understanding industrial technological systems as global and unevenly distributed phenomena have, by and large, not contaminated mainstream conceptions of technologies as politically neutral and fundamentally innocent manifestations of enlightenment, detachable from the societal contexts in which they have emerged. Social theory nevertheless offers perspectives for a radical rethinking of this conventional ontology of modern technology. If the premises of actor–network theory, material culture studies, Marxism and poststructuralist critiques of power and inequalities are combined with the perspectives of ecological economics on global social metabolism, the fossil-fuelled textile factories of 19th-century Britain can be reinterpreted as social instruments for appropriating embodied human labour and natural space from elsewhere in the global system. A renewed ‘anthropology of technology’ might focus on the observation that technology is not simply a matter of putting nature to work, but a strategy of putting other sectors of global society to work. 1
A survey of tag clouds as tools for information retrieval and content representation
Authors: Torres Parejo Úrsula , Campaña Jesús R , Vila M Amparo , Delgado Miguel
Published: November 2020

Tag clouds are tools that have been widely used on the Internet since their conception. The main applications of these textual visualizations are information retrieval, content representation and browsing of the original text from which the tags are generated. Despite the extensive use of tag clouds, their enormous popularity and the amount of research related to different aspects of them, few studies have summarized their most important features when they work as tools for information retrieval and content representation. In this paper we present a summary of the main characteristics of tag clouds found in the literature, such as their different functions, designs and negative aspects. We also present a summary of the most popular metrics used to capture the structural properties of a tag cloud generated from the query results, as well as other measures for evaluating the goodness of the tag cloud when it works as a tool for content representation. The different methods for tagging and the semantic association processes in tag clouds are also considered. Finally we give a list of alternative for visual interfaces, which makes this study a useful first help for researchers who want to study the content representation and information retrieval interfaces in greater depth.
Genetic variation in CARD8, a gene coding for an NLRP3 inflammasome-associated protein, alters the genetic risk for diabetic nephropathy in the context of type 2 diabetes mellitus
Authors: Tsetsos Fotis , Roumeliotis Athanasios , Tsekmekidou Xanthippi , Alexouda Sophia , Roumeliotis Stefanos , Theodoridis Marios , Thodis Elias , Panagoutsos Stylianos , Papanas Nikolaos , Papazoglou Dimitrios , Kotsa Kalliopi , Yovos John G , Maltezos Efstratios , Passadakis Ploumis , Paschou Peristera , Georgitsi Marianthi
Published: November 2020

Background:

Approximately one third of type 2 diabetes mellitus (T2DM) cases present with diabetic nephropathy (DN), the leading cause of end-stage renal disease. Inflammation plays an important role in T2DM disease and DN pathogenesis. NLRP3 inflammasomes are complexes that regulate interleukin-1B (IL-1B) and IL-18 secretion, both involved in inflammatory responses. Activation of NLRP3 is associated with DN onset and progression. Here, we explore whether DN is associated with variants in genes encoding key members of the NLRP3 inflammasome pathway.

Methods:

Using genome-wide association data, we performed a pilot case-control association study, between 101 DN-T2DM and 185 non-DN-T2DM cases from the Hellenic population across six NLRP3 inflammasome pathway genes.

Results:

Three common CARD8 variants confer decreased risk for DN, namely rs11665831 (OR = 0.62, p = 0.016), rs11083925 (OR = 0.65, p = 0.021), and rs2043211 (OR = 0.66, p = 0.026), independent of sex or co-inheritance with an IL-1B variant.

Conclusion:

CARD8 acts as an NLRP3, NF-κB and caspase-1 inhibitor; perhaps, alterations in the cross-talk between CARD8, NF-κB, and NLRP3, which could affect the pro-inflammatory environment in T2DM, render diabetic carriers of certain common CARD8 variants potentially less likely to develop T2DM-related pro-inflammatory responses followed by DN. These preliminary, yet novel, observations will require validation in larger cohorts from several ethnic groups.
Cerebellar Theta-Burst Stimulation Combined With Physiotherapy in Subacute and Chronic Stroke Patients: A Pilot Randomized Controlled Trial
Authors: Liao Ling-Yi , Xie Yun-Juan , Chen Yi , Gao Qiang
Published: November 2020

Background

Intermittent theta-burst stimulation (iTBS) has been suggested to improve poststroke rehabilitation. The cerebellum is considered crucial for motor control. However, the effects of cerebellar iTBS with routine physical therapy on balance and motor recovery in subacute and chronic stroke patients have not been explored.

Objective

To measure the short-term effects of cerebellar iTBS with physiotherapy on the balance and functional outcomes in subacute and chronic stroke patients with hemiparesis.

Methods

Thirty hemiparetic patients were recruited for this randomized, double-blinded, sham-controlled trial, and randomized into either the treatment or sham group. Both groups participated in physiotherapy 5 times per week for 2 weeks, and cerebellar iTBS or sham iTBS was performed daily, immediately before physiotherapy. The primary outcome was the Berg balance scale (BBS) score. Secondary outcomes included the trunk impairment scale (TIS) score, Fugl-Meyer assessment scale score for lower extremities (FMA-LE), Barthel index (BI), and corticospinal excitability, as measured by transcranial magnetic stimulation. The outcomes were measured before and 1 week and 2 weeks after the intervention.

Results

Compared with those at baseline, significant increases were identified in all clinical scores (BBS, TIS, FMA-LE, and BI) in both groups after the 2-week intervention. The BBS and TIS scores improved more in the iTBS group than in the sham group.

Conclusions

Cerebellar iTBS with physiotherapy promotes balance and motor recovery in poststroke patients. Therefore, this method can be used in low-cost, fast, and efficient protocols for stroke rehabilitation (Chinese Clinical Trial Registry: ChiCTR1900026450).
Added Value of QEEG for the Differential Diagnosis of Common Forms of Dementia
Authors: Livinț Popa Livia , Dragoș Hanna-Maria , Strilciuc Ștefan , Pantelemon Cristina , Mureșanu Ioana , Dina Constantin , Văcăraș Vitalie , Mureșanu Dafin
Published: November 2020

Introduction

Quantitative electroencephalography (QEEG) has been documented as a helpful tool in the differential diagnosis of Alzheimer’s disease (AD) with common forms of dementia. The main objective of the study was to assess the role of QEEG in AD differential diagnosis with other forms of dementia: Lewy body dementia (LBD), Parkinson’s disease dementia (PDD), frontotemporal dementia (FTD), and vascular dementia (VaD).

Methods

We searched PubMed, Embase, and PsycNET, for articles in English published in peer-reviewed journals from January 1, 1980 to April 23, 2019 using adapted search strategies containing keywords quantitative EEG and Alzheimer. The risk of bias was assessed by applying the QUADAS tool. The systematic review was conducted in line with the PRISMA methodology.

Results

We identified 10 articles showcasing QEEG features used in diagnosing dementia, EEG slowing phenomena in AD and PDD, coherence changes in AD and VaD, the role of LORETA in dementia, and the controversial QEEG pattern in FTD. Results vary significantly in terms of sociodemographic features of the studied population, neuropsychological assessment, signal acquisition and processing, and methods of analysis.

Discussion

This article provides a comparative synthesis of existing evidence on the role of QEEG in diagnosing dementia, highlighting some specific features for different types of dementia (eg, the slow-wave activity has been remarked in both AD and PDD, but more pronounced in PDD patients, a diminution in anterior and posterior alpha coherence was noticed in AD, and a lower alpha coherence in the left temporal-parietal-occipital regions was observed in VaD).

Conclusion

QEEG may be a useful investigation for settling the diagnosis of common forms of dementia. Further research of quantitative analyses is warranted, particularly on the association between QEEG, neuropsychological, and imaging features. In conjunction, these methods may provide superior diagnostic accuracy in the diagnosis of dementia.
Field-Based Decisions on the Collection of Archaeological Materials: Monitoring and Ethics
Authors: Brennan Ellen
Published: November 2020

Cultural resource managers are faced with increasing challenges regarding decisions to collect archaeological artifacts from site contexts. Increased visitation, information sharing through social media, and recreation contribute to challenges to preserving archaeological sites and the undisturbed artifacts they contain. Many National Park Service cultural resource managers and staff are directed to manage archaeological resources in-situ. To our tribal colleagues, archaeological sites and artifacts represent links to their oral histories and their ancestors. To others, artifacts provide insights to past ways of life and add an intangible and irreplaceable quality to archaeological sites. Under normal circumstances materials gathered during data recovery projects are curated as they should be. Grab-samples and artifacts from unexcavated archaeological contexts, that is surface collection, must be carefully evaluated prior to gathering archaeological materials, otherwise we run the risk of storing artifacts for decades that are not analyzed, curated, or used to further our knowledge about the past. This article presents a case study of how monitoring information and field-based decision-making guided the collection, but not the accession, of an archaeological artifact from an in-situ context.
A genetic modifier of venous thrombosis in zebrafish reveals a functional role for fibrinogen AαE in early hemostasis
Authors: Freire Cristina , Fish Richard J. , Vilar Rui , Di Sanza Corinne , Grzegorski Steven J. , Richter Catherine E. , Shavit Jordan A. , Neerman-Arbez Marguerite
Published: November 2020

Plasma fibrinogen molecules comprise 2 copies of Aα, Bβ, and γ chains folded into a hexameric protein. A minor fibrinogen isoform with an extended Aα chain (AαE) is more abundant in newborn human blood than in adults. Larval zebrafish produce predominantly AαE-containing fibrinogen, but its functional significance is unclear. In 3-day-old zebrafish, when hemostasis is reliant on fibrinogen and erythrocyte-rich clotting but is largely thrombocyte-independent, we measured the time to occlusion (TTO) in a laser-induced venous thrombosis assay in 3 zebrafish strains (AB, TU, and AB × TL hybrids). AB larvae showed delayed TTO compared with the TU and AB × TL strains. Mating AB with TU or TL produced larvae with a TU-like TTO. In contrast to TU, AB larvae failed to produce fibrinogen AαE, due to a mutation in the AαE-specific coding region of fibrinogen α-chain gene (fga). We investigated whether the lack of AαE explained the delayed AB TTO. Transgenic expression of AαE, but not Aα, shortened the AB TTO to that of TU. AαE rescued venous occlusion in fibrinogen mutants or larvae with morpholino-targeted fibrinogen α-chain messenger RNA, but Aα was less effective. In 5-day-old larvae, circulating thrombocytes contribute to hemostasis, as visualized in Tg(itga2b:EGFP) transgenics. Laser-induced venous thrombocyte adhesion and aggregation is reduced in fibrinogen mutants, but transgenic expression of Aα or AαE restored similar thrombocyte accumulation at the injury site. Our data demonstrate a genetic modifier of venous thrombosis and a role for fibrinogen AαE in early developmental blood coagulation, and suggest a link between differentially expressed fibrinogen isoforms and the cell types available for clotting.
Secondary CNL after SAA reveals insights in leukemic transformation of bone marrow failure syndromes
Authors: Schmied Laurent , Olofsen Patricia A. , Lundberg Pontus , Tzankov Alexandar , Kleber Martina , Halter Jörg , Uhr Mario , Valk Peter J. M. , Touw Ivo P. , Passweg Jakob , Drexler Beatrice
Published: November 2020

Acquired aplastic anemia and severe congenital neutropenia (SCN) are bone marrow (BM) failure syndromes of different origin, however, they share a common risk for secondary leukemic transformation. Here, we present a patient with severe aplastic anemia (SAA) evolving to secondary chronic neutrophilic leukemia (CNL; SAA-CNL). We show that SAA-CNL shares multiple somatic driver mutations in CSF3R, RUNX1, and EZH2/SUZ12 with cases of SCN that transformed to myelodysplastic syndrome or acute myeloid leukemia (AML). This molecular connection between SAA-CNL and SCN progressing to AML (SCN-AML) prompted us to perform a comparative transcriptome analysis on nonleukemic CD34high hematopoietic stem and progenitor cells, which showed transcriptional profiles that resemble indicative of interferon-driven proinflammatory responses. These findings provide further insights in the mechanisms underlying leukemic transformation in BM failure syndromes.
Processing methods and storage duration impact extracellular vesicle counts in red blood cell units
Authors: Gamonet Clementine , Desmarets Maxime , Mourey Guillaume , Biichle Sabeha , Aupet Sophie , Laheurte Caroline , François Anne , Resch Eric , Bigey Frédéric , Binda Delphine , Bardiaux Laurent , Naegelen Christian , Marpaux Nadine , Delettre Fanny Angelot , Saas Philippe , Morel Pascal , Tiberghien Pierre , Lacroix Jacques , Capellier Gilles , Vidal Chrystelle , Garnache-Ottou Francine
Published: November 2020

Extracellular vesicles (EVs) are active components of red blood cell (RBC) concentrates and may be associated with beneficial and adverse effects of transfusion. Elucidating controllable factors associated with EV release in RBC products is thus important to better manage the quality and properties of RBC units. Erythrocyte-derived EVs (EEVs) and platelet-derived EVs (PEVs) were counted in 1226 RBC units (administered to 280 patients) using a standardized cytometry-based method. EV size and CD47 and annexin V expression were also measured. The effects of donor characteristics, processing methods, and storage duration on EV counts were analyzed by using standard comparison tests, and analysis of covariance was used to determine factors independently associated with EV counts. PEV as well as EEV counts were higher in whole-blood–filtered RBC units compared with RBC-filtered units; PEV counts were associated with filter type (higher with filters associated with higher residual platelets), and CD47 expression was higher on EEVs in RBC units stored longer. Multivariate analysis showed that EEV counts were strongly associated with filter type (P < .0001), preparation, and storage time (+25.4 EEV/µL per day [P = .01] and +42.4 EEV/µL per day [P < .0001], respectively). The only independent factor associated with PEV counts was the residual platelet count in the unit (+67.1 PEV/µL; P < .0001). Overall, processing methods have an impact on EV counts and characteristics, leading to large variations in EV quantities transfused into patients. RBC unit processing methods might be standardized to control the EV content of RBC units if any impacts on patient outcomes can be confirmed. The IMIB (Impact of Microparticles in Blood) study is ancillary to the French ABLE (Age of Transfused Blood in Critically Ill Adults) trial (ISRCTN44878718).
DeepCryoPicker: fully automated deep neural network for single protein particle picking in cryo-EM
Authors: Al-Azzawi Adil , Ouadou Anes , Max Highsmith , Duan Ye , Tanner John J. , Cheng Jianlin
Published: November 2020

Background

Cryo-electron microscopy (Cryo-EM) is widely used in the determination of the three-dimensional (3D) structures of macromolecules. Particle picking from 2D micrographs remains a challenging early step in the Cryo-EM pipeline due to the diversity of particle shapes and the extremely low signal-to-noise ratio of micrographs. Because of these issues, significant human intervention is often required to generate a high-quality set of particles for input to the downstream structure determination steps.

Results

Here we propose a fully automated approach (DeepCryoPicker) for single particle picking based on deep learning. It first uses automated unsupervised learning to generate particle training datasets. Then it trains a deep neural network to classify particles automatically. Results indicate that the DeepCryoPicker compares favorably with semi-automated methods such as DeepEM, DeepPicker, and RELION, with the significant advantage of not requiring human intervention.

Conclusions

Our framework combing supervised deep learning classification with automated un-supervised clustering for generating training data provides an effective approach to pick particles in cryo-EM images automatically and accurately.
Gene expression kinetics of Exaiptasia pallida innate immune response to Vibrio parahaemolyticus infection
Authors: Seneca François , Davtian David , Boyer Laurent , Czerucka Dorota
Published: November 2020

Background

Recent sequencing projects on early-diverging metazoans such as cnidarians, have unveiled a rich innate immunity gene repertoire; however, little is known about immunity gene regulation in the host’s early response against marine bacterial pathogens over time. Here, we used RNA-seq on the sea anemone Exaiptasia pallida (Ep) strain CC7 as a model to depict the innate immune response during the onset of infection with the marine pathogenic bacteria Vibrio parahaemolyticus (Vp) clinical strain O3:K6, and lipopolysaccharides (LPS) exposure. Pairwise and time series analyses identified the genes responsive to infection as well as the kinetics of innate immune genes over time. Comparisons between the responses to live Vp and purified LPS was then performed.

Results

Gene expression and functional analyses detected hundreds to thousands of genes responsive to the Vp infection after 1, 3, 6 and 12 h, including a few shared with the response to LPS. Our results bring to light the first indications that non-canonical cytoplasmic pattern recognition receptors (PRRs) such as NOD-like and RIG-I-like receptor homologs take part in the immune response of Ep. Over-expression of several members of the lectin-complement pathways in parallel with novel transmembrane and Ig containing ficolins (CniFLs) suggest an active defense against the pathogen. Although lacking typical Toll-like receptors (TLRs), Ep activates a TLR-like pathway including the up-regulation of MyD88, TRAF6, NF-κB and AP-1 genes, which are not induced under LPS treatment and therefore suggest an alternative ligand-to-PRR trigger. Two cytokine-dependent pathways involving Tumor necrosis factor receptors (TNFRs) and several other potential downstream signaling genes likely lead to inflammation and/or apoptosis. Finally, both the extrinsic and intrinsic apoptotic pathways were strongly supported by over-expression of effector and executioner genes.

Conclusions

To our knowledge, this pioneering study is first to follow the kinetics of the innate immune response in a cnidarian during the onset of infection with a bacterial pathogen. Overall, our findings reveal the involvement of both novel immune gene candidates such as NLRs, RLRs and CniFLs, and previously identified TLR-like and apoptotic pathways in anthozoan innate immunity with a large amount of transcript-level evidence.
Skin pigmentation polymorphisms associated with increased risk of melanoma in a case-control sample from southern Brazil
Authors: Reis Larissa B. , Bakos Renato M. , Vianna Fernanda S. L. , Macedo Gabriel S. , Jacovas Vanessa C. , Ribeiro-dos-Santos André M. , Santos Sidney , Bakos Lúcio , Ashton-Prolla Patricia
Published: November 2020

Background

Melanoma is the most aggressive type of skin cancer and is associated with environmental and genetic risk factors. It originates in melanocytes, the pigment-producing cells. Single nucleotide polymorphisms (SNPs) in pigmentation genes have been described in melanoma risk modulation, but knowledge in the field is still limited.

Methods

In a case-control approach (107 cases and 119 controls), we investigated the effect of four pigmentation gene SNPs (TYR rs1126809, HERC2 rs1129038, SLC24A5 rs1426654, and SLC45A2 rs16891982) on melanoma risk in individuals from southern Brazil using a multivariate logistic regression model and multifactor dimensionality reduction (MDR) analysis.

Results

Two SNPs were associated with an increased risk of melanoma in a dominant model: rs1129038AA and rs1426654AA [OR = 2.094 (95% CI: 1.106–3.966), P = 2.3 10− 2 and OR = 7.126 (95% CI: 1.873–27.110), P = 4.0 10− 3, respectively]. SNP rs16891982CC was associated with a lower risk to melanoma development in a log-additive model when the allele C was inherited [OR = 0.081 (95% CI: 0.008–0.782), P = 3 10− 2]. In addition, MDR analysis showed that the combination of the rs1426654AA and rs16891982GG genotypes was associated with a higher risk for melanoma (P = 3 10− 3), with a redundant effect.

Conclusions

These results contribute to the current knowledge and indicate that epistatic interaction of these SNPs, with an additive or correlational effect, may be involved in modulating the risk of melanoma in individuals from a geographic region with a high incidence of the disease.
Establishment of an immune-related gene pair model to predict colon adenocarcinoma prognosis
Authors: Luo Jihang , Liu Puyu , Wang Leibo , Huang Yi , Wang Yuanyan , Geng Wenjing , Chen Duo , Bai Yuju , Yang Ze
Published: November 2020

Background

Colon cancer is the most common type of gastrointestinal cancer and has high morbidity and mortality. Colon adenocarcinoma (COAD) is the main pathological type of colon cancer, and much evidence has supported the correlation between the prognosis of COAD and the immune system. The current study aimed to develop a robust prognostic immune-related gene pair (IRGP) model to estimate the overall survival of patients with COAD.

Methods

The gene expression profiles and clinical information of patients with colon adenocarcinoma were obtained from the TCGA and GEO databases and were divided into training and validation cohorts. Immune genes were selected that showed a significant association with prognosis.

Results

Among 1647 immune genes, a model with 17 IRGPs was built that was significantly associated with OS in the training cohort. In the training and validation datasets, the IRGP model divided patients into the high-risk group and low-risk group, and the prognosis of the high-risk group was significantly worse (P<0.001). Univariate and multivariate Cox proportional hazard analyses confirmed the feasibility of this model. Functional analysis confirmed that multiple tumor progression and stem cell growth-related pathways were upregulated in the high-risk groups. Regulatory T cells and macrophages M0 were significantly highly expressed in the high-risk group.

Conclusion

We successfully constructed an IRGP model that can predict the prognosis of COAD, providing new insights into the treatment strategy of COAD.
Network governance forms in healthcare: empirical evidence from two Italian cancer networks
Authors: Romiti Anna , Del Vecchio Mario , Sartor Gino
Published: November 2020

Background

This study focuses on the application of Provan and Kenis’ modes of network governance to the specific field of public healthcare networks, extending the framework to an analysis of systems in which networks are involved. Thus, the aim of this study is to analyze and compare the governance of two cancer networks in two Italian regions that underwent system reconfiguration processes due to reforms in the healthcare system.

Methods

A qualitative study of two clinical networks in the Italian healthcare system was conducted. The sample for interviews included representatives of the regional administration (n = 4), network coordinators (n = 6), and general and clinical directors of health organizations involved in the two networks (n = 25). Data were collected using semi-structured interviews.

Results

Our study shows that healthcare system reforms have a limited impact on network governance structures. In fact, strong inertial tendencies characterize networks, especially network administrative organization models (NAO). Networks tend to find their own balance with respect to the trade-offs analyzed using a mix of formal and informal ties. Our study confirms the general validity of Provan and Kenis’ framework and shows how other specific factors and contingencies may affect the possibility that cancer networks find positive equilibria between competing needs of inclusivity and efficiency, internal and external legitimacy, and stability and flexibility. It also shows how networks react to external changes.

Conclusions

Our study shows the importance of considering three factors and contingencies that may affect network effectiveness: a) the importance of looking at network governance modes not in isolation, but in relationship to the governance of regional systems; b) the influence of a specific network’s governance structure on the network’s ability to respond to tensions and to achieve its goals; and c) the need to take into account the role of professionals in network governance.
ZBTB7A, a potential biomarker for prognosis and immune infiltrates, inhibits progression of endometrial cancer based on bioinformatics analysis and experiments
Authors: Geng Rong , Zheng Yuhua , zhou Donghua , Li Qingdong , Li Ruiman , Guo Xiaoling
Published: November 2020

Backgroud

ZBTB protein is an important member of the C2H2 zinc finger protein family. As a transcription factor, it is widely involved in the transcriptional regulation of genes, cell proliferation, differentiation, and apoptosis. The ZBTB7A has been largely linked to different kinds of tumors due to its diverse function. However, the value for ZBTB7A in uterine corpus endometrial carcinoma (UCEC) is unclear.

Methods

In our work, we assessed the importance of ZBTB7A in UCEC. Firstly, Using Oncomine and Tumor Immunoassay Resource (TIMER) databases to evaluate the expression of ZBTB7A. Secondly, we explored the co-expression network of ZBTB7A through the cBioPortal online tool, Metascape, and LinkedOmics. TIMER was also used to explore the relationship between ZBTB7A and tumor immune invasion, and to detect the correlation between the ZBTB7A and the marker genes related to immune infiltration. Finally, CCK8, migration, ChIP assays were introduced to partly validate ZBTB7A function in endometrial cancer cells.

Results

We found the ZBTB7A expression in TIMER was associated with various cancers, especially UCEC. The decreased expression of ZBTB7A was markedly related to the stage and prognosis of UCEC. Furthermore, ZBTB7A was also related to the expression of various immune markers such as Neutrophils, Dendritic cell, T cell (general), Th1, Th2, and Treg. Finally, we verified that ZBTB7A repressed E2F4 transcription and inhibited cells proliferation and migration. These results indicate that ZBTB7A may play a vital role in regulating immune cell infiltration in UCEC, and is a valuable prognostic marker.

Conclusions

In summary, we demonstrate that ZBTB7A is notably downregulated in UCEC, plays a vital role in regulating immune cell infiltration, possesses diagnostic and prognostic values and attenuates E2F4 transcription and cell proliferation, migration in vitro.
Climate factors and gestational diabetes mellitus risk – a systematic review
Authors: Preston Emma V. , Eberle Claudia , Brown Florence M. , James-Todd Tamarra
Published: November 2020

Background

Current and projected increases in global temperatures and extreme climate events have led to heightened interest in the impact of climate factors (i.e. ambient temperature, season/seasonality, and humidity) on human health. There is growing evidence that climate factors may impact metabolic function, including insulin sensitivity. Gestational diabetes mellitus (GDM) is a common pregnancy complication, with an estimated global prevalence of up to 14%. While lifestyle and genetic risk factors for GDM are well established, environmental factors may also contribute to GDM risk. Previous reviews have summarized the growing evidence of environmental risk factors for GDM including endocrine disrupting chemicals and ambient air pollution. However, studies of the effects of climate factors on GDM risk have not been systematically evaluated. Therefore, we conducted a systematic review to summarize and evaluate the current literature on the associations of climate factors with GDM risk.

Methods

We conducted systematic searches in PubMed and EMBASE databases for original research articles on associations of climate factors (i.e. ambient temperature, season/seasonality, and humidity) with GDM and/or related glycemic outcomes for all publication dates through September 20th, 2020.

Results

Our search identified 16 articles on the associations of ambient temperature and/or season with GDM and maternal glycemic outcomes during pregnancy, which were included in this review. Despite inconsistencies in exposure and outcome assessment, we found consistent evidence of a seasonal effect on GDM risk, with higher prevalence of GDM and higher pregnancy glucose levels in summer months. We found suggestive evidence of an association between higher ambient temperature and elevated glucose levels from GDM screening tests.

Conclusion

Climate factors may be associated with GDM risk. However, further research is needed to evaluate these associations and to elucidate the specific mechanisms involved.
Measuring the association of objective and perceived neighborhood environment with physical activity in older adults: challenges and implications from a systematic review
Authors: Peters Manuela , Muellmann Saskia , Christianson Lara , Stalling Imke , Bammann Karin , Drell Carina , Forberger Sarah
Published: November 2020

Background

A supportive environment is a key factor in addressing the issue of health among older adults. There is already sufficient evidence that objective and self-reported measures of the neighborhood environment should be taken into account as crucial components of active aging, as they have been shown to influence physical activity; particularly in people aged 60+. Thus, both could inform policies and practices that promote successful aging in place. An increasing number of studies meanwhile consider these exposures in analyzing their impact on physical activity in the elderly. However, there is a wide variety of definitions, measurements and methodological approaches, which complicates the process of obtaining comparable estimates of the effects and pooled results. The aim of this review was to identify and summarize these differences in order to emphasize methodological implications for future reviews and meta analyzes in this field and, thus, to create a sound basis for synthesized evidence.

Methods

A systematic literature search across eight databases was conducted to identify peer-reviewed articles examining the association of objective and perceived measures of the neighborhood environment and objectively measured or self-reported physical activity in adults aged ≥ 60 years. Two authors independently screened the articles according to predefined eligibility criteria, extracted data, and assessed study quality. A qualitative synthesis of the findings is provided.

Results

Of the 2967 records retrieved, 35 studies met the inclusion criteria. Five categories of methodological approaches, numerous measurement instruments to assess the neighborhood environment and physical activity, as well as several clusters of definitions of neighborhood, were identified.

Conclusions

The strength of evidence of the associations of specific categories of environmental attributes with physical activity varies across measurement types of the outcome and exposures as well as the physical activity domain observed and the operationalization of neighborhood. The latter being of great importance for the targeted age group. In the light of this, future reviews should consider these variations and stratify their summaries according to the different approaches, measures and definitions. Further, underlying mechanisms should be explored.