bluuebunny/crossref_metadata_2025 huggingface dataset:
The Role of the Microbiome in Age-Related Macular Degeneration: A Review of the Literature
Authors: Zisimopoulos Athanasios , Klavdianou Olga , Theodossiadis Panagiotis , Chatziralli Irini
Published: February 2021

Background: Age-related macular degeneration (AMD) is a progressive, multifactorial, degenerative disease and the leading cause of severe visual loss in the elderly population. The exact pathogenesis of AMD remains elusive, being the combination of genetic, environmental, metabolic, and functional processes. A better understanding of the disease’s pathophysiology can lead to new treatment targets. The human microbiome seems to be a potential therapeutic pathway for AMD, as it has been recently proven to play a role in its pathogenesis. Summary: This review sheds light on the association between the microbiome and AMD. Key Messages: The current evidence based on the existing literature shows that there are differences in taxonomical and functional profiles in the human microbiome between patients with AMD and controls, suggesting that the microbiome is implicated in AMD onset and progression, being a link between AMD and nutrition/diet. Additionally, specific bacterial classes have been proposed as potential biomarkers for AMD diagnosis. Further randomized clinical studies with a large sample are needed to elucidate the role of the microbiome in AMD and to draw more solid conclusions.
Estradiol Regulates Polysialylated Form of the Neural Cell Adhesion Molecule Expression and Connectivity of O-LM Interneurons in the Hippocampus of Adult Female Mice
Authors: Perez-Rando Marta , Guirado Ramon , Tellez-Merlo Guillermina , Carceller Hector , Nacher Juan
Published: February 2021

The estrous cycle is caused by the changing concentration of ovarian hormones, particularly 17β-estradiol, a hormone whose effect on excitatory circuits has been extensively reported. However, fewer studies have tried to elucidate how this cycle, or this hormone, affects the plasticity of inhibitory networks and the structure of interneurons. Among these cells, somatostatin-expressing O-LM neurons of the hippocampus are especially interesting. They have a role in the modulation of theta oscillations, and they receive direct input from the entorhinal cortex, which place them in the center of hippocampal function. In this study, we report that the expression of polysialylated form of the neural cell adhesion molecule (PSA-NCAM) in the hippocampus, a molecule involved in the plasticity of somatostatin-expressing interneurons in the adult brain, fluctuated through the different stages of the estrous cycle. Likewise, these stages and the expression of PSA-NCAM affected the density of dendritic spines of O-LM cells. We also describe that 17β-estradiol replacement of adult ovariectomized female mice caused an increase in the perisomatic inhibitory puncta in O-LM interneurons as well as an increase in their axonal bouton density. Interestingly, this treatment also induced a decrease in their dendritic spine density, specifically in O-LM interneurons lacking PSA-NCAM expression. Finally, using an ex vivo real-time assay with entorhinal-hippocampal organotypic cultures, we show that this hormone decreased the dynamics in spinogenesis, altogether highlighting the modulatory effect that 17β-estradiol has on inhibitory circuits.
Evaluation of Axial Length Measurement Using Enhanced Retina Visualization Mode of the Swept-Source Optical Coherence Tomography Biometer in Dense Cataract
Authors: Tamaoki Akeno , Kojima Takashi , Hasegawa Asato , Yamamoto Mana , Kaga Tatsushi , Tanaka Kiyoshi , Ichikawa Kazuo
Published: February 2021

Introduction: It has been reported that even using the swept-source (SS) optical coherence biometer, it is challenging to measure the axial length (AL) in cases with advanced cataracts. The enhanced retina visualization (ERV) mode, which is equipped with OCTB1 (ARGOS), shifts the peak of measurement sensitivity to the retinal side so that the AL can be measured even if the light energy is attenuated. The aim of the present study was to evaluate the accuracy and efficacy of the ERV mode in measuring the AL of dense cataracts. Methods: This was a single-center retrospective observational case series conducted in Japan. We included 213 eyes of 213 consecutive patients with advanced cataracts who underwent preoperative evaluation. The AL was measured before and after surgery using two SS optical coherence tomography biometers (OCTB1 and OCTB2; IOLMaster 700). Cases in which OCTB1 the standard mode failed to measure AL, OCTB1 with the ERV mode was used instead. Primary outcome measures were the acquisition rate and the AL measurement accuracy using the ERV mode. The χ2 test, the Kruskal-Wallis test, and the Wilcoxon signed-rank test were used to compare the acquisition rate and differences between pre- and postoperative AL values, respectively. In the ERV subgroup, Bland-Altman plots were used to compare the pre- and postoperative AL values measured using OCTB1-ERV mode. A p-value of less than 5% was considered statistically significant. Results: The AL acquisition rate was not significantly different between OCTB1 with the standard mode and OCTB2. The AL of 65 eyes (30.5%) could not be measured using OCTB1 with the standard mode. Conversely, the AL of 51 of these eyes (78.5%) was successfully measured using OCTB1 with the ERV mode. In these 51 eyes, a difference of ≤0.2 mm and of ≤0.1 mm between pre- and postoperative AL measurements was observed in 40 (78.4%) and 30 eyes (58.8%), respectively. The Bland-Altman plot found no systematic error between pre- and postoperative AL values measured using the ERV mode. Conclusion: In patients with dense cataracts, AL measurement using the standard mode of an SS-OCT biometer is challenging. Furthermore, the ERV mode could be promising for AL measurement in such cases.
Ablation Versus Drug Therapy for Atrial Fibrillation in Heart Failure
Authors: Packer Douglas L. , Piccini Jonathan P. , Monahan Kristi H. , Al-Khalidi Hussein R. , Silverstein Adam P. , Noseworthy Peter A. , Poole Jeanne E. , Bahnson Tristram D. , Lee Kerry L. , Mark Daniel B. ,   For the CABANA Investigators
Published: February 2021

Background:

In patients with heart failure and atrial fibrillation (AF), several clinical trials have reported improved outcomes, including freedom from AF recurrence, quality of life, and survival, with catheter ablation. This article describes the treatment-related outcomes of the AF patients with heart failure enrolled in the CABANA trial (Catheter Ablation Versus Antiarrhythmic Drug Therapy for Atrial Fibrillation).

Methods:

The CABANA trial randomized 2204 patients with AF who were ≥65 years old or <65 years old with ≥1 risk factor for stroke at 126 sites to ablation with pulmonary vein isolation or drug therapy including rate or rhythm control drugs. Of these, 778 (35%) had New York Heart Association class >II at baseline and form the subject of this article. The CABANA trial’s primary end point was a composite of death, disabling stroke, serious bleeding, or cardiac arrest.

Results:

Of the 778 patients with heart failure enrolled in CABANA, 378 were assigned to ablation and 400 to drug therapy. Ejection fraction at baseline was available for 571 patients (73.0%), and 9.3% of these had an ejection fraction <40%, whereas 11.7% had ejection fractions between 40% and 50%. In the intention-to-treat analysis, the ablation arm had a 36% relative reduction in the primary composite end point (hazard ratio, 0.64 [95% CI, 0.41–0.99]) and a 43% relative reduction in all-cause mortality (hazard ratio, 0.57 [95% CI, 0.33–0.96]) compared with drug therapy alone over a median follow-up of 48.5 months. AF recurrence was decreased with ablation (hazard ratio, 0.56 [95% CI, 0.42–0.74]). The adjusted mean difference for the AFEQT (Atrial Fibrillation Effect on Quality of Life) summary score averaged over the entire 60-month follow-up was 5.0 points, favoring the ablation arm (95% CI, 2.5–7.4 points), and the MAFSI (Mayo Atrial Fibrillation-Specific Symptom Inventory) frequency score difference was –2.0 points, favoring ablation (95% CI, –2.9 to –1.2).

Conclusions:

In patients with AF enrolled in the CABANA trial who had clinically diagnosed stable heart failure at trial entry, catheter ablation produced clinically important improvements in survival, freedom from AF recurrence, and quality of life relative to drug therapy. These results, obtained in a cohort most of whom had preserved left ventricular function, require independent trial verification.

Registration:

URL:
https://www.clinicaltrials.gov/ct2/show/NCT00911508
; Unique identifier: NCT0091150.
A Frontal Account of False Alarms
Authors: Festini Sara B. , Katz Benjamin
Published: February 2021

Prior research has demonstrated that the frontal lobes play a critical role in the top–down control of behavior, and damage to the frontal cortex impairs performance on tasks that require executive control [Burgess, P. W., & Stuss, D. T. Fifty years of prefrontal cortex research: Impact on assessment. Journal of the International Neuropsychological Society, 23, 755–767, 2017; Stuss, D. T., & Levine, B. Adult clinical neuropsychology: Lessons from studies of the frontal lobes. Annual Review of Psychology, 53, 401–433, 2002]. Across executive functioning tasks, performance deficits are often quantified as the number of false alarms per total number of nontarget trials. However, most studies of frontal lobe function focus on individual task performance and do not discuss commonalities of errors committed across different tasks. Here, we describe a neurocognitive account that explores the link between deficient frontal lobe function and increased false alarms across an array of experimental tasks from a variety of task domains. We review evidence for heightened false alarms following frontal deficits in episodic long-term memory tests, working memory tasks (e.g., n-back), attentional tasks (e.g., continuous performance tasks), interference control tasks (e.g., recent probes), and inhibitory control tasks (e.g., go/no-go). We examine this relationship via neuroimaging studies, lesion studies, and across age groups and pathologies that impact the pFC, and we propose 11 issues in cognitive processing that can result in false alarms. In our review, some overlapping neural regions were implicated in the regulation of false alarms. Ultimately, however, we find evidence for the fractionation and localization of certain frontal processes related to the commission of specific types of false alarms. We outline avenues for additional research that will enable further delineation of the fractionation of the frontal lobes' regulation of false alarms.
Hypothalamic–Pituitary–Adrenal Axis Activity in Childhood Predicts Emotional Memory Effects and Related Neural Circuitry in Adolescent Girls
Authors: Shields Grant S. , Hostinar Camelia E. , Vilgis Veronika , Forbes Erika E. , Hipwell Alison E. , Keenan Kate , Guyer Amanda E.
Published: February 2021

Negative emotional experiences can be more difficult to forget than neutral ones, a phenomenon termed the “emotional memory effect.” Individual differences in the strength of the emotional memory effect are associated with emotional health. Thus, understanding the neurobiological underpinnings of the emotional memory effect has important implications, especially for individuals at risk for emotional health problems. Although the neural basis of emotional memory effects has been relatively well defined, less is known about how hormonal factors that can modulate emotional memory, such as glucocorticoids, relate to that neural basis. Importantly, probing the role of glucocorticoids in the stress- and emotion-sensitive period of late childhood to adolescence could provide actionable points of intervention. We addressed this gap by testing whether hypothalamic–pituitary–adrenal (HPA) axis activity during a parent–child conflict task at 11 years of age predicted emotional memory and its primary neural circuitry (i.e., amygdala–hippocampus functional connectivity) at 16 years of age in a longitudinal study of 147 girls (104 with complete data). Results showed that lower HPA axis activity predicted stronger emotional memory effects, r(124) = −.236, p < .01, and higher emotional memory-related functional connectivity between the right hippocampus and the right amygdala, β = −.385, p < .001. These findings suggest that late childhood HPA axis activity may modulate the neural circuitry of emotional memory effects in adolescence, which may confer a potential risk trajectory for emotional health among girls.
Coordination of Pupil and Saccade Responses by the Superior Colliculus
Authors: Wang Chin-An , Munoz Douglas P.
Published: February 2021

The appearance of a salient stimulus evokes saccadic eye movements and pupil dilation as part of the orienting response. Although the role of the superior colliculus (SC) in saccade and pupil dilation has been established separately, whether and how these responses are coordinated remains unknown. The SC also receives global luminance signals from the retina, but whether global luminance modulates saccade and pupil responses coordinated by the SC remains unknown. Here, we used microstimulation to causally determine how the SC coordinates saccade and pupil responses and whether global luminance modulates these responses by varying stimulation frequency and global luminance in male monkeys. Stimulation frequency modulated saccade and pupil responses, with trial-by-trial correlations between the two responses. Global luminance only modulated pupil, but not saccade, responses. Our results demonstrate an integrated role of the SC on coordinating saccade and pupil responses, characterizing luminance independent modulation in the SC, together elucidating the differentiated pathways underlying this behavior.
Regimes of Evidence in Complexity Sciences
Authors: Li Vigni Fabrizio
Published: February 2021

Since their inception in the 1980s, complexity sciences have been described as a revolutionary new domain of research. By describing some of the practices and assumptions of its representatives, the present article shows that this field is an association of subdisciplines laying on existing disciplinary footholds. The general question guiding us here is: On what basis do complexity scientists consider their inquiry methods and results as valuable? To answer it, I describe five “epistemic argumentative regimes,” namely the ways in which complexity scientists argue the credibility of their research, and five “ontological views,” that is the ways in which they interpret the material and formal causes of their study objects and models. Finally, the article proposes the term of “regime of evidence” to designate the specific combination of one ontological view with one or more epistemic argumentative regimes.
Enjoying Each Other’s Company: Gaining Other-Gender Friendships Promotes Positive Gender Attitudes Among Ethnically Diverse Children
Authors: Halim May Ling D. , Martin Carol Lynn , Andrews Naomi C. Z. , Zosuls Kristina M. , Ruble Diane N.
Published: February 2021

Gender segregation is ubiquitous and may lead to increased bias against other-gender peers. In this study, we examined whether individual differences in friendships with other-gender children reduce gender bias, and whether these patterns vary by gender or ethnicity. Using a 1-year longitudinal design ( N = 408 second graders [ Mage = 7.56 years] and fourth graders [ Mage = 9.48 years]), we found that, across groups, gaining more other-gender friendships over the year led to (a) increased positive cognitive-based attitudes toward the other gender and (b) increased positive and decreased negative affect when with the other gender. We also tested the reverse pattern and found support for a bidirectional link. Girls and Latinx children often showed more gender bias than did boys and European American children. Implications for promoting positive relationships between girls and boys are discussed.
Incorporating Intersectionality in Public Policy: A Systematic Literature Review
Authors: Garcia Teresa C. , Zajicek Anna
Published: February 2021

Intersectionality is an ascending perspective in public policy research, gaining ever wider recognition in the discipline. The purpose of this study is to systematically review the literature to assess the current state of intersectional public policy research. This study describes the temporal and research site trends, discipline, type of research methodology, multiple categories of intersectionality in public policy studies, and policy area. Particular attention is given to the categorization of the multiple applications of intersectionality in public policy studies identified in this review: intersectional framework, intersectional perspective, and intersectional critique. The results give a comprehensive picture of existing research on the topic, thus providing researchers with a solid foundation for further study.
Notes From the Field: Applying the Consolidated Framework for Implementation Research in a Qualitative Evaluation of Implementation of the Queensland Aboriginal and Torres Strait Islander Brief Intervention Training Program
Authors: Sebastian Saji , Thomas David P. , Brimblecombe Julie , Cunningham Frances C.
Published: February 2021

This paper describes the applicability of the Consolidated Framework for Implementation Research (CFIR) to the qualitative evaluation of the implementation of the Queensland Aboriginal and Torres Strait Islander Brief Intervention Training Program, the B.strong Program. Interviews were conducted with 20 B.strong Program trainees and four health service managers from eight purposively sampled Indigenous primary health care services in Queensland to collect their perceptions of the B.strong Program implementation. The 26 constructs of the CFIR were used to guide data collection and analysis. Additional constructs were developed for two program implementation aspects, “quality improvement” and “cultural suitability.” Findings are presented from the application of the CFIR to the evaluation of the implementation of a brief intervention training program in the Australian Indigenous context. While demonstrating the applicability of the CFIR in this evaluation, this study also highlights that it may require modification, to ensure identification of the different contextual factors that influence program implementation.
Cardiohelp System use in school age children and adolescents at a center with interfacility mobile extracorporeal membrane oxygenation capability
Authors: Ignat Teodora , Desai Ajay , Hoschtitzky Andreas , Smith Rosie , Jackson Tim , Frall Diane , Evans Eleri , Trimlett Richard , Ledot Stephane , Chan-Dominy Amy
Published: February 2021

Cardiohelp System use for pediatric extracorporeal membrane oxygenation (ECMO) beyond the transport setting is sparsely described in literature. We report the use of Getinge’s Cardiohelp System in children and integrated utilization of Mobile ECMO Retrieval Team (MERT) at an all-age specialized cardiorespiratory center. Electronic database of all patients under 16 years of age who received ECMO with use of the Cardiohelp System between January 2018 and March 2020 was retrospectively reviewed and analyzed for demographics, set-up, complications, and outcomes. Out of 41 patients, seven patients (four in middle childhood, three in early teenage) with median age of 10 years (range 8.8–15.6) were supported with use of Cardiohelp System. Median weight and height were 34 kg (range 28–53) and 145 cm (range 134–166) respectively. Initial ECMO deployment was veno-arterial (V-A) in five patients and veno-venous (V-V) in two. There were three interhospital transfers by our MERT, and 12 intrahospital transfers for interventions or imaging. The median ECMO therapy was 7 days (range 4–25), with standard 3/8-inch tubing and ECMO flow rate range at 56–100 mL/kg/min (1.89–5.0 LPM). There were two circuit changes and three reconfigurations of support. Two patients received continuous veno-venous hemofiltration via ECMO circuit. The 90-day and 180-day survival rates were 100% (including two heart transplants at day 7 and day 8). There were no transport-related or circuit-related complications during the 1750 h of Cardiohelp use. Cardiohelp System use is safe in pediatric patients for diverse application of ECMO support including inter- and intrahospital transfers.
Remembering (to forget) English: The crises of world literature in Jotirao Phule’s slavery
Authors: Punyashloka Rahee
Published: February 2021

Discursive history of the English language has been vital to analysing ‘the postcolonial condition’ in the Indian subcontinent, with a broadly overarching emphasis on how English is a ‘usurper language’. Simultaneous to this, however, there exists a hitherto understudied history featuring subaltern, ‘organic intellectuals’ from the lower castes. Not only does this ‘subaltern history of English’ exhibit a more positive affect toward the English language – by invoking its emancipatory potential in an economy of deeply casteist vernacular languages – but it also complicates multiple assertions that the postcolonial apparatus has so far held as a priori. Jotirao Phule’s Slavery/Gulamgiri (1873) is one of the foremost examples of such a position; its preface, which lucidly announces this seemingly unique position, is quite possibly the first explicitly political treatise written in the English language in the history of the subcontinent. This paper highlights the enormous shifts that take place in our understanding of the history of English – and (post)colonial modernity – if we were to (aptly) classify Phule’s preface as a key text in the history of ‘Indian writing in English’. Subsequently, it is argued that Phule’s work crystallizes into a radically alternate – and far more egalitarian – conception of ‘world literature’ contra Tagore’s well-known idea of visva sahitya.
A Discrete Choice Experimental Approach to Understand Sports Event Tourists’ In-Stadium Beer Consumption Preferences
Authors: Lyu Seong Ok , Hwang Jinsoo
Published: February 2021

While drinking beer is an important component of sports event tourists’ ceremonial behaviors, there is surprisingly limited information regarding what features of beer service offerings at professional sporting events are most preferred. Using a sample of sports event tourists attending South Korean professional baseball games, the main purpose of this study is to provide an opportunity for improved knowledge regarding how spectators show their willingness to pay for in-stadium beer services. Applying a discrete choice experiment, we also intend to identify spectators’ heterogeneous preference systems, which vary depending on their levels of everyday alcohol use. Results suggest that respondents place great importance on serving temperatures and waiting time in line for purchasing beer at concession stands. The two drinker groups segmented based on the Alcohol Use Disorders Identification Test scores show different tastes for beer services. Several management implications are discussed to improve in-stadium entertainment and prevent alcohol-fueled misbehaviors.
What’s wrong with everyday lookism?
Authors: Mason Andrew
Published: February 2021

Everyday lookism, by which I mean the widespread practice of commenting upon and judging the appearance of others, is often regarded as morally troubling. But when, and why, is it morally problematic? I argue that in many cases everyday lookism is wrongful because it involves morally objectionable appearance discrimination. I consider various respects in which everyday lookism can be morally objectionable in virtue of the acts of wrongful discrimination it involves. I argue that these acts are wrongful when they are demeaning, or when they have unjust consequences whether singly or cumulatively. There are a number of ways in which they may have unjust consequences. First, the appearance norms in which these acts are rooted may be biased in such a way that the acts contribute to creating an unjust distribution of benefits and burdens. Second, these acts may combine to make everyday lookism oppressive in virtue of impairing the personal autonomy of its victims or contributing to doing so. Third, these acts may be unjustly harmful in terms of their effects.
The Effects of Food-Simulating Liquids on Surface Roughness, Surface Hardness, and Solubility of Bulk-Fill Composites
Authors: Cabadag˘ Özge Gizem , Gönülol Nihan
Published: February 2021

Aim:

To investigate the surface roughness, surface hardness, and solubility of bulk-fill composites after exposure to food-simulating liquids (FSLs).

Materials and Methods:

A total of 200 disc-shaped samples (8 mm diameter × 4 mm depth) were prepared using four bulk-fill composites (SonicFillTM, Tetric® EvoCeram Bulk Fill, Beautifil-Bulk Restorative, FiltekTM Bulk Fill Posterior Restorative) and a microhybrid composite (FiltekTM Z250) ( n = 40). Following the measurement of initial weights of the samples ( m1), the surface roughness measurements were gauged using a contact-profilometer. The samples were stored in four different FSLs for 7 days, and then the second surface roughness values were recorded. The samples were stored in a desiccator to reach the constant mass and the values were recorded as m2, then the solubility levels were calculated. The Vickers microhardness values of the samples were determined. A total of 20 specimens were evaluated in terms of surface morphology with a scanning electron microscope (SEM). Data were statistically analyzed with the two-way ANOVA and Bonferroni tests ( P < .05).

Results:

Beautifil-Bulk Restorative was affected at most in terms of surface roughness after storage in FSLs and citric acid caused the highest values in this group ( P < .005). Beautifil-Bulk Restorative and Filtek Z250 showed the highest surface hardness values, while the Tetric EvoCeram group had the lowest. The highest solubility values were found in Beautifil-Bulk Restorative, and citric acid and ethanol yielded the highest solubility values for all of the composites.

Conclusion:

Beautifil-Bulk Restorative is the most affected group in all parameters evaluated and also affected overly by citric acid among the FSLs in consequence of its prereacted glass ionomer fillers.
A 10-Years Risk of Cardiovascular Disease Among HIV-Positive Individuals Using BMI-Based Framingham Risk Score in Indonesia
Authors: Lindayani Linlin , purnama Heni , Nurhayati Nunung , Sudrajat Diwa Agus , Taryudi Taryudi
Published: February 2021

Introduction

Cardiovascular disease (CVD) is the primary cause of death in HIV patients. The number of HIV patients suffering from cardiovascular disease is almost twice as high as that of patients who are not HIV-positive.

Objective

The purpose of this study was to evaluate risk of cardiovascular disease among HIV-positive persons.

Methods

We conducted a cross-sectional study with HIV positive individuals at public health center and non-AIDS govermental organization. We enrolled people diagnosed with HIV, age over 30 years old, and on CVD medications. We collected data of demographic, anthropometric and clinical information, smoking history, and non-fasting cholesterol and blood glucose. Estimation of 10-years CVD risk was calculated using the BMI-based Framingham Risk Score.

Results

Of 150 participants enrolled, 66.7% were male and mean age was 38.09 (SD = 7.99) years. The mean current CD4 counts was 493.3 (SD = 139.8) cells/mm3. Female were younger, had a shorter duration living with HIV and a shorted duration of receiving ART than males. About 8.7% of respondents had a high risk of developing a CVD event in the next 10 years, and higher among females than males. The most common CVD risk factors were smoking, high blood pressure, and hypercholestrolemia.

Conclusion

Our study demonstrates that HIV positive persons who are at risk for developing CVD in the next 10-years. There is an increasing need for educational programs on CVD prevention for the HIV-positive person and to further facilitate the identification of persons at elevated risk in routine practice.
Highly-Sensitive DNA Hydroxymethylation Analysis in Myelodysplastic Syndromes (MDS)
Authors: Li Jia , Wei Yue , Lee Minjung , Yang Hui , Class Caleb , Siwko Stefan , Zhou Yubin , Sun Deqiang , Garcia-Manero Guillermo , Huang Yun
Published: February 2021

Aberrant DNA hydroxymethylcytosine (5hmC) levels have been reported in patients with myelodysplastic syndromes (MDS). The dysregulation of 5hmC is not only observed in patients with TET2 mutations, but also those bearing other genetic defects, suggesting that 5hmC might act as a valuable epigenetic mark to reflect the status of MDS. We report herein a highly-sensitive 5hmC analysis method using low input DNA (10 ng), which was used to obtain a comprehensive atlas of the DNA hydroxymethylome in MDS patients. Our systematic bioinformatic analysis unveiled that 5hmC signatures could be used to separate patients with good and poor clinical outcomes. At the molecular level, we observed dynamic changes of 5hmC within several key transcription factor binding motifs that are essential for hematopoiesis and myeloid lineage specification, which might result in impaired transcriptional outputs during leukemogenesis. Interestingly, we also observed massive changes in 5hmC and transcriptomes in patient showing response to hypomethylating agent (HMA) treatment, suggesting the prognostic value of 5hmC in evaluating epigenetic therapy. Overall, our highly-sensitive 5hmC analysis method provides a useful means to potentially facilitate the clinical evaluation of MDS patients.

Disclosures

Garcia-Manero: AbbVie: Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Onconova: Research Funding; Amphivena Therapeutics: Research Funding; Astex Pharmaceuticals: Consultancy, Honoraria, Research Funding; Merck: Research Funding; Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Research Funding; Jazz Pharmaceuticals: Consultancy; Acceleron Pharmaceuticals: Consultancy, Honoraria; H3 Biomedicine: Research Funding; Helsinn Therapeutics: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding.
Potent Interaction between CMV Reactivation and Gvhd: Immunologic Evidence for Blunting of CMV-Driven Immune Reconstitution in the Setting of Gvhd
Authors: Suessmuth Yvonne , Betz Kayla , Yu Alison , Bratrude Brandi , Watkins Benjamin , Qayed Muna , Horan John T. , Kean Leslie , Langston Amelia
Published: February 2021

Allogeneic hematopoietic cell transplantation (HCT) may be curative for patients with marrow and immune disorders, but graft-vs-host-disease (aGVHD) and infections cause significant morbidity and non-relapse mortality. We have conducted a multicenter, double blind, placebo-controlled phase II trial of costimulation blockade with abatacept (Aba) combined with standard GVHD prophylaxis with a calcineurin inhibitor and methotrexate (CNI + MTX) following HLA matched unrelated donor transplant (n=142).

In order to assess the effects of Aba on immune reconstitution, and to assess whether this reconstitution is influenced during CMV reactivation, we longitudinally evaluated post-transplant whole blood samples with multiparameter flow cytometry using markers for CD3, CD4, CD8, CD197 and CD45RA to measure reconstitution of CD4 and CD8 T cell populations and their respective memory subsets over time.

Results: We observe that post-transplant CMV reactivation induces a marked expansion of CD8 effector memory (EM) cells, which is similar in magnitude for Aba vs placebo patients. We found that development of moderate (gr 2-4) or severe (gr 3-4) GVHD was not associated with an increased frequency of CMV reactivation, but patients with moderate GVHD showed a blunted expansion of CD8 EM cells compared to those without GVHD, and CD8 EM expansion was essentially absent among CMV reactivating patients with severe aGVHD. Clinical correlates will be presented.

Conclusions: Our results suggest that adding abatacept to CNI/MTX does not materially affect reconstitution of T cell immunity in the presence or absence of CMV reactivation, but aGVHD remains a major driver of compromised immune recovery after HCT.

Disclosures

Watkins: Bristol Myers Squibb: Research Funding. Qayed:Mesoblast: Consultancy; Novartis: Consultancy. Horan:Bristol Myers Squib: Honoraria, Research Funding. Kean:gilead: Research Funding; bluebird bio: Research Funding; fortyseven: Consultancy; magenta: Research Funding; regeneron: Research Funding; hifibio: Consultancy; kymab: Consultancy; Bristol Meyers Squibb: Research Funding; novartis: Consultancy. Langston:Kadmon Corporation: Research Funding; Bristol Myers Squib: Research Funding; Incyte: Research Funding; Chimerix: Research Funding; Takeda: Research Funding; Astellas Pharmaceuticals: Research Funding; Jazz Pharmaceuticals: Research Funding.
Large-Scale Proteomic Analysis of Soluble Compartment in Pediatric Acute Lymphoblastic Leukemia
Authors: Gentilcore Giusy , Deola Sara , Herrera Sheanna M , Lachica Che-Ann , Yousif Tayseer Abbas , Ahmed Areeg , Al Mulla Naima , Saleh Ayman , Mina Tommaso , Comoli Patrizia , Grivel Jean-Charles , Cugno Chiara
Published: February 2021

Introduction

Acute Lymphoblastic Leukemia (ALL) is the most common malignancy in children and represents 75-80% of leukemia cases. Despite its recognized role in the initiation of the disease, the bone marrow (BM) microenvironment is not well understood especially in its non-cellular component.

High-throughput protein detection represent an opportunity to unveil new biomarkers for leukemia diagnosis, prognosis, monitoring, and to potentially identify biological targets.

Methods

In the present exploratory study, we evaluated the soluble compartment of BM and peripheral blood (PB) in 16 ALL pediatric patients by the means of the SOMAscan assay, a highly multiplexed, affinity proteomics platform able to measure 1305 proteins in as little as 65µl of sample using modified protein-binding single-stranded DNA aptamers called SOMAmers, revealed on a high dimension oligo-probe array. The raw hybridization data were normalized using hybridization controls and were log2-transformed. Transformed HybNormalized BM and PB plasma data were compared using GraphPad PRISM 8. Multiple comparisons were set with an FDR threshold of 0.01%.

Results

The comparative analysis between plasma samples from BM and PB showed that 228 proteins are differentially expressed in BM and PB plasma irrespective of the nature of disease (fig1). A more detailed mix-effect analysis of protein expression in the different patient categories and compartment defined in Table 1 revealed that out of these 228 proteins, 92 showed a significant differential expression when performing a mixed-effect analysis between the different groups. Among the top 20 proteins differentially expressed between BM and PB, 18 show differential expression between patient groups. The patient group effect is dominated by the differences between BM and PB plasma in ALL Common patients , which account for 17 of the observed differences in protein levels. In spite of the limited sample size, the analysis revealed a difference in NOTC2 level between ALL Common PB and ALL Pro-B PB.

Conclusion

In our study we applied a quantitative large-scale proteomic analysis on BM and PB plasma in children suffering from ALL, identifying differential protein expression between the two compartments.

In the last few years, SomaScan has emerged as a very attractive method due to its high throughput capacity, faster discovery mode compared to other proteomic platforms and small sample size required, which make it ideal for the identification of novel biomarkers. In spite of the limiting samples sizes, some differences in protein expression were revealed. We are taking this analysis further by analyzing more patients in different groups and including normal donor samples.

Table 1

Table

Disclosures

No relevant conflicts of interest to declare.
Magnetic Nanoparticles to Unique DNA Tracers: Effect of Functionalization on Physico-chemical Properties
Authors: Sharma Anuvansh , Foppen Jan Willem , Banerjee Abhishek , Sawssen Slimani , Bachhar Nirmalya , Peddis Davide , Bandyopadhyay Sulalit
Published: February 2021

To monitor and manage hydrological systems such as brooks, streams, rivers, the use of tracers is a well-established process. Limited number of potential tracers such as salts, isotopes and dyes, make study of hydrological processes a challenge. Traditional tracers find limited use due to lack of multiplexed, multipoint tracing and background noise, among others. In this regard, DNA based tracers possess remarkable advantages including, environmentally friendly, stability, and high sensitivity in addition to showing great potential in the synthesis of ideally unlimited number of unique tracers capable of multipoint tracing. To prevent unintentional losses in the environment during application and easy recovery for analysis, we hereby report DNA encapsulation in silica containing magnetic cores (iron oxide) of two different shapes—spheres and cubes. The iron oxide nanoparticles having size range 10–20 nm, have been synthesized using co-precipitation of iron salts or thermal decomposition of iron oleate precursor in the presence of oleic acid or sodium oleate. Physico-chemical properties such as size, zeta potential, magnetism etc. of the iron oxide nanoparticles have been optimized using different ligands for effective binding of dsDNA, followed by silanization. We report for the first time the effect of surface coating on the magnetic properties of the iron oxide nanoparticles at each stage of functionalization, culminating in silica shells. Efficiency of encapsulation of three different dsDNA molecules has been studied using quantitative polymerase chain reaction (qPCR). Our results show that our DNA based magnetic tracers are excellent candidates for hydrological monitoring with easy recoverability and high signal amplification.

Graphic Abstract
Contribution of Small RNA Pathway to Interactions of Rice with Pathogens and Insect Pests
Authors: Feng Qin , Li Yan , Zhao Zhi-Xue , Wang Wen-Ming
Published: February 2021

Small RNAs (sRNAs) are mainly classified into microRNAs (miRNAs) and small interfering RNAs (siRNAs) according to their origin. miRNAs originate from single-stranded RNA precursors, whereas siRNAs originate from double-stranded RNA precursors that are synthesized by RNA-dependent RNA polymerases. Both of single-stranded and double-stranded RNA precursors are processed into sRNAs by Dicer-like proteins. Then, the sRNAs are loaded into ARGONAUTE proteins, forming RNA-induced silencing complexes (RISCs). The RISCs repress the expression of target genes with sequences complementary to the sRNAs through the cleavage of transcripts, the inhibition of translation or DNA methylation. Here, we summarize the recent progress of sRNA pathway in the interactions of rice with various parasitic organisms, including fungi, viruses, bacteria, as well as insects. Besides, we also discuss the hormone signal in sRNA pathway, and the emerging roles of circular RNAs and long non-coding RNAs in rice immunity. Obviously, small RNA pathway may act as a part of rice innate immunity to coordinate with growth and development.
Efficient Gene Stacking in Rice Using the GAANTRY System
Authors: Hathwaik Leyla T. , Horstman James , Thomson James G. , Thilmony Roger
Published: February 2021

Genetic engineering of rice provides a means for improving rice grain quality and yield, and the introduction and expression of multiple genes can produce new traits that would otherwise be difficult to obtain through conventional breeding. GAANTRY (Gene Assembly in Agrobacterium by Nucleic acid Transfer using Recombinase technologY) was previously shown to be a precise and robust system to stably stack ten genes (28 kilobases (kb)) within an Agrobacterium virulence plasmid Transfer-DNA (T-DNA) and obtain high-quality Arabidopsis and potato transgenic events. To determine whether the GAANTRY system can be used to engineer a monocotyledonous crop, two new T-DNA constructs, carrying five (16.9 kb) or eleven (37.4 kb) cargo sequences were assembled and transformed into rice. Characterization of 53 independent transgenic events demonstrated that more than 50% of the plants carried all of the desired cargo sequences and exhibited the introduced traits. Additionally, more than 18% of the lines were high-quality events containing a single copy of the introduced transgenes and were free of sequences from outside of the T-DNA. Therefore, GAANTRY provides a simple, precise and versatile tool for transgene stacking in rice and potentially other cereal grain crops.
Correction to: First reported case of penile prosthesis infection from brucellosis: case report
Authors: Moohialdin Nabil N. , Shamsodini Ahmad , Wilson Steven K. , Abdeljaleel Osama , Alnadhari Ibrahim , Abdulmuhsin Ausama Saadi
Published: February 2021

Following publication of the original article [1], the authors identified an error in an author’s name.
Evidence for multiple introductions of an invasive wild bee species currently under rapid range expansion in Europe
Authors: Lanner Julia , Gstöttenmayer Fabian , Curto Manuel , Geslin Benoît , Huchler Katharina , Orr Michael C. , Pachinger Bärbel , Sedivy Claudio , Meimberg Harald
Published: February 2021

Background

Invasive species are increasingly driving biodiversity decline, and knowledge of colonization dynamics, including both drivers and dispersal modes, are important to prevent future invasions. The bee speciesMegachile sculpturalis(Hymenoptera: Megachilidae), native to East-Asia, was first recognized in Southeast-France in 2008, and has since spread throughout much of Europe. The spread is very fast, and colonization may result from multiple fronts.

Result

To track the history of this invasion, codominant markers were genotyped using Illumina sequencing and the invasion history and degree of connectivity between populations across the European invasion axis were investigated. Distinctive genetic clusters were detected with east–west differentiations in Middle-Europe.

Conclusion

We hypothesize that the observed cluster formation resulted from multiple, independent introductions of the species to the European continent. This study draws a first picture of an early invasion stage of this wild bee and forms a foundation for further investigations, including studies of the species in their native Asian range and in the invaded range in North America.
The association between clinical laboratory data and chest CT findings explains disease severity in a large Italian cohort of COVID-19 patients
Authors:   on behalf of the Reggio Emilia COVID-19 Working Group;, Canovi Simone , Besutti Giulia , Bonelli Efrem , Iotti Valentina , Ottone Marta , Albertazzi Laura , Zerbini Alessandro , Pattacini Pierpaolo , Giorgi Rossi Paolo , Colla Rossana , Fasano Tommaso
Published: February 2021

Background

Laboratory data and computed tomography (CT) have been used during the COVID-19 pandemic, mainly to determine patient prognosis and guide clinical management. The aim of this study was to evaluate the association between CT findings and laboratory data in a cohort of COVID-19 patients.

Methods

This was an observational cross-sectional study including consecutive patients presenting to the Reggio Emilia (Italy) province emergency rooms for suspected COVID-19 for one month during the outbreak peak, who underwent chest CT scan and laboratory testing at presentation and resulted positive for SARS-CoV-2.

Results

Included were 866 patients. Total leukocytes, neutrophils, C-reactive protein (CRP), creatinine, AST, ALT and LDH increase with worsening parenchymal involvement; an increase in platelets was appreciable with the highest burden of lung involvement. A decrease in lymphocyte counts paralleled worsening parenchymal extension, along with reduced arterial oxygen partial pressure and saturation. After correcting for parenchymal extension, ground-glass opacities were associated with reduced platelets and increased procalcitonin, consolidation with increased CRP and reduced oxygen saturation.

Conclusions

Pulmonary lesions induced by SARS-CoV-2 infection were associated with raised inflammatory response, impaired gas exchange and end-organ damage. These data suggest that lung lesions probably exert a central role in COVID-19 pathogenesis and clinical presentation.
Correction to: Individual-and community-level determinants of neonatal mortality in the emerging regions of Ethiopia: a multilevel mixed-effect analysis
Authors: Tesema Getayeneh Antehunegn , Worku Misganaw Gebrie
Published: February 2021

An amendment to this paper has been published and can be accessed via the original article.
One year of procarbazine lomustine and vincristine is poorly tolerated in low grade glioma: a real world experience in a national neuro-oncology centre
Authors: Keogh Rachel J. , Aslam Razia , Hennessy Maeve A. , Coyne Zac , Hennessy Bryan T. , Breathnach Oscar S. , Grogan Liam , Morris Patrick G.
Published: February 2021

Background

Following optimal local therapy, adjuvant Procarbazine, Lomustine and Vincristine (PCV) improves overall survival (OS) in low-grade glioma (LGG). However, 1 year of PCV is associated with significant toxicities. In the pivotal RTOG 9802 randomised control trial, approximately half of the patients discontinued treatment after 6 months. As patients on clinical trials may be fitter, we aimed to further explore the tolerability of PCV chemotherapy in routine clinical practice.

Methods

We conducted a retrospective study between 2014 and 2018 at a National Neuro-Oncology centre. Patients who had received PCV during this time period were included. The primary objective was to assess tolerability of treatment. Secondary objectives included evaluation of treatment delays, dose modifications and toxicities.

Results

Overall, 41 patients were included, 24 (58%) were male and 21 (51%) aged ≥40 years. 38 (93%) underwent surgical resection and all patients received adjuvant radiotherapy prior to chemotherapy. The median number of cycles completed was 3,2,4 for procarbazine, lomustine and vincristine respectively. Only 4 (10%) completed all 6 cycles of PCV without dose modifications. There was a universal decline in dose intensity as cycles of chemotherapy progressed. Dose intensity for cycle 1 versus cycle 6 respectively: procarbazine (98% versus 46%), lomustine (94% versus 48%) and vincristine (93% versus 50%). Haematological toxicities were common. Six (14%) patients experienced Grade III-IV thrombocytopaenia and 13 (31%) experienced Grade III-IV neutropaenia.

Conclusion

Toxicities are frequently observed with the PCV regimen in clinical practice. It might be preferable to adjust doses from the start of chemotherapy to improve tolerability or consider alternative chemotherapy, particularly in older patients with LGG.
Nd:YAG capsulotomy for Ahmed glaucoma drainage implant occlusion by the anterior capsule: a case report
Authors: Ertel Monica Kenney , Gelinas Nathaniel Ryan , Slingsby Taylor John , Seibold Leonard Keith , Kahook Malik Yaser , SooHoo Jeffrey Raymond
Published: February 2021

Background

Glaucoma drainage implants have been used with increasing frequency for the management of glaucoma. Patients who are candidates for glaucoma drainage devices often have more severe disease and are at risk of vision loss with post-operative elevations in intraocular pressure (IOP). One post-operative complication that can result in IOP elevation after glaucoma drainage device implantation is occlusion of the tube lumen.

Case presentation

Here, we present a novel case of tube occlusion by the anterior capsule in a patient who underwent combined phacoemulsification and Ahmed glaucoma valve implantation. The tube occlusion was successfully managed with Nd:YAG capsulotomy with immediate IOP lowering.

Conclusions

While there have been previous reports of occlusion of the tube lumen by vitreous, iris, blood and fibrin, to our knowledge this is the first report of tube occlusion by the anterior lens capsule and the first report to describe its successful management.