bluuebunny/crossref_metadata_2025_split huggingface dataset:
Corneoscleral Topography Measured with Fourier-based Profilometry and Scheimpflug Imaging
Authors: Bandlitz Stefan , Esper Patrick , Stein Magdalena , Dautzenberg Torsten , Wolffsohn James S. 
Published: September 2020

SIGNIFICANCE
Precise measurement of corneoscleral topography makes a valuable contribution to the understanding of anterior eye anatomy and supports the fitting process of contact lenses. Sagittal height data, determined by newer noninvasive techniques, are particularly useful for initial scleral lens selection.

PURPOSE
The purpose of this study was to investigate the agreement and repeatability of Fourier-based profilometry and Scheimpflug imaging, in the measurement of sagittal height and toricity of the corneoscleral region.

METHODS
Minimal (Minsag), maximal (Maxsag) sagittal height, toricity (Maxsag − Minsag), and the maximum possible measurement zone diameter of 38 subjects were compared using the Eye Surface Profiler (ESP; Eagle Eye, Houten, the Netherlands) and the corneoscleral profile module of the Pentacam (Oculus, Wetzlar, Germany) at two different sessions. Correlations between the instruments were analyzed using the Pearson coefficient. Differences between sessions and instruments were analyzed using Bland-Altman and paired t tests.

RESULTS
For an equal chord length, the measurement with Pentacam was significantly greater for Minsag (344 μm; 95% confidence interval [CI], 322 to 364 μm; P < .001) and significantly greater for Maxsag (280 μm; 95% CI, 256 to 305 μm; P < .001), but significantly smaller for toricity (−63 μm; 95% CI, −95 to −31 μm; P < .001). Maximum possible measurement zone diameter with ESP (16.4 ± 1.3 mm) was significantly greater than with Pentacam (14.8 ± 1.1 mm) (P < .001). Repeated measurements from session 1 and session 2 were not significantly different for Pentacam and ESP (P = .74 and P = .64, respectively). The 95% CIs around differences indicate good repeatability for Pentacam (mean difference, −0.9 μm; 95% CI, −6.7 to 4.8 μm) and ESP (4.6 μm; −22.4 to 31.6).

CONCLUSIONS
Although both instruments deliver useful data especially for the fitting of scleral and soft contact lenses, the sagittal height and the toricity measurements cannot be considered as interchangeable.
Targeting Metabolic Pathways in Kidney Cancer
Authors: Hoerner Christian R. , Miao Susanna Y. , Hsieh James J. , Fan Alice C. 
Published: September 2020

Abstract
Alterations in cellular sugar, amino acid and nucleic acid, and lipid metabolism, as well as in mitochondrial function, are a hallmark of renal cell carcinoma (RCC). The activation of oncogenes such as hypoxia-inducible factor and loss of the von Hippel-Lindau function and other tumor suppressors frequently occur early on during tumorigenesis and are the drivers for these changes, collectively known as “metabolic reprogramming,” which promotes cellular growth, proliferation, and stress resilience. However, tumor cells can become addicted to reprogrammed metabolism. Here, we review the current knowledge of metabolic addictions in clear cell RCC, the most common form of RCC, and to what extent this has created therapeutic opportunities to interfere with such altered metabolic pathways to selectively target tumor cells. We highlight preclinical and emerging clinical data on novel therapeutics targeting metabolic traits in clear cell RCC to provide a comprehensive overview on current strategies to exploit metabolic reprogramming clinically.
Immune Related Adverse Events
Authors: Zengin Zeynep B. , Salgia Nicholas J. , Chehrazi-Raffle Alexander , Meza Luis , Malhotra Jasnoor , Pal Sumanta K. 
Published: September 2020

Abstract
Recent therapeutic advancements have incorporated immune checkpoint inhibitors (ICIs) into the management of metastatic renal cell carcinoma. Pivotal phase III trials have resulted in Food and Drug Administration approval for anti–programmed death 1/programmed death ligand 1 ICIs, either in combination with anti–cytotoxic T-lymphocyte antigen 4 ICIs or with vascular endothelial growth factor–directed targeted therapies, as standard-of-care frontline regimens. Immune checkpoint inhibitors offer improved clinical outcomes when compared to previous treatment options. However, these agents also present unique toxicity profiles collectively referred to as immune-related adverse events. Common immune-related adverse events include colitis, hepatitis, dermatitis, and thyroiditis. Rare toxicities, such as myocarditis and pneumonitis, have the potential for causing severe harm. Herein, we provide a case-based discussion of how to identify, grade, and manage irAEs in metastatic renal cell carcinoma.
Smartphone-based Assessment of Preoperative Decision Conflict and Postoperative Physical Activity Among Patients Undergoing Cancer Surgery
Authors: Panda Nikhil , Solsky Ian , Cauley Christy E. , Lipsitz Stuart , Desai Eesha V. , Huang Emily J. , Benjamin Evan M. , Lubitz Carrie C. , Onnela Jukka-Pekka , Haynes Alex B. 
Published: September 2020

Objective:
To determine the prevalence of clinically significant decision conflict (CSDC) among patients undergoing cancer surgery and associations with postoperative physical activity, as measured through smartphone accelerometer data.

Background:
Patients with cancer face challenging treatment decisions, which may lead to CSDC. CSDC negatively affects patient-provider relationships, psychosocial functioning, and health-related quality of life; however, physical manifestations of CSDC remain poorly characterized.

Methods:
Adult smartphone-owners undergoing surgery for breast, skin-soft-tissue, head-and-neck, or abdominal cancer (July 2017–2019) were approached. Patients downloaded the Beiwe application that delivered the Decision Conflict Scale (DCS) preoperatively and collected smartphone accelerometer data continuously from enrollment through 6 months postop-eratively. Restricted-cubic-spline regression, adjusting for a priori potential confounders (age, type of surgery, support status, and postoperative complications) was used to determine trends in postoperative daily physical activity among patients with and without CSDC (DCS score >25/100).

Results:
Among 99 patients who downloaded the application, 85 completed the DCS (86% participation rate). Twenty-three (27%) reported CSDC. These patients were younger (mean age 48.3 years [standard deviation 14.2]-vs–55.0 [13.3], P = 0.047) and more frequently lived alone (22%-vs–6%, P = 0.042). There were no differences in preoperative physical activity (115.4 minutes [95%CI 90.9, 139.9]-vs–110.8 [95%CI 95.7, 126.0], P = 0.753). Adjusted postoperative physical activity was lower among patients reporting CSDC at 30 days (difference 33.1 minutes [95%CI 5.93,60.2], P = 0.017), 60 days 35.5 [95%CI 8.50, 62.5], P = 0.010 and 90 days 31.8 [95%CI 5.44, 58.1], P = 0.018 postoperatively.

Conclusions:
CSDC was prevalent among patients who underwent cancer surgery and associated with lower postoperatively daily physical activity. These data highlight the importance of addressing modifiable decisional needs of patients through enhanced shared decision-making.
Unraveling the Developmental Dynamic of Visual Exploration of Social Interactions in Autism
Authors: Kojovic Nada , Cekic Sezen , Castañón Santiago Herce , Franchini Martina , Sperdin Holger Franz , Sandini Corrado , Jan Reem Kais , Zöller Daniela , Ben Hadid Lylia , Bavelier Daphné , Schaer Marie 
Published: September 2020

AbstractAtypical deployment of social gaze is present early on in toddlers with autism spectrum disorders (ASDs). Yet, studies characterizing the developmental dynamic behind it are scarce. Here we used a data-driven method to delineate the developmental change in visual exploration of social interaction over childhood years in autism. Longitudinal eye-tracking data were acquired as children with ASD and their typically developing (TD) peers freely explored a short cartoon movie. We found divergent moment-to-moment gaze patterns in children with ASD compared to their TD peers. This divergence was particularly evident in sequences that displayed social interactions between characters and even more so in children with lower developmental and functional levels. The basic visual properties of the animated scene did not account for the enhanced divergence. Over childhood years, these differences dramatically increased to become more idiosyncratic. These findings suggest that social attention should be targeted early in clinical treatments.
Targeted Proteomics Reveals Quantitative Differences in Low Abundance Glycosyltransferases of Patients with Congenital Disorders of Glycosylation
Authors: Sakson Roman , Beedgen Lars , Bernhard Patrick , Alp Keziban M. , Lübbehusen Nicole , Röth Ralph , Niesler Beate , Mayer Matthias P. , Thiel Christian , Ruppert Thomas 
Published: September 2020

AbstractProtein glycosylation is essential in all domains of life and its mutational impairment in humans can result in severe diseases named Congenital Disorders of Glycosylation (CDGs). Studies on molecular level are however challenging, because many glycosyltransferases in the endoplasmic reticulum (ER) are low abundance membrane proteins. We established a comprehensive multiple reaction monitoring (MRM) assay to quantify most human glycosyltransferases involved in the processes ofN-glycosylation,O- andC-mannosylation in the ER. To increase reproducibility, a membrane protein fraction of isotopically labeled HEK 293T cells was used as an internal standard. With this internal standard the MRM assay is easily transferable between laboratories. 22 glycosyltransferases could be reliably quantified from whole cell lysates of HEK 293T cells, HeLa cells and skin fibroblast cell lines. We then analyzed fibroblasts derived from CDG type I patients with mutations in theALG1,ALG2orALG11gene. Mutations inALG1orALG2gene strongly reduced the levels of the ALG1 and ALG2 protein, respectively. In contrast, the levels of all other glycosyltransferases remained unchanged, which was unexpected given evidence that the ALG1, ALG2 and ALG11 proteins form a stable complex. This study describes an efficient workflow for the development of MRM assays for low abundance proteins, establishes a ready-to-use tool for the comprehensive quantification of ER-localized glycosyltransferases and provides new insight into the organization of disease-relevant glycosylation processes.
Distinctive properties of cones in the retinal clock and the circadian system
Authors: Sandu Cristina , Wongchitrat Prapimpun , Mazzaro Nadia , Jaeger Catherine , Calligaro Hugo , Mendoza Jorge , Hicks David , Felder-Schmittbuhl Marie-Paule 
Published: September 2020

AbstractThe circadian system is a hierarchical network of cell and tissue-specific oscillators synchronized to the environmental light/dark cycle. Entrainment is mediated by the retina through diverse photosensitive cells and pigments. The retina is itself a complex circadian system whose cellular constitutive elements have not been fully characterized. By using theNrl-/-cone gain-of-function mouse model we here show that the retinal network comprises an autonomous oscillator harbored in cones. We further provide novel evidence for an input from cones to the master clock, as revealed under constant light condition.
Conductance-Based Structural Brain Connectivity in Aging and Dementia
Authors: Frau-Pascual Aina , Augustinak Jean , Varadarajan Divya , Yendiki Anastasia , Salat David H. , Fischl Bruce , Aganj Iman ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: September 2020

AbstractBackgroundStructural brain connectivity has been shown to be sensitive to the changes that the brain undergoes during Alzheimer’s disease (AD) progression.MethodsIn this work, we used our recently proposed structural connectivity quantification measure derived from diffusion MRI, which accounts for both direct and indirect pathways, to quantify brain connectivity in dementia. We analyzed data from the ADNI-2 and OASIS-3 datasets to derive relevant information for the study of the changes that the brain undergoes in AD. We also compared these datasets to the HCP dataset, as a reference, and eventually validated externally on two cohorts of the EDSD database.ResultsOur analysis shows expected trends of mean conductance with respect to age and cognitive scores, significant age prediction values in aging data, and regional effects centered among sub-cortical regions, and cingulate and temporal cortices.DiscussionResults indicate that the conductance measure has prediction potential, especially for age, that age and cognitive scores largely overlap, and that this measure could be used to study effects such as anti-correlation in structural connections.Impact statementThis work presents a methodology and a set of analyses that open new possibilities in the study of healthy and pathological aging. The methodology used here is sensitive to direct and indirect pathways in deriving brain connectivity measures from dMRI, and therefore provides information that many state-of-the-art methods do not account for. As a result, this technique may provide the research community with ways to detect subtle effects of healthy aging and AD.
Contemporary risk of extinction in an extreme environment
Authors: Vincenzi Simone 
Published: September 2020

AbstractThe increased frequency and intensity of extreme events are recognized among the most worrisome aspects of climate change. However, despite increased attention from scientists and conservationists, developing and testing general theories and hypotheses on the effects of extreme events on natural populations remains intrinsically challenging.Using numerical simulations with general—but realistic for moderately fast-leaving species—parameter values, I tested some of the hypotheses on risk of extinction and population and genetic dynamics in an environment in which both climate (e.g., temperature, rainfall) and point (e.g., fires, floods) extremes occur. In the simulations, a quantitative trait is selected for by a climate variable, but point extremes cause trait-independent massive mortalities.I found additive effects between age at first reproduction and fecundity on risk of extinction. The extent of population bottlenecks (operationally, the number of years in which a population was at low numbers) was a good predictor of allelic richness for the quantitative trait selected for by the climate. Simple models including basic demographic and vital rates information of the species, along with climate/environmental measures, provided excellent predictions of contemporary risk of population extinction. Mean and minimum population size measured in a 10-year “observation window” were largely the most important predictors of risk of population extinction in the following 10-year “prediction window”.
Evaluations of CRC2631 toxicity, tumor colonization, and genetic stability in the TRAMP prostate cancer model
Authors: Kazmierczak Robert A. , Dhagat-Mehta Bakul , Gulden Elke , Lee Li , Ma Lixin , Davis-Stober Clintin P. , Barnett Austen A. , Chabu Yves C. 
Published: September 2020

AbstractConventional cancer chemotherapies are not fully efficacious and do not target tumors, leading to significant treatment-related morbidities. A number of genetically attenuated cancer-targeting bacteria are being developed to safely target tumorsin vivo. Here we report the toxicological, tumor-targeting, and efficacy profiles ofSalmonella entericaserovar Typhimurium CRC2631 in a syngeneic and autochthonous TRAMP model of aggressive prostate cancer. CRC2631 preferentially colonize primary and metastatic tumors in the TRAMP animals. In addition, longitudinal whole genome sequencing studies of CRC2631 recovered from prostate tumor tissues demonstrate that CRC2631 is genetically stable. Moreover, tumor-targeted CRC2631 generates an anti-tumor immune response. Combination of CRC2631 with checkpoint blockade reduces metastasis burden. Collectively, these findings demonstrate a potential for CRC2631 in cancer immunotherapy strategies.
Phase Separation Can Increase Enzyme Activity by Concentration and Molecular Organization
Authors: Peeples William , Rosen Michael K. 
Published: September 2020

AbstractBiomolecular condensates concentrate macromolecules into discrete cellular foci without an encapsulating membrane. Condensates are often presumed to increase enzymatic reaction rates through increased concentrations of enzymes and substrates (mass action), although this idea has not been widely tested and other mechanisms of modulation are possible. Here we describe a synthetic system where the SUMOylation enzyme cascade is recruited into engineered condensates generated by liquid-liquid phase separation of multidomain scaffolding proteins. SUMOylation rates can be increased up to 36-fold in these droplets compared to the surrounding bulk, depending on substrate KM. This dependency produces substantial specificity among different substrates. Analyses of reactions above and below the phase separation threshold lead to a quantitative model in which reactions in condensates are accelerated by mass action and by changes in substrate KM, likely due to scaffold-induced molecular organization. Thus, condensates can modulate reaction rates both by concentrating molecules and by physically organizing them.
Bromelain Inhibits SARS-CoV-2 Infection in VeroE6 Cells
Authors: Sagar Satish , Rathinavel Ashok Kumar , Lutz William E. , Struble Lucas R. , Khurana Surender , Schnaubelt Andy T , Mishra Nitish Kumar , Guda Chittibabu , Broadhurst Mara J. , Reid St. Patrick M. , Bayles Kenneth W. , Borgstahl Gloria E. O. , Radhakrishnan Prakash 
Published: September 2020

AbstractCoronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The initial interaction between Transmembrane Serine Protease 2 (TMPRSS2) primed SARS-CoV-2 spike (S) protein and host cell receptor angiotensin-converting enzyme 2 (ACE-2) is a pre-requisite step for this novel coronavirus pathogenesis. Here, we expressed a GFP-tagged SARS-CoV-2 S-Ectodomain in Tni insect cells. That contained sialic acid-enriched N- and O-glycans. Surface resonance plasmon (SPR) and Luminex assay showed that the purified S-Ectodomain binding to human ACE-2 and immunoreactivity with COVID-19 positive samples. We demonstrate that bromelain (isolated from pineapple stem and used as a dietary supplement) treatment diminishes the expression of ACE-2 and TMPRSS2 in VeroE6 cells and dramatically lowers the expression of S-Ectodomain. Importantly, bromelain treatment reduced the interaction between S-Ectodomain and VeroE6 cells. Most importantly, bromelain treatment significantly diminished the SARS-CoV-2 infection in VeroE6 cells. Altogether, our results suggest that bromelain or bromelain rich pineapple stem may be used as an antiviral against COVID-19.HighlightsBromelain inhibits / cleaves the expression of ACE-2 and TMPRSS2Bromelain cleaves / degrades SARS-CoV-2 spike proteinBromelain inhibits S-Ectodomain binding and SARS-CoV-2 infection
Shared and distinct genetic influences between cognitive domains and psychiatric disorder risk based on genome-wide data
Authors: Carey CE , Huang Y , Strong RW ,   23andMe Research Team, Aslibekyan S , Gentleman RC , Smoller JW , Wilmer JB , Robinson EB , Germine L 
Published: September 2020

AbstractGroup-level cognitive performance differences are found in psychiatric disorders ranging from depression to autism to schizophrenia. To investigate the genetics of individual differences in fluid and crystallized cognitive abilities and their associations with psychiatric disorder risk, we conducted genome-wide association studies (GWAS) of a total of 335,227 consented 23andMe customers of European descent between the ages of 50 and 85, who completed at least one online test of crystallized cognitive ability (vocabulary knowledge, N=188,434) and/or fluid cognitive ability (visual change detection, N=158 888; digit-symbol substitution, N=132,807). All cognitive measures were significantly heritable (h2=0.10-0.16), and GWAS identified 25 novel genome-wide significant loci. Genetic correlation analyses highlight variable profiles of genetic relationships across tasks and disorders. While schizophrenia had moderate negative genetic correlations with tests of fluid cognition (visual change detectionrg=−0.27, p<9.2e-24; digit-symbol substitutionrg=−0.26, p<5.2e-27), it was only weakly negatively associated with crystalized cognition (vocabulary knowledgerg=−0.07, p<0.004). Autism, in contrast, showed a robust positive genetic correlation with vocabulary knowledge (rg=0.30, p<5.6e-13) and little to no genetic correlation with either fluid cognition task (rg’s<0.08, p’s>0.005). Crystalized and fluid cognitive abilities thus have correlated but distinct genetic architectures that relate to those of psychiatric disorders. Understanding the genetic underpinnings of specific cognitive abilities, and their relationships to psychiatric disorder risk, can inform the understanding of disease biology nosology and etiology.
Refining pairwise sequence alignments of membrane proteins by the incorporation of anchors
Authors: Staritzbichler René , Sarti Edoardo , Yaklich Emily , Aleksandrova Antoniya , Stamm Markus , Khafizov Kamil , Forrest Lucy R 
Published: September 2020

AbstractThe alignment of primary sequences is a fundamental step in the analysis of protein structure, function, and evolution. Integral membrane proteins pose a significant challenge for such sequence alignment approaches, because their evolutionary relationships can be very remote, and because a high content of hydrophobic amino acids reduces their complexity. Frequently, biochemical or biophysical data is available that informs the optimum alignment, for example, indicating specific positions that share common functional or structural roles. Currently, if those positions are not correctly aligned by a standard pairwise alignment procedure, the incorporation of such information into the alignment is typically addressed in an ad hoc manner, with manual adjustments. However, such modifications are problematic because they reduce the robustness and reproducibility of the alignment. An alternative approach is the use of restraints, or anchors, to incorporate such position-matching explicitly during alignment. Here we introduce position anchoring in the alignment tool AlignMe as an aid to pairwise sequence alignment of membrane proteins. Applying this approach to realistic scenarios involving distantly-related and low complexity sequences, we illustrate how the addition of even a single anchor can dramatically improve the accuracy of the alignments, while maintaining the reproducibility and rigor of the overall alignment.