bluuebunny/crossref_metadata_2025_split huggingface dataset:
In vitro fluorescence assay to measure GDP/GTP exchange of guanine nucleotide exchange factors of Rho family GTPases
Authors: Blaise Alyssa M , Corcoran Ellen E , Wattenberg Eve S , Zhang Yan-Ling , Cottrell Jeffrey R , Koleske Anthony J 
Published: December 2021

Abstract
Guanine nucleotide exchange factors (GEFs) are enzymes that promote the activation of GTPases through GTP loading. Whole exome sequencing has identified rare variants in GEFs that are associated with disease, demonstrating that GEFs play critical roles in human development. However, the consequences of these rare variants can only be understood through measuring their effects on cellular activity. Here, we provide a detailed, user-friendly protocol for purification and fluorescence-based analysis of the two GEF domains within the protein, Trio. This analysis offers a straight-forward, quantitative tool to test the activity of GEF domains on their respective GTPases, as well as utilize high-throughput screening to identify regulators and inhibitors. This protocol can be adapted for characterization of other Rho family GEFs. Such analyses are crucial for the complete understanding of the roles of GEF genetic variants in human development and disease.
Inhibiting mitochondrial fission rescues degeneration in hereditary spastic paraplegia neurons
Authors: Chen Zhenyu , Chai Eric , Mou Yongchao , Roda Ricardo H , Blackstone Craig , Li Xue-Jun 
Published: December 2021

Abstract
Hereditary spastic paraplegias are characterized by lower limb spasticity resulting from degeneration of long corticospinal axons. SPG11 is one of the most common autosomal recessive hereditary spastic paraplegias, and the SPG11 protein spatacsin forms a complex with the SPG15 protein spastizin and heterotetrameric AP5 adaptor protein complex, which includes the SPG48 protein AP5Z1. Using the integration-free episomal method, we established SPG11 patient-specific induced pluripotent stem cells (iPSCs) from patient fibroblasts. We differentiated SPG11 iPSCs, as well as SPG48 iPSCs previously established, into cortical projection neurons and examined protective effects by targeting mitochondrial dynamics using P110, a peptide that selectively inhibits mitochondrial fission GTPase Drp1. P110 treatment mitigates mitochondrial fragmentation, improves mitochondrial motility, and restores mitochondrial health and ATP levels in SPG11 and SPG48 neurons. Neurofilament aggregations are increased in SPG11 and SPG48 axons, and these are also suppressed by P110. Similarly, P110 mitigates neurofilament disruption in both SPG11 and SPG48 knockdown cortical projection neurons, confirming the contribution of hereditary spastic paraplegia gene deficiency to subsequent neurofilament and mitochondrial defects. Strikingly, neurofilament aggregations in SPG11 and SPG48 deficient neurons double stain with ubiquitin and autophagy related proteins, resembling the pathological hallmark observed in SPG11 autopsy brain sections. To confirm the cause-effect relationship between the SPG11 mutations and disease phenotypes, we knocked-in SPG11 disease mutations to human embryonic stem cells (hESCs) and differentiated these stem cells into cortical projection neurons. Reduced ATP levels and accumulated neurofilament aggregations along axons are observed, and both are mitigated by P110. Furthermore, rescue experiment with expression of wild-type SPG11 in cortical projection neurons derived from both SPG11 patient iPSCs and SPG11 disease mutation knock-in hESCs leads to rescue of mitochondrial dysfunction and neurofilament aggregations in these SPG11 neurons. Finally, in SPG11 and SPG48 long-term cultures, increased release of phosphoNF-H, a biomarker for nerve degeneration, is significantly reduced by inhibiting mitochondrial fission pharmacologically using P110 and genetically using Drp1 shRNA. Taken together, our results demonstrate that impaired mitochondrial dynamics underlie both cytoskeletal disorganization and axonal degeneration in SPG11 and SPG48 neurons, highlighting the importance of targeting these pathologies therapeutically.
Propofol anesthesia concentration rather than abrupt behavioral unresponsiveness linearly degrades responses in the rat primary auditory cortex
Authors: Bergman Lottem , Krom Aaron J , Sela Yaniv , Marmelshtein Amit , Hayat Hanna , Regev Noa , Nir Yuval 
Published: December 2021

Abstract
Despite extensive knowledge of its molecular and cellular effects, how anesthesia affects sensory processing remains poorly understood. In particular, it remains unclear whether anesthesia modestly or robustly degrades activity in primary sensory regions, and whether such changes are linked to anesthesia drug concentration versus behavioral unresponsiveness, which are typically confounded. Here, we used slow gradual intravenous propofol anesthesia induction together with auditory stimulation and intermittent assessment of behavioral responsiveness while recording epidural electroencephalogram, and neuronal spiking activity in primary auditory cortex (PAC) of eight rats. We found that all main components of neuronal activity including spontaneous firing rates, onset response magnitudes, onset response latencies, postonset neuronal silence duration, late-locking to 40 Hz click-trains, and offset responses, gradually changed in a dose-dependent manner with increasing anesthesia levels without showing abrupt shifts around loss of righting reflex or other time-points. Thus, the dominant factor affecting PAC responses is the anesthesia drug concentration rather than any sudden, dichotomous behavioral state changes. Our findings explain a wide array of seemingly conflicting results in the literature that, depending on the precise definition of wakefulness (vigilant vs. drowsy) and anesthesia (light vs. deep/surgical), report a spectrum of effects in primary regions ranging from minimal to dramatic differences.
Family Systems and Emotional Functioning in Deaf or Hard-of-Hearing Preschool Children
Authors: Yuen Shannon , Li Boya , Tsou Yung-Ting , Meng Qi , Wang Liyan , Liang Wei , Rieffe Carolien 
Published: December 2021

Abstract
This study examined how deaf or hard-of-hearing (DHH) and typically hearing (TH) children may differ in their family system and emotional functioning and examined the relations between family system and children’s emotional functioning. Parents of 106 DHH and 99 TH children (2–6 years) reported on family cohesion and adaptability, parental emotion communication, and their child’s emotional functioning. The DHH children were rated lower on family cohesion and positive emotion expression than the TH children. Higher levels of family cohesion related to more positive emotion expression in TH children but not in DHH children. For all children, higher levels of family cohesion related to fewer negative emotion expressions and more parental emotion communication related to more negative emotion expression. The results emphasize the importance of sharing leisure activities together and open communication within the family, which can support DHH and TH children’s experience of emotions and their expressions of them.
Clinical applications of cardiac computed tomography: a consensus paper of the European Association of Cardiovascular Imaging—part II
Authors: Pontone Gianluca , Rossi Alexia , Guglielmo Marco , Dweck Marc R , Gaemperli Oliver , Nieman Koen , Pugliese Francesca , Maurovich-Horvat Pal , Gimelli Alessia , Cosyns Bernard , Achenbach Stephan 
Published: December 2021

Abstract
Cardiac computed tomography (CT) was initially developed as a non-invasive diagnostic tool to detect and quantify coronary stenosis. Thanks to the rapid technological development, cardiac CT has become a comprehensive imaging modality which offers anatomical and functional information to guide patient management. This is the second of two complementary documents endorsed by the European Association of Cardiovascular Imaging aiming to give updated indications on the appropriate use of cardiac CT in different clinical scenarios. In this article, emerging CT technologies and biomarkers, such as CT-derived fractional flow reserve, perfusion imaging, and pericoronary adipose tissue attenuation, are described. In addition, the role of cardiac CT in the evaluation of atherosclerotic plaque, cardiomyopathies, structural heart disease, and congenital heart disease is revised.
Association of transcatheter edge-to-edge repair with improved survival in older patients with severe, symptomatic degenerative mitral regurgitation
Authors: Benfari Giovanni , Sorajja Paul , Pedrazzini Giovanni , Taramasso Maurizio , Gavazzoni Mara , Biasco Luigi , Essayagh Benjamin , Grigioni Francesco , Bae Richard , Tribouilloy Christophe , Vanoverschelde Jean-Louis , Michelena Hector , Bapat Vinayak N , Vancraynest David , Klersy Catherine , Curti Moreno , Thapa Prabin , Enriquez-Sarano Maurice 
Published: December 2021

Abstract

Background
Randomized clinical trials demonstrated transcatheter edge-to-edge repair (TEER) efficacy in improving outcome vs. medical management for functional mitral regurgitation, but limited randomized data are available for the treatment of degenerative mitral regurgitation (DMR). We aimed to compare the outcome of older patients treated with TEER vs. unoperated DMR.

Methods and results
Registries including consecutive patients ≥65 years with symptomatic severe DMR treated with TEER (MitraSwiss and Minneapolis Heart Institute registries) or unoperated (MIDA registry) were analysed. Survival was compared overall and after matching for age, sex, EuroSCORE II, and ejection fraction. The study included 1187 patients (872 treated with TEER and 315 unoperated). During 24 ± 17 months of follow-up, 430 patients died, 18 ± 1% at 1 year and 50 ± 2% at 4 years. Patients undergoing TEER had similar age (82 ± 6 vs. 82 ± 7 years) and sex to unoperated patients, but higher surgical risk/comorbidity (EuroSCORE II 3.98 ± 4.28% vs. 2.77 ± 2.46%), more symptoms, and atrial fibrillation (P &lt; 0.0001). Transcatheter edge-to-edge repair was associated with lower mortality accounting for age, sex, EuroSCORE II, New York Heart Association class, atrial fibrillation, and ejection fraction [hazard ratio (HR): 0.47, 95% confidence interval (CI): 0.37–0.58; P &lt; 0.0001]. After propensity matching (247 pairs of patients), TEER consistently showed better survival compared with unoperated patients (49 ± 6% vs. 37 ± 3% at 4 years, P &lt; 0.0001) even in comprehensive multivariable analysis (HR: 0.60, 95% CI: 0.40–0.91; P = 0.03). Procedural failure was infrequent but post-procedural mitral regurgitation, remaining moderate-to-severe in 66 (7.6%) patients, was associated with excess mortality vs. trivial residual regurgitation (30 ± 6% vs. 11 ± 1% at 1 year, P &lt; 0.0001).

Conclusion
Amongst older patients with severe symptomatic DMR at high surgical risk, mitral TEER was associated with higher survival vs. unoperated patients. Successful control of mitral regurgitation was key to survival improvement with mitral TEER, which should be actively considered in patients deemed inoperable.
Management of ventricular tachycardia in patients with ischaemic cardiomyopathy: contemporary armamentarium
Authors: Kahle Ann-Kathrin , Jungen Christiane , Alken Fares-Alexander , Scherschel Katharina , Willems Stephan , Pürerfellner Helmut , Chen Shaojie , Eckardt Lars , Meyer Christian 
Published: December 2021

Abstract
Worldwide, ∼4 million people die from sudden cardiac death every year caused in more than half of the cases by ischaemic cardiomyopathy (ICM). Prevention of sudden cardiac death after myocardial infarction by implantation of a cardioverter-defibrillator (ICD) is the most common, even though not curative, therapy to date. Optimized ICD programming should be strived for in order to decrease the incidence of ICD interventions. Catheter ablation reduces the recurrence of ventricular tachycardias (VTs) and is an important adjunct to sole ICD-based treatment or pharmacological antiarrhythmic therapy in patients with ICM, as conclusively demonstrated by seven randomized controlled trials (RCTs) in the last two decades. However, none of the conducted trials was powered to reveal a survival benefit for ablated patients as compared to controls. Whereas thorough consideration of an early approach is necessary following two recent RCTs (PAUSE-SCD, BERLIN VT), catheter ablation is particularly recommended in patients with recurrent VT after ICD therapy. In this context, novel, pathophysiologically driven ablation strategies referring to deep morphological and functional substrate phenotyping based on high-resolution mapping and three-dimensional visualization of scars appear promising. Emerging concepts like sympathetic cardiac denervation as well as radioablation might expand the therapeutical armamentarium especially in patients with therapy-refractory VT. Randomized controlled trials are warranted and on the way to investigate how these translate into improved patient outcome. This review summarizes therapeutic strategies currently available for the prevention of VT recurrences, the optimal timing of applicability, and highlights future perspectives after a PAUSE in BERLIN.
Visual Difficulty, Race and Ethnicity, and Activity Limitation Trajectories Among Older Adults in the United States: Findings From the National Health and Aging Trends Study
Authors: Ehrlich Joshua R , Hu Mengyao , Zhou Yunshu , Kai Rohan , De Lott Lindsey B 
Published: December 2021

Abstract

Objectives
To characterize the influence of visual difficulty on activity limitation trajectories in older U.S. adults and investigate whether this varied across racial/ethnic groups.

Methods
We used data from 8,077 participants in the nationally representative National Health and Aging Trends Study from 2011 to 2019. Using mixed-effects regression models, we investigated the association of self-reported visual difficulty and race/ethnicity with activity limitation trajectories.

Results
Higher levels of visual difficulty and belonging to a minority racial/ethnic group were associated with greater mobility, self-care, and household activity limitations. Visual difficulty was associated with mobility and self-care activity limitation trajectories, and race/ethnicity was significantly associated with mobility and household activity limitation trajectories. Among those with the highest levels of visual difficulty, non-Hispanic Black participants experienced a faster rate of decline in self-care activities compared to non-Hispanic White participants.

Discussion
Promoting optimal aging for all requires an understanding of the factors that influence disparities in key outcomes. Our study provides evidence from a diverse national sample that visual difficulty appears to disproportionately affect activity limitation trajectories among older adults from minority racial/ethnic groups and particularly among non-Hispanic “Black individuals.” Further research is needed to determine whether interventions to promote healthy vision may positively affect overall activity and independence and ameliorate disparities in late-life activity limitation trajectories.
Quantifying low-frequency acoustic fields in urban environments
Authors: McComas Sarah , Arrowsmith Stephen , Hayward Chris , Stump Brian , McKenna Taylor Mihan H 
Published: December 2021

SUMMARY
Infrasound data contain contributions from incoherent noise, coherent noise and signals of interest. The design of an infrasound array to target sources of interest requires a quantification of array response, individual sensor response, propagation effects (topography and meteorological conditions), signal spectrum and the noise environment. The Comprehensive Nuclear-Test-Ban Treaty community has spent significant effort in quantifying the acoustic field in rural environments for frequencies up to 7 Hz. Given that the nuclear monitoring and tactical infrasound community have growing interests in monitoring sources in or near populated regions, there is an emergent need to measure and understand acoustic fields in these environments as well. This paper focuses on quantification of the acoustic field in three different urban environments: (1) arrays installed within Dallas, TX, a metropolitan area, (2) an array installed at the rural–suburban interface near San Diego, CA and (3) an array installed in Vicksburg, MS, a small city with multiple major transportation corridors. A minimum of five months of data was recorded and used for each site characterization. The analysis focuses on frequencies from 0.1 to 45 Hz. The quantification of the data from these three sites is accomplished with statistical noise models that capture the total ambient acoustic field, separation of the coherent portion of the field and trend analysis to link temporal and seasonal variations to wind speed and anthropogenic activities. The resulting physical interpretation of the data demonstrates that the total acoustic field in urban regions is overall higher and inversely related to the number of coherent detections observed by an array. Furthermore, this study presents an analysis framework for characterizing additional urban arrays and provides a basis for future array site selection and installation.
Experimental and numerical analysis of laminated carbon fibre-reinforced polymer gears with implicit model for coefficient-of-friction evaluation
Authors: Černe B , Bergant Z , Šturm R , Tavčar J , Zorko D 
Published: December 2021

Abstract
Laminated composites have so far received little attention as a potential material for gear drive applications. In the presented study, the thermomechanical performance of a newly developed type of epoxy impregnated, autoclave-cured carbon fibre-reinforced polymer gear—running in pair with a steel pinion—was analysed, using a combination of experimental and numerical approaches. The employed methods enabled the identification of the composite’s mechanical, thermal, and tribological characteristics, as related to the studied gear pair application. A newly proposed, finite-element-analysis-based iterative procedure enabled an implicit evaluation of the analysed material pair’s coefficient of friction (COF), which is a key parameter in determining the gear pair’s thermomechanical characteristics. For the considered material pair, a value of 0.34 was identified for the coefficient in the quasi-steady region. As the coefficient is strongly correlated with frictional heat generation and significantly affects the surface shear stress, it can consequently have a meaningful influence on the composite’s wear rate. The developed COF identification procedure was validated using a reciprocating cylinder-on-flat tribological test method. The composite gear’s service life was additionally tested at various running loads, resulting in pitch contact pressures ranging between 400 and 540 MPa. Lifetime gear test results showed a markedly superior performance compared to the high-temperature thermoplastic polyether ether ketone, which is typically employed in the most demanding polymer gear applications. Several methods are additionally proposed that could further improve the developed composite gears’ performance.
3D full-time anisotropic TEM modelling using a mixed BDF2/SAI method
Authors: Huang Kui , Lu Kailiang , Zhou Jianmei , Li Xiu , Meng Lifei 
Published: December 2021

Abstract
Transient electromagnetic (TEM) data are affected by resistivity anisotropy, which should be considered in 3D modelling. The influence of anisotropy on full-time response is the main focus of this research. For spatial discretisation of an anisotropic model, the mimetic finite volume approach was applied. The accuracy of the shift-and-invert (SAI) Krylov subspace approach and the two-step backward differentiation formula (BDF2) for modelling 3D full-time electromagnetic data has been demonstrated. However, both algorithms require time-consuming calculations. The SAI technique requires a number of projection subspace constructions, whereas the BDF2 algorithm necessitates numerous coefficient matrix decompositions. We proposed a novel mixed BDF2/SAI algorithm in this paper, which combines the advantages of the two algorithms. The on-time response is computed using BDF2, while the off-time response is computed using the SAI-Krylov subspace method. The forward results of a 1D model with a half-sine waveform demonstrated that the new algorithm is accurate and faster than both the BDF2 algorithm and the SAI algorithm. During the full-time period, the forward results of a 3D anisotropic model with half-sine waveform show that abnormal responses can be induced. It was shown that the relative abnormal of ${{{\bf b}}_{\boldsymbol{z}}}$ is higher during the on-time period, while the relative abnormal of $\partial {{{\bf b}}_{\boldsymbol{z}}}/\partial t$ is higher during the off-time period. Furthermore, the change in relative anomaly is more obvious as the anisotropic block rotates around the x-axis. And the larger the rotation angle, the larger the relative anomaly.
Multisource stress data constraints on Cretaceous—present regional tectonic stress field evolution in the southern Jinzhou area, North China Craton
Authors: Yang Chengwei , Wang Chenghu , Jiao Mingruo , Li Yujiang , Wang Pu 
Published: December 2021

Abstract
Regional tectonic stress fields are key crustal stress elements that drive tectonic movements and are associated with regional tectonics and geological resources. Regional tectonic stress field evolution of the Jinzhou area, located in the eastern block of the North China Craton (NCC), may provide a deeper understanding of tectonics of western Liaoning and the NCC. This work conducted borehole television, hydraulic fracturing and focal mechanism solutions to invert the paleo and present regional tectonic stress fields. Four groups of tensile fracture in the southern Jinzhou area were identified via borehole television, and their azimuths were NNW–SSE, NWW–SEE, nearly W–E and NE–SW in temporal order representing four stages of extensional tectonic events. Hydraulic fracturing and focal mechanism solutions showed that the stress status was normal fault and strike-slip, revealing that the southern Jinzhou area is undergoing NEE–SWW-oriented compression and nearly N–S-oriented extension in accordance with the strike-slip mechanism. From the Early Cretaceous to the present, the direction of the regional extensional stress in the southern Jinzhou area has evolved counterclockwise and sequentially from NNW–SSE to NWW–SEE, W–E, NE–SW and nearly N–S, and the regional tectonic mechanism has transited from extension to extension-strike-slip to strike-slip, leading to the current tectonic framework.
Laparoscopic treatment of an unruptured cystic artery pseudo-aneurysm in the presence of calculous emphysematous cholecystitis
Authors: Kelly Sarah , Shah Krisha , Motizada Jasneet , Soggiu Fiametta , Sheth Hemant 
Published: December 2021

Abstract
Cystic artery pseudoaneurysm is a rare complication of invasive biliary procedures or of acute or chronic cholecystitis and pancreatitis. Emphysematous cholecystitis is an acute inflammatory process of the gallbladder due to gas forming organisms such as Escherichia coli and Clostridium perfringens. We report the case of a 34-year-old gentleman admitted with a 3-day history of generalized abdominal pain, vomiting and markedly raised inflammatory markers. A computed tomography scan demonstrated acute calculus cholecystitis and an incidental CAP. This was successfully treated with an emergency laparoscopic cholecystectomy. CAPs are reported in the literature as rare and are usually diagnosed after rupture with severe haemorrhage. In this report, we highlight that a non-ruptured CAP identified preoperatively can be safely managed simultaneously with a laparoscopic approach, thus avoiding the need for invasive angiographic procedures or open surgery.