bluuebunny/crossref_metadata_2025 huggingface dataset:
Internal limiting membrane graft as a treatment for the retinal detachment secondary to an optic disc coloboma
Authors: Fernández-Engroba Jorge , Saman Muhsen , Nadal Jeroni
Published: February 2021

Purpose:

To report our anatomical outcome with the internal limiting membrane (ILM) graft procedure in the management of rhegmatogenous retinal detachment (RRD) secondary to optic disc coloboma (ODC).

Methods:

Description of a new surgical procedure in one eye of one patient who underwent pars plana vitrectomy (PPV) combined with ILM graft technique. Subsequent follow-up included optical coherence tomography (OCT) and visual acuity.

Results:

After only 1 week, the OCT revealed the ILM graft plugging the retinal tear with complete resorption of subretinal fluid. The sealing effect of this graft persisted after 6 months. However, visual outcome was poor and corrected distance visual acuity was 20/200 as a result of the previous long-standing retinal detachment with loss of photoreceptors.

Conclusion:

We suggest that ILM graft could be performed as a first line treatment in the management of RRD secondary to ODC. This direct closure of the retinal tears, allows a quick and effective interruption of the communication between the subretinal space and the vitreous cavity. Detecting these retinal tears and applying this technique as soon as possible could achieve not only an earlier anatomical success but obtain good visual results in retinal tears with RRD secondary to ODC. Further studies will be necessary to provide more evidences
Ballot spoilage as a response to limitations on choice and influence
Authors: Silva Patrick Cunha , Crisp Brian F
Published: February 2021

Electoral systems vary in terms of the choice and influence they offer voters. Beyond selecting between parties, preferential systems allow for choices within parties. More proportional systems make it likely that influence over who determines the assembly’s majority will be distributed across relatively more voters. In response to systems that limit choice and influence, we hypothesize that voters will cast more blank, null, or spoiled ballots on purpose. We use a regression discontinuity opportunity in French municipal elections to test this hypothesis. An exogenously chosen and arbitrary cutpoint is used to determine the electoral rules municipalities use to select their assemblies. We find support for our reasoning—systems that do not allow intraparty preference votes and that lead to disproportional outcomes provoke vote spoilage. Rates of vote spoilage are frequently sufficient to change control over the assembly if those votes had instead been cast validly for the second-place party.
Practices and Perceptions of Local Health Officers/Commissioners Regarding Tobacco 21 Policy Advocacy
Authors: Juarez Ruben , Haidar Salma , Brookins-Fisher Jodi , Hancher-Rauch Heidi , Ohneck Mallory , Thompson Amy , Papenfuse Daryn
Published: February 2021

Progress has been made in reducing adolescent cigarette smoking. However, the popularity of vaping products has increased concerns regarding tobacco use. One policy recently passed at the national level is Tobacco 21 (T21), which aims to reduce adolescent’s access to tobacco products. Since local health officers/commissioners play a crucial role in the development of policies that protect their respective communities from the harms of tobacco, it is important to characterize their views on the T21 legislation and advocacy activities among them. This was a cross-sectional pilot study of three Midwestern states taken prior to a number of key tobacco-related events in 2019. Results show almost 70% of respondents had high interest in influencing public policy, more than 80% thought the public policy makers’ actions regarding T21 were highly important to the health and well-being of the public, and 89% had in some capacity acted to support a T21 initiative. Involvement with legislative efforts was not high, despite evidence showing high popularity of the measure among the public. The top perceived benefits included a decrease in tobacco use among adolescents, improvements to community or state health, and delay in tobacco use initiation. Top barriers listed were issues with enforcement, lack of money or resources, competing health priorities, and policy makers’ attitudes and values. Respondents overall had significantly lower confidence in performing activities at the state versus local level. Findings suggest there may be a need for more advocacy training on effective advocacy strategies in changing health policy.
Remembering the Battle of Pezi Sla (Greasy Grass—aka Little Bighorn) with the Lakota, Northern Cheyenne, and Arapaho Victory Riders: An Autoethnographic Photo Essay
Authors: Creef Elena Tajima , Petersen Carl J.
Published: February 2021

If one travels to Little Bighorn Battlefield National Park in late June, one can witness at least three events that simultaneously take place each year commemorating what has been called “one of the great mythic and mysterious military battles of American history” (Frosch, 2010). The National Park Service rangers give “battle talks” on the hour to visiting tourists. Two miles away, the privately run U.S. Cavalry School also performs a scripted reenactment called “Custer’s Last Ride”—with riders who have been practicing all week to play the role of soldiers from the doomed regiment of Custer’s 7th Cavalry. On this same day, a traveling band of men, women, and youth from the Lakota, Northern Cheyenne, and Arapaho Nations who have journeyed by horseback and convoy from the Dakotas and Wyoming will reach Last Stand Hill to remember this “Victory Day” from 1876—one that historians have called the “last stand of the Indians” during the period of conflict known as the “Great Sioux War.” This photo essay offers an autoethnographic account of what some have dubbed the annual “Victory Ride” to Montana based upon my participation as a non-Native supporter of this Ride in 2017, 2018, and 2019.
Environmental Influences on the STEM Identity and Career Intentions of Latinx STEM Postdoctoral Scholars
Authors: Mendez Sylvia L. , Starkey Kathryn E. , Cooksey Sarah E. , Conley Valerie Martin
Published: February 2021

This study employs an instrumental case study design to explore the environmental context of Latinx postdoctoral scholars in relation to their STEM identity and intended STEM career pathway. Interviews were conducted using an interactionist approach to STEM identity development. Deductive data analysis techniques reveal the impact of supervisor relationships on the work environment, the importance of fostering a mentoring atmosphere for others, and the value of seeking and creating safe and supportive spaces.
Teaching at Holocaust memorial sites: Swedish teachers’ understanding of the educational values of visiting Holocaust memorial sites
Authors: Flennegård Ola , Mattsson Christer
Published: February 2021

The present article focuses on teaching and learning about the Holocaust in Sweden, conducted as study trips to Holocaust memorial sites. Although about a quarter of Swedish teenagers visit the Auschwitz-Birkenau State Museum each year, this study is the first to examine these Swedish study trips. Since there are no centralised systems for arranging these study trips, this study regards dedicated teachers as the main stakeholders. By deploying critical discourse analysis of transcripts of nine in-depth interviews with teachers, the study terms the discursive order of the teachers’ talk about the study trips ritual democratic catharsis. The teachers’ two main purposes are the use of the study trips as a vehicle for the social dynamics in the group to evolve in order to promote personal growth among the students, and the students’ learning about democracy and human rights. Their overarching didactic strategy of focusing on the suffering of the victims is meant to evoke empathy among the students, but lacks an explanatory aim. The study critically points out the teachers’ unreflected relationship to historiographic Holocaust content as a subject, making their teaching vulnerable to contemporary political influences, jeopardising the democratic purpose of these trips.
Making a Tough Choice: Teacher Target-Setting and Student Achievement in a Teacher Performance System Using Student Learning Objectives
Authors: Atteberry Allison , LaCour Sarah E.
Published: February 2021

The use of student learning objectives (SLOs) as part of teacher performance systems has gained traction quickly in the United States, yet little is known about how teachers select specific students’ learning goals. When teachers are evaluated—and sometimes compensated—based on whether their students meet the very objectives the teachers set at the start of the year, there may be an incentive to set low targets. SLO systems rely on teachers’ willingness and ability to set appropriately ambitious SLOs. We describe teachers’ SLO target-setting behavior in one school-district. We document the accuracy/ambitiousness of targets and find that teachers regularly set targets that students did not meet. We also find that, within the same year, a student’s spring test scores tend to be higher on the assessments for which they received higher targets. This raises the intriguing possibility that receiving higher targets might cause students to perform better than they otherwise would have.
Cognitive Reserve and Digital Confidence among Older Adults as New Paradigm for Resilient Aging
Authors: Ranieri Jessica , Guerra Federica , Angione Anna Lucia , Di Giacomo Dina , Passafiume Domenico
Published: February 2021

Objective

The purpose of this study was to examine the digital confidence of elder adults and identify behavioral patterns for technology that are related to cognitive abilities among elders.

Method

An observational study was conducted using a sample of 94 elders, aged 53 to 86 years. Neuropsychological and emotional measures were used, and technology use was assessed.

Results

Finding showed elders by resilient neuropsychological aspects can have a good affinity for technology. We examined the role of not only cognitive reserve levels but also demographic characteristics (i.e., age, educational level) and found that elderly were more adherent to digital resources. Technology can be a beneficial resource to those with medium levels of cognitive reserve and make them feel “like they are leading an active lifestyle.”

Conclusions

The focal point of our findings is the relevance of cognitive reserve during older adulthood as a key factor that should be examined in investigations on successful aging; it would be more interesting to examine these factors within the context of analyses on the impact of technology on aging and digital living.
Is There an Association Between Social Support and Pain Among Individuals Living With Multiple Sclerosis?
Authors: Alphonsus Khrisha B. , D’Arcy Carl
Published: February 2021

Context.

Pain is one of the most common symptoms reported by patients living with Multiple Sclerosis (MS). Risk factors associated with pain may include individual’s cognitive thinking process, emotional and behavioural response to pain and amount of social support. There is a lack of research on the influence on the amount of social support and its association to pain outcomes.

Objective.

The primary objective of this study was to determine the association between amount and of social support and its association with odds of pain among individuals with MS.

Methods.

The Survey on Living with Neurological Conditions in Canada (SLNCC) 2011-2012 linked to the Canadian Community Health Survey (CCHS) 2010-2011 was used to carry out a logistic regression model for this analysis (N = 78,623).

Main outcome measures.

The factors that were assessed were psychological factors, problems with sleeping, self-perceived general health, self-perceived level of stress, number of years living with MS, as well as social factors. The outcome variable was pain.

Results.

The amount of social support was found to be significant in that individuals who had 3 or fewer types of social support were 3.02 times more likely (95% CI 1.06 to 8.59) to report being in pain as opposed to individuals who had 4 types of support. The results indicate the importance of self efficacy in overcoming symptoms of MS and the need for more home care services.
Practitioner-friendly design method to improve the seismic performance of RC frame buildings
Authors: Arroyo Orlando , Liel Abbie , Gutiérrez Sergio
Published: February 2021

Reinforced concrete (RC) frame buildings are a widely used structural system around the world. These buildings are customarily designed through standard code-based procedures, which are well-suited to the workflow of design offices. However, these procedures typically do not aim for or achieve seismic performance higher than code minimum objectives. This article proposes a practical design method that improves the seismic performance of bare RC frame buildings, using only information available from elastic structural analysis conducted in standard code-based design. Four buildings were designed using the proposed method and the prescriptive approach of design codes, and their seismic performance is evaluated using three-dimensional nonlinear (fiber) models. The findings show that the seismic performance is improved with the proposed method, with reductions in the collapse fragility, higher deformation capacity, and greater overstrength. Furthermore, an economic analysis for a six-story building shows that these improvements come with only a 2% increase in the material bill, suggesting that the proposed method is compatible with current project budgets as well as design workflow. The authors also provide mathematical justification of the method.
Clinicopathologic Determinants of Survival in Monomorphic Epitheliotropic Intestinal T-Cell Lymphoma (MEITL): Analysis of a Pooled Database
Authors: Haddad Philip A , Dadi Neelakanta
Published: February 2021

Introduction:

MEITL is a rare and rapidly progressive extranodal T-cell lymphoma that arises from the intestinal intraepithelial T lymphocytes. Established in the 2016 WHO classification, this entity was carved out of what was previously known as type 2 enteropathy-associated T-cell lymphoma. MEITL usually affects the young-old and is not associated with celiac disease. We conducted this analysis to explore the clinicopathologic determinants of survival in this newly established T-cell entity.

Methods:

In order to study the demographic characteristics, molecular and immunohistochemical signatures, therapeutic interventions, survival, and prognostic factors, we compiled a pooled database of 116 cases. Kaplan-Meier survival curves were constructed. Cox proportional-hazards model and Log-rank tests were used to assess the influence of demographic and clinicopathologic factors on overall survival (OS).

Results:

A total of 116 patients with confirmed MEITL were identified. The median age was 59.5 years with a peak incidence between ages 56 and 68. There was a male predominance with M:F ratio of 2. The jejunum was the most commonly involved site (71%). Median OS of the whole group was 11 months. The most common presentations were abdominal pain, followed by perforation, diarrhea, and weight loss. The majority presented at stages I&II (78%). The median duration of symptoms prior to diagnosis was 4 months. Compared to no treatment, combination chemotherapy and stem cell transplant (SCT) were statistically superior with a median OS of 2, 9, and 34 months respectively (p=0.0005). Further analysis revealed that surgical resection imparted a survival advantage on its own and in conjunction with combination chemotherapy and SCT. When surgical resection was incorporated in the analysis, median OS amounted to 2, 5, 7, 11, 13, 24 months for no treatment, surgery alone, chemotherapy, surgery+chemotherapy, SCT, and surgery+SCT respectively (p=0.0015). The quality of response to treatment also seemed to impact the outcome (p=0.0005) with median OS of 6, 36, and 60 months for none/transient, PR, and CR respectively. OS was not impacted by sex, presentation with obstruction or perforation, or anatomic site involvement. While older age, weight loss, and TCRγδ seemed to negatively impact OS, they did not reach statistical significance.

Conclusions:

This study presents an updated clinicopathologic data from a pooled cohort of patients with MEITL. It identifies quality of response, treatment modalities as well as surgical resection as major determinants of OS in this rare disease.

Disclosures

No relevant conflicts of interest to declare.
Assay Specificity and Sensitivity Evaluation of Cepheid GeneXpert® NPM1 Prototype for Mutation Detection in Acute Myeloid Leukemia
Authors: Yang Xi , Shridhar Krupa , Sanjeeviraman Jayashree , Day Gwo-Jen
Published: February 2021

Background:

Mutations in thenucleophosmin1 (NPM1) are considered as founder mutations in acute myeloid leukemia (AML). NPM1 mutations in exon 12 occur in about 60% adult AML patients with normal karyotype. Among all NPM1 subtypes, type A (69.15%), type B (7.41%) and type D (7.41%) are found to be most frequent. The evaluation of minimal residual disease (MRD) has been considered critical to more precisely define AML response to clinical treatment, thereby refining disease risk stratification. Currently, AML with NPM1 gene mutations is recognized as a distinct entity, due to its unique clinical features. A large body of evidence demonstrated a significant independent prognosis factor of molecular MRD monitoring in NPM1-mutated AML.

Objectives:

Here we present GeneXpert NPM1 prototype, a fast and promising test for use in AML mutation detection (this prototype is for research use only, not for use in diagnostic procedures, and not reviewed by any regulatory body). NPM1 prototype is an easy-to-use-sample in/results out, and highly sensitive assay. The turnaround time is as fast as less than 3 hours. NPM1 prototype is designed for the quantitative detection of NPM1 mutant mRNA transcripts (types A, B and D in exon 12) and the ABL endogenous control mRNA transcript in peripheral blood of AML patients. This test is also designed for use as an aid in the monitoring of mutant NPM1 mRNA transcript levels in patients diagnosed with NPM1-mutated AML. This test does not differentiate between A, B or D type mutant NPM1 transcripts and does not detect or monitor other rare types of mutant NPM1.

Results:

Through assay optimization, we were able to reach limit of detection (LoD) within 0.05% for three NPM1 subtypes among all screened EDTA donor blood samples. Ct-copy number regression curve aligns well among three subtypes, within detection range. Our assay specificity has been above 95% among 30 screened EDTA donor blood samples.

Conclusion:

In summary, GeneXpert NPM1 prototype shows promise as a fast test for use in AML mutation detection.The presented NPM1 prototype has a great advantage covering most prevalent NPM1 mutation types up to 94% of all NPM1 subtypes. Our results demonstrated that our prototype shows satisfactory assay specificity and sensitivity. Clinical samples will be included for our clinical validation in the future.

Disclosures

No relevant conflicts of interest to declare.
Estrogen: Friend or Foe in Monge's Disease?
Authors: Azad Priti , Villafuerte Francisco , Haddad Gabriel
Published: February 2021

Rationale: Chronic mountain sickness (CMS), or Monge's disease, is a progressive debilitating syndrome caused by chronic (years) exposure to high altitude hypoxia, as experienced by people living in the Andean region. Excessive erythrocytosis (EE) is one of the critical traits of CMS and this excessive pathobiologic response has deleterious effects since a high hematocrit would increase blood viscosity and reduce blood flow to hypoxia-sensitive organs (brain and heart), often resulting in myocardial infarction or stroke in young adults. Within the population of Cerro de Pasco in the Andes, CMS prevalence is vastly different between males and females, being rare in females. Of interest is that there is a sharp increase in CMS incidence in females after menopause. This suggests the role of gender and sex hormones in altering disease manifestation.

Methods: In order to understand the molecular basis for polycythemia of high altitude, we have generated a disease in-the dish-model by re-programming fibroblasts and native CD34+ve cells from CMS and non-CMS subjects and converting them to RBC. Using this in-vitro platform, we are now studying the interactions between genetic factors and sex hormones (Testosterone, Estrogen and Progesterone) and their effect on RBC production in the CMS and non-CMS subjects at high altitude.

Results: While we found that testosterone increased RBC production mildly (insignificantly), estrogen in physiologic concentrations (10nM), in sharp contrast, reduced the CD235a (Glycophorin A- marker of mature RBC) remarkably (from 56% in the untreated CMS sample to 10% in the treated CMS) and eliminated the CMS EE phenotype. There is also stage-specificity and dose response effects for estrogen. This strongly suggests that estrogen has a protective role against the polycythemia phenotype. To probe further, we studied the effect of estrogen (10nM) on GATA1, a critical link with erythropoiesis. There was a sharp 5 fold decrease in GATA1 (p<0.01) and its target genes such as Alas2 (p<0.001) in erythroid cells. This decreased expression resulted in marked reduction (>50%) in RBC production, demonstrating that estrogen constrains RBC production in females.

Conclusion: Our results demonstrate that estrogen inhibits GATA1 expression and prevents excessive erythropoiesis and Monge's disease in females at high altitude. We believe that these studies not only shed light on the role of sex hormones on hypoxia-induced excessive erythropoiesis but have a broader application in their regulation of erythropoiesis and related blood disorders.

Disclosures

No relevant conflicts of interest to declare.
Aberrant Expression of Mir-20a in Serum Exosomes of Multiple Myeloma Lead Abnormal Expression of HIF-1 Signaling Pathway Related Proteins
Authors: Zhang Zhiyao , Zhou Huixing , Geng Chuanying , Gao Wen , Chen Wenming
Published: February 2021

Objective To determine the abnormal expression of miRNA in plasma exosomes of patients with multiple myeloma (MM) and its effect on the expression of HIF signaling pathway related proteins.

Methods Microarray analysis was performed on the exosomal miRNA analysis of 12 MM patients to determine how it might participate in MM. Then a co-expression network was performed to discover the potential role of miRNAs in regulating tumorigenesis and disease progression of MM. The expression of miR-20a in the exosomes of 48 MM patients was detected and the potential target genes were verified.

Results Differential expression of 43 miRNAs was observed in exosomes of multiple myeloma (MM) patients compared to healthy individuals. Among them, 7 miRNAs were significantly up-regulated in patients with multiple myeloma, and 35 miRNAs were significantly decreased compared with healthy controls. The results of microarray analysis showed that the seven miRNAs up-regulated in MM exosomes were mainly involved in NF-κB signaling, tumor necrosis factor-mediated signaling pathway regulation while 37 down-regulated miRNAs are mainly involved in HIF-1 signaling pathway, vascular development, cell adhesion. Decreased expression of miR-20a was associated with MM aggressiveness in the MM cohort compared with healthy individuals. We identified HIF-1 signaling pathway related proteins SENP1 and sumo as a potential target gene of miR-20a which were upregulation in MM.

Conclusion The microarray chip confirmed the differential expression of miRNA in plasma exosomes of patients with myeloma and healthy controls. Abnormally expressed miRNAs may be involved in the occurrence and development of tumors. These results may provide further evidence for exosomes as novel biomarkers for predicting MM recurrence.

Disclosures

No relevant conflicts of interest to declare.
Combination of Bortezomib and Venetoclax Induces Synergistic Killing of Epstein-Barr Virus-Driven Lymphoproliferative Diseases By Targeting the Pro-Survival Function of Latent Membrane Protein-1 and Epstein-Barr Nuclear Antigen-3C
Authors: Chiang Alan Kwok Shing , Tam Kam Pui , Au-Yeung Rex Kwok Him
Published: February 2021

Epstein-Barr virus (EBV) is strongly associated with lymphoproliferative diseases (LPDs), in particular B cell, in both immunocompetent and immunocompromised hosts. The virus is able to manipulate host cell machineries such as the ubiquitin-proteasome system and regulators of Bcl-2 family to enable the persistence of the virus and the survival of the host cells through expression of various viral proteins in distinct latency patterns. Latent membrane protein-1 (LMP-1) is a constitutively active CD40 receptor homolog and activates NF-κB signaling pathways to induce Bcl-2 expression whilst Epstein-Barr nuclear antigen-3C (EBNA-3C) interacts with and mediates proteasomal degradation of Bcl-6 protein which, in turn, increases Bcl-2 expression. We hypothesize that combining a proteasome inhibitor, bortezomib, with a Bcl-2 inhibitor, venetoclax, will induce synergistic killing of EBV-driven LPDs expressing both LMP-1 and EBNA-3C in the latency III pattern. Isobologram showed that combination of bortezomib and venetoclax could synergistically induce potent apoptosis of spontaneous lymphoblastoid cell lines (sLCL), derived from patients with post-transplant lymphoproliferative disorder (PTLD), expressing LMP-1 and EBNA-3C proteins. The mechanism of killing was related to the suppression of NF-κB signaling pathway induced by LMP-1. The phosphorylation of serine 70 of Bcl-2, which enhances the anti-apoptotic activity of Bcl-2 through stabilization of its interaction with other pro-apoptotic proteins such as Bak and Bim, was decreased in the sLCL, but not in the LMP-1 or EBNA-3C knockdown LCL, upon treatment with the drug combination. Activation of DNA damage response and production of reactive oxygen species were observed in the sLCL, contributing to the synergistic cell death. Bortezomib induced the expression of pro-apoptotic initiator, NOXA, to enhance the susceptibility of the sLCL to apoptosis upon treatment with venetoclax whilst knockdown of NOXA in the sLCL led to the resistance of the cells to apoptosis induced by the drug combination. In-vivo study demonstrated that the drug combination significantly inhibited the growth of xenograft of sLCL in SCID mice (p<0.001). Taken together, we conclude that the combination of bortezomib and venetoclax induces synergistic killing of EBV-driven LPDs such as PTLD by targeting the pro-survival function of LMP-1 and EBNA-3C.

Disclosures

No relevant conflicts of interest to declare.
Secreted modular calcium-binding protein 1 binds and activates thrombin to account for platelet hyperreactivity in diabetes
Authors: Delgado Lagos Fredy , Elgheznawy Amro , Kyselova Anastasia , Meyer zu Heringdorf Dagmar , Ratiu Corina , Randriamboavonjy Voahanginirina , Mann Alexander W. , Fisslthaler Beate , Siragusa Mauro , Fleming Ingrid
Published: February 2021

Secreted modular calcium-binding protein 1 (SMOC1) is an osteonectin/SPARC-related matricellular protein, whose expression is regulated by microRNA-223 (miR-223). Given that platelets are rich in miR-223, this study investigated the expression of SMOC1 and its contribution to platelet function. Human and murine platelets expressed SMOC1, whereas platelets from SMOC1+/− mice did not present detectable mature SMOC1 protein. Platelets from SMOC1+/− mice demonstrated attenuated responsiveness to thrombin (platelet neutrophil aggregate formation, aggregation, clot formation, Ca2+ increase, and β3 integrin phosphorylation), whereas responses to other platelet agonists were unaffected. SMOC1 has been implicated in transforming growth factor-β signaling, but no link to this pathway was detected in platelets. Rather, the SMOC1 Kazal domain directly bound thrombin to potentiate its activity in vitro, as well as its actions on isolated platelets. The latter effects were prevented by monoclonal antibodies against SMOC1. Platelets from miR-223–deficient mice expressed high levels of SMOC1 and exhibited hyperreactivity to thrombin that was also reversed by preincubation with monoclonal antibodies against SMOC1. Similarly, SMOC1 levels were markedly upregulated in platelets from individuals with type 2 diabetes, and the SMOC1 antibody abrogated platelet hyperresponsiveness to thrombin. Taken together, we have identified SMOC1 as a novel thrombin-activating protein that makes a significant contribution to the pathophysiological changes in platelet function associated with type 2 diabetes. Thus, strategies that target SMOC1 or its interaction with thrombin may be attractive therapeutic approaches to normalize platelet function in diabetes.
Excretable, ultrasmall hexagonal NaGdF4:Yb50% nanoparticles for bimodal imaging and radiosensitization
Authors: Damasco Jossana A. , Ohulchanskyy Tymish Y. , Mahajan Supriya , Chen Guanying , Singh Ajay , Kutscher Hilliard L. , Huang Haoyuan , Turowski Steven G. , Spernyak Joseph A. , Singh Anurag K. , Lovell Jonathan F. , Seshadri Mukund , Prasad Paras N.
Published: February 2021

Background

In this study, we report on the synthesis, imaging, and radiosensitizing properties of ultrasmall β-NaGdF4:Yb50% nanoparticles as a multifunctional theranostic platform. The synthesized nanoparticles act as potent bimodal contrast agents with superior imaging properties compared to existing agents used for magnetic resonance imaging (MRI) and computed tomography (CT). Clonogenic assays demonstrated that these nanoparticles can act as effective radiosensitizers, provided that the nanoparticles are taken up intracellularly.

Results

Our ultrasmall β-NaGdF4:Yb50% nanoparticles demonstrate improvement in T1-weighted contrast over the standard clinical MR imaging agent Gd-DTPA and similar CT signal enhancement capabilities as commercial agent iohexol. A 2 Gy dose of X-ray induced ~ 20% decrease in colony survival when C6 rat glial cells were incubated with non-targeted nanoparticles (NaGdF4:Yb50%), whereas the same X-ray dose resulted in a ~ 60% decrease in colony survival with targeted nanoparticles conjugated to folic acid (NaGdF4:Yb50%-FA). Intravenous administration of nanoparticles resulted in clearance through urine and feces within a short duration, based on the ex vivo analysis of Gd3+ ions via ICP-MS.

Conclusion

These biocompatible and in vivo clearable ultrasmall NaGdF4:Yb50% are promising candidates for further evaluation in image-guided radiotherapy applications.
The heritable landscape of near-infrared and Raman spectroscopic measurements to improve lipid content in Atlantic salmon fillets
Authors: Difford Gareth F. , Horn Siri S. , Dankel Katinka R. , Ruyter Bente , Dagnachew Binyam S. , Hillestad Borghild , Sonesson Anna K. , Afseth Nils K.
Published: February 2021

Background

Product quality and production efficiency of Atlantic salmon are, to a large extent, influenced by the deposition and depletion of lipid reserves. Fillet lipid content is a heritable trait and is unfavourably correlated with growth, thus genetic management of fillet lipid content is needed for sustained genetic progress in these two traits. The laboratory-based reference method for recording fillet lipid content is highly accurate and precise but, at the same time, expensive, time-consuming, and destructive. Here, we test the use of rapid and cheaper vibrational spectroscopy methods, namely near-infrared (NIR) and Raman spectroscopy both as individual phenotypes and phenotypic predictors of lipid content in Atlantic salmon.

Results

Remarkably, 827 of the 1500 individual Raman variables (i.e. Raman shifts) of the Raman spectrum were significantly heritable (heritability (h2) ranging from 0.15 to 0.65). Similarly, 407 of the 2696 NIR spectral landscape variables (i.e. wavelengths) were significantly heritable (h2= 0.27–0.40). Both Raman and NIR spectral landscapes had significantly heritable regions, which are also informative in spectroscopic predictions of lipid content. Partial least square predicted lipid content using Raman and NIR spectra were highly concordant and highly genetically correlated with the lipid content values ($${r}_{\text{g}}$$rg= 0.91–0.98) obtained with the reference method using Lin’s concordance correlation coefficient (CCC = 0.63–0.90), and were significantly heritable ($${h}^{2}$$h2= 0.52–0.67).

Conclusions

Both NIR and Raman spectral landscapes show substantial additive genetic variation and are highly genetically correlated with the reference method. These findings lay down the foundation for rapid spectroscopic measurement of lipid content in salmonid breeding programmes.
GMO Genetic Elements Thesaurus (GMO-GET): a controlled vocabulary for the consensus designation of introduced or modified genetic elements in genetically modified organisms
Authors: Adamse Paulien , Dagand Emilie , Bohmert-Tatarev Karen , Wahler Daniela , Miranda Manoela , Kok Esther J. , Bendiek Joachim
Published: February 2021

Background

Various databases on genetically modified organisms (GMOs) exist, all with their specific focus to facilitate access to information needed for, e. g., the assistance in risk assessment, the development of detection and identification strategies or inspection and control activities. Each database has its unique approach towards the subject. Often these databases use different terminology to describe the GMOs. For adequate GMO addressing and identification and exchange of GMO-related information it is necessary to use commonly agreed upon concepts and terminology.

Result

A hierarchically structured controlled vocabulary describing the genetic elements inserted into conventional GMOs, and GMOs developed by the use of gen(om)e-editing is presented: the GMO genetic element thesaurus (GMO-GET). GMO-GET can be used for GMO-related documentation, including GMO-related databases. It has initially been developed on the basis of two GMO databases, i.e. the Biosafety Clearing-House and the EUginius database.

Conclusion

The use of GMO-GET will enable consistent and compatible information (harmonisation), also allowing an accurate exchange of information between the different data systems and thereby facilitating their interoperability. GMO-GET can also be used to describe genetic elements that are altered in organisms obtained through current targeted genome-editing techniques.
Eosinophil-to-monocyte ratio is a potential biomarker in the prediction of functional outcome among patients with acute ischemic stroke
Authors: Yu Shuhong , Luo Yi , Zhang Tan , Huang Chenrong , Fu Yu , Zhang Qiang , Zeng Fangyue , Huang Hao , Zhang Chunyuan , Guo Zhiliang
Published: February 2021

Background

It has been shown that eosinophils are decreased and monocytes are elevated in patients with acute ischemic stroke (AIS), but the impact of eosinophil-to-monocyte ratio (EMR) on clinical outcomes among AIS patients remains unclear. We aimed to determine the relationship between EMR on admission and 3-month poor functional outcome in AIS patients.

Methods

A total of 521 consecutive patients admitted to our hospital within 24 h after onset of AIS were prospectively enrolled and categorized in terms of quartiles of EMR on admission between August 2016 and September 2018. The endpoint was the poor outcome defined as modified Rankin Scale score of 3 to 6 at month 3 after admission.

Results

As EMR decreased, the risk of poor outcome increased (p < 0.001). Logistic regression analysis revealed that EMR was independently associated with poor outcome after adjusting potential confounders (odds ratio, 0.09; 95% CI 0.03–0.34; p = 0.0003), which is consistent with the result of EMR (quartile) as a categorical variable (odds ratio, 0.23; 95% CI 0.10–0.52; ptrend < 0.0001). A non-linear relationship was detected between EMR and poor outcome, whose point was 0.28. Subgroup analyses further confirmed these associations. The addition of EMR to conventional risk factors improved the predictive power for poor outcome (net reclassification improvement: 2.61%, p = 0.382; integrated discrimination improvement: 2.41%, p < 0.001).

Conclusions

EMR on admission was independently correlated with poor outcome in AIS patients, suggesting that EMR may be a potential prognostic biomarker for AIS.
Targeted enrichment of novel chloroplast-based probes reveals a large-scale phylogeny of 412 bamboos
Authors: Wang Jiongliang , Mu Weixue , Yang Ting , Song Yue , Hou Yin Guang , Wang Yu , Gao Zhimin , Liu Xin , Liu Huan , Zhao Hansheng
Published: February 2021

Background

The subfamily Bambusoideae belongs to the grass family Poaceae and has significant roles in culture, economy, and ecology. However, the phylogenetic relationships based on large-scale chloroplast genomes (CpGenomes) were elusive. Moreover, most of the chloroplast DNA sequencing methods cannot meet the requirements of large-scale CpGenome sequencing, which greatly limits and impedes the in-depth research of plant genetics and evolution.

Results

To develop a set of bamboo probes, we used 99 high-quality CpGenomes with 6 bamboo CpGenomes as representative species for the probe design, and assembled 15 M unique sequences as the final pan-chloroplast genome. A total of 180,519 probes for chloroplast DNA fragments were designed and synthesized by a novel hybridization-based targeted enrichment approach. Another 468 CpGenomes were selected as test data to verify the quality of the newly synthesized probes and the efficiency of the probes for chloroplast capture. We then successfully applied the probes to synthesize, enrich, and assemble 358 non-redundant CpGenomes of woody bamboo in China. Evaluation analysis showed the probes may be applicable to chloroplasts in Magnoliales, Pinales, Poales et al. Moreover, we reconstructed a phylogenetic tree of 412 bamboos (358 in-house and 54 published), supporting a non-monophyletic lineage of the genus Phyllostachys. Additionally, we shared our data by uploading a dataset of bamboo CpGenome into CNGB (https://db.cngb.org/search/project/CNP0000502/) to enrich resources and promote the development of bamboo phylogenetics.

Conclusions

The development of the CpGenome enrichment pipeline and its performance on bamboos recommended an inexpensive, high-throughput, time-saving and efficient CpGenome sequencing strategy, which can be applied to facilitate the phylogenetics analysis of most green plants.
Completeness of the operating room to intensive care unit handover: a matter of time?
Authors: Dusse Fabian , Pütz Johanna , Böhmer Andreas , Schieren Mark , Joppich Robin , Wappler Frank
Published: February 2021

Background

Handovers of post-anesthesia patients to the intensive care unit (ICU) are often unstructured and performed under time pressure. Hence, they bear a high risk of poor communication, loss of information and potential patient harm.

The aim of this study was to investigate the completeness of information transfer and the quantity of information loss during post anesthesia handovers of critical care patients.

Methods

Using a self-developed checklist, including 55 peri-operative items, patient handovers from the operation room or post anesthesia care unit to the ICU staff were observed and documented in real time. Observations were analyzed for the amount of correct and completely transferred patient data in relation to the written documentation within the anesthesia record and the patient’s chart.

Results

During a ten-week study period, 97 handovers were included. The mean duration of a handover was 146 seconds, interruptions occurred in 34% of all cases. While some items were transferred frequently (basic patient characteristics [72%], surgical procedure [83%], intraoperative complications [93.8%]) others were commonly missed (underlying diseases [23%], long-term medication [6%]). The completeness of information transfer is associated with the handover’s duration [B coefficient (95% CI): 0.118 (0.084-0.152), p<0.001] and increases significantly in handovers exceeding a duration of 2 minutes (24% ± 11.7 vs. 40% ± 18.04, p<0.001).

Conclusions

Handover completeness is affected by time pressure, interruptions, and inappropriate surroundings, which increase the risk of information loss. To improve completeness and ensure patient safety, an adequate time span for handover, and the implementation of communication tools are required.
Clinical outcomes of postoperative extracorporeal membrane oxygenation support in Stanford type a aortic dissection
Authors: Fan Fudong , Zhou Qing , Pan Jun , Cao Hailong , Li Kai , Xue Yunxing , Ge Min , Luo Xuan , Chen Yang , Wang Dongjin
Published: February 2021

Background

Extracorporeal membrane oxygenation (ECMO) support may be considered to reduce mortality but survival and clinical outcomes are uncertain after Stanford type A Aortic dissection (TAAD). We analyzed the data of TAAD patients with postoperative ECMO support in our institution to investigate clinical outcomes.

Methods

In this retrospective cohort study, all clinical data of TAAD patients with postoperative ECMO support from January 2013 to October 2019 in our institution were harvested. Cases with redo or incomplete records were excluded.

Results

22 cases were enrolled, 18 male and 4 female. The mean age was52.85±10.91 years. 20 patients underwent VA-ECMO treatment and 2 patients received VV-ECMO support. The support time was92.54±78.71 hours. 9 patients were successfully weaned from ECMO. 30-day in-hospital survival rate was 27.27 % (6/22). The follow-up duration is from 5 to 74 months. The median follow-up time is 35 months. Only four patients were still alive at the end of the follow-up period.

Conclusions

The mortality of TAAD patients with postoperativesevere circulatory and respiratory dysfunctions is high. ECMO would be considered as a valuable contribution to save lives. But more experience needs to be accumulated to improve clinical outcome.
Dysregulation of serum miR-361-5p serves as a biomarker to predict disease onset and short-term prognosis in acute coronary syndrome patients
Authors: Zhang Wenqing , Chang Guannan , Cao Liya , Ding Gang
Published: February 2021

Background

Serum microRNAs (miRNAs) have been used as novel biomarkers for various diseases, including acute coronary syndrome (ACS). This study aimed to investigate the expression and clinical significance of microRNA-361-5p (miR-361-5p) in patients with ACS.

Methods

This study included 118 ACS patients, 78 patients with stable coronary heart disease (SCHD) and 66 healthy controls. MiR-361-5p expression was measured by qRT-PCR. The diagnostic value of miR-361-5p was evaluated by the ROC analysis. A 30-day follow-up was performed for the patients from hospitalization, and Kaplan–Meier curves and logistics analysis were used to evaluate the ability of miR-361-5p to predict the occurrence of major adverse cardiac events (MACE). ELISA kits were used to detect the levels of endothelial dysfunction (ED) markers, including vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1) and E-selectin.

Results

The expression of miR-361-5p was significantly increased in patients with SCHD and ACS, and positively correlated with Gensini scores. Serum miR-361-5p expression had a high diagnostic accuracy for distinguishing ACS from health controls and SCHD patients. ACS patients with high expression of miR-361-5p had a higher probability of developing MACE. MiR-361-5p expression was an independent risk factor for the occurrence of MACE in ACS patients, and was positively correlated with the levels of VCAM-1, ICAM-1 and E-selectin.

Conclusion

All data indicated that miR-361-5p expression was significantly increased in ACS patients. Aberrant miR-361-5p expression in ACS might be a candidate biomarker for ACS diagnosis and the the prediction of MACE onset.
Telephone peer recruitment and interviewing during a respondent-driven sampling (RDS) survey: feasibility and field experience from the first phone-based RDS survey among men who have sex with men in Côte d’Ivoire
Authors:   for the research team ANRS 12323 DOD-CI, Inghels Maxime , Kouassi Arsène Kra , Niangoran Serge , Bekelynck Anne , Carillon Séverine , Sika Lazare , Koné Mariatou , Danel Christine , Desgrées du Loû Annabel , Larmarange Joseph
Published: February 2021

Background

Many respondent-driven sampling (RDS) methodologies have been employed to investigate hard-to-reach populations; however, these methodologies present some limits. We describe a minimally investigated RDS methodology in which peer recruitment and interviewing are phone-based. The feasibility of the methodology, field experiences, validity of RDS assumptions and characteristics of the sample obtained are discussed.

Methods

We conducted a phone-based RDS survey among men who have sex with men (MSM) aged 18 or above and living in Côte d’Ivoire. Eight initial MSM across Côte d’Ivoire were selected. Participants were asked to call a hotline to be registered and interviewed by phone. After the participants completed the questionnaire, they were asked to recruit a maximum of 3 MSM from their acquaintances.

Results

During the 9 months of the survey, 576 individuals called the hotline, and 518 MSM completed the questionnaire. The median delay between the invitation to participate and the completion of the questionnaire by peer-recruited MSM was 4 days [IQR: 1–12]. The recruitment process was not constant, with high variation in the number of people who called the hotline during the survey period.

RDS chain convergence to equilibrium was reached within 6 waves for most of the selected variables. For the network size estimation assumption, participants who incorrectly estimated their network size were observed.

Regarding the sample obtained, MSM were recruited from all the regions of Côte d’Ivoire with frequent interregional recruitment; 23.5% of MSM were recruited by someone who does not live in the same region. Compared to the MSM who participated in two other surveys in Côte d’Ivoire, the MSM in our sample were less likely to know about an MSM non-governmental organisation. However, MSM aged 30 years old and above and those with a low level of education were underrepresented in our sample.

Conclusion

We show that phone-based RDS surveys among MSM are feasible in the context of sub-Saharan Africa. Compared to other classical RDS survey methodologies, the phone-based RDS methodology seems to reduce selection bias based on geography and proximity with the MSM community. However, similar to other methodologies, phone-based RDS fails to reach older and less-educated MSM.