bluuebunny/crossref_metadata_2025_split huggingface dataset:
Superficial and Deep Macula Vessel Density in Healthy, Glaucoma Suspect, and Glaucoma Eyes
Authors: El-Nimri Nevin W. , Manalastas Patricia Isabel C. , Zangwill Linda M. , Proudfoot James A. , Bowd Christopher , Hou Huiyuan , Moghimi Sasan , Penteado Rafaella C. , Rezapour Jasmin , Ekici Eren , Shoji Takuhei , Ghahari Elham , Yarmohammadi Adeleh , Weinreb Robert N. 
Published: April 2021

Precis:
Macular superficial capillary plexus (SCP) vessel density is more informative than deep capillary plexus (DCP) vessel density for the detection of glaucoma.

Purpose:
The purpose of this study was to characterize optical coherence tomography angiography macular SCP and projection-resolved DCP vessel densities and compare their diagnostic accuracies with ganglion cell complex (GCC) thickness in healthy, glaucoma suspect, and glaucoma eyes.

Materials and Methods:
Sixty-eight eyes of 44 healthy subjects, 26 eyes of 16 preperimetric glaucoma suspects, and 161 eyes of 124 glaucoma patients from the Diagnostics Innovations in Glaucoma Study with good quality high-density 6×6 mm2 macula optical coherence tomography angiography images were included. The diagnostic accuracy of SCP vessel density, projection-resolved DCP vessel density and GCC thickness were compared among groups.

Results:
Mean whole image vessel density (wiVD; % of area occupied by vessels containing flowing blood) in the SCP layer was highest in healthy eyes (49.7%), followed by glaucoma suspect eyes (46.0%), and glaucoma eyes (40.9%) (P<0.001). Mean wiVD in the DCP layer was similar in healthy (50.6%), glaucoma suspect (47.3%), and glaucoma eyes (45.7%) (P=0.925). Diagnostic accuracy of both GCC thickness and SCP wiVD was significantly higher than DCP wiVD for classifying healthy and glaucoma eyes [adjusted area under the receiver operating characteristic curve (95% confidence interval): GCC=0.86 (0.72, 0.94), SCP=0.80 (0.66, 0.91) and DCP=0.44 (0.30, 0.57)] (P<0.001).

Conclusions:
SCP vessel densities have better diagnostic accuracy for detecting glaucoma than DCP vessel densities. Although the diagnostic accuracy of the macula SCP is relatively modest, it is more informative than the DCP.
Preparing for the Worst or Hoping for the Best? The State of Fall Training in Prosthesis Users
Authors: Noble Charles , Fiedler Goeran 
Published: April 2021

ABSTRACT

Introduction
The risk of accidental falls is greater in people with lower-limb loss than in their able-bodied peers. Most popular strategies to mitigate injuries from such falls include technical solutions that prevent falls or protect vulnerable body segments from destructive forces. Fall training is another effective intervention, but little evidence on its use in prosthesis users has been published. This research had the goal to investigate to what extent fall training is provided to the target population and what factors may be obstacles to its wider adoption.

Methods
An online questionnaire was developed and administered nationwide, targeting people with lower-limb loss. Descriptive statistics were used to describe the availability of fall training, and a logistic regression was performed to investigate variables that predict whether an individual receives fall training or not.

Results
A total of 180 responses was recorded, 166 of which were included in the analysis. More than two-thirds of respondents had not received fall training. Those who had physical therapy as part of their rehabilitation regimen were 3.7 times more likely to also have had fall training.

Discussion
Our data suggest that the potential benefits of providing fall training to people with lower-limb loss are not being fully realized. Interdisciplinary collaboration between prosthetists and therapists can help expand access to fall training interventions to better prepare patients for the likely event of an accidental fall.
Lipid effects of glucagon-like peptide 1 receptor analogs
Authors: Berberich Amanda J. , Hegele Robert A. 
Published: April 2021

Purpose of review
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are becoming more prominent as a therapeutic choice in diabetes management and their use is being expanded to other indications, such as obesity. Dyslipidemia and cardiovascular disease are common co-morbidities in these populations and understanding the impact of this class of medications on the lipid profile may be an important consideration.

Recent findings
Several GLP-1RAs trials demonstrate them to be safe and potentially beneficial for cardiovascular outcomes; improvements in surrogate markers of atherosclerosis have also been observed. Lipid data collected as secondary outcomes from large clinical trials as well as some smaller dedicated trials show that GLP-1RAs can modestly lower low-density lipoprotein (LDL) and total cholesterol (C), and most show modest fasting triglyceride (TG) lowering. Effects on high-density lipoprotein-C have been less consistent. Some have also demonstrated substantial blunting of the postprandial rise in serum TGs. Favorable effects on lipoprotein metabolism, with reduced levels of small dense LDL particles and decreased atherogenic potential of oxidized LDL, have also been seen. Mechanisms underlying these observations have been investigated.

Summary
This review summarizes the data available on the lipid effects of GLP-1RAs, and explores the current understanding of the mechanisms underlying these observed effects.
Consensus Recommendations for Blood Culture Use in Critically Ill Children Using a Modified Delphi Approach*
Authors: Woods-Hill Charlotte Z. , Koontz Danielle W. , Voskertchian Annie , Xie Anping , Shea Judy , Miller Marlene R. , Fackler James C. , Milstone Aaron M. 
Published: April 2021

Objectives:
Blood cultures are fundamental in evaluating for sepsis, but excessive cultures can lead to false-positive results and unnecessary antibiotics. Our objective was to create consensus recommendations focusing on when to safely avoid blood cultures in PICU patients.

Design:
A panel of 29 multidisciplinary experts engaged in a two-part modified Delphi process. Round 1 consisted of a literature summary and an electronic survey sent to invited participants. In the survey, participants rated a series of recommendations about when to avoid blood cultures on five-point Likert scale. Consensus was achieved for the recommendation(s) if 75% of respondents chose a score of 4 or 5, and these were included in the final recommendations. Any recommendations that did not meet these a priori criteria for consensus were discussed during the in-person expert panel review (Round 2). Round 2 was facilitated by an independent expert in consensus methodology. After a review of the survey results, comments from round 1, and group discussion, the panelists voted on these recommendations in real-time.

Setting:
Experts’ institutions; in-person discussion in Baltimore, MD.

Subjects:
Experts in pediatric critical care, infectious diseases, nephrology, oncology, and laboratory medicine.

Interventions:
None.

Measurements and Main Results:
Of the 27 original recommendations, 18 met criteria for achieving consensus in Round 1; some were modified for clarity or condensed from multiple into single recommendations during Round 2. The remaining nine recommendations were discussed and modified until consensus was achieved during Round 2, which had 26 real-time voting participants. The final document contains 19 recommendations.

Conclusions:
Using a modified Delphi process, we created consensus recommendations on when to avoid blood cultures and prevent overuse in the PICU. These recommendations are a critical step in disseminating diagnostic stewardship on a wider scale in critically ill children.
Laser-free super-resolution microscopy
Authors: Prakash Kirti 
Published: April 2021

We report that high-density single-molecule super-resolution microscopy can be achieved with a conventional epifluorescence microscope set-up and a mercury arc lamp. The configuration termed as laser-free super-resolution microscopy (LFSM) is an extension of single-molecule localization microscopy (SMLM) techniques and allows single molecules to be switched on and off (a phenomenon termed as ‘blinking’), detected and localized. The use of a short burst of deep blue excitation (350–380 nm) can be further used to reactivate the blinking, once the blinking process has slowed or stopped. A resolution of 90 nm is achieved on test specimens (mouse and amphibian meiotic chromosomes). Finally, we demonstrate that stimulated emission depletion and LFSM can be performed on the same biological sample using a simple commercial mounting medium. It is hoped that this type of correlative imaging will provide a basis for a further enhanced resolution.
This article is part of the Theo Murphy meeting issue ‘Super-resolution structured illumination microscopy (part 1)’.
Impact of national and regional lockdowns on COVID-19 epidemic waves: Application to the 2020 spring wave in France
Authors: Roux Jonathan , Massonnaud Clément , Colizza Vittoria , Cauchemez Simon , Crépey Pascal 
Published: April 2021

AbstractSeveral countries have implemented lockdowns to control their COVID-19 epidemic. However, questions like “where” and “when” still require answers. We assessed the impact of national and regional lockdowns considering the French first epidemic wave of COVID-19 as a case study. In a regional lockdown scenario aimed at preventing intensive care units (ICU) saturation, almost all French regions would have had to implement a lockdown within 10 days and 96% of ICU capacities would have been used. For slowly growing epidemics, with a lower reproduction number, the expected delays between regional lockdowns increases. However, the public health costs associated with these delays tend to grow exponentially with time. In a quickly growing pandemic wave, defining the timing of lockdowns at a regional rather than national level delays by a few days the implementation of a nationwide lockdown but leads to substantially higher morbidity, mortality and stress on the healthcare system.
Imputation of PaO2 from SpO2 values from the MIMIC-III Critical Care Database Using Machine-Learning Based Algorithms
Authors: Ren Shuangxia , Zupetic Jill , Nouraie Mehdi , Lu Xinghua , Boyce Richard D. , Lee Janet S. 
Published: April 2021

AbstractBackgroundThe partial pressure of oxygen (PaO2)/fraction of oxygen delivered (FIO2) ratio is the reference standard for assessment of hypoxemia in mechanically ventilated patients. Non-invasive monitoring with the peripheral saturation of oxygen (SpO2) is increasingly utilized to estimate PaO2 because it does not require invasive sampling. Several equations have been reported to impute PaO2/FIO2 from SpO2 /FIO2. However, machine-learning algorithms to impute the PaO2 from the SpO2 has not been compared to published equations.Research QuestionHow do machine learning algorithms perform at predicting the PaO2 from SpO2 compared to previously published equations?MethodsThree machine learning algorithms (neural network, regression, and kernel-based methods) were developed using 7 clinical variable features (n=9,900 ICU events) and subsequently 3 features (n=20,198 ICU events) as input into the models from data available in mechanically ventilated patients from the Medical Information Mart for Intensive Care (MIMIC) III database. As a regression task, the machine learning models were used to impute PaO2 values. As a classification task, the models were used to predict patients with moderate-to-severe hypoxemic respiratory failure based on a clinically relevant cut-off of PaO2/FIO2 ≤ 150. The accuracy of the machine learning models was compared to published log-linear and non-linear equations. An online imputation calculator was created.ResultsCompared to seven features, three features (SpO2, FiO2 and PEEP) were sufficient to impute PaO2/FIO2 ratio using a large dataset. Any of the tested machine learning models enabled imputation of PaO2/FIO2 from the SpO2/FIO2 with lower error and had greater accuracy in predicting PaO2/FIO2 ≤ 150 compared to published equations. Using three features, the machine learning models showed superior performance in imputing PaO2 across the entire span of SpO2 values, including those ≥ 97%.InterpretationThe improved performance shown for the machine learning algorithms suggests a promising framework for future use in large datasets.
Predicting the end of Covid-19 infection for various countries using a stochastic agent-based model taking into account vaccination rates and the new mutant
Authors: Eissler Manfred 
Published: April 2021

AbstractUsing a stochastic, agent-based model, the course of infection since the first occurrence of a Covid-19 infection is simulated for various countries, taking into account the new, more infectious mutant and the vaccinations. The simulation shows that the course of infection for the United Kingdom (UK) and Israel is surprisingly good. For the other countries, an end date for the infection can be predicted based on the course of the simulation. For Germany, the course is calculated in a second scenario, assuming a higher vaccination rate.
Household transmission of SARS-CoV-2 from humans to pets in Washington and Idaho: burden and risk factors
Authors: Meisner Julianne , Baszler Timothy V. , Kuehl Kathryn H. , Ramirez Vickie , Baines Anna , Frisbie Lauren A. , Lofgren Eric T. , DeAvila David M. , Wolking Rebecca M. , Bradway Dan S. , Wilson Hannah , Lipton Beth , Kawakami Vance , Rabinowitz Peter M. 
Published: April 2021

AbstractSARS-CoV-2 is believed to have emerged from an animal reservoir; however, the frequency of and risk factors for inter-species transmission remain unclear. We carried out a community-based study of pets in households with one or more confirmed SARS-CoV-2 infection in humans. Among 119 dogs and 57 cats with completed surveys, clinical signs consistent with SARS-CoV-2 were reported in 20 dogs (21%) and 19 cats (39%). Out of 81 dogs and 32 cats sampled for testing, 40% of dogs and 43% of cats were seropositive, and 5% of dogs and 8% of cats were PCR positive; this discordance may be due to delays in sampling. Respondents commonly reported close human-animal contact and willingness to take measures to prevent transmission to their pets. Reported preventative measures showed a slightly protective trend for both illness and seropositivity in pets, while sharing of beds and bowls had slight harmful effects.
Kaposi’s Sarcoma-associated Herpesvirus Promotes Mesenchymal-to-Endothelial Transition by Resolving the Bivalent Chromatin of PROX1 Gene
Authors: Ding Yao , Chen Weikang , Lu Zhengzhou , Wang Yan , Yuan Yan 
Published: April 2021

AbstractHuman mesenchymal stem cells (MSCs) are highly susceptible to Kaposi’s sarcoma-associated herpesvirus (KSHV) infection, and the infection promotes mesenchymal-to-endothelial transition (MEndT) and acquisition of Kaposi’s sarcoma (KS)-like phenotypes. Increasing evidence suggests that KS may arise from KSHV-infected MSCs. To understand how KSHV induces MEndT and transforms MSCs to KS cells, we investigated the mechanism underlying KSHV-mediated MSC endothelial lineage differentiation. Like embryonic stem cells, MSC differentiation and fate determination are under epigenetic control. Prospero homeobox 1 (PROX1) is a master regulator that controls lymphatic vessel development and endothelial differentiation. We found that the PROX1 gene in MSCs harbors a distinctive bivalent epigenetic signature consisting of both active marker H3K4me3 and repressive marker H3K27me3, which poises expression of the genes, allowing timely activation upon differentiation signals or environmental stimuli. KSHV infection effectively resolved the bivalent chromatin by decreased H3K27me3 and increased H3K4me3 to activate the PROX1 gene. vIL-6 signaling leads to the recruitment of MLL2 and Set1 complexes to the PROX1 promoter to increase H3K4me3, and the vGPCR-VEGF-A axis is responsible for removing PRC2 from the promoter to reduce H3K27me3. Therefore, through a dual signaling process, KSHV activates PROX1 gene expression and initiates MEndT, which renders MSC tumorigenic features including angiogenesis, invasion and migration.
Super-resolution microscopy informs on the molecular architecture of alpha-synuclein inclusions in model systems and in the human brain
Authors: Weish Patrick , Lázaro Diana F. , Palmares Luís , Santos Patrícia I. , Stadelmann Christine , Höglinger Günter U. , Rizzoli Silvio O. , Outeiro Tiago F. 
Published: April 2021

AbstractLewy bodies (LBs) and Lewy neurites are pathological hallmarks of Parkinson’s disease and other progressive neurodegenerative disorders known as Lewy body diseases (LBD). These proteinaceous deposits are immunopositive for alpha-synuclein (aSyn) and several other proteins, as neurofilament components. The structural organization and composition of aSyn inclusions is still unclear and needs to be addressed in greater detail, as this may open novel avenues for our understanding of the disease-relevant pathological events.In this study, we investigated the molecular architecture of aSyn inclusions, both in cell models and in human brain tissue, using state-of-art super resolution X10 Expansion microscopy (ExM). This approach physically expands specimens embedded into a swellable gel, preserving their biological information. Then, the specimen can be analyzed using standard epifluorescence microscopes, thereby obtaining nanoscale information.The combination of different cell models, mouse and human brain tissue enabled us to distinguish different types aSyn assemblies (e.g. ring shape or tubular structures), and a conserved pattern of aSyn inclusions surrounded/encaged by intermediate filament proteins. Overall, X10 ExM enabled us to gain insight into the architecture and biology of aSyn inclusions and constitutes a powerful tool in the quest to understanding underlying disease mechanisms in synucleinopathies.
Engineering a super-secreting strain ofEscherichia coliby directed co-evolution of the multiprotein Tat translocation machinery
Authors: Taw May N. , Li Mingji , Kim Daniel , Rocco Mark A. , Waraho-Zhmayev Dujduan , DeLisa Matthew P. 
Published: April 2021

AbstractEscherichia coliremains one of the preferred hosts for biotechnological protein production due to its robust growth in culture and ease of genetic manipulation. It is often desirable to export recombinant proteins into the periplasmic space for reasons related to proper disulfide bond formation, prevention of aggregation and proteolytic degradation, and ease of purification. One such system for expressing heterologous secreted proteins is the twin-arginine translocation (Tat) pathway, which has the unique advantage of delivering correctly folded proteins into the periplasm. However, transit times for proteins through the Tat translocase, comprised of the TatABC proteins, are much longer than for passage through the SecYEG pore, the translocase associated with the more widely utilized Sec pathway. To date, a high protein flux through the Tat pathway has yet to be demonstrated. To address this shortcoming, we employed a directed co-evolution strategy to isolate mutant Tat translocases for their ability to deliver higher quantities of heterologous proteins into the periplasm. Three super-secreting translocases were selected that each exported a panel of recombinant proteins at levels that were significantly greater than that observed for wildtype TatABC or SecYEG translocases. Interestingly, all three of the evolved Tat translocases exhibited quality control suppression, suggesting that increased translocation flux was gained by relaxation of substrate proofreading. Overall, our discovery of highly efficient translocase variants paves the way for the use of the Tat system as a powerful complement to the Sec pathway for secreted production of both commodity and high value-added proteins.
Systematic analysis of Epstein-Barr virus genes and their individual contribution to virus production and composition
Authors: Chen Yen-Fu Adam , Mocanu Bianca , Akidil Ezgi , Pich Dagmar , Mautner Josef , Hammerschmidt Wolfgang 
Published: April 2021

AbstractEpstein-Barr virus (EBV), a member of the large herpesvirus family is a very complex humanγ-herpesvirus. Its complexity with respect to viral gene regulation, its preferred latent life style and technical difficulties are major obstacles, which hinder efficient virus generationin vitroto mass-produce or establish recombinant wild-type EBV or mutant derivatives. To explore conditions optimizing and improving virus production, we established and tested an EBV gene library with 77 expression plasmids and a set of designed shRNAs. With this tool set we investigated the contributions of individual viral genes in the context of virus synthesis and virion functions. Engineered virus stocks were systematically analyzed with respect to physical and bioparticle concentration, virus titer and virus uptake by primary human B cells, EBV’s target cellsin vivo. To quantitate virus uptake by these cells, we developed a novelß-lactamase-based assay that can monitor fusion events of the viral envelope with membranes of recipient cells at the level of single cells. Based on our findings, EBV does not encode a dominant regulator that governs virus production, but our results identified several EBV genes such as BALF4, BVLF1 and BKRF4, encoding a viral glycoprotein, a transcriptional regulator of late viral genes, and a possible tegument protein, respectively, that improve virus production regarding virus yield, virus composition and quality, and virus uptake by primary human B cells.ImportanceFor more than 20 years HEK293 cells have been instrumental to produce virus stocks of recombinant EBV. The identification of this cell line as a source of infectious EB virions was unexpected because HEK293 cells are very distant from B cells and in particular plasma cells which produce EBV progenyin vivo. To our knowledge, no systematic analysis has addressed the fundamental question whether virus yield with respect to virus concentration, virion composition and functionality can be improved to produce recombinant EBV stocks in HEK293 cells. We tackled this question and analyzed 77 individual EBV genes for their possible contribution to virus yield. To analyze and compare different virus stocks we used established and developed novel assays to characterize important parameters of EB virions and their functions.
Deconvolving multiplexed histone modifications in single cells
Authors: Yeung Jake , Florescu Maria , Zeller Peter , de Barbanson Buys Anton , van Oudenaarden Alexander 
Published: April 2021

ABSTRACTRecent advances have enabled mapping of histone modifications in single cells1–12, but current methods are constrained to profile only one histone modification per cell. Here we present an integrated experimental and computational framework, scChIX (single-cell chromatin immunocleavage and unmixing), to map multiple histone modifications in single cells. scChIX multiplexes two histone modification profiles together in single cells, then computationally deconvolves the signal using training data from respective histone modification profiles. We first validate this method using purified blood cells and show that although the two repressive marks, H3K27me3 and H3K9me3, are generally mutually exclusive, the transitions between the two regions can vary between cell types. Next we apply scChIX to a heterogenous cell population from mouse bone marrow to generate linked maps of active (H3K4me1) and repressive (H3K27me3) chromatin landscapes in single cells, where coordinates in the active modification map correspond to coordinates in the repressive map. Linked analysis reveals that immunoglobulin genes in theIgkvregion are in a repressed chromatin state in pro-B cells, but become activated in B cells. Overall, scChIX unlocks systematic interrogation of the interplay between histone modifications in single cells.