bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative evaluation of a new frugal binocular indirect ophthalmoscope
Authors: Kousha Obaid , Ganesananthan Sharma , Shahin Bayan , Ellis John , Blaikie Andrew 
Published: December 2021

Abstract
Objectives
We compare the optical quality and design characteristic a new low cost solar powered binocular indirect ophthalmoscope (BIO), Holo, to Keeler BIO.

Methods
Twenty-four participants each examined 10 simulation eyes using both the Holo and the Keeler BIO with a 30-diopter condensing lens. Number of Lea symbols printed on the retina of simulation eyes seen and time taken to identify them was recorded. Stereoacuity of 12 participants was tested while using the BIOs. Using 7-point Likert scale, participants gave feedback on design characteristic of both BIOs.

Results
There was no statistical difference in number of Lea symbols correctly identified (15.63/20 for Holo vs. 15/20 for Keeler BIO, p = 0.366, paired t test) or time taken to correctly identify each symbol (Holo 0.39 s faster; 95% confidence interval −2.24 to 3.03 s, p = 0.763) using each device. 12 out of 12 participants achieved stereoacuity of 60 arcsec using the Holo while with the Keeler BIO 11 achieved 60 arcsec and one 90 arcsec. There was no statistically significant difference in the scores for clarity of view, quality of illumination, field of view, binocularity, eye strain and robustness between the two devices. The Holo, scored higher for ease of use (6.5 vs. 6, p = 0.00488, Wilcoxon signed-rank test), comfort of wear (6 vs. 5, p = 0.000337) and portability (7 vs. 6, p = 0.000148).

Conclusion
The Holo has the potential to be a clinically useful yet affordable diagnostic tool suitable for the first time of equipping eye care workers in low resource settings with a BIO at volume.
Broadly neutralizing antibodies target a haemagglutinin anchor epitope
Authors: Guthmiller Jenna J. , Han Julianna , Utset Henry A. , Li Lei , Lan Linda Yu-Ling , Henry Carole , Stamper Christopher T. , McMahon Meagan , O’Dell George , Fernández-Quintero Monica L. , Freyn Alec W. , Amanat Fatima , Stovicek Olivia , Gentles Lauren , Richey Sara T. , de la Peña Alba Torrents , Rosado Victoria , Dugan Haley L. , Zheng Nai-Ying , Tepora Micah E. , Bitar Dalia J. , Changrob Siriruk , Strohmeier Shirin , Huang Min , García-Sastre Adolfo , Liedl Klaus R. , Bloom Jesse D. , Nachbagauer Raffael , Palese Peter , Krammer Florian , Coughlan Lynda , Ward Andrew B. , Wilson Patrick C. 
Published: December 2021

AbstractBroadly neutralizing antibodies that target epitopes of haemagglutinin on the influenza virus have the potential to provide near universal protection against influenza virus infection1. However, viral mutants that escape broadly neutralizing antibodies have been reported2,3. The identification of broadly neutralizing antibody classes that can neutralize viral escape mutants is critical for universal influenza virus vaccine design. Here we report a distinct class of broadly neutralizing antibodies that target a discrete membrane-proximal anchor epitope of the haemagglutinin stalk domain. Anchor epitope-targeting antibodies are broadly neutralizing across H1 viruses and can cross-react with H2 and H5 viruses that are a pandemic threat. Antibodies that target this anchor epitope utilize a highly restricted repertoire, which encodes two public binding motifs that make extensive contacts with conserved residues in the fusion peptide. Moreover, anchor epitope-targeting B cells are common in the human memory B cell repertoire and were recalled in humans by an oil-in-water adjuvanted chimeric haemagglutinin vaccine4,5, which is a potential universal influenza virus vaccine. To maximize protection against seasonal and pandemic influenza viruses, vaccines should aim to boost this previously untapped source of broadly neutralizing antibodies that are widespread in the human memory B cell pool.
Identification and mechanism of G protein-biased ligands for chemokine receptor CCR1
Authors: Shao Zhehua , Shen Qingya , Yao Bingpeng , Mao Chunyou , Chen Li-Nan , Zhang Huibing , Shen Dan-Dan , Zhang Chao , Li Weijie , Du Xufei , Li Fei , Ma Honglei , Chen Zhi-Hua , Xu H. Eric , Ying Songmin , Zhang Yan , Shen Huahao 
Published: December 2021

AbstractBiased signaling of G protein-coupled receptors describes an ability of different ligands that preferentially activate an alternative downstream signaling pathway. In this work, we identified and characterized different N-terminal truncations of endogenous chemokine CCL15 as balanced or biased agonists targeting CCR1, and presented three cryogenic-electron microscopy structures of the CCR1–Gi complex in the ligand-free form or bound to different CCL15 truncations with a resolution of 2.6–2.9 Å, illustrating the structural basis of natural biased signaling that initiates an inflammation response. Complemented with pharmacological and computational studies, these structures revealed it was the conformational change of Tyr291 (Y2917.43) in CCR1 that triggered its polar network rearrangement in the orthosteric binding pocket and allosterically regulated the activation of β-arrestin signaling. Our structure of CCL15-bound CCR1 also exhibited a critical site for ligand binding distinct from many other chemokine–receptor complexes, providing new insights into the mode of chemokine recognition.
Temporal single-cell tracing reveals clonal revival and expansion of precursor exhausted T cells during anti-PD-1 therapy in lung cancer
Authors: Liu Baolin , Hu Xueda , Feng Kaichao , Gao Ranran , Xue Zhiqiang , Zhang Sujie , Zhang Yuanyuan , Corse Emily , Hu Yi , Han Weidong , Zhang Zemin 
Published: December 2021

AbstractAnti-PD-1 treatment has shown unprecedented clinical success in the treatment of non-small-cell lung cancer (NSCLC), but the underlying mechanisms remain incompletely understood. Here, we performed temporal single-cell RNA and paired T-cell receptor sequencing on 47 tumor biopsies from 36 patients with NSCLC following PD-1-based therapies. We observed increased levels of precursor exhausted T (Texp) cells in responsive tumors after treatment, characterized by low expression of coinhibitory molecules and high expression of GZMK. By contrast, nonresponsive tumors failed to accumulate Texp cells. Our data suggested that Texp cells were unlikely to be derived from the reinvigoration of terminally exhausted cells; instead, they were accumulated by (1) local expansion and (2) replenishment by peripheral T cells with both new and pre-existing clonotypes, a phenomenon we named clonal revival. Our study provides insights into mechanisms underlying PD-1-based therapies, implicating clonal revival and expansion of Texp cells as steps to improve NSCLC treatment.
DNA methylation clocks tick in naked mole rats but queens age more slowly than nonbreeders
Authors: Horvath Steve , Haghani Amin , Macoretta Nicholas , Ablaeva Julia , Zoller Joseph A. , Li Caesar Z. , Zhang Joshua , Takasugi Masaki , Zhao Yang , Rydkina Elena , Zhang Zhihui , Emmrich Stephan , Raj Ken , Seluanov Andrei , Faulkes Chris G. , Gorbunova Vera 
Published: December 2021

AbstractNaked mole rats (NMRs) live an exceptionally long life, appear not to exhibit age-related decline in physiological capacity and are resistant to age-related diseases. However, it has been unknown whether NMRs also evade aging according to a primary hallmark of aging: epigenetic changes. To address this question, we profiled n = 385 samples from 11 tissue types at loci that are highly conserved between mammalian species using a custom array (HorvathMammalMethylChip40). We observed strong epigenetic aging effects and developed seven highly accurate epigenetic clocks for several tissues (pan-tissue, blood, kidney, liver, skin clocks) and two dual-species (human–NMR) clocks. The skin clock correctly estimated induced pluripotent stem cells derived from NMR fibroblasts to be of prenatal age. The NMR epigenetic clocks revealed that breeding NMR queens age more slowly than nonbreeders, a feature that is also observed in some eusocial insects. Our results show that despite a phenotype of negligible senescence, the NMR ages epigenetically.
H-NOX proteins in the virulence of pathogenic bacteria
Authors: Lee-Lopez Cameron , Yukl Erik 
Published: December 2021

Abstract
Nitric oxide (NO) is a toxic gas encountered by bacteria as a product of their own metabolism or as a result of a host immune response. Non-toxic concentrations of NO have been shown to initiate changes in bacterial behaviors such as the transition between planktonic and biofilm-associated lifestyles. The heme nitric oxide/oxygen binding proteins (H-NOX) are a widespread family of bacterial heme-based NO sensors that regulate biofilm formation in response to NO. The presence of H-NOX in several human pathogens combined with the importance of planktonic–biofilm transitions to virulence suggests that H-NOX sensing may be an important virulence factor in these organisms. Here we review the recent data on H-NOX NO signaling pathways with an emphasis on H-NOX homologs from pathogens and commensal organisms. The current state of the field is somewhat ambiguous regarding the role of H-NOX in pathogenesis. However, it is clear that H-NOX regulates biofilm in response to environmental factors and may promote persistence in the environments that serve as reservoirs for these pathogens. Finally, the evidence that large subgroups of H-NOX proteins may sense environmental signals besides NO is discussed within the context of a phylogenetic analysis of this large and diverse family.
N-terminal pro-brain natriuretic peptide and adverse outcomes in Chinese patients with hypertrophic cardiomyopathy
Authors: Zhang Zeng-Lei , Xu Yan-Yan , Qin Zhen , Lu Yong-Zheng , Liu Tian-Ding , Zhang Li , Shangguan Jia-Hong , Wang Wei , Tang Jun-Nan , Zhang Jin-Ying 
Published: December 2021

Abstract
Background: Although numerous studies have suggested that elevated N-terminal pro-brain natriuretic peptide (NT-proBNP) is positively correlated with cardiovascular events, especially the heart failure and heart failure-related death (HFRD), evidence of the association between NT-proBNP and the adverse outcomes of hypertrophic cardiomyopathy (HCM) is still relatively limited. The present study was performed to evaluate the relationship between NT-proBNP and outcomes in patients with HCM.
Methods: Observational cohort methodology was used in the present study, and a total of 227 patients were included. And the patients were followed for 44.97 ± 16.37 months. Patients were categorized into three groups according to these NT-proBNP tertiles: first tertile (≤910 pg/ml, n=68), second tertile (913–2141 pg/ml, n=68), and third tertile (≥2151 pg/ml, n=69). The adverse outcomes of the present study were all-cause death (ACD) and cardiac death (CD).
Results: According to the risk category of NT-proBNP, the incidence of ACD (P=0.005) and CD (P=0.032) among the three groups showed significant differences. Multivariate Cox regression analysis suggested that the ACD and CD in the third tertile have 7.022 folds (hazard risk [HR] = 7.022 [95% confidence interval [CI]: 1.397–35.282], P=0.018) and 7.129 folds (HR = 7.129 [95% CI: 1.329–38.237], P=0.022) increased risks as compared with those in the first tertile. Kaplan–Meier survival analyses showed that the cumulative risks of ACD and CD in patients with HCM tended to increase.
Conclusion: The present study indicated NT-proBNP was a novel biomarker suitable for predicting adverse prognosis in patients with HCM, which may be used for early recognition and risk stratification.
Reading Comprehension and Processing Time When People With Aphasia Use Text-to-Speech Technology With Personalized Supports and Features
Authors: Knollman-Porter Kelly , Brown Jessica A. , Hux Karen , Wallace Sarah E. , Crittenden Allison 
Published: December 2021

Background:
Person-centered approaches promote consistent use of supportive technology and feelings of empowerment for people with disabilities. Feature personalization is an aspect of person-centered approaches that can affect the benefit people with aphasia (PWA) derive from using text-to-speech (TTS) technology as a reading support.

Aims:
This study's primary purpose was to compare the comprehension and processing time of PWA when performing TTS-supported reading with preferred settings for voice, speech output rate, highlighting type, and highlighting color versus unsupported reading. A secondary aim was to examine initial support and feature preference selections, preference changes following TTS exposure, and anticipated functional reading activities for utilizing TTS technology.

Method and Procedure:
Twenty PWA read passages either via written text or text combined with TTS output using personally selected supports and features. Participants answered comprehension questions, reevaluated their preference selections, and provided feedback both about feature selections and possible future TTS technology uses.

Outcomes and Results:
Comprehension accuracy did not vary significantly between reading conditions; however, processing time was significantly less in the TTS-supported condition, thus suggesting TTS support promoted greater reading speed without compromising comprehension. Most participants preferred the TTS condition and several anticipated benefits when reading lengthy and difficult materials. Alterations to initial settings were relatively rare.

Conclusions:
Personalizing TTS systems is relevant to person-centered interventions. Reading with desired TTS system supports and features promotes improved reading efficiency by PWA compared with reading without TTS support. Attending to client preferences is important when customizing and implementing TTS technology as a reading support.
Optimal reactive power planning using oppositional grey wolf optimization by considering bus vulnerability analysis
Authors: Babu Rohit , Raj Saurav , Dey Bishwajit , Bhattacharyya Biplab 
Published: December 2021

AbstractPower system instability primarily results from the deviation of the frequency from its predefined rated value. This deviation causes voltage collapse, which further leads to sudden blackouts of the power system network. It is often triggered by a lack of reactive capacity. The solution to the reactive capacity problem can be obtained in two stages. In the first stage, the vulnerable buses, also known as ‘weak buses’, where voltage failure might occur are identified, and the Var compensating devices are mounted at those locations. The proposed approach utilizes three simple vulnerable bus detection methods: the fast voltage stability index, line stability index, and voltage collapse proximity index (VCPI). In the second stage, various optimization algorithms are implemented to determine the optimal setting of Var sources, such as particle swarm optimization, differential evolution, the whale optimization algorithm, the grasshopper optimization algorithm, the salp swarm algorithm, grey wolf optimization, and oppositional grey wolf optimization (OGWO). The results indicate that the best approach to poor bus recognition is the VCPI, and the OGWO technique provides a much less expensive system than other optimization strategies used for problems of optimal reactive power planning.
Near-IR narrow-band imaging with CIRCE at the Gran Telescopio Canarias: Searching for Lyα-emitters atz ∼ 9.3
Authors: Cabello C. , Gallego J. , Cardiel N. , Pascual S. , Guzmán R. , Herrero A. , Manrique A. , Marín-Franch A. , Mas-Hesse J. M. , Rodríguez-Espinosa J. M. , Salvador-Solé E. 
Published: December 2021

Context.Identifying very high-redshift galaxies is crucial for understanding the formation and evolution of galaxies. However, many questions still remain, and the uncertainty on the epoch of reionization is large. In this approach, some models allow a double-reionization scenario, although the number of confirmed detections at very highzis still too low to serve as observational proof.Aims.The main goal of this project is studying whether we can search for Lyman-αemitters (LAEs) atz ∼ 9 using a narrow-band (NB) filter that was specifically designed by our team and was built for this experiment.Methods.We used the NB technique to select candidates by measuring the flux excess due to the Lyαemission. The observations were taken with an NB filter (full width at half minimum of 11 nm and central wavelengthλc =  1.257 μm) and the CIRCE near-infrared camera for the Gran Telescopio Canarias. We describe a data reduction procedure that was especially optimized to minimize instrumental effects. With a total exposure time of 18.3 h, the final NB image covers an area of ∼6.7 arcmin2, which corresponds to a comoving volume of 1.1 × 103Mpc3atz = 9.3.Results.We pushed the source detection to its limit, which allows us to analyze an initial sample of 97 objects. We detail the different criteria we applied to select the candidates. The criteria included visual verifications in different photometric bands. None of the objects resembled a reliable LAE, however, and we found no robust candidate down to an emission-line flux of 2.9 × 10−16erg s−1cm−2, which corresponds to a Lyαluminosity limit of 3 × 1044erg s−1. We derive an upper limit on the Lyαluminosity function atz ∼ 9 that agrees well with previous constraints. We conclude that deeper and wider surveys are needed to study the LAE population at the cosmic dawn.
Flux rope and dynamics of the heliospheric current sheet
Authors: Réville V. , Fargette N. , Rouillard A. P. , Lavraud B. , Velli M. , Strugarek A. , Parenti S. , Brun A. S. , Shi C. , Kouloumvakos A. , Poirier N. , Pinto R. F. , Louarn P. , Fedorov A. , Owen C. J. , Génot V. , Horbury T. S. , Laker R. , O’Brien H. , Angelini V. , Fauchon-Jones E. , Kasper J. C. 
Published: December 2021

Context. Solar Orbiter and Parker Solar Probe jointly observed the solar wind for the first time in June 2020, capturing data from very different solar wind streams: calm, Alfvénic wind and also highly dynamic large-scale structures.
Context. Our aim is to understand the origin and characteristics of the highly dynamic solar wind observed by the two probes, particularly in the vicinity of the heliospheric current sheet (HCS).
Methods. We analyzed the plasma data obtained by Parker Solar Probe and Solar Orbiter in situ during the month of June 2020. We used the Alfvén-wave turbulence magnetohydrodynamic solar wind model WindPredict-AW and we performed two 3D simulations based on ADAPT solar magnetograms for this period.
Results. We show that the dynamic regions measured by both spacecraft are pervaded by flux ropes close to the HCS. These flux ropes are also present in the simulations, forming at the tip of helmet streamers, that is, at the base of the heliospheric current sheet. The formation mechanism involves a pressure-driven instability followed by a fast tearing reconnection process. We further characterize the 3D spatial structure of helmet streamer born flux ropes, which appears in the simulations to be related to the network of quasi-separatrices.
Anti-inflammatory Strategies in Atherosclerosis
Authors: Bugger Heiko , Zirlik Andreas 
Published: December 2021

AbstractAtherosclerotic vascular disease and its related complications are the major cause of mortality in Western societies. Atherosclerosis is a chronic inflammatory disease of the arterial wall triggered by traditional and nontraditional risk factors and mediated by inflammatory and immune responses. Recent clinical trials provided compelling evidence corroborating that atherosclerosis is an inflammatory disease and demonstrated efficacy of anti-inflammatory interventions in reducing cardiovascular events and mortality. Traditional risk factors drive vascular inflammation, further justifying the instrumental role of intensified risk factor management in attenuating and preventing atherosclerotic disease and complications. Promising therapeutic approaches specifically related to inhibition of inflammation span traditional anti-inflammatory drugs, specific immunomodulation, and development of vaccination against atherosclerotic disease. Here, we review the inflammatory component in atherogenesis, the available evidence from clinical trials evaluating efficacy of therapeutic anti-inflammatory interventions in patients with high cardiovascular risk, and discuss potential future targets for anti-inflammatory or immune modulatory treatment in atherosclerotic cardiovascular disease.
Single-Dose Ibuprofen-Arginine as a Preventive for Pain, Edema, and Trismus After Impacted Lower Third Molar Surgery: A Randomized Split-Mouth Clinical Trial
Authors: Ramos Edith Umasi , Benetti Luan Pier , Oliveira Júlio César Silva , Bassi Ana Paula Farnezi 
Published: December 2021

Abstract
Objective We examined if the association of ibuprofen with arginine has a better anti-inflammatory effect on pain, edema, and trismus after surgery of the impacted mandibular third molar than ibuprofen alone.
Materials and Methods The study included 21 patients, 18 to 30 years of age, each with an impacted, and bilateral and symmetric third molar (total n = 21) that required transalveolar extraction. Patients were randomly assigned numbers from 1 to 21. Group A received ibuprofen-arginine as preoperative medication, while Group B received only ibuprofen. Both groups received the same postoperative medications: amoxicillin + acetaminophen. All patients were evaluated for pain at 6, 12, and 24 hours. They were evaluated for edema and trismus before surgery; immediately after surgery; and at 24, 48, and 72 hours postoperatively. Postoperative pain scores used the visual analog scale (BS-11). For facial edema and trismus, linear measurements used the method modified by Gabka and Matsumura.
Statistical Analysis For the evaluation of data between Group A and Group B, we used the statistical software SPSS version 22. The Shapiro-Wilk, analysis of variance, the Bonferroni comparisons, and the Wilcoxon test were used. All tests were based on a significance level of 0.05.
Results The study results reveal that the facial edema scores of Group A and Group B presented statistically significant differences (p < 0.05), while for postoperative trismus, there was no statistically significant difference (p > 0.05) between the scores of Group A and Group B.
Conclusion As a conclusion, we can state that the use of ibuprofen-arginine allows for significantly better control of pain and edema, and shows a tendency toward better recovery from trismus, although without statistical significance. Based on this, we can assert that arginine improves the anti-inflammatory power of ibuprofen, thus generating better tissue healing after surgery of the impacted third molar.