bluuebunny/crossref_metadata_2025_split huggingface dataset:
Environmental Transport of Gyrotactic Microorganisms in an Open‐Channel Flow
Authors: Li Guangmiao , Gong Zheng , Jiang Weiquan , Zhan Jie , Wang Bohan , Fu Xudong , Xu Mengzhen , Wu Zi 
Published: March 2023

AbstractThe rich and complex phenomena of the transport of active particles like microorganisms in shear flows are of great significance to various biological and environmental applications. Recent studies have shown that the motility and gyrotaxis of algae could greatly influence their transport in waters. However, little attention has been paid to the initial and transient transport regime when the classical Taylor dispersion model is not applicable. To tackle this problem, we resort to Gill's generalized dispersion model for passive particles like solute, which has the potential for accurately describing the entire transport process. For the first time, we extend Gill's model to the active particles, and the effects of swimming, gyrotaxis, and flow shear on the microorganism dispersion in an open‐channel flow have been thoroughly investigated. We first theoretically solve the transient drift and dispersion coefficients, based on which we obtain analytical solutions for concentration distributions of microorganisms, and further validate these results by numerically solving the governing equation. We find that when there is no flow, the longitudinal dispersion of microorganisms can be weakened by the gravitactic accumulation in the vicinity of water surface, while enhanced by a stronger swimming ability of the microorganisms. The effect of the flow shear does not affect the form of the asymptotic concentration distribution, but can greatly enhance the transient drift velocity and the dispersivity. We further analyze the effect of turbulence on microorganisms' dispersion by combing the direct numerical simulation and the random walk simulation. The increase of turbulence is shown to decrease the vertical non‐uniformity of the concentration distribution, as well as the relative contribution of active behavior to both the drift and Taylor dispersivity during transport.
A Morphological and Spatial Analysis of Volcanoes on Venus
Authors: Hahn Rebecca M. , Byrne Paul K. 
Published: March 2023

AbstractVenus is home to many thousands of volcanic landforms that range in size from much less than 5 km to well over 100 km in diameter. Volcanism is clearly a major, widespread process on Venus, and is a principal expression of the planet's secular loss of interior heat. Without sufficient in situ data to clearly determine its internal structure, we can use the morphological and spatial properties of volcanoes across the planet to help place constraints on our understanding of the volcanic characteristics and history of Venus. With the Magellan synthetic‐aperture radar full‐resolution radar map left‐ and right‐look global mosaics at 75 m‐per‐pixel resolution, we developed a global catalog of volcanoes on Venus that contains ∼85,000 edifices, ∼99% of which are <5 km in diameter. We find that Venus hosts far more volcanoes than previously mapped, and that although they are distributed across virtually the entire planet, size–frequency distribution analysis reveals a relative lack of edifices in the 20–100 km diameter range, which could be related to magma availability and eruption rate. Through spatial density analysis of volcanoes alongside assessments of geophysical data sets and proximal tectonic and volcanic structures, we report on the morphological and spatial patterns of volcanism on Venus to help gain new insights into the planet's geological evolution.
Mesenchymal stem cell-derived extracellular vesicles subvert Th17 cells by destabilizing RORγt through posttranslational modification
Authors: Jung Sunyoung , Lee Sunho , Kim Hyun Je , Kim Sueon , Moon Ji Hwan , Chung Hyunwoo , Kang Seong-Jun , Park Chung-Gyu 
Published: March 2023

AbstractMesenchymal stem cell (MSC)-derived small extracellular vesicles (MSC-sEVs) are known to exert immunosuppressive functions. This study showed that MSC-sEVs specifically convert T helper 17 (Th17) cells into IL-17 low-producer (ex-Th17) cells by degrading RAR-related orphan receptor γt (RORγt) at the protein level. In experimental autoimmune encephalomyelitis (EAE)-induced mice, treatment with MSC-sEVs was found to not only ameliorate clinical symptoms but also to reduce the number of Th17 cells in draining lymph nodes and the central nervous system. MSC-sEVs were found to destabilize RORγt by K63 deubiquitination and deacetylation, which was attributed to the EP300-interacting inhibitor of differentiation 3 (Eid3) contained in the MSC-sEVs. Small extracellular vesicles isolated from the Eid3 knockdown MSCs by Eid3-shRNA failed to downregulate RORγt. Moreover, forced expression of Eid3 by gene transfection was found to significantly decrease the protein level of RORγt in Th17 cells. Altogether, this study reveals the novel immunosuppressive mechanisms of MSC-sEVs, which suggests the feasibility of MSC-sEVs as an attractive therapeutic tool for curing Th17-mediated inflammatory diseases.
Risk-prediction models for intravenous immunoglobulin resistance in Kawasaki disease: Risk-of-Bias Assessment using PROBAST
Authors: Wang Shuhui , Huang Hongbiao , Hou Miao , Xu Qiuqin , Qian Weiguo , Tang Yunjia , Li Xuan , Qian Guanghui , Ma Jin , Zheng Yiming , Shen Yueping , Lv Haitao 
Published: March 2023

AbstractBackgroundThe prediction model of intravenous immunoglobulin (IVIG) resistance in Kawasaki disease can calculate the probability of IVIG resistance and provide a basis for clinical decision-making. We aim to assess the quality of these models developed in the children with Kawasaki disease.MethodsStudies of prediction models for IVIG-resistant Kawasaki disease were identified through searches in the PubMed, Web of Science, and Embase databases. Two investigators independently performed literature screening, data extraction, quality evaluation, and discrepancies were settled by a statistician. The checklist for critical appraisal and data extraction for systematic reviews of prediction modeling studies (CHARMS) was used for data extraction, and the prediction models were evaluated using the Prediction Model Risk of Bias Assessment Tool (PROBAST).ResultsSeventeen studies meeting the selection criteria were included in the qualitative analysis. The top three predictors were neutrophil measurements (peripheral neutrophil count and neutrophil %), serum albumin level, and C-reactive protein (CRP) level. The reported area under the curve (AUC) values for the developed models ranged from 0.672 (95% confidence interval [CI]: 0.631–0.712) to 0.891 (95% CI: 0.837–0.945); The studies showed a high risk of bias (ROB) for modeling techniques, yielding a high overall ROB.ConclusionIVIG resistance models for Kawasaki disease showed high ROB. An emphasis on improving their quality can provide high-quality evidence for clinical practice.Impact statementThis study systematically evaluated the risk of bias (ROB) of existing prediction models for intravenous immunoglobulin (IVIG) resistance in Kawasaki disease to provide guidance for future model development meeting clinical expectations.This is the first study to systematically evaluate the ROB of IVIG resistance in Kawasaki disease by using PROBAST. ROB may reduce model performance in different populations.Future prediction models should account for this problem, and PROBAST can help improve the methodological quality and applicability of prediction model development.
Rehabilitating a severely worn dentition with removable prosthodontics
Authors: Hackett Stephanie , Newton Richard , Ali Rahat 
Published: March 2023

AbstractIn the next part of this series on tooth wear management, we discuss the indications and clinical stages for the provision of removable prostheses for the treatment of severely worn and depleted dentitions. The general design features of a complex prosthesis are described for reorganised occlusal schemes and maintenance guidelines are explained. In addition, the clinical stages for three different situations are described: removable-only approaches, and combined fixed and removable in the same arch and separate arches. The value of providing removable prostheses in worn dentitions allows the immediate rehabilitation of severely worn teeth taking a non-invasive and retrievable approach when the remaining dentition is of poor quality or structure and/or there are missing teeth.
Managing tooth wear with respect to quality of life: an evidence-based decision on when to intervene
Authors: Mehta Shamir B. , Loomans Bas A. C. , van Sambeek Roos M. F. , Pereira-Cenci Tatiana , O’Toole Saoirse 
Published: March 2023

AbstractPatients with more severe forms of tooth wear may require restorative rehabilitation. The decision to commence treatment must be taken carefully and there are a multitude of factors to consider. Alongside the clinical signs and symptoms typically associated with tooth wear, there is also the need to assess the impact of the condition on the patient's oral health-related quality of life. As part of the discussions relating to the attainment of informed consent for the restoration of the worn dentition, not only is it relevant to appropriately appraise the risks, benefits, costs, reasonable alternatives and likely prognosis of the proposed treatments, but to also elaborate on the expected impact of the intervention on the patient's oral health-related quality of life. The aim of this article is to review the evidence relating to the impact of the quality of life with the management of tooth wear, with the introduction of the concept of an evidence-based approach to decision-making when planning care.
Monitoring of erosive tooth wear: what to use and when to use it
Authors: O’Toole Saoirse , Marro Francisca , Loomans Bas A. C. , Mehta Shamir B. 
Published: March 2023

AbstractAlthough we are increasingly recognising the need to assess patients for accelerated rates of tooth wear progression, it is often difficult to do so within a feasible diagnostic window. This paper aims to provide evidence-based timelines which a diagnosing clinician can expect to assess tooth wear progression in study models, clinical indices, clinical photographs and visually with intraoral scans. It also discusses new technologies emerging for the quantitative assessment of tooth wear, timelines for diagnosis, and caveats in the 3D scan registration and analysis process.
Calpain activity is negatively regulated by a KCTD7–Cullin-3 complex via non-degradative ubiquitination
Authors: Sharma Jaiprakash , Mulherkar Shalaka , Chen Uan-I , Xiong Yan , Bajaj Lakshya , Cho Byoung-Kyu , Goo Young Ah , Leung Hon-Chiu Eastwood , Tolias Kimberley F. , Sardiello Marco 
Published: March 2023

AbstractCalpains are a class of non-lysosomal cysteine proteases that exert their regulatory functions via limited proteolysis of their substrates. Similar to the lysosomal and proteasomal systems, calpain dysregulation is implicated in the pathogenesis of neurodegenerative disease and cancer. Despite intensive efforts placed on the identification of mechanisms that regulate calpains, however, calpain protein modifications that regulate calpain activity are incompletely understood. Here we show that calpains are regulated by KCTD7, a cytosolic protein of previously uncharacterized function whose pathogenic mutations result in epilepsy, progressive ataxia, and severe neurocognitive deterioration. We show that KCTD7 works in complex with Cullin-3 and Rbx1 to execute atypical, non-degradative ubiquitination of calpains at specific sites (K398 of calpain 1, and K280 and K674 of calpain 2). Experiments based on single-lysine mutants of ubiquitin determined that KCTD7 mediates ubiquitination of calpain 1 via K6-, K27-, K29-, and K63-linked chains, whereas it uses K6-mediated ubiquitination to modify calpain 2. Loss of KCTD7-mediated ubiquitination of calpains led to calpain hyperactivation, aberrant cleavage of downstream targets, and caspase-3 activation. CRISPR/Cas9-mediated knockout of Kctd7 in mice phenotypically recapitulated human KCTD7 deficiency and resulted in calpain hyperactivation, behavioral impairments, and neurodegeneration. These phenotypes were largely prevented by pharmacological inhibition of calpains, thus demonstrating a major role of calpain dysregulation in KCTD7-associated disease. Finally, we determined that Cullin-3–KCTD7 mediates ubiquitination of all ubiquitous calpains. These results unveil a novel mechanism and potential target to restrain calpain activity in human disease and shed light on the molecular pathogenesis of KCTD7-associated disease.
Avacincaptad pegol for geographic atrophy secondary to age-related macular degeneration: 18-month findings from the GATHER1 trial
Authors: Patel Sunil S. , Lally David R. , Hsu Jason , Wykoff Charles C. , Eichenbaum David , Heier Jeffrey S. , Jaffe Glenn J. , Westby Keith , Desai Dhaval , Zhu Liansheng , Khanani Arshad M. 
Published: March 2023

Abstract
Background/Objectives
To assess the safety and efficacy of avacincaptad pegol (ACP), a C5 inhibitor, for geographic atrophy (GA) secondary to age-related macular degeneration (AMD) over an 18-month treatment course.

Subjects/Methods
This study was an international, prospective, randomized, double-masked, sham-controlled, phase 2/3 clinical trial that consisted of 2 parts. In part 1, 77 participants were randomized 1:1:1 to receive monthly intravitreal injections of ACP 1 mg, ACP 2 mg, or sham. In part 2, 209 participants were randomized 1:2:2 to receive monthly ACP 2 mg, ACP 4 mg, or sham. The mean rate of change of GA over 18 months was measured by fundus autofluorescence.

Results
Compared with their respective sham cohorts, monthly ACP treatment reduced the mean GA growth (square root transformation) over 18 months by 28.1% (0.168 mm, 95% CI [0.066, 0.271]) for the 2 mg cohort and 30.0% (0.167 mm, 95% CI [0.062, 0.273]) for the 4 mg cohort. ACP treatment was generally well tolerated over 18 months, with most ocular adverse events (AEs) related to the injection procedure. Macular neovascularization (MNV) was more frequent in both 2 mg (11.9%) and 4 mg (15.7%) cohorts than their respective sham control groups (2.7% and 2.4%).

Conclusions
Over this 18-month study, ACP 2 mg and 4 mg showed continued reductions in the progression of GA growth compared to sham and continued to be generally well tolerated. A pivotal phase 3 GATHER2 trial is currently underway to support the efficacy and safety of ACP as a potential treatment for GA.
Modulation of metal species as control point for Ni-catalyzed stereodivergent semihydrogenation of alkynes with water
Authors: Wu Yuanqi , Ao Yuhui , Li Zhiming , Liu Chunhui , Zhao Jinbo , Gao Wenyu , Li Xuemeng , Wang Hui , Liu Yongsheng , Liu Yu 
Published: March 2023

AbstractA base-assisted metal species modulation mechanism enables Ni-catalyzed stereodivergent transfer semihydrogenation of alkynes with water, delivering both olefinic isomers smoothly using cheap and nontoxic catalysts and additives. Different from most precedents, in which E-alkenes derive from the isomerization of Z-alkene products, the isomers were formed in orthogonal catalytic pathways. Mechanistic studies suggest base as a key early element in modulation of the reaction pathways: by adding different bases, nickel species with disparate valence states could be accessed to initiate two catalytic cycles toward different stereoisomers. The practicability of the method is showcased with nearly 70 examples, including internal and terminal triple bonds, enynes and diynes, affording semi-hydrogenated products in high yields and selectivity.
Predicting vaccine effectiveness against severe COVID-19 over time and against variants: a meta-analysis
Authors: Cromer Deborah , Steain Megan , Reynaldi Arnold , Schlub Timothy E. , Khan Shanchita R. , Sasson Sarah C. , Kent Stephen J. , Khoury David S. , Davenport Miles P. 
Published: March 2023

AbstractVaccine protection from symptomatic SARS-CoV-2 infection has been shown to be strongly correlated with neutralising antibody titres; however, this has not yet been demonstrated for severe COVID-19. To explore whether this relationship also holds for severe COVID-19, we performed a systematic search for studies reporting on protection against different SARS-CoV-2 clinical endpoints and extracted data from 15 studies. Since matched neutralising antibody titres were not available, we used the vaccine regimen, time since vaccination and variant of concern to predict corresponding neutralising antibody titres. We then compared the observed vaccine effectiveness reported in these studies to the protection predicted by a previously published model of the relationship between neutralising antibody titre and vaccine effectiveness against severe COVID-19. We find that predicted neutralising antibody titres are strongly correlated with observed vaccine effectiveness against symptomatic (Spearman $$\rho$$
ρ
= 0.95, p < 0.001) and severe (Spearman $$\rho$$
ρ
= 0.72, p < 0.001 for both) COVID-19 and that the loss of neutralising antibodies over time and to new variants are strongly predictive of observed vaccine protection against severe COVID-19.
The m6A reader PRRC2A is essential for meiosis I completion during spermatogenesis
Authors: Tan Xinshui , Zheng Caihong , Zhuang Yinghua , Jin Pengpeng , Wang Fengchao 
Published: March 2023

AbstractN6-methyladenosine (m6A) and its reader proteins YTHDC1, YTHDC2, and YTHDF2 have been shown to exert essential functions during spermatogenesis. However, much remains unknown about m6A regulation mechanisms and the functions of specific readers during the meiotic cell cycle. Here, we show that the m6A reader Proline rich coiled-coil 2A (PRRC2A) is essential for male fertility. Germ cell-specific knockout of Prrc2a causes XY asynapsis and impaired meiotic sex chromosome inactivation in late-prophase spermatocytes. Moreover, PRRC2A-null spermatocytes exhibit delayed metaphase entry, chromosome misalignment, and spindle disorganization at metaphase I and are finally arrested at this stage. Sequencing data reveal that PRRC2A decreases the RNA abundance or improves the translation efficiency of targeting transcripts. Specifically, PRRC2A recognizes spermatogonia-specific transcripts and downregulates their RNA abundance to maintain the spermatocyte expression pattern during the meiosis prophase. For genes involved in meiotic cell division, PRRC2A improves the translation efficiency of their transcripts. Further, co-immunoprecipitation data show that PRRC2A interacts with several proteins regulating mRNA metabolism or translation (YBX1, YBX2, PABPC1, FXR1, and EIF4G3). Our study reveals post-transcriptional functions of PRRC2A and demonstrates its critical role in the completion of meiosis I in spermatogenesis.
Temporal and spatial assembly of inner ear hair cell ankle link condensate through phase separation
Authors: Wang Huang , Du Haibo , Ren Rui , Du Tingting , Lin Lin , Feng Zhe , Zhao Dange , Wei Xiaoxi , Zhai Xiaoyan , Wang Hongyang , Dong Tingting , Sun Jin-Peng , Wu Hao , Xu Zhigang , Lu Qing 
Published: March 2023

AbstractStereocilia are actin-based cell protrusions of inner ear hair cells and are indispensable for mechanotransduction. Ankle links connect the ankle region of developing stereocilia, playing an essential role in stereocilia development. WHRN, PDZD7, ADGRV1 and USH2A have been identified to form the so-called ankle link complex (ALC); however, the detailed mechanism underlying the temporal emergence and degeneration of ankle links remains elusive. Here we show that WHRN and PDZD7 orchestrate ADGRV1 and USH2A to assemble the ALC through liquid-liquid phase separation (LLPS). Disruption of the ALC multivalency for LLPS largely abolishes the distribution of WHRN at the ankle region of stereocilia. Interestingly, high concentration of ADGRV1 inhibits LLPS, providing a potential mechanism for ALC disassembly. Moreover, certain deafness mutations of ALC genes weaken the multivalent interactions of ALC and impair LLPS. In conclusion, our study demonstrates that LLPS mediates ALC formation, providing essential clues for understanding the pathogenesis of deafness.
Intranasal trimeric sherpabody inhibits SARS-CoV-2 including recent immunoevasive Omicron subvariants
Authors: Mäkelä Anna R. , Uğurlu Hasan , Hannula Liina , Kant Ravi , Salminen Petja , Fagerlund Riku , Mäki Sanna , Haveri Anu , Strandin Tomas , Kareinen Lauri , Hepojoki Jussi , Kuivanen Suvi , Levanov Lev , Pasternack Arja , Naves Rauno A. , Ritvos Olli , Österlund Pamela , Sironen Tarja , Vapalahti Olli , Kipar Anja , Huiskonen Juha T. , Rissanen Ilona , Saksela Kalle 
Published: March 2023

AbstractThe emergence of increasingly immunoevasive SARS-CoV-2 variants emphasizes the need for prophylactic strategies to complement vaccination in fighting the COVID-19 pandemic. Intranasal administration of neutralizing antibodies has shown encouraging protective potential but there remains a need for SARS-CoV-2 blocking agents that are less vulnerable to mutational viral variation and more economical to produce in large scale. Here we describe TriSb92, a highly manufacturable and stable trimeric antibody-mimetic sherpabody targeted against a conserved region of the viral spike glycoprotein. TriSb92 potently neutralizes SARS-CoV-2, including the latest Omicron variants like BF.7, XBB, and BQ.1.1. In female Balb/c mice intranasal administration of just 5 or 50 micrograms of TriSb92 as early as 8 h before but also 4 h after SARS-CoV-2 challenge can protect from infection. Cryo-EM and biochemical studies reveal triggering of a conformational shift in the spike trimer as the inhibitory mechanism of TriSb92. The potency and robust biochemical properties of TriSb92 together with its resistance against viral sequence evolution suggest that TriSb92 could be useful as a nasal spray for protecting susceptible individuals from SARS-CoV-2 infection.
Transmission modeling to infer tuberculosis incidence prevalence and mortality in settings with generalized HIV epidemics
Authors: Dodd Peter J. , Shaweno Debebe , Ku Chu-Chang , Glaziou Philippe , Pretorius Carel , Hayes Richard J. , MacPherson Peter , Cohen Ted , Ayles Helen 
Published: March 2023

AbstractTuberculosis (TB) killed more people globally than any other single pathogen over the past decade. Where surveillance is weak, estimating TB burden estimates uses modeling. In many African countries, increases in HIV prevalence and antiretroviral therapy have driven dynamic TB epidemics, complicating estimation of burden, trends, and potential intervention impact. We therefore develop a novel age-structured TB transmission model incorporating evolving demographic, HIV and antiretroviral therapy effects, and calibrate to TB prevalence and notification data from 12 African countries. We use Bayesian methods to include uncertainty for all TB model parameters, and estimate age-specific annual risks of TB infection, finding up to 16.0%/year in adults, and the proportion of TB incidence from recent (re)infection, finding a mean across countries of 34%. Rapid reduction of the unacceptably high burden of TB in high HIV prevalence settings will require interventions addressing progression as well as transmission.