bluuebunny/crossref_metadata_2025 huggingface dataset:
Classification and Interpretation for 11 FBN1 Variants Responsible for Marfan Syndrome and Pre-implantation Genetic Testing (PGT) for Two Families Successfully Blocked Transmission of the Pathogenic Mutations
Authors: Chen Songchang , Fei Hongjun , Zhang Junyun , Chen Yiyao , Huang Hefeng , Lu Daru , Xu Chenming
Published: December 2021

Background: The lifespan of Marfan Syndrome (MFS) patients is shortened, especially in patients without early diagnostics, preventive treatment, and elective surgery. Clinically, MFS diagnosis is mainly dependent on phenotypes, but for children, sporadic cases, or suspicious MFS patients, molecular genetic testing, and mainly FBN1 mutation screening, plays a significant role in the diagnosis of MFS. PGT-M gives couples that had a family history of monogenic disorders the opportunity to avoid the occurrence of MFS.

Methods: In this study, 11 families with MFS were recruited and complete clinical features were collected. Variants were classified and interpreted through pedigree analysis according to guidelines. Two families chose to undergo PGT-M; 16 blastocysts were biopsied and amplified. Haplotype analysis was performed to deduce the embryo’s genotype by using single nucleotide polymorphisms (SNPs) identified in each sample.

Results: We identified 11 potential disease-causing FBN1 variants, six of which are novel. All variants were assessed with prediction tools to assess mutation pathogenicity, population databases to evaluate population allele frequency, literature databases to identify whether the variant had been reported in MFS patients, and multiple sequence alignment to carry out conservative analysis. Finally, nine variants were classified as likely pathogenic/pathogenic variants. Among 11 variants, eight variants were missense, and seven of them were located in the Ca-binding EGF-like motifs, moreover, half of them substituted conserved Cysteine residues. We also identified a splice site variant, a frameshift variant, and a synonymous variant. There are two variants that are de novo variants. PGT-M helped two MFS families give birth to a healthy baby not carrying the FBN1 mutation.

Conclusions: In the present study, the FBN1 mutation spectrum was enriched, and may help further elucidate the pathogenesis, benefiting clinical diagnosis and management of MFS. We make use of a reliable PGT-M method for the successful birth of healthy babies to two MFS families.
Interactive Associations of Neuropsychiatry Inventory-Questionnaire Assessed Sleep Disturbance and Vascular Risk on Alzheimer’s Disease Stage Progression in Clinically Normal Older Adults
Authors: Bubu Omonigho M. , Williams Ellita T. , Umasabor-Bubu Ogie Q. , Kaur Sonya S. , Turner Arlener D. , Blanc Judite , Cejudo Jaime Ramos , Mullins Anna E. , Parekh Ankit , Kam Korey , Osakwe Zainab T. , Nguyen Ann W. , Trammell Antoine R. , Mbah Alfred K. , de Leon Mony , Rapoport David M. , Ayappa Indu , Ogedegbe Gbenga , Jean-Louis Girardin , Masurkar Arjun V. , Varga Andrew W. , Osorio Ricardo S.
Published: December 2021

Background: To determine whether sleep disturbance (SD) and vascular-risk interact to promote Alzheimer’s disease (AD) stage-progression in normal, community-dwelling older adults and evaluate their combined risk beyond that of established AD biomarkers.

Methods: Longitudinal data from the National Alzheimer’s Coordinating Center Uniform-Dataset. SD data (i.e., SD+ vs. SD-), as characterized by the Neuropsychiatric Inventory-Questionnaire, were derived from 10,600 participants at baseline, with at-least one follow-up visit. A subset (n = 361) had baseline cerebrospinal fluid (CSF) biomarkers and MRI data. The Framingham heart study general cardiovascular disease (FHS-CVD) risk-score was used to quantify vascular risk. Amnestic mild cognitive impairment (aMCI) diagnosis during follow-up characterized AD stage-progression. Logistic mixed-effects models with random intercept and slope examined the interaction of SD and vascular risk on prospective aMCI diagnosis.

Results: Of the 10,600 participants, 1,017 (9.6%) reported SD and 6,572 (62%) were female. The overall mean (SD) age was 70.5 (6.5), and follow-up time was 5.1 (2.7) years. SD and the FHS-CVD risk-score were each associated with incident aMCI (aOR: 1.42 and aOR: 2.11, p < 0.01 for both). The interaction of SD and FHS-CVD risk-score with time was significant (aOR: 2.87, p < 0.01), suggesting a synergistic effect. SD and FHS-CVD risk-score estimates remained significantly associated with incident aMCI even after adjusting for CSF (Aβ, T-tau, P-tau) and hippocampal volume (n = 361) (aOR: 2.55, p < 0.01), and approximated risk-estimates of each biomarker in the sample where data was available.

Conclusions: Clinical measures of sleep and vascular risk may complement current AD biomarkers in assessing risk of cognitive decline in older adults.
Alteration of Behavioral Inhibitory Control in High-Altitude Immigrants
Authors: Wang Jiazheng , Zheng Liqin , Wang Zedong , Wu Xiao , Ma Ning , Zhang Tao , Chen Kai , Biswal Bharat B. , Yang Qun , Ma Hailin
Published: December 2021

Behavioral inhibitory control (BIC) acts as a key cognitive ability, which is essential for humans to withhold inappropriate behaviors. Meanwhile, many studies reported that long-term exposure to high altitude (HA) may affect cognitive ability. However, it is not clear whether long-term exposure to HAs may affect the BIC of an individual. To clarify the role of altitude in the behavioral control of adults and the underlying neural mechanism, we explored the BIC neural activity profiles of healthy immigrants from low-altitude (LA) regions to HA regions. Combining a two-choice oddball paradigm and electrophysiological techniques, this study monitored the N2 and P3 event-related components and neural oscillations across LA and HA groups. Results showed longer reaction times (RTs) for the HA group than the LA group. Relative to the LA group, lower N2 and P3 amplitudes were observed for the HA group. Significant positive correlations were also found between P3 amplitude and theta/delta band power across both groups. Importantly, lower theta/delta band powers were only observed for the HA group under the deviant condition. Collectively, these findings suggest that long-term exposure to HAs may attenuate BIC during the response inhibition stage and provide valuable insights into the neurocognitive implications of environmental altitude on BIC.
Chronic Anxiety- and Depression-Like Behaviors Are Associated With Glial-Driven Pathology Following Repeated Blast Induced Neurotrauma
Authors: Dickerson Michelle R. , Murphy Susan F. , Urban Michael J. , White Zakar , VandeVord Pamela J.
Published: December 2021

Long-term neuropsychiatric impairments have become a growing concern following blast-related traumatic brain injury (bTBI) in active military personnel and Veterans. Neuropsychiatric impairments such as anxiety and depression are common comorbidities that Veterans report months, even years following injury. To understand these chronic behavioral outcomes following blast injury, there is a need to study the link between anxiety, depression, and neuropathology. The hippocampus and motor cortex (MC) have been regions of interest when studying cognitive deficits following blast exposure, but clinical studies of mood disorders such as major depressive disorder (MDD) report that these two regions also play a role in the manifestation of anxiety and depression. With anxiety and depression being common long-term outcomes following bTBI, it is imperative to study how chronic pathological changes within the hippocampus and/or MC due to blast contribute to the development of these psychiatric impairments. In this study, we exposed male rats to a repeated blast overpressure (~17 psi) and evaluated the chronic behavioral and pathological effects on the hippocampus and MC. Results demonstrated that the repeated blast exposure led to depression-like behaviors 36 weeks following injury, and anxiety-like behaviors 2-, and 52-weeks following injury. These behaviors were also correlated with astrocyte pathology (glial-fibrillary acid protein, GFAP) and dendritic alterations (Microtubule-Associated Proteins, MAP2) within the hippocampus and MC regions at 52 weeks. Overall, these findings support the premise that chronic glial pathological changes within the brain contribute to neuropsychiatric impairments following blast exposure.
Sensorimotor Self-organization via Circular-Reactions
Authors: He Dongcheng , Ogmen Haluk
Published: December 2021

Newborns demonstrate innate abilities in coordinating their sensory and motor systems through reflexes. One notable characteristic is circular reactions consisting of self-generated motor actions that lead to correlated sensory and motor activities. This paper describes a model for goal-directed reaching based on circular reactions and exocentric reference-frames. The model is built using physiologically plausible visual processing modules and arm-control neural networks. The model incorporates map representations with ego- and exo-centric reference frames for sensory inputs, vector representations for motor systems, as well as local associative learning that result from arm explorations. The integration of these modules is simulated and tested in a three-dimensional spatial environment using Unity3D. The results show that, through self-generated activities, the model self-organizes to generate accurate arm movements that are tolerant with respect to various sources of noise.
Friend or Foe? The Varied Faces of Homeostatic Synaptic Plasticity in Neurodegenerative Disease
Authors: Taylor Henry B. C. , Jeans Alexander F.
Published: December 2021

Homeostatic synaptic plasticity (HSP) regulates synaptic strength both pre- and postsynaptically to ensure stability and efficient information transfer in neural networks. A number of neurological diseases have been associated with deficits in HSP, particularly diseases characterised by episodic network instability such as migraine and epilepsy. Recently, it has become apparent that HSP also plays a role in many neurodegenerative diseases. In this mini review, we present an overview of the evidence linking HSP to each of the major neurodegenerative diseases, finding that HSP changes in each disease appear to belong to one of three broad functional categories: (1) deficits in HSP at degenerating synapses that contribute to pathogenesis or progression; (2) HSP induced in a heterosynaptic or cell non-autonomous manner to support the function of networks of which the degenerating synapses or cells are part; and (3) induction of HSP within the degenerating population of synapses to preserve function and to resist the impact of synapse loss. Understanding the varied manifestations of HSP in neurodegeneration will not only aid understanding mechanisms of disease but could also inspire much-needed novel approaches to therapy.
Retinal Organoids Long-Term Functional Characterization Using Two-Photon Fluorescence Lifetime and Hyperspectral Microscopy
Authors: Xue Yuntian , Browne Andrew W. , Tang William C. , Delgado Jeffrey , McLelland Bryce T. , Nistor Gabriel , Chen Jacqueline T. , Chew Kaylee , Lee Nicolas , Keirstead Hans S. , Seiler Magdalene J.
Published: December 2021

Pluripotent stem cell-derived organoid technologies have opened avenues to preclinical basic science research, drug discovery, and transplantation therapy in organ systems. Stem cell-derived organoids follow a time course similar to species-specific organ gestation in vivo. However, heterogeneous tissue yields, and subjective tissue selection reduce the repeatability of organoid-based scientific experiments and clinical studies. To improve the quality control of organoids, we introduced a live imaging technique based on two-photon microscopy to non-invasively monitor and characterize retinal organoids’ (RtOgs’) long-term development. Fluorescence lifetime imaging microscopy (FLIM) was used to monitor the metabolic trajectory, and hyperspectral imaging was applied to characterize structural and molecular changes. We further validated the live imaging experimental results with endpoint biological tests, including quantitative polymerase chain reaction (qPCR), single-cell RNA sequencing, and immunohistochemistry. With FLIM results, we analyzed the free/bound nicotinamide adenine dinucleotide (f/b NADH) ratio of the imaged regions and found that there was a metabolic shift from glycolysis to oxidative phosphorylation. This shift occurred between the second and third months of differentiation. The total metabolic activity shifted slightly back toward glycolysis between the third and fourth months and stayed relatively stable between the fourth and sixth months. Consistency in organoid development among cell lines and production lots was examined. Molecular analysis showed that retinal progenitor genes were expressed in all groups between days 51 and 159. Photoreceptor gene expression emerged around the second month of differentiation, which corresponded to the shift in the f/b NADH ratio. RtOgs between 3 and 6 months of differentiation exhibited photoreceptor gene expression levels that were between the native human fetal and adult retina gene expression levels. The occurrence of cone opsin expression (OPN1 SW and OPN1 LW) indicated the maturation of photoreceptors in the fourth month of differentiation, which was consistent with the stabilized level of f/b NADH ratio starting from 4 months. Endpoint single-cell RNA and immunohistology data showed that the cellular compositions and lamination of RtOgs at different developmental stages followed those in vivo.
Multiple-Timescale Neural Networks: Generation of History-Dependent Sequences and Inference Through Autonomous Bifurcations
Authors: Kurikawa Tomoki , Kaneko Kunihiko
Published: December 2021

Sequential transitions between metastable states are ubiquitously observed in the neural system and underlying various cognitive functions such as perception and decision making. Although a number of studies with asymmetric Hebbian connectivity have investigated how such sequences are generated, the focused sequences are simple Markov ones. On the other hand, fine recurrent neural networks trained with supervised machine learning methods can generate complex non-Markov sequences, but these sequences are vulnerable against perturbations and such learning methods are biologically implausible. How stable and complex sequences are generated in the neural system still remains unclear. We have developed a neural network with fast and slow dynamics, which are inspired by the hierarchy of timescales on neural activities in the cortex. The slow dynamics store the history of inputs and outputs and affect the fast dynamics depending on the stored history. We show that the learning rule that requires only local information can form the network generating the complex and robust sequences in the fast dynamics. The slow dynamics work as bifurcation parameters for the fast one, wherein they stabilize the next pattern of the sequence before the current pattern is destabilized depending on the previous patterns. This co-existence period leads to the stable transition between the current and the next pattern in the non-Markov sequence. We further find that timescale balance is critical to the co-existence period. Our study provides a novel mechanism generating robust complex sequences with multiple timescales. Considering the multiple timescales are widely observed, the mechanism advances our understanding of temporal processing in the neural system.
Endovascular Treatment of Medial Tentorial Dural Arteriovenous Fistula Through the Dural Branch of the Pial Artery
Authors: Chu Chan-Lin , Chu Yu-Cheng , Lam Chee-Tat , Lee Tsong-Hai , Chien Shih-Chao , Yeh Chih-Hua , Wu Yi-Ming , Wong Ho-Fai
Published: December 2021

Background: Tentorial dural arteriovenous fistula is a rare subtype of intracranial dural arteriovenous fistula (DAVF) with a deteriorating natural course, which may be attributed to its pial angioarchitecture. TDAVF often harbors feeders arising from pial arteries (FPAs). Reports have revealed that, if these feeders are not obliterated early, the restricted venous outflow during the embolization process may cause upstream congestion in the fragile pial network, which increases the risk of hemorrhagic complications. Because most reported cases of TDAVF were embolized through feeders from non-pial arteries (FNPAs), little is known of the feasibility of direct embolization through FPAs.

Methods: We present three patients with medial TDAVFs that were embolized through the dural branches of the posterior cerebral and superior cerebellar arteries. Findings from brain magnetic resonance imaging, computed tomography, angiography, and clinical outcomes are described. Furthermore, we performed a review of the literature on TDAVFs with FPAs.

Results: The fistulas were completely obliterated in two patients; both recovered well with no procedure-related complications. The fistula was nearly obliterated in one patient, who developed left superior cerebellum and midbrain infarct due to the reflux of the embolizer into the left superior cerebellar artery. Including our cases, eight cases of TDAVFs with direct embolization through the FPAs have been reported, and ischemic complications occurred in three (37.5%).

Conclusions: Advancing microcatheter tips as close to the fistula point as possible and remaining highly aware of potential embolizer flow back into the pial artery are key factors in achieving successful embolization. Balloon-assisted embolization may be an option for treating TDAVFs with FPAs in the future.
White Matter Hyperintensities as a Risk Factor for Ischemic Stroke in Patients With Systemic Lupus Erythematosus
Authors: Sano Eri , Arawaka Shigeki
Published: December 2021

Objective: The occurrence of ischemic stroke in patients with systemic lupus erythematosus (SLE) can cause extended periods of reduced daily activities. However, the risk factors for ischemic stroke in SLE patients are not fully elucidated. Herein, we examined the effect of white matter hyperintensities (WMH) on the occurrence of ischemic stroke in SLE patients.

Methods: We analyzed the relationship between WMH burden and ischemic stroke using follow-up brain magnetic resonance imaging (MRI) data of 79 patients with SLE. Of these patients, 16 developed stroke during the observation period. WMH on MRI were classified into periventricular hyperintensities and deep white matter hyperintensities (DWMH), while the lesion extent was graded using the Fazekas scale.

Results: Kaplan–Meier curves showed that ischemic stroke events were significantly associated with age at initial brain MRI of ≥40 years (p = 0.015) and history of anti-phospholipid syndrome (p = 0.030). Additionally, ischemic stroke events were significantly associated with a one grade deterioration of periventricular hyperintensities (p = 0.003) and a one grade deterioration of DWMH (p = 0.002). Multivariate analysis using the logistic regression model showed that a one grade deterioration of DWMH was an independent risk factor for ischemic stroke (hazard ratio, 6.0; 95% confidence interval, 1.3–27.4).

Conclusions: Although several factors affect the occurrence of ischemic stroke, SLE patients show increased risk of ischemic stroke via development of DWMH. An observation of DWMH deterioration on follow-up brain MRI may be useful for assessing the risk of ischemic stroke in SLE patients.
Listening in the Moment: How Bilingualism Interacts With Task Demands to Shape Active Listening
Authors: Krizman Jennifer , Tierney Adam , Nicol Trent , Kraus Nina
Published: December 2021

While there is evidence for bilingual enhancements of inhibitory control and auditory processing, two processes that are fundamental to daily communication, it is not known how bilinguals utilize these cognitive and sensory enhancements during real-world listening. To test our hypothesis that bilinguals engage their enhanced cognitive and sensory processing in real-world listening situations, bilinguals and monolinguals performed a selective attention task involving competing talkers, a common demand of everyday listening, and then later passively listened to the same competing sentences. During the active and passive listening periods, evoked responses to the competing talkers were collected to understand how online auditory processing facilitates active listening and if this processing differs between bilinguals and monolinguals. Additionally, participants were tested on a separate measure of inhibitory control to see if inhibitory control abilities related with performance on the selective attention task. We found that although monolinguals and bilinguals performed similarly on the selective attention task, the groups differed in the neural and cognitive processes engaged to perform this task, compared to when they were passively listening to the talkers. Specifically, during active listening monolinguals had enhanced cortical phase consistency while bilinguals demonstrated enhanced subcortical phase consistency in the response to the pitch contours of the sentences, particularly during passive listening. Moreover, bilinguals’ performance on the inhibitory control test related with performance on the selective attention test, a relationship that was not seen for monolinguals. These results are consistent with the hypothesis that bilinguals utilize inhibitory control and enhanced subcortical auditory processing in everyday listening situations to engage with sound in ways that are different than monolinguals.
Automated Segmentation of Trigeminal Nerve and Cerebrovasculature in MR-Angiography Images by Deep Learning
Authors: Lin Jinghui , Mou Lei , Yan Qifeng , Ma Shaodong , Yue Xingyu , Zhou Shengjun , Lin Zhiqing , Zhang Jiong , Liu Jiang , Zhao Yitian
Published: December 2021

Trigeminal neuralgia caused by paroxysmal and severe pain in the distribution of the trigeminal nerve is a rare chronic pain disorder. It is generally accepted that compression of the trigeminal root entry zone by vascular structures is the major cause of primary trigeminal neuralgia, and vascular decompression is the prior choice in neurosurgical treatment. Therefore, accurate preoperative modeling/segmentation/visualization of trigeminal nerve and its surrounding cerebrovascular is important to surgical planning. In this paper, we propose an automated method to segment trigeminal nerve and its surrounding cerebrovascular in the root entry zone, and to further reconstruct and visual these anatomical structures in three-dimensional (3D) Magnetic Resonance Angiography (MRA). The proposed method contains a two-stage neural network. Firstly, a preliminary confidence map of different anatomical structures is produced by a coarse segmentation stage. Secondly, a refinement segmentation stage is proposed to refine and optimize the coarse segmentation map. To model the spatial and morphological relationship between trigeminal nerve and cerebrovascular structures, the proposed network detects the trigeminal nerve, cerebrovasculature, and brainstem simultaneously. The method has been evaluated on a dataset including 50 MRA volumes, and the experimental results show the state-of-the-art performance of the proposed method with an average Dice similarity coefficient, Hausdorff distance, and average surface distance error of 0.8645, 0.2414, and 0.4296 on multi-tissue segmentation, respectively.
Clinical and Prognostic Significance of Tumor-Infiltrating CD8+ T Cells and PD-L1 Expression in Primary Gastrointestinal Stromal Tumors
Authors: Sun Xiangfei , Shu Ping , Fang Yong , Yuan Wei , Zhang Qiang , Sun Jianyi , Fu Min , Xue Anwei , Gao Xiaodong , Shen Kuntang , Hou Yingyong , Sun Yihong , Qin Jing , Qin Xinyu
Published: December 2021

Purpose

Immunotherapy for gastrointestinal stromal tumors (GISTs) remains a clinical challenge. The present study aimed to explore the clinical and prognostic significance of immune cell infiltration and PD-L1 expression in GISTs.

Methods

A total of 507 clinical tissue specimens of primary GISTs were collected for immunohistochemical analysis of immune cell infiltration and PD-L1 expression. Influencing factors of survival were evaluated by Kaplan–Meier analysis. Univariate and multivariate analyses were performed using the Cox regression model.

Results

There were significant differences in sex, tumor location, size, mitotic index, NIH risk grade, and cell morphology between different gene mutation types of GISTs. Immune cell infiltration in GISTs mainly involved macrophages and T cells. PD-1 was expressed in 48.5% of the tissue specimens, and PD-L1 expression was detected in 46.0% of the samples. PD-L1 expression was negatively correlated with the tumor size and mitotic index but positively correlated with the number of CD8+ T cells. There were significant differences in the number of CD8+ T cells between different gene mutation types. Wild type-mutant GISTs were enriched with CD8+ T cells as compared with KIT- and PDGFRA-mutant GISTs. The number of CD8+ T cells was higher in non-gastric GISTs. PD-L1 and CD8+ T cells were independent predictors for better relapse-free survival of GISTs.

Conclusions

PD-L1 expression is a predictive biomarker for better prognosis of GISTs. Non-gastric GIST patients with wild-type mutations may be the beneficiaries of PD-1/PD-L1 inhibitors.
Changes in Eating Habits and Sedentary Behavior During the COVID-19 Pandemic in Adolescents With Chronic Conditions
Authors: Mazzolani Bruna Caruso , Smaira Fabiana Infante , Astley Camilla , Iraha Amanda Yuri , Pinto Ana Jessica , Marques Isabela Gouveia , Cordeiro Amarante Milla , Rezende Nathalia Saffioti , Sieczkowska Sofia Mendes , Franco Tathiane Christine , Miranda Luana Cristina do Amaral , Lindoso Lívia , Helito Alberto Carame , Oba Jane , Queiroz Ligia Bruni , Pereira Rosa Maria R. , Roschel Hamilton , Silva Clovis Artur , Gualano Bruno
Published: December 2021

Introduction: Among healthy adolescents, school closures and home confinement were shown to increase unhealthier eating habits and sedentary behavior. It remains unknown to which extent the pandemic has impacted the lifestyle of adolescents with chronic conditions. Thus, the aim of this study is to report on the impact of the COVID-19 outbreak on eating habits and sedentary behavior among adolescents with multiple chronic conditions (n = 347) from a tertiary, referral hospital vs. healthy peers.

Methods: This observational study was conducted in São Paulo (Brazil) between July and October 2020, period in which a set of social distancing measures to contain the pandemic.

Results: The main findings of this study were that adolescents with chronic conditions and health peers showed important changes in eating habits (e.g., more often cooking and eating in front of television than before quarantine). Also, 86.8% of adolescents with chronic conditions and 91.6% of healthy adolescents reported increasing screen time during pandemic. No major differences were observed between patients and controls.

Conclusions: Adolescents with chronic conditions and healthy peers exposed to pandemic showed substantial changes in lifestyle, stressing the need for specific care to mitigate poor eating habits and excessive sedentary behavior for patients and healthy adolescents.
An Overview of Vascular Dysfunction and Determinants: The Case of Children of African Ancestry
Authors: Matjuda Edna N. , Engwa Godwill Azeh , Sewani-Rusike Constance R. , Nkeh-Chungag Benedicta N.
Published: December 2021

The balance between dilatory and constrictive factors is important as it keeps blood vessels in a homeostatic state. However, altered physiological processes as a result of obesity, hypertension, oxidative stress, and other cardiovascular risk factors may lead to vascular damage, causing an imbalance of vasoactive factors. Over time, the sustained imbalance of these vasoactive factors may lead to vascular dysfunction, which can be assessed by non-invasive methods, such as flow-mediated dilation, pulse wave velocity, flow-mediated slowing, retinal vessel analysis, peripheral vascular reactivity, and carotid intima-media thickness assessment. Although there is increasing prevalence of cardiovascular risk factors (obesity and hypertension) in children in sub-Saharan Africa, little is known about how this may affect vascular function. This review focuses on vasoactive factors implicated in vascular (dys)function, highlighting the determinants and consequences of vascular dysfunction. It further describes the non-invasive methods used for vascular (dys)function assessments and, last, describes the impact of cardiovascular risk factors on vascular dysfunction in children of African ancestry.
Efficacy of Ceftazidime-Avibactam Versus Polymyxin B and Risk Factors Affecting Clinical Outcomes in Patients With Carbapenem-Resistant Klebsiella pneumoniae Infections a Retrospective Study
Authors: Fang Jie , Li Hui , Zhang Min , Shi Guochao , Liu Mengying , Wang Yujie , Bian Xiaolan
Published: December 2021

Background: The worldwide outbreak of carbapenem-resistant Klebsiella pneumoniae (CRKP) has become an urgent public health problem. High mortality and lack of effective treatments further pose new challenges to control this infection. However, studies about the evaluation of available antibiotics for CRKP infection are limited. The present study aimed to compare the efficacy of polymyxin B versus ceftazidime-avibactam (CAZ/AVI) in Chinese patients with CRKP infections and to identify risk factors affecting 7-day bacterial eradication and 28-day all-cause mortality.

Methods: From January 8, 2018, to July 6, 2020, a total of 115 adult CRKP infected patients from two tertiary teaching hospitals in Shanghai, China were enrolled based on the inclusion and exclusion criteria. By reviewing electronic medical records of these patients, demographic and clinical data were extracted. The selected patients were divided into polymyxin B and CAZ/AVI groups according to primary antibiotic exposure to compare therapeutic effects. Binary logistic and cox’s regression analysis were performed to identify risk factors for 7-day bacterial eradication and all-cause mortality.

Results: One hundred and five patients were treated with polymyxin B (67.8%) or CAZ/AVI (32.2%). Patients in the CAZ/AVI group had significantly lower rates of 28-day mortality (8.1 vs 29.5%, p = 0.013), higher microbiological eradication and 28-day clinical success. Multivariate analysis showed that Charlson comorbidity index (≥3) and prior antibiotic use within 90 days were independent risk factors for poor microbiological eradication. Cox’s regression analysis indicated that the length of hospitalization after CRKP infection and baseline creatinine clearance negatively affected 28-day mortality.

Conclusion: CAZ/AVI was more effective than polymyxin B and appeared to be a promising drug for CRKP infection, especially for critically ill patients.
Investigation Into Magnetic Reconnection Formation on Propellant Ignition in Electrical Explosion
Authors: Zhang Jiangbo , Liu Wei , Xiao Fei , Liang Taixin , Zhao Shusen
Published: December 2021

In magnetic reconnection, magnetic lines break and reconnect to change their topology to a lower-energy state. This process can liberate stored magnetic field energy and accelerate particles during unsteady explosive events. Here, we report the observations of the magnetic reconnection and kink instability of plasma jet in single wire electrical explosion and their effect on propellant ignition. The results showed that the initial velocity of plasma was ∼2,000 m/s, and when the magnetic reconnection occurred, the velocity increased by ∼400–∼2,400 m/s. The evaluated Alfvén velocity was ∼500 m/s, the Alfvén time was ∼20 µs, and the Lundquist number S = 1.7 × 107. Based on these experimental results and model, the three-dimensional magnetic field topology and its evolution process was evaluated and presented. Furthermore, the magnetic reconnection occurred when its curvature reached a certain value due to the fact that the motion of the current sheet changes the topology of the magnetic field, and then, the plasma jet was accelerated and exhausted. The plasma jet angle was ∼50° in experiment 1, and it was consistent with the calculated results. The resulting magnetic reconnection plays an important role in propellant ignition, which enhances the ignition ability of wire electrical explosion. Furthermore, the results represent a key step towards resolving one of the most important problems of plasma physics and can be used to improve the understanding of wire array explosion and propellant ignition.
Global Mean Sea Level. Time Trends and Persistence with Long Range Dependent Data
Authors: Gil-Alana Luis Alberiko
Published: December 2021

Global mean sea level data are examined in this work by looking at the presence of time trends in the context of long memory or long range dependent processes. By looking at both seasonal signals retained and seasonal signals removed data from 1992 to 2020, the results show that the two series display significant time trend coefficients and high levels of persistence.
Reliability of Peak Running Velocity Obtained on the Track Field in Runners of Different Performance Levels
Authors: Manoel Francisco de Assis , Peserico Cecília Segabinazi , Machado Fabiana Andrade
Published: December 2021

The aim of this study was to verify the reliability of peak running velocity obtained on the track field (Vpeak_TF) in runners of different performance levels. 39 male endurance runners were divided into two groups: trained runners (TR; n = 22; 10-km time running performance of 35.2 ± 1.7 min), and recreational runners (RR; n = 17; 10-km time running performance of 51.3 ± 4.8 min). They performed three maximal incremental running tests on the official track field (400 m), with an interval of 1 week between trials to determine the reliability of Vpeak_T. The Vpeak_TF showed high reliability, presenting an intraclass correlation coefficient and coefficient of variation of 0.97 and 1.28%, and 0.90 and 1.24% for TR and RR, respectively. Both TR and RR showed lowest bias and limits of agreement between test and retest (Vpeak_TF1 and Vpeak_TF2). In addition, there was no statistical test-retest difference for Vpeak_TF. In addition, the HR and RPE submaximal values were reliable for both TR and RR. Therefore, the Vpeak_TF showed high reliability in both TR and RR. These findings reinforce that the protocol for determining Vpeak_TF, using increments of 1 km h–1 every 3 min is reliable regardless of the performance level of the runners.
Changes of Morphology, Chemical Compositions, and the Biosynthesis Regulations of Cuticle in Response to Chilling Injury of Banana Fruit During Storage
Authors: Huang Hua , Wang Ling , Qiu Diyang , Zhang Nan , Bi Fangcheng
Published: December 2021

The plant cuticle covers almost all the outermost surface of aerial plant organs, which play a primary function in limiting water loss and responding to the environmental interactions. Banana fruit is susceptible to thermal changes with chilling injury below 13°C and green ripening over 25°C. Herein, the changes of surface morphology, chemical compositions of cuticle, and the relative expression of cuticle biosynthesis genes in banana fruit under low-temperature storage were investigated. Banana fruit exhibited chilling injury rapidly with browned peel appearance stored at 4°C for 6 days. The surface altered apparently from the clear plateau with micro-crystals to smooth appearance. As compared to normal ones, the overall coverage of the main cuticle pattern of waxes and cutin monomers increased about 22% and 35%, respectively, in browned banana stored under low temperature at 6 days. Fatty acids (C16–C18) and ω-OH, mid-chain-epoxy fatty acids (C18) dominated cutin monomers. The monomers of fatty acids, the low abundant ω, mid-chain-diOH fatty acids, and 2-hydroxy fatty acids increased remarkably under low temperature. The cuticular waxes were dominated by fatty acids (> C19), n-alkanes, and triterpenoids; and the fatty acids and aldehydes were shifted to increase accompanied by the chilling injury. Furthermore, RNA-seq highlighted 111 cuticle-related genes involved in fatty acid elongation, biosynthesis of very-long-chain (VLC) aliphatics, triterpenoids, and cutin monomers, and lipid-transfer proteins were significantly differentially regulated by low temperature in banana. Results obtained indicate that the cuticle covering on the fruit surface was also involved to respond to the chilling injury of banana fruit after harvest. These findings provide useful insights to link the cuticle on the basis of morphology, chemical composition changes, and their biosynthesis regulations in response to the thermal stress of fruit during storage.
Face Masks Bolsters the Characteristics From Looking at a Face Even When Facial Expressions Are Impaired
Authors: Lau Wee Kiat
Published: December 2021

Face masks impact social interactions because emotion recognition is difficult due to face occlusion. However, is this enough to conclude that face masks negatively impact social interactions? We investigated the impact of face masks on invariant characteristics (sex, age), trait-like characteristics (trustworthiness, attractiveness, and approachability), and emotional expressions (happiness and excitability). Participants completed an online survey and rated masked and no-masked faces. The same face remained masked or no-masked throughout the survey. Results revealed that, when compared to no-masked faces, masked happy faces appeared less happy. Face masks did not negatively impact the ratings of other characteristics. Participants were better at judging the sex of masked faces. Masked faces also appeared younger, more trustworthy, more attractive, and more approachable. Therefore, face masks did not always result in unfavorable ratings. An additional post hoc modeling revealed that trustworthiness and attractiveness ratings for masked faces predicted the same trait ratings for no-masked faces. However, approachability ratings for no-masked faces predicted the same trait ratings for masked faces. This hinted that information from masked/no-masked faces, such as from the eye and eye region, could aid in the understanding of others during social interaction. Future directions were proposed to expand the research.
A Phenomenological Study on the Positive and Negative Experiences of Chinese International University Students From Hong Kong Studying in the U.K. and U.S. in the Early Stage of the COVID-19 Pandemic
Authors: Lai Agnes Yuen-kwan , Sit Shirley Man-man , Lam Stanley Kam-ki , Choi Asa Ching-man , Yiu Denise Yee-shan , Lai Theresa Tze-kwan , Ip Mary Sau-man , Lam Tai-hing
Published: December 2021

Background: The COVID-19 pandemic has caused distress in students globally. The mental health of international students studying abroad has been neglected during the COVID-19 pandemic, especially Chinese students who have been unfairly targeted.

Objective: To explore and document the positive and negative experiences of a group of Hong Kong Chinese international students studying in the U.K. and U.S. from an insider perspective in the early stage of the COVID-19 pandemic.

Methods: The qualitative study used four 1.5-h online focus group interviews of 20 Chinese international students from Hong Kong aged 18 or older studying in universities in the United Kingdom or the United States, from 3 May to 12 May 2020. A framework approach with a semi-structured interview guide was used to reflect students' stressors, cognitive appraisals, coping, and outcomes (negative impacts and positive gains), in the early stages of COVID-19. Different strategies were used to ensure the credibility, dependability, confirmability, and transferability of the study. Transcripts were analyzed using qualitative thematic content analysis.

Results: Twenty full-time international University students (60% female, 90% aged 18–25 years and 65% undergraduates) were recruited. Students reported (i) stress from personal (e.g., worries about health and academic attainment), interpersonal (e.g., perceived prejudice and lack of social support), and environmental factors (e.g., uncertainties about academic programme and unclear COVID-19-related information); (ii) significant differences in culture and cognitive appraisal in the levels of perceived susceptibility and severity; (iii) positive thinking and using alternative measures in meeting challenges, which included effective emotion and problem coping strategies, and the importance of support from family, friends and schools; and (iv) negative psychological impact (e.g., worries and stress) and positive personal growth in crisis management and gains in family relationships.

Conclusions: With the rise in sinophobia and uncertain developments of the pandemic, proactive support from government and academic institutions are urgently needed to reduce stress and promote the well-being of international students, especially Chinese students in the U.K. and U.S. Clear information, public education and policies related to the pandemic, appropriate academic arrangements from universities and strong support systems play important roles in maintaining students' psychological health.

Clinical Trial Registration: The study was registered with the National Institutes of Health (https://clinicaltrials.gov/, identifier: NCT04365361).
Lifestyle Behaviors and Quality of Life Among Older Adults After the First Wave of the COVID-19 Pandemic in Hubei China
Authors: Duan Yanping , Peiris D. L. I. H. K. , Yang Min , Liang Wei , Baker Julien Steven , Hu Chun , Shang Borui
Published: December 2021

Background: Older adult quality of life (QoL) is facing huge challenges during the COVID-19 pandemic. New normal lifestyle behaviors, including getting adequate physical activity (PA), consuming sufficient fruits and vegetables (FV) and enacting individual preventive behaviors (frequent hand washing, facemask wearing, and social distancing), as a significant determinant for QoL, have not been adequately addressed in older adults during the pandemic. This study aimed to investigate the characteristics of QoL in Chinese older adults after the first wave of the COVID-19 pandemic in Hubei China. The objective of the study was to examine any associations of lifestyle behaviors with QoL, and to identify the moderating role of socioeconomic indicators in the associations identified.

Methods: A cross-sectional study was conducted in Hubei, China, from June 15, 2020, to July 10, 2020. Five hundred sixteen older adults completed an online survey (mean age = 67.6 ± 6.6; 57.9% women). The questionnaire consisted of demographic information, covariates (chronic diseases and infected cases of acquaintances), lifestyle behaviors [PA stage, FV intake (FVI) stage and three preventive behaviors], and QoL. T-tests, ANOVA tests, multiple linear regression models with simple slope analyses were used to test the hypotheses.

Results: QoL significantly differed in relation to economic situation, chronic diseases, marital status, education, living situation, age group, and professional status. Participants' economic situation (βaverage vs. below average = 0.17, p < 0.01; βabove average vs. below average = 0.15, p < 0.01), chronic diseases (βyes vs. no = 0.19, p < 0.001), FVI stage (β = 0.21, p < 0.001), and preventive behaviors (β = 0.10, p < 0.05) indicated a significant association with QoL. Education level and economic situation significantly interacted with preventive behaviors on QoL, respectively (βpreventive behaviors × educational level = −1.3, p < 0.01; βpreventive behaviors × economic situation = −0.97, p < 0.05).

Conclusions: Findings emphasize the importance of enhancing FVI and preventive behaviors on QoL improvement in older adults during the COVID-19 pandemic. Older adults who are in a lower economic situation with lower education levels should be given priority when implementing interventions to improve preventive behaviors and QoL in older adults.
Regional Differences in Hospital Costs of Acute Ischemic Stroke in China: Analysis of Data From the Chinese Acute Ischemic Stroke Treatment Outcome Registry
Authors: Lu Yuxuan , Sun Weiping , Shen Zhiyuan , Sun Wei , Liu Ran , Li Fan , Shu Junlong , Tai Liwen , Li Guozhong , Chen Huisheng , Zhang Guiru , Zhang Lei , Sun Xuwen , Qiu Jinhua , Wei Yan , Jin Haiqiang , Huang Yining
Published: December 2021

Background and Purpose: Studies on the regional differences in hospital costs of acute ischemic stroke (AIS) are scarce in China. We aimed to explore the regional differences in hospital costs and identify the determinants of hospital costs in each region.

Methods: Data were collected from the Chinese Acute Ischemic Stroke Treatment Outcome Registry (CASTOR), a multicenter prospective study on patients diagnosed with AIS and hospitalized from 2015 to 2017. Univariate and multivariate analyses were undertaken to identify the determinants of hospital costs of AIS.

Results: A total of 8,547 patients were included in the study, of whom 3,700 were from the eastern area, 2,534 were from the northeastern area, 1,819 were from the central area, and 494 were from the western area. The median hospital costs presented a significant difference among each region, which were 2175.9, 2175.1, 2477.7, and 2282.4 dollars in each area, respectively. Each region showed a similar hospital cost proportion size order of cost components, which was Western medicine costs, other costs, diagnostic costs, and traditional medicine costs, in descending order. Male sex, diabetes mellitus, severe stroke symptoms, longer length of stay, admission to the intensive care unit, in-hospital complications of hemorrhage, and thrombectomy were independently associated with hospital costs in most regions.

Conclusion: Hospital costs in different regions showed a similar proportion size order of components in China. Each region had different determinants of hospital costs, which reflected its current medical conditions and provided potential determinants for increasing medical efficiency according to each region's situation.
Rate of Social Isolation by Geographic Location Among Older Adults: AAA LongROAD Study
Authors: Lynch Laura , Mielenz Thelma J. , Li Guohua , Eby David W. , Molnar Lisa J. , Betz Marian E. , DiGuiseppi Carolyn , Hill Linda L. , Jones Vanya , Strogatz David
Published: December 2021

Introduction: Social isolation is a modifiable risk factor for negative health outcomes among older adults. This work assessed the relationship between geography (i.e., urban vs. non-urban residence) and social isolation in a cohort of older drivers.

Methods: The AAA LongROAD cohort with 2,989 older adult drivers from across the country were included. Social isolation was measured at baseline and at two subsequent annual follow-ups using PROMIS v2.0 Social Isolation 4a. The effect of geographic location with social isolation was assessed through with multivariable regression using a generalized estimating equation model.

Results: The rate of social isolation in urban areas was 21% lower (adjusted RR 0.79, 95% CI 0.46, 1.36) compared to non-urban areas after adjusting for covariates, though not significant.

Discussion: Social isolation is a predictor of poor health outcomes and geographic considerations have been lacking in the literature. The panel data in this analysis provides more evidence for causality though the under-representation of non-urban areas potentially reduces the power for the results.

Conclusions: It is important to understand the needs and risk of social isolation in various geographic settings to ensure resources and interventions are appropriately modified for a greater public health impact.