bluuebunny/crossref_metadata_2025 huggingface dataset:
Safety and Efficacy of Scleral Lenses for Keratoconus
Authors: Fuller Daniel G. , Wang Yueren
Published: September 2020

SIGNIFICANCE

This study affirms the long-term safety and efficacy of scleral contact lens use in patients with keratoconus.

PURPOSE

This study aimed to evaluate the safety and efficacy of contemporary scleral contact lenses in the visual rehabilitation of the keratoconic population.

METHODS

A retrospective study of keratoconic subjects examined between 2013 and 2018 was conducted. Subjects were included regardless of age, sex, pre-existing morbidity, or scleral lens design. Only eyes fit successfully with scleral contact lenses for ≥1 year were included. Exclusion criteria were prior corneal surgery, dystrophy, degeneration, and trauma.

RESULTS

A total of 157 eyes of 86 subjects met the study criteria. The mean Keratoconus Severity Score at initial fitting was 3.6 ± 1.0. Lenses were gas-permeable and nonfenestrated, with a mean overall diameter of 15.8 ± 0.6 mm and 70.1% toric scleral periphery. Physiological adverse events occurred in 9.6% of eyes, including microbial keratitis (0.6%), phlyctenulosis (0.6%), corneal abrasion (1.3%), contact lens–induced acute red eye (1.3%), corneal infiltrative events (1.3%), pingueculitis (1.3%), and hydrops (3.2%). Lens-related adverse events were documented in 55.4% of eyes. Adverse events related to surface issues included poor wetting in 1.9%, handling in 3.8%, reservoir fogging in 7.0%, lens intolerance in 7.6%, deposit in 8.9%, and broken lenses in 26.1% of eyes. The most common management strategies involved refits (54.0% of interventions), patient reeducation (29.5%), medical treatment (5.5%), surgical referral (6.8%), adjustment to wear time (2.5%), surface treatment (1.2%), and lens replacement (0.6%). Best-corrected distance logMAR visual acuity improved significantly from a mean of 0.50 in spectacles to a mean of 0.08 in scleral lenses (P < .0001). During the study period, 14.6% of eyes lost best-corrected scleral lens visual acuity, all from keratoconus progression.

CONCLUSIONS

Consistent with other groups, our study demonstrates excellent safety and efficacy of scleral contact lenses in subjects with keratoconus.
Aerobic Exercise After Left-Sided Stroke Improves Gait Speed and Endurance
Authors: Catapani Ligia Brancalion , dos Santos Tamyris Padovani , Toffano Giovana Cristina , Souza Hugo Celso Dutra , de Araujo João Eduardo
Published: September 2020

Objective

The aim of the study was to investigate the effects of aerobic exercise on individuals who have had a stroke and showed baseline scores lower than the standard scores for the 6-min and 10-meter walk tests.

Design

Individuals were assigned to groups according to gait performance, defined by the standard values in the 6-min and 10-meter walk tests (standard baseline score and lower baseline score), and brain injury side. Aerobic exercise, 30 mins per day, 2 times a week, for a total of 12 wks. The 6-min and 10-meter walk tests in five assessments: initial, after 4, 8, 12 wks, and 4 wks of follow-up, analyzed by multivariate analysis, with P value of less than 0.05.

Results

The 6-min walk test data showed an increase in endurance for lower baseline score and left-brain injury, during assessments 4, and follow-up, compared with standard baseline score (F
4,84 = 14.64). Lower baseline score showed endurance increase for assessments 2, 3, 4, and follow-up compared with assessment 1 (F
4,84 = 7.70). The 10-meter walk test data showed an increase in speed for lower baseline score and left-brain injury, during assessments 3, 4, and follow-up, compared with assessment 1, 4, and follow-up, compared with assessment 2 (F
4,84 = 5.33).

Conclusions

Aerobic exercise increases gait endurance and speed in individuals who have had a stroke, with left-brain injury, and lower baseline score in the 6-min and 10-meter walk tests.
Home- and Clinic-Based Pediatric HIV Index Case Testing in Kenya: Uptake, HIV Prevalence, Linkage to Care, and Missed Opportunities
Authors: Mugo Cyrus , Wang Jiayu , Begnel Emily R. , Njuguna Irene N. , Maleche-Obimbo Elizabeth , Inwani Irene , Slyker Jennifer A. , John-Stewart Grace , Wamalwa Dalton C. , Wagner Anjuli D.
Published: September 2020

Introduction:

Gaps in HIV testing of children persist, particularly among older children born before the expansion of the prevention of mother-to-child transmission of HIV programs.

Methods:

The Counseling and Testing for Children at Home study evaluated an index-case pediatric HIV testing approach. Caregivers receiving HIV care at 7 health facilities in Kenya (index cases), who had children of unknown HIV status aged 0–12 years, were offered the choice of clinic-based testing (CBT) or home-based testing (HBT). Testing uptake and HIV prevalence were compared between groups choosing HBT and CBT; linkage to care, missed opportunities, and predictors of HIV-positive diagnosis were identified.

Results:

Among 493 caregivers, 70% completed HIV testing for ≥1 child. Most caregivers who tested children chose CBT (266/347, 77%), with 103 (30%) agreeing to same-day testing of an untested accompanying child. Overall HIV prevalence among 521 tested children was 5.8% (CBT 6.8% vs HBT 2.4%; P = 0.07). Within 1 month of diagnosis, 88% of 30 HIV-positive children had linked to care, and 54% had started antiretroviral treatment. For 851 children eligible for testing, the most common reason for having an unknown HIV status was that the child's mother was not tested for HIV or had tested HIV negative during pregnancy (82%).

Conclusion:

Testing uptake and HIV prevalence were moderate with nonsignificant differences between HBT and CBT. Standardized offer to test children accompanying caregivers is feasible to scale-up with little additional investment. Linkage to care for HIV-positive children was suboptimal. Lack of peripartum maternal testing contributed to gaps in pediatric testing.
CT Dosimetry
Authors: Damilakis John
Published: September 2020

Radiation dose in computed tomography (CT) has become a hot topic due to an upward trend in the number of CT procedures worldwide and the relatively high doses associated with these procedures. The main aim of this review article is to provide an overview of the most frequently used metrics for CT radiation dose characterization, discuss their strengths and limitations, and present patient dose assessment methods. Computed tomography dosimetry is still based on a CT dose index (CTDI) measured using 100-mm-long pencil ionization chambers and standard dosimetry phantoms (CTDI100). This dose index is easily measured but has important limitations. Computed tomography dose index underestimates the dose generated by modern CT scanners with wide beam collimation. Manufacturers should report corrected CTDI values in the consoles of CT systems. The size-specific dose estimate has been proposed to provide an estimate of the average dose at the center of the scan volume along the z-axis of a CT scan. Size-specific dose estimate is based on CTDI and conversion factors and, therefore, its calculation incorporates uncertainties associated with the measurement of CTDI. Moreover, the calculation of size-specific dose estimate is straightforward only when the tube current modulation is not activated and when the patient body diameter does not change considerably along the z-axis of the scan. Effective dose can be used to provide typical patient dose values from CT examinations, compare dose between modalities, and communicate radiogenic risks. In practice, effective dose has been used incorrectly, for example, to characterize a CT procedure as a low-dose examination. Organ or tissue doses, not effective doses, are required for assessing the probability of cancer induction in exposed individuals. Monte Carlo simulation is a powerful technique to estimate organ and tissue dose from CT. However, vendors should make available to the research community the required information to model the imaging process of their CT scanners. Personalized dosimetry based on Monte Carlo simulation and patient models allows accurate organ dose estimation. However, it is not user friendly and fast enough to be applied routinely. Future research efforts should involve the development of advanced artificial intelligence algorithms to overcome drawbacks associated with the current equipment-specific and patient-specific dosimetry.
Eucalyptol inhibits biofilm formation of Streptococcus pyogenes and its mediated virulence factors
Authors: Vijayakumar Karuppiah , Manigandan Vajravelu , Jeyapragash Danaraj , Bharathidasan Veeraiyan , Anandharaj Balaiyan , Sathya Madhavan
Published: September 2020

Introduction.

Streptococcus pyogenes

is a diverse virulent synthesis pathogen responsible for invasive systemic infections. Establishment of antibiotic resistance in the pathogen has produced a need for new antibiofilm agents to control the biofilm formation and reduce biofilm-associated resistance development.

Aim. The present study investigates the in vitro antibiofilm activity of eucalyptol against

S. pyogenes

.

Methodology. The antibiofilm potential of eucalyptol was assessed using a microdilution method and their biofilm inhibition efficacy was visualized by microscopic analysis. The biochemical assays were performed to assess the influence of eucalyptol on virulence productions. Real-time PCR analysis was performed to evaluate the expression profile of the virulence genes.

Results. Eucalyptol showed significant antibiofilm potential in a dose-dependent manner without affecting bacterial growth. Eucalyptol at 300 µg ml−1 (biofilm inhibitory concentration) significantly inhibited the initial stage of biofilm formation in

S. pyogenes

. However, eucalyptol failed to diminish the mature biofilms of

S. pyogenes

at biofilm inhibitory concentration and it effectively reduced the biofilm formation on stainless steel, titanium, and silicone surfaces. The biochemical assay results revealed that eucalyptol greatly affects the cell-surface hydrophobicity, auto-aggregation, extracellular protease, haemolysis and hyaluronic acid synthesis. Further, the gene-expression analysis results showed significant downregulation of virulence gene expression upon eucalyptol treatment.

Conclusion. The present study suggests that eucalyptol applies its antibiofilm assets by intruding the initial biofilm formation of

S. pyogenes

. Supplementary studies are needed to understand the mode of action involved in biofilm inhibition.
Words Matter: Political and gender analysis of speeches made by heads of government during the COVID-19 pandemic
Authors: Dada Sara , Ashworth Henry , Bewa Marlene Joannie , Dhatt Roopa
Published: September 2020

Background

The COVID-19 pandemic has put a spotlight on political leadership and decision-making around the world. Differences in how leaders address the pandemic through public messages have practical implications for building trust and an effective response within a country.

Methods

We analyzed the public statements and speeches made by 20 heads of government around the world (Bangladesh, Belgium, Bolivia, Brazil, Dominican Republic, Finland, France, Germany, India, Indonesia, New Zealand, Niger, Norway, Russia, South Africa, Scotland, Sint Maarten, United Kingdom, United States, Taiwan) to highlight the differences between men and women leaders in discussing COVID-19 and pandemic response. We used a deductive analytical approach, coding speeches for specific themes based on language used and content discussed.

Findings

Five primary themes emerged across a total of 122 speeches on COVID-19, made by heads of government: economics and financial relief, social welfare and vulnerable populations, nationalism, responsibility and paternalism, and emotional appeals. While all leaders described the economic impact of the pandemic, women leaders spoke more frequently about the impact on local or individual scale. Women leaders were also more often found describing a wider range of social welfare services, including addressing to: mental health, substance abuse, and domestic violence. Both men and women from lower-resource settings described detailed financial relief and social welfare support that would impact the majority of their citizen population. While 17 of the 20 leaders used war metaphors to describe the COVID-19 virus and response, men largely used these with greater volume and frequency.

Conclusion

While this analysis does not attempt to answer whether men or women are more effective leaders in responding to the COVID-19 pandemic, it does provide insight into the rhetorical tools and types of language used by different leaders during a national and international crisis. This analysis provides additional knowledge on the importance and impact of political leaders speeches, messages, and priorities to inspire citizens adhesion to the social contract in the adoption of response and recovery measures.
Characterization and Phase 1 Trial of a B Cell Activating Anti-CD73 Antibody for the Immunotherapy of COVID-19
Authors: Willingham Stephen B. , Criner Gerard , Hill Craig , Hu Shenshen , Rudnick Jenny A. , Daine-Matsuoka Barbara , Hsieh Jessica , Mashhedi Haider , Hotson Andrew N. , Brody Joshua , Marron Thomas , Piccione Emily , Buggy Joseph J. , Mahabhashyam Suresh , Jones William B. , Mobasher Mehrdad , Miller Richard A.
Published: September 2020

COVID-19 is a global pandemic that has resulted in over 800,000 deaths. Robust humoral anti-viral immune responses have the potential to generate a diverse set of neutralizing antibodies to eliminate viruses and protect against re-infection, transmission, and the evolution of mutations that escape targeted therapeutics. CD73 is present on the majority of human B cells and a subset of T cells where it plays a role in lymphocyte activation and migration. CD73 also functions as an ectoenzyme that converts AMP into adenosine, which can be immunosuppressive. Here we report on CPI-006, a humanized FcγR binding-deficient IgG1 anti-CD73 antibody that blocks CD73 enzymatic activity and directly activates CD73POS B cells, inducing differentiation into plasmablasts, immunoglobulin class switching, and antibody secretion independent of adenosine. Immunophenotypic analysis of peripheral blood from advanced cancer patients receiving CPI-006 revealed evidence of B cell activation, clonal expansion, and development of memory B cells. These immune effects suggested that CPI-006 may be effective at enhancing the magnitude, diversity, and duration of humoral and cellular responses to viruses such as SARS-CoV-2. We have therefore initiated a Phase 1, single-dose, dose-escalation trial in hospitalized patients with mild to moderate COVID-19. The objectives of this trial are to evaluate the safety of CPI-006 in COVID-19 patients and to determine effects of CPI-006 on anti-SARS-CoV-2 antibody responses and the development of memory B cell and T cells. Ten patients have been enrolled in the trial receiving doses of 0.3 mg/kg or 1.0 mg/kg. All evaluable patients had low pre-treatment serum levels of anti-viral antibodies to the SARS-CoV-2 trimeric spike protein and its receptor binding domain, independent of the duration of their COVID-19 related symptoms prior to enrollment. Anti-viral antibody responses were induced 7 days after CPI-006 treatment and titers continued to rise past Day 56. Increases in the frequency of memory B cells and effector/memory T cells were observed 28 days after treatment. These preliminary results suggest that CPI-006 activates B cells and may enhance and prolong anti-SARS-CoV-2 antibody responses in patients with COVID-19. This approach may be useful for treating COVID-19 or as an adjuvant to enhance the efficacy of vaccines.
Safety and Efficacy of the combined use of ivermectin, dexamethasone, enoxaparin and aspirin against COVID 19
Authors: Héctor Carvallo , Roberto Hirsch , Eugenia Farinella María
Published: September 2020

From the first outbreak in Wuhan (China) in December 2019, until today the number of deaths worldwide due to the coronavirus pandemic exceeds eight hundred thousand people and the number of infected people arises to more than 25 million.

No treatment tested worldwide has shown unquestionable efficacy in the fight against COVID 19, according to NICE reports.

We have designed an experimental treatment called IDEA based on four affordable drugs already available on the market in Argentina, based on the following rationale:

- Ivermectin solution at a relatively high dose to lower the viral load in all stages of COVID 19

- Dexamethasone 4-mg injection, as anti-inflammatory drug to treat hyperinflammatory reaction to COVID-infection

- Enoxaparin injection as anticoagulant to treat hypercoagulation in severe cases.

- Aspirin 250-mg tablets to prevent hypercoagulation in mild and moderate cases

Except for Ivermection oral solution, which was used in a higher dose than approved for parasitosis, all other drugs were used in the already approved dose and indication. Regarding Ivermectin safety, several oral studies have shown it to be safe even when used at daily doses much higher than those approved already.

A clinical study has been conducted on COVID-19 patients at Eurnekian Hospital in the Province of Buenos Aires, Argentina. The study protocol and its final outcomes are described in this article. Results were compared with published data and data from patients admitted to the hospital receiving other treatments.

None of the patient presenting mild symptoms needed to be hospitalized. Only one patient died (0.59 % of all included patients vs. 2.1 % overall mortality for the disease in Argentina today; 3.1 % of hospitalized patients vs. 26.8 % mortality in published data). IDEA protocol appears to be a useful alternative to prevent disease progression of COVID-19 when applied to mild cases and to decrease mortality in patients at all stages of the disease with a favorable risk-benefit ratio.
Attention and reinforcement learning in Parkinson’s disease
Authors: McCoy Brónagh , Lawson Rebecca P. , Theeuwes Jan
Published: September 2020

Dopamine is known to be involved in several important cognitive processes, most notably in learning from rewards and in the ability to attend to task-relevant aspects of the environment. Both of these features of dopaminergic signalling have been studied separately in research involving Parkinson’s disease (PD) patients, who exhibit diminished levels of dopamine. Here, we tie together some of the commonalities in the effects of dopamine on these aspects of cognition by having PD patients (ON and OFF dopaminergic medication) and healthy controls (HCs) perform two tasks that probe these processes. Within-patient behavioural measures of distractibility, from an attentional capture task, and learning performance, from a probabilistic classification reinforcement learning task, were included in one model to assess the role of distractibility during learning. Dopamine medication state and distractibility level were found to have an interactive effect on learning performance; less distractibility in PD ON was associated with higher accuracy during learning, and this was altered in PD OFF. Functional magnetic resonance imaging (fMRI) data acquired during the learning task furthermore allowed us to assess multivariate patterns of positive and negative outcomes in fronto-striatal and visual brain regions involved in both learning processes and the executive control of attention. Here, we demonstrate that while PD ON show a clearer distinction between outcomes than OFF in dorsolateral prefrontal cortex (DLPFC) and putamen, PD OFF show better distinction of activation patterns in visual regions that respond to the stimuli presented during the task. These results demonstrate that dopamine plays a key role in modulating the interaction between attention and learning at the level of both behaviour and activation patterns in the brain.
Are we there yet? An adaptive SIR model for continuous estimation of COVID-19 infection rate and reproduction number in the United States
Authors: Shapiro Mark B , Karim Fazle , Muscioni Guido , Augustine Abel Saju
Published: September 2020

The dynamics of the COVID-19 epidemic vary due to local population density and policy measures. When making decisions, policy makers consider an estimate of the effective reproduction numberwhich is the expected number of secondary infections by a single infected individual. We propose a simple method for estimating the time-varying infection rate and reproduction numberusing a sliding window approach applied to a Susceptible-Infectious-Removed model. The infection rate is estimated using the reported cases for a seven-day window to obtain continuous estimation of. We demonstrate that the proposed adaptive SIR (aSIR) model can quickly adapt to an increase in the number of tests and associated increase in the reported cases of infections. Our results also suggest that intensive testing may be one of the effective methods of reducing. TheaSIRmodel was applied to data at the state and county levels.
Somatic mutations in Parkinson disease are enriched in synaptic and neuronal processes
Authors: Lobon Irene , Solís-Moruno Manuel , Juan David , Muhaisen Ashraf , Abascal Federico , Esteller-Cucala Paula , García-Pérez Raquel , Martí Maria Josep , Tolosa Eduardo , Ávila Jesús , Rahbari Raheleh , Casals Ferran , Marques-Bonet Tomas , Soriano Eduardo
Published: September 2020

The role of somatic mutations in complex diseases, including neurodevelopmental and neurodegenerative disorders, is becoming increasingly clear. To explore their relevance in sporadic Parkinson disease, we performed whole-exome sequencing in blood and four brain regions of ten patients. We identified 59 candidate somatic single nucleotide variants (sSNVs) through sensitive calling and extensive filtering. We validated 27 of them with amplicon-based deep sequencing, with a 70% validation rate for the highest-confidence variants. Most of the sSNVs were exclusively called in blood but were also found in the brain tissues with the ultra-deep amplicon sequencing, demonstrating the strength of multi-tissue sampling designs. We could confirm between 0 and 6 sSNVs per patient and generally those with a shorter lifespan carried more variants. Remarkably, the validated sSNVs are enriched in genes with synaptic functions that are co-expressed with genes previously associated with Parkinson disease.
Neutrophil-to-lymphocyte ratio on admission to predict the severity and mortality of COVID-19 patients: a meta-analysis
Authors: Simadibrata Daniel Martin , Calvin Julius , Wijaya Alya Darin , Ibrahim Naufal Arkan Abiyyu
Published: September 2020

The neutrophil-to-lymphocyte ratio (NLR), an inflammatory marker, was suggested to be predictive of severity and mortality in COVID-19 patients, thus allowing early risk stratification. In this study, we investigated whether NLR levels on admission could predict the severity and mortality of COVID-19 patients. A literature search was conducted on 23 July 2020 to retrieve all published articles, including grey literature and preprints, investigating the association between on-admission NLR values and severity or mortality in COVID-19 patients. The risk of bias was assessed using the Newcastle Ottawa Scale (NOS). A meta-analysis was performed to determine the overall standardized mean difference (SMD) in NLR values and the pooled risk ratio (RR) for severity and mortality with the 95% Confidence Interval (95%CI). Meta-regression analysis was done to identify potential confounders. A total of 38 articles, including 5699 patients with severity outcomes and 6033 patients with mortality outcomes, were included. The meta-analysis showed that severe and non-survivors of COVID-19 had higher on-admission NLR levels than non-severe and survivors (SMD 0.88; 95%CI 0.72-1.04; I2=75% and 1.68; 95%CI 0.98-2.39; I2=99%, respectively). Regardless of the different NLR cut-off values, the pooled mortality RR in patients with elevated vs. normal NLR levels was 2.75 (95%CI 0.97-7.72). Meta-regression analysis showed that the association between NLR levels on admission and COVID-19 severity and mortality was unaffected by age (p=0.236; p=0.213, respectively). High NLR levels on admission were associated with severe COVID-19 and mortality. Further studies need to focus on determining the optimal cut-off value for NLR before clinical use.

Key Points

High neutrophil-to-lymphocyte ratio (NLR) is associated with severe COVID-19 and mortality

NLR is a simple, accessible, near real-time, and cost-effective biomarker recommended for use in resource-limited healthcare settings
Elucidating the Joint Genetic Architecture of Mood Disorder and Schizophrenia
Authors: Lam Max , Thompson Meiling , Li Baijia , Edwards Alexis C. , Chen Chia-Yen , Ge Tian , Cai Na , Bigdeli Tim , Lencz Todd , Kendler Kenneth , Huang Hailiang
Published: September 2020

Introduction

Recent advances in psychiatric genomics have enabled large-scale genome-wide scans that elucidated genetic architecture both in mood disorder and schizophrenia across individuals of East Asian and European descent. Investigating joint genetic architecture of these psychiatric traits enables the identification of common and diverging etiological mechanisms underlying these psychiatric illnesses. Here, we leverage on the largest GWAS of schizophrenia and mood disorder conducted to date in East Asian and European descent samples to elucidate the joint genetic architecture that underlie these psychiatric disorders.

Methodology

We carried out GWAS meta-analysis on both European (EUR) and East Asian (EAS) Ancestry summary statistics for Major Depressive Disorder (MDD) and Schizophrenia via Multi-Trait Analysis of GWAS. Downstream pathway, eQTL, chromatin interaction analysis were carried out to characterize genome-wide results. In addition we carried out genetic correlations and polygenic risk prediction analysis to further study the joint genetic architectures of mood disorder and schizophrenia.

Results

There were 308 loci that was significantly associated with at least one trait. Specifically, there were 98 independent loci in EUR-MDD, 5 loci for MTAGx-EAS-MDD, 121 loci for MTAGx-EUR-MDD, 8 independent loci for EAS-SZ, 171 independent loci for EUR-SZ, 124 independent loci for MTAGx-EAS-SZ, and 159 independent loci for MTAGx-EUR-SZ. In all, 61 loci were novel across traits. SOAT1 and FOXO3 genes were implicated based on genome-wide associations. 114 gene(s) were implicated in eQTL analysis of gene expression in brain tissue. Gene-set analysis show support for GABA-egic pathways implicated in MDD, driven by several GABA-alpha receptor genes as well as more peripheral PLCL1 and NISCH genes that are responsible for endocytosis and neuronal trafficking. Cross-Ancestry genetic correlations ascertained that the CONVERGE MDD phenotype generally holds higher SNP based heritability and is likely driven by case-ascertainment procedures. Finally, polygenic risk score modelling indicates that MTAGx procedures were effective in enriching GWAS signals in the EAS-MDD for prediction in an independent case-control sample.

Discussion

Here we are able to demonstrate that cross-trait cross-ancestry approaches in schizophrenia and MDD not only yields new discoveries to the genetic architecture of these illnesses; we were able to identify new biological underpinnings within the GABA pathways for depressive disorders. The evidence in the current report underscores the importance of taking into consideration both phenotype and ancestry complexities in genome-wide studies.
What is the Relationship Between Obesity and new Circadian Rhythm Parameters in Turkish Children and Adolescents? A Case-Control Study
Authors: Karadag Mehmet , Yilmaz Gulay Can
Published: September 2020

Although the relationship between circadian rhythm parameters and obesity in children and adolescents are widely recognized, there are still not enough studies. The concept of Sleep Corrected Social Jet lag (SJLsc) has been formulated recently and its relationship with childhood obesity has not been established. In this study, we aimed to compare circadian rhythm parameters between obese and normal-weight children and adolescents. Seventy-nine obese and eighty-two normal-weighted children and adolescents aged between 8–17 years participated in this case-control study which took place in Turkey’s Mardin province. Sociodemographic information, Childhood Chronotype Questionnaire, and anthropometric data were collected. The average age of the obese and controls were 12.3 ± 2.3, 12.4±2.2 respectively. Obese young had more evening preference, sleep dept duration, SJL duration, SJLsc duration and morning Evening Scale (MeScale) scores; less mean sleep duration (p<0.005). In regression analyses, BMI z scores were significant correlated with all circadian rhythm parameters, except SJLsc duration, WC z scores were significant correlated with all circadian rhythm parameters, except mean sleep duration. After adjustment, the high mescale scores (OR:1.142, p<0.05) and the presence of a psychiatric disease in the mother (OR:15.075, p<0.05) were associated with obesity. Circadian rhythm parameters can play an important role in the etiology of obesity. Future studies with larger samples and fewer confounding factors are needed to clarify the etiological factors.
Adaptive Cardiac Resynchronization Therapy Effect on Electrical Dyssynchrony (aCRT-ELSYNC): a randomized controlled trial
Authors: Haq Kazi T. , Rogovoy Nichole M. , Thomas Jason A. , Hamilton Christopher , Lutz Katherine J. , Wirth Ashley , Bender Aron B. , German David M. , Przybylowicz Ryle , van Dam Peter , Dewland Thomas A. , Dalouk Khidir , Stecker Eric , Nazer Babak , Jessel Peter M. , MacMurdy Karen S. , Zarraga Ignatius Gerardo E. , Beitinjaneh Bassel , Henrikson Charles A. , Raitt Merritt , Fuss Cristina , Ferencik Maros , Tereshchenko Larisa G.
Published: September 2020

Introduction

Adaptive cardiac resynchronization therapy (aCRT) is known to have clinical benefits over conventional CRT; however, their effects on the electrical dyssynchrony have not been compared.

Methods

We conducted a double-blind, randomized controlled trial in patients receiving CRT for routine clinical indications. Participants underwent cardiac computed tomography and 128-electrodes body surface mapping. We measured electrical dyssynchrony on the epicardial surface using noninvasive electrocardiographic imaging (ECGI) before and 6 months post-CRT. Ventricular electrical uncoupling (VEU) was calculated as the difference between the mean left ventricular (LV) and right ventricular (RV) activation times. An electrical dyssynchrony index (EDI) was computed as the standard deviation of local epicardial activation times.

Results

We randomized 27 participants (mean age 64±12 y; 34% female; 53% ischemic cardiomyopathy; LV ejection fraction 28±8%; QRS duration 155±21 ms; strict left bundle branch block (LBBB) in 13%). In atypical LBBB (n=11;41%) with S-waves in V5-V6, conduction block occurred in the anterior RV, as opposed to the interventricular groove in those who met the strict LBBB criteria. As compared to baseline, VEU reduced post-CRT in aCRT (median reduction 18.9(interquartile range 4.3-29.2 ms; P=0.034), but not in conventional CRT (21.4(−30.0 to 49.9 ms; P=0.525) group. There were no differences in the degree of change in VEU and EDI indices between treatment groups.

Conclusion

The effect of aCRT and conventional CRT on electrical dyssynchrony is largely similar. Further studies are needed to investigate if atypical LBBB with prominent S wave in V5-V6responds to His bundle pacing.
Experimental evidence that UV/yellow colouration functions as a signal of parental quality in the blue tit
Authors: García-Campa Jorge , Müller Wendt , Morales Judith
Published: September 2020

In bi-parental species, reproduction is not only a crucial life-history stage where individuals must take fitness-relevant decisions, but these decisions also need to be adjusted to the behavioural strategies of a partner. Hence, communication is required, which could be facilitated by condition-dependent signals of parental quality. Yet, these traits have (co-)evolved in multiple contexts within the family, as during reproduction different family members may coincide and interact at the site of breeding. In this study we explore whether a condition-dependent trait acts a quality signal and regulates intra-family interactions in a bird species, the blue tit (Cyanistes caeruleus). As a family is a complex network where signals could be perceived by multiple receivers, we expected that experimentally blocking the reflectance of an adult’s UV/yellow colouration of breast feathers may affect the behavioural strategies of all family members. We found an increase of parental investment in nests with an UV-blocked adult, as the partner compensated for the perceived lower rearing capacity. As the UV-blocked adult did not change its provisioning behaviour, as was to be expected, their partner must have responded to the (manipulated) signal but not to a behavioural change. However, offspring did not co-adjust their begging intensity to a signal of parental quality. Opposite to adults, we propose that offspring respond to the behaviour but not to the parental signal. Overall, our results show experimentally at the first time that UV/yellow colouration of blue tits acts as a quality signal revealing the rearing capacity to mates.
Hyaluronic Acid Fuels Pancreatic Cancer Growth
Authors: Kim Peter K. , Halbrook Christopher J. , Kerk Samuel A. , Wisner Stephanie , Kremer Daniel M. , Sajjakulnukit Peter , Hou Sean W. , Thurston Galloway , Anand Abhinav , Yan Liang , Salamanca-Cardona Lucia , Welling Samuel D. , Zhang Li , Pratt Matthew R. , Keshari Kayvan R. , Ying Haoqiang , Lyssiotis Costas A.
Published: September 2020

Rewired metabolism is a hallmark of pancreatic ductal adenocarcinomas (PDA). Previously, we demonstrated that PDA cells enhance glycosylation precursor biogenesis through the hexosamine biosynthetic pathway (HBP) via activation of the rate limiting enzyme, glutamine-fructose 6-phosphate amidotransferase 1 (GFAT1). Here, we genetically ablated GFAT1 in PDA cell lines, which completely blocked proliferation in vitro and led to cell death. In contrast, GFAT1 knockout did not impair tumor growth, suggesting that cancer cells can maintain fidelity of glycosylation precursor pools by scavenging nutrients from the tumor microenvironment. Here, we show that hyaluronic acid (HA), an abundant carbohydrate polymer in pancreatic tumors composed of repeating N-acetyl-glucosamine (GlcNAc) and glucuronic acid sugars, can bypass GFAT1 to refuel the HBP via the GlcNAc salvage pathway. Furthermore, HA facilitates proliferation in nutrient-starved wild-type PDA. Together, these data show HA can serve as a nutrient fueling PDA metabolism beyond its previously appreciated structural and signaling roles.
ASXL1 Directs Neutrophilic Differentiation via Modulation of MYC and RNA Polymerase II
Authors: Braun Theodore P. , Estabrook Joseph , Darmusey Lucie , Coleman Daniel J. , Schonrock Zachary , Smith Brittany M. , Taherinasab Akram , Enright Trevor , Coblentz Cody , Yashar William , Callahan Rowan , Mohammed Hisham , Druker Brian J. , Lusardi Theresa A. , Maxson Julia E.
Published: September 2020

Mutations in the gene Additional Sex-Combs Like 1 (ASXL1) are recurrent in myeloid malignancies as well as the pre-malignant condition clonal hematopoiesis, where they are universally associated with poor prognosis. An epigenetic regulator, ASXL1 canonically directs the deposition of H3K27me3 via the polycomb repressive complex 2. However, its precise role in myeloid lineage maturation is incompletely described. We utilized single cell RNA sequencing (scRNA-seq) on a murine model of hematopoietic-specific ASXL1 deletion and identified a specific role for ASXL1 in terminal granulocyte maturation. Terminal maturation is accompanied by down regulation of Myc expression and cell cycle exit. ASXL1 deletion leads to hyperactivation of Myc in granulocyte precursors and a quantitative decrease in neutrophil production. This failure of normal developmentallyassociated Myc suppression is not accompanied by significant changes in the landscape of covalent histone modifications including H3K27me3. Examining the genome-wide localization of ASXL1 in myeloid progenitors revealed strong co-localization with RNA Polymerase II (RNAPII) at the promoters and spread across the gene bodies of transcriptionally active genes. ASXL1 deletion results in a decrease in RNAPII promoter-proximal pausing in granulocyte progenitors, indicative of a global increase in productive transcription, consistent with the known role of ASXL1 as a mediator of RNAPII pause release. These results suggest that ASXL1 inhibits productive transcription in granulocyte progenitors, identifying a new role for this epigenetic regulator and highlighting a novel potential oncogenic mechanism for ASXL1 mutations in myeloid malignancies.
SARS-CoV-2 nucleocapsid protein forms condensates with viral genomic RNA
Authors: Jack Amanda , Ferro Luke S. , Trnka Michael J. , Wehri Eddie , Nadgir Amrut , Nguyenla Xammy , Costa Katelyn , Stanley Sarah , Schaletzky Julia , Yildiz Ahmet
Published: September 2020

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes COVID-19, a pandemic that seriously threatens global health. SARS-CoV-2 propagates by packaging its RNA genome into membrane enclosures in host cells. The packaging of the viral genome into the nascent virion is mediated by the nucleocapsid (N) protein, but the underlying mechanism remains unclear. Here, we show that the N protein forms biomolecular condensates with viral genomic RNA both in vitro and in mammalian cells. Phase separation is driven, in part, by hydrophobic and electrostatic interactions. While the N protein forms spherical assemblies with unstructured RNA, it forms asymmetric condensates with viral RNA strands that contain secondary structure elements. Cross-linking mass spectrometry identified a region that forms interactions between N proteins in condensates, and truncation of this region disrupts phase separation. We also identified small molecules that alter the formation of N protein condensates. These results suggest that the N protein may utilize biomolecular condensation to package the SARS-CoV-2 RNA genome into a viral particle.
Discovery of new antibacterial accramycins from a genetic variant of the soil bacterium,Streptomycessp. MA37
Authors: Maglangit Fleurdeliz , Zhang Yuting , Kyeremeh Kwaku , Deng Hai
Published: September 2020

Continued mining of natural products from the strainStreptomycessp. MA37 in our laboratory led to the discovery of a minor specialised metabolite (SM) called accramycin A. Owing to its low yield (0.2mg/L) in the wild type strain, we investigated the roles of regulatory genes in the corresponding biosynthetic gene cluster (accBGC) through gene inactivation with the aim of improving the titre of this compound. One of the resulting mutants (ΔaccJ) dramatically upregulated the production of accramycin A1by 330-fold (66mg/L). Furthermore, ten new metabolites, accramycins B-K2-11, were discovered, together with two known compounds, naphthacemycin B112and fasamycin C13from the mutant extract. This suggested thataccJ, annotated as Multiple Antibiotic Resistance Regulator (MarR), is a negative regulator gene in the accramycin biosynthesis. Compounds1-13inhibited the Gram-positive pathogens (S. aureus, E. faecalis) and clinical isolates,E. faecium(K59-68 and K60-39), andS. haemolyticuswith minimal inhibitory concentration (MIC) values in the range of 1.5-12.5µg/mL. Remarkably, compounds1-13displayed superior activity against K60-39 (MIC = 3.1-6.3µg/mL) than ampicillin (MIC = 25µg/mL), and offer promising potential for the development of accramycin-based antibiotics that target multidrug-resistantEnterococcusclinical isolates. Our results highlight the importance of identifying the roles of regulatory genes in natural product discovery.
Ageratina adenophoraandLantana camarain Kailash Sacred Landscape, India: Current distribution and future climatic scenarios through modeling
Authors: Chaudhary Alka , Sarkar Mriganka Shekhar , Adhikari Bhupendra Singh , Rawat Gopal Singh
Published: September 2020

The Himalayan region is one of the global biodiversity hotspots. However, its biodiversity and ecosystems are threatened due to abiotic and biotic drivers. One of the major biotic threats to biodiversity in this region is the rapid spread of invasive alien species (IAS). Natural forests and grasslands are increasingly getting infested by IAS affecting regeneration of native species and decline in availability of bio-resources. Assessing the current status of IAS and prediction of their future spread would be vital for evolving specific species management interventions. Keeping this in view, we conducted an in-depth study on two IASs, viz.,Ageratina adenophoraandLantana camarain the Indian part of Kailash Sacred Landscape (KSL), Western Himalaya. Intensive field surveys were conducted to collect the presence ofA. adenophora(n= 567) andL. camara(n= 120) along an altitudinal gradient between 300 and 3000 m a.s.l. We performed Principle Component Analysis to nullify the multi-colinearity effects of the environmental predictors followingMaxEntspecies distribution model in the current and future climatic scenarios for both the species. All current and future model precision (i.e. Area Under the Curve; AUC) for both species was higher than 0.81. It is predicted that under the current rate of climate change and higher emission (i.e. RCP8.5 pathway),A. adenophorawill spread 45.3% more than its current distribution and is likely to reach up to 3029 m a.s.l. Whereas,L. camarawill spread 29.8% more than its current distribution range and likely to reach up to 3018 m a.s.l. Our results will help in future conservation planning and participatory management of forests and grasslands in the KSL– India.
Linking mountaintop removal mining to water quality for imperiled species using satellite data
Authors: Evans Michael J. , Kay Kathryn , Proctor Chelsea , Thomas Christian , Malcom Jacob W.
Published: September 2020

Environmental laws need sound data to protect species and ecosystems. In 1996, a proliferation of mountaintop removal coal mines in a region home to over 50 federally protected species was approved under the Endangered Species Act. Although this type of mining can degrade terrestrial and aquatic habitats, the available data and tools limited the ability to analyze spatially extensive, aggregate effects of such a program. We used two large, public datasets to quantify the relationship between mountaintop removal coal mining and water quality measures important to the survival of imperiled species at a landscape scale across Kentucky, Tennessee, Virginia, and West Virginia. We combined an annual map of the extent of surface mines in this region from 1985 to 2015 generated from Landsat satellite imagery with public water quality data collected over the same time period from 4,260 monitoring stations within the same area. The water quality data show that chronic and acute thresholds for levels of aluminum, arsenic, cadmium, conductivity, copper, lead, manganese, mercury, pH, selenium, and zinc safe for aquatic life were exceeded thousands of times between 1985 and 2015 in streams that are important to the survival and recovery of species on the Endangered Species List. Linear mixed models showed that levels of manganese, sulfate, sulfur, total dissolved solids, total suspended solids, and zinc increased by 6.73E+01 to 6.87E+05 µg/L and conductivity by 3.30E+06 µS /cm for one percent increase in the mined proportion of the area draining into a monitoring station. The proportion of a drainage area that was mined also increased the likelihood that chronic thresholds for copper, lead, and zinc required to sustain aquatic life were exceeded. Finally, the proportion of a watershed that was mined was positively related to the likelihood that a waterway would be designated as impaired under the Clean Water Act. Together these results demonstrate that the extent of mountaintop removal mining, which can be derived from public satellite data, is predictive of water quality measures important to imperiled species - effects that must be considered under environmental law. These findings and the public data used in our analyses are pertinent to ongoing re-evaluations of the effects of current mine permitting regulations to the recovery and survival of federally protected species.
Fusion and fission events regulate endosome maturation and viral escape
Authors: Castro Mario , Lythe Grant , Smit Jolanda M. , Molina-París Carmen
Published: September 2020

Many intra-cellular processes rely on transport by endosomes. Recent experimental techniques have provided insights into organelle maturation and its specific role in, for instance, the ability of a virus to escape an endosome and release its genetic material in the cytoplasm. Endosome maturation and dynamics depend on GTPases called Rabs, found on their membrane. Here, we introduce a mathematical framework, combining coagulation and fragmentation of endosomes with two variables internal to each organelle, to model endosomes as intra-cellular compartments characterised by their levels of (active) Rab5 and Rab7. The key element in our framework is the “per-cell endosomal distribution” and its its dynamical equation or Boltzmann equation. The Boltzmann equation, then, allows one to deduce simple equations for the total number of endosomes in a cell, and for the mean and standard deviation of the Rab5 and Rab7 levels. We compare our solutions with experimental data sets of Dengue viral escape from endosomes. The relationship between endosomal Rab levels and pH suggests a mechanism which can account for the observed variability in viral escape times, which in turn regulate the viability of a viral intra-cellular infection.

Author summary

Endosomes are intra-cellular receptacle-like organelles, which transport endocytosed cargo upon internalisation from the plasma membrane. These early endosomes, also known as sorting endosomes, mature to late endosomes, with a lower pH than early ones, as a consequence of the intricate dynamics of a family of molecules called Rabs. Viruses exploit this endosomal pH drop to their advantage. Here we bring together experimental data on Dengue viral escape times from endosomes and a novel mathematical framework inspired by the theory of droplet coalescence, to improve our understanding of endosome maturation, and in turn to quantify the large variability of viral escape times. This mathematical framework can easily be generalised to model the dynamics of other intra-cellular organelles, such as mitochondria or the endoplasmic reticulum.
Memory specificity is linked to repetition effects in event-related potentials across the lifespan
Authors: Sommer Verena R. , Mount Luzie , Weigelt Sarah , Werkle-Bergner Markus , Sander Myriam C.
Published: September 2020

The specificity with which past experiences can be remembered varies across the lifespan, possibly due to differences in how precisely information is encoded. Memory formation can be investigated through repetition effects, the common finding that neural activity is altered when stimuli are repeated. However, whether differences in this indirect measure of memory formation relate to lifespan differences in memory specificity has not yet been established. In the present study, we examined repetition effects in event-related potentials and their relation to recognition. During incidental encoding, children (aged 7–9 years), young adults (18–30 years), and older adults (65–76 years) viewed repeated object images from different categories. During subsequent recognition, we distinguished memory for the specific items versus the general categories. We identified repetition suppression in all age groups, and repetition enhancement for adults. Furthermore, individual item recognition performance comprising lure discrimination was positively associated with the magnitude of the neural repetition effects, which did not differ between groups, indicating common neural mechanisms of memory formation. Our findings demonstrate that neural repetition effects reflect the formation of highly specific memory representations and highlight their significance as a neural indicator of individual differences in episodic memory encoding across the lifespan.