bluuebunny/crossref_metadata_2025 huggingface dataset:
Shear Motion Characteristics Analysis of Electrorheological Fluids Between Flat Disk and Corrugated Disk
Authors: Li Chunyu , Chen Bingsan , Huang Yijian
Published: March 2022

In order to improve the transmission torque caused by the electrorheological effect, a corrugated disk is proposed to replace traditional flat disk by changing the electrode surface shape. The new mechanism puts the device in a shear-squeeze mode of operation. Based on the constitutive equation of electrorheological fluids, the shear motion characteristics of the ER fluids between the flat disk and the corrugated disk are analyzed, including the pressure distribution, torque equations, and the comparison with double-flat-disk mechanism. The analysis shows that compared with the double-flat-disk structure, the flat-disk-corrugated-disk structure can enhance the transmitted torque over 2.6 times under the same operating parameters. The magnification of the torque is not related with the curve number of the corrugated disc, but mainly depends on the structural parameters of the device and corrugations, and the characteristic parameters of electrorheological fluid. It is proved that the mechanism can provide new ideas and new methods for the engineering application of electrorheological transmission technology.
Association of Fluid Management With Mortality of Sepsis Patients With Congestive Heart Failure: A Retrospective Cohort Study
Authors: Dong Ning , Gao Nan , Hu Wenxin , Mu Yuhang , Pang Li
Published: March 2022

Sepsis management includes intravenous fluid (IVF) resuscitation, but patients with pre-existing congestive heart failure (CHF) have a higher risk of fluid overload. Further, patients with sepsis with concomitant CHF present worse clinical outcomes. Nevertheless, there is limited evidence of the association between fluid management and the outcomes of patients with concomitant sepsis and CHF. This retrospective cohort study aimed to evaluate the association between fluid management and in-hospital mortality in patients with sepsis and concomitant heart failure (HF). The patients' data were extracted from the Multi-parameter Intelligent Monitoring in Intensive Care III Database. The primary outcome was in-hospital mortality. A restricted cubic spline model was used to explore the relationship between variables and in-hospital mortality. Logistic models were built using the linear spline function and design variables to investigate the association of fluid balance (FB), fluid intake (FI), and fluid accumulation index (FAI, calculated as the FB/FI ratio) with mortality. Overall, 1,801 patients were included. The overall mortality rate was 27.7%. After adjusting for confounding variables, FAI was found to be associated with in-hospital mortality, whereas FB and FI were not. With FAI values of 0–0.42 set as references, FAI values <0 were not associated with in-hospital mortality [odds ratio (OR): 1.078; 95% confidence interval (CI): 0.774–1.503], whereas FAI values > 0.42 were significantly associated with higher in-hospital mortality (OR: 1.461; 95% CI: 1.099–1.954). High FAI values (>0.42) were associated with high in-hospital mortality in patients with sepsis with HF, while FB and FI were not. Proper fluid management may improve the outcomes of patients with sepsis and concomitant HF.
The Spring Festival Is Associated With Increased Mortality Risk in China: A Study Based on 285 Chinese Locations
Authors: He Guanhao , Cai Min , Meng Ruilin , Hu Jianxiong , Peng Ke , Hou Zhulin , Zhou Chunliang , Xu Xiaojun , Xiao Yize , Yu Min , Huang Biao , Lin Lifeng , Liu Tao , Xiao Jianpeng , Gong Weiwei , Hu Ruying , Li Junhua , Jin Donghui , Qin Mingfang , Zhao Qinglong , Xu Yiqing , Zeng Weilin , Li Xing , Huang Cunrui , Si Lei , Yang Xingfen , Ma Wenjun
Published: March 2022

Background

The Spring Festival is one of the most important traditional festivals in China. This study aimed to estimate the mortality risk attributable to the Spring Festival.

Methods

Between 2013 and 2017, daily meteorological, air pollution, and mortality data were collected from 285 locations in China. The Spring Festival was divided into three periods: pre-Spring Festival (16 days before Lunar New Year's Eve), mid-Spring Festival (16 days from Lunar New Year's Eve to Lantern Festival), and post-Spring Festival (16 days after Lantern Festival). The mortality risk attributed to the Spring Festival in each location was first evaluated using a distributed lag nonlinear model (DLNM), and then it was pooled using a meta-analysis model.

Results

We observed a dip/rise mortality pattern during the Spring Festival. Pre-Spring Festival was significantly associated with decreased mortality risk (ER: −1.58%, 95%CI: −3.09% to −0.05%), and mid-Spring Festival was unrelated to mortality risks, while post-Spring Festival was significantly associated with increased mortality risk (ER: 3.63%, 95%CI: 2.15–5.12%). Overall, a 48-day Spring Festival period was associated with a 2.11% (95%CI: 0.91–3.33%) increased mortality. We also found that the elderly aged over 64 years old, women, people with cardiovascular disease (CVD), and people living in urban areas were more vulnerable to the Spring Festival.

Conclusion

Our study found that the Spring Festival significantly increased the mortality risk in China. These findings suggest that it is necessary to develop clinical and public health policies to alleviate the mortality burden associated with the Spring Festival.
Changes of Dry Eye Parameters Especially Meibomian Gland Functions After Punctal Plugs Insertion in Aqueous-Deficient Dry Eye Patients
Authors: Liu Tingting , Liu Shulin , Gan Meiqi , He Yuqin , Fu Hongxue , Xu Mei
Published: March 2022

Background

The study aimed at investigating the changes of dry eye parameters, especially the meibomian gland function in dry eye patients with primary Sjögren's syndrome (SS) and non-Sjögren's syndrome (non-SS) before and after punctal plugs insertion.

Material and Methods

The SS and non-SS dry eye patients that received punctal plugs insertion were prospectively investigated. This study recruited fifty patients. The standardized patient evaluation of eye dryness (SPEED), ocular surface disease index (OSDI), tear meniscus height (TMH), non-invasive Keratographic breakup time (NIKBUT), Schirmer test without anesthesia (Schirmer I Test, SI T), corneal fluorescein staining (CFS), the meibomian gland dropout (meiboscore), meibum expressibility score (MES), meibum quality score (MQS), lid margin abnormalities and the lipid layer thickness (LLT) were analyzed at pre-obstruction, 2 weeks, 2 months and 6 months following the obstruction.

Results

Our study observed a statistically significant improvement in ocular symptom scores (SPEED and OSDI scores) after punctal plugs insertion at every visit in both SS and non-SS patients (all p < 0.05). A similar pattern was observed in TMH, SI T, NIKBUT and CFS score in both groups (all p < 0.05), except that NIKBUT and CFS score had no obvious change in SS group at 6 months (P > 0.05). In terms of the meibomian gland evaluation, meiboscore did not change significantly, MES decreased at 2 and 6 months and MQS decreased only at 2 months in both groups. The lid margin abnormalities of the non-SS group were significantly improved at 2 and 6 months, while that of the SS group had changes only at 2 months. Interestingly, LLT in non-SS group continued to rise, reaching a higher level at 2 months (p < 0.05), while LLT in SS group increased only at 2 months (p < 0.05). Meanwhile, after the puntcal plugs insertion, non-SS group showed better outcomes concerning some parameters, such as lower ocular symptom scores, higher TMH and significantly greater LLT, compared with that in SS group (all p < 0.05).

Conclusions

Our study revealed that dry eye symptoms and signs, including meibomian gland function, improved for at least 6 months in non-SS dry eye patients as well as in SS dry eye patients after punctal plugs insertion.
Chitosan Treatment Promotes Wound Healing of Apple by Eliciting Phenylpropanoid Pathway and Enzymatic Browning of Wounds
Authors: Ackah Sabina , Xue Sulin , Osei Richard , Kweku-Amagloh Francis , Zong Yuanyuan , Prusky Dov , Bi Yang
Published: March 2022

Chitosan is an elicitor that induces resistance in fruits against postharvest diseases, but there is little knowledge about the wound healing ability of chitosan on apple fruits. Our study aimed at revealing the effect of chitosan on the phenylpropanoid pathway by determining some enzyme activities, products metabolites, polyphenol oxidase activity, color (L*, b*, a*), weight loss, and disease index during healing. Apple (cv. Fuji) fruits wounded artificially were treated with 2.5% chitosan and healed at 21–25°C, relative humidity = 81–85% for 7 days, and non-wounded fruits (coated and non-coated) were used as control. The result shows that chitosan treatment significantly decreased weight loss of wounded fruits and disease index of Penicillium expansum inoculated fruits. The activities of phenylalanine ammonia-lyase (PAL), cinnamic acid 4-hydroxylase (C4H), 4-coumaryl coenzyme A ligase (4CL), cinnamoyl-CoA reductase (CCR), and cinnamyl alcohol dehydrogenase (CAD) were elicited throughout the healing period by chitosan, which increased the biosynthesis of cinnamic acid, caffeic acid, ferulic acid, sinapic acid, p-coumaric acid, p-coumaryl alcohol, coniferyl alcohol, and sinapyl alcohol. Also, total phenol, flavonoid, and lignin contents were significantly increased at the fruits wounds. In addition, chitosan’s ability to enhance polyphenol oxidase activity stimulated enzymatic browning of wounds. Although wounding increased phenylpropanoid enzymes activities before healing, chitosan caused higher enzyme activities for a significant healing effect compared with the control. These findings imply that chitosan accelerates apple wound healing by activating the phenylpropanoid pathway and stimulating enzymatic browning of wounds.
UPMaBoSS: A Novel Framework for Dynamic Cell Population Modeling
Authors: Stoll Gautier , Naldi Aurélien , Noël Vincent , Viara Eric , Barillot Emmanuel , Kroemer Guido , Thieffry Denis , Calzone Laurence
Published: March 2022

Mathematical modeling aims at understanding the effects of biological perturbations, suggesting ways to intervene and to reestablish proper cell functioning in diseases such as cancer or in autoimmune disorders. This is a difficult task for obvious reasons: the level of details needed to describe the intra-cellular processes involved, the numerous interactions between cells and cell types, and the complex dynamical properties of such populations where cells die, divide and interact constantly, to cite a few. Another important difficulty comes from the spatial distribution of these cells, their diffusion and motility. All of these aspects cannot be easily resolved in a unique mathematical model or with a unique formalism. To cope with some of these issues, we introduce here a novel framework, UPMaBoSS (for Update Population MaBoSS), dedicated to modeling dynamic populations of interacting cells. We rely on the preexisting tool MaBoSS, which enables probabilistic simulations of cellular networks. A novel software layer is added to account for cell interactions and population dynamics, but without considering the spatial dimension. This modeling approach can be seen as an intermediate step towards more complex spatial descriptions. We illustrate our methodology by means of a case study dealing with TNF-induced cell death. Interestingly, the simulation of cell population dynamics with UPMaBoSS reveals a mechanism of resistance triggered by TNF treatment. Relatively easy to encode, UPMaBoSS simulations require only moderate computational power and execution time. To ease the reproduction of simulations, we provide several Jupyter notebooks that can be accessed within the CoLoMoTo Docker image, which contains all software and models used for this study.
The Regulation of Glutamate Transporter 1 in the Rapid Antidepressant-Like Effect of Ketamine in Mice
Authors: Chen Yaping , Shen Mengxin , Liu Xu , Xu Jiangping , Wang Chuang
Published: March 2022

Accumulating evidence suggests that glutamate clearance plays a critical role in the pathophysiology and treatment of depression. Preclinical and clinical studies have demonstrated that ketamine provides an immediate and sustained antidepressant effect. However, the precise mechanism of its action remains to be elucidated. Glutamate transporter 1 (GLT1) participates in glutamate clearance; therefore, we hypothesized that GLT1 may play an important role in the antidepressant effect of ketamine. In this study, we determined that GLT1 inhibition blocks the antidepressant-like properties of ketamine and alters the phosphorylation of the mammalian target of rapamycin (mTOR) in the prefrontal cortex (PFC). Our results show that pretreatment with dihydrokainic acid (DHK), a GLT1 inhibitor, alleviated the antidepressant-like effect of ketamine, and decreased the level of phosphorylated mTOR (pmTOR) in mice (which is normally upregulated by ketamine). In addition, inhibition of α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor and L-type voltage-dependent calcium channel (L-VDCC) significantly abolished the antidepressant-like effect of ketamine. Moreover, inhibition of L-VDCC significantly blocked the upregulation of GLT1 and BDNF in the PFC of mice. The inhibition of the AMPA receptor only significantly alleviated BDNF. Our results provide insight into the role of GLT1 as the critical presynaptic molecule participating in the pathophysiological mechanism of depression and contributing to the antidepressant-like effect of ketamine. In addition, our study confirms that both AMPA receptor and L-VDCC are crucial factors in the immediate antidepressant-like effect of ketamine.
The Effects of 30 Minutes of Artificial Gravity on Cognitive and Sensorimotor Performance in a Spaceflight Analog Environment
Authors: Tays Grant D. , McGregor Heather R. , Lee Jessica K. , Beltran Nichole , Kofman Igor S. , De Dios Yiri Eleana , Mulder Edwin , Bloomberg Jacob J. , Mulavara Ajitkumar P. , Wood Scott J. , Seidler Rachael D.
Published: March 2022

The altered vestibular signaling and somatosensory unloading of microgravity result in sensory reweighting and adaptation to conflicting sensory inputs. Aftereffects of these adaptive changes are evident postflight as impairments in behaviors such as balance and gait. Microgravity also induces fluid shifts toward the head and an upward shift of the brain within the skull; these changes are well-replicated in strict head-down tilt bed rest (HDBR), a spaceflight analog environment. Artificial gravity (AG) is a potential countermeasure to mitigate these effects of microgravity. A previous study demonstrated that intermittent (six, 5-mins bouts per day) daily AG sessions were more efficacious at counteracting orthostatic intolerance in a 5 day HDBR study than continuous daily AG. Here we examined whether intermittent daily AG was also more effective than continuous dosing for mitigating brain and behavioral changes in response to 60 days of HDBR. Participants (n = 24) were split evenly between three groups. The first received 30 mins of continuous AG daily (cAG). The second received 30 mins of intermittent AG daily (6 bouts of 5 mins; iAG). The third received no AG (Ctrl). We collected a broad range of sensorimotor, cognitive, and brain structural and functional assessments before, during, and after the 60 days of HDBR. We observed no significant differences between the three groups in terms of HDBR-associated changes in cognition, balance, and functional mobility. Interestingly, the intermittent AG group reported less severe motion sickness symptoms than the continuous group during centrifugation; iAG motion sickness levels were not elevated above those of controls who did not undergo AG. They also had a shorter duration of post-AG illusory motion than cAG. Moreover, the two AG groups performed the paced auditory serial addition test weekly while undergoing AG; their performance was more accurate than that of controls, who performed the test while in HDBR. Although AG did not counteract HDBR-induced gait and balance declines, iAG did not cause motion sickness and was associated with better self-motion perception during AG ramp-down. Additionally, both AG groups had superior cognitive performance while undergoing AG relative to controls; this may reflect attention or motivation differences between the groups.
Somatovisceral Convergence in Sleep-Wake Cycle: Transmitting Different Types of Information via the Same Pathway
Authors: Levichkina Ekaterina , Pigareva Marina L. , Limanskaya Alexandra , Pigarev Ivan N.
Published: March 2022

Convergence of somatic and visceral inputs occurs at the levels of nervous system ranging from spinal cord to cerebral cortex. This anatomical organization gave explanation to a referred pain phenomenon. However, it also presents a problem: How does the brain know what information is coming for processing—somatic or visceral - if both are transferred by the same spinal cord fibers by means of the standard neuronal spikes? Recent studies provided evidence for cortical processing of interoceptive information largely occurring in sleep, when somatosensation is suppressed, and for the corresponding functional brain networks rearrangement. We suggest that convergent units of the spinal cord would be able to collectively provide mainly somatosensory information in wakefulness and mainly visceral in sleep, solving the puzzle of somatovisceral convergence. We recorded spiking activity from the spinal cord lemniscus pathway during multiple sleep-wake cycles in freely behaving rabbits. In wakefulness high increased spiking corresponded to movements. When animals stopped moving this activity ceased, the fibers remained silent during passive wakefulness. However, upon transition to sleep fibers began firing again. Analysis of spiking patterns of individual fibers revealed that in the majority of them spiking rates recovered in slow wave sleep. Thus, despite cessation of motion and a corresponding decrease of somatic component of the convergent signal, considerable ascending signaling occurs during sleep, that is likely to be visceral. We also recorded evoked responses of the lemniscus pathway to innocuous electrostimulation of the abdominal viscera, and uncovered the existence of two groups of responses depending upon the state of vigilance. Response from an individual fiber could be detected either during wakefulness or in sleep, but not in both states. Wakefulness-responsive group had lower spiking rates in wakefulness and almost stopped spiking in sleep. Sleep-responsive retained substantial spiking during sleep. These groups also differed in spike amplitudes, indicative of fiber diameter differences; however, both had somatic responses during wakefulness. We suggest a mechanism that utilizes differences in somatic and visceral activities to extract both types of information by varying transmission thresholds, and discuss the implications of this mechanism on functional networks under normal and pathological conditions.
J147 Reduces tPA-Induced Brain Hemorrhage in Acute Experimental Stroke in Rats
Authors: Jin Rong , Wang Min , Zhong Wei , Kissinger Charles R. , Villafranca J. Ernest , Li Guohong
Published: March 2022

Background and purpose

J147, a novel neurotrophic compound, was originally developed to treat aging-associated neurological diseases. Based on the broad spectrum of cytoprotective effects exhibited by this compound, we investigated whether J147 has cerebroprotection for acute ischemic stroke and whether it can enhance the effectiveness of thrombolytic therapy with tissue plasminogen activator (tPA).

Methods

Rats were subjected to transient occlusion of the middle cerebral artery (tMCAO) by insertion of an intraluminal suture or embolic middle cerebral artery occlusion (eMCAO), and treated intravenously with J147 alone or in combination with tPA.

Results

We found that J147 treatment significantly reduced infarct volume when administered at 2 h after stroke onset in the tMCAO model, but had no effect in eMCAO without tPA. However, combination treatment with J147 plus tPA at 4 h after stroke onset significantly reduced infarct volume and neurological deficits at 72 h after stroke compared with saline or tPA alone groups in the eMCAO model. Importantly, the combination treatment significantly reduced delayed tPA-associated brain hemorrhage and secondary microvascular thrombosis. These protective effects were associated with J147-mediated inhibition of matrix metalloproteinase-9 (MMP9), 15-lipoxygenase-1, and plasminogen activator inhibitor (PAI) expression in the ischemic hemispheres (predominantly in ischemic cerebral endothelium). Moreover, the combination treatment significantly reduced circulating platelet activation and platelet-leukocyte aggregation compared with saline or tPA alone groups at 24 h after stroke, which might also contribute to reduced microvascular thrombosis and neuroinflammation (as demonstrated by reduced neutrophil brain infiltration and microglial activation).

Conclusion

Our results demonstrate that J147 treatment alone exerts cerebral cytoprotective effects in a suture model of acute ischemic stroke, while in an embolic stroke model co-administration of J147 with tPA reduces delayed tPA-induced intracerebral hemorrhage and confers cerebroprotection. These findings suggest that J147-tPA combination therapy could be a promising approach to improving the treatment of ischemic stroke.
The Impact of Ischemic Stroke on Gray and White Matter Injury Correlated With Motor and Cognitive Impairments in Permanent MCAO Rats: A Multimodal MRI-Based Study
Authors: Yang Le , Li Manzhong , Zhan Yu , Feng Xuefeng , Lu Yun , Li Mingcong , Zhuang Yuming , Lei Jianfeng , Zhao Hui
Published: March 2022

Background

Identifying the alterations of the cerebral gray and white matter is an important prerequisite for developing potential pharmacological therapy for stroke. This study aimed to assess the changes of gray and white matter after permanent middle cerebral artery occlusion (pMCAO) in rats using magnetic resonance imaging (MRI), and to correlate them with the behavior performance.

Methods

Rats were subjected to pMCAO or sham surgery and reared for 30 days. Motor and cognitive function of the rats were examined by gait and Morris water maze (MWM) tests, respectively. Multimodal MRI was conducted to examine the functional and structural changes of the gray and white matter followed with luxol fast blue (LFB) staining.

Results

The gait and MWM tests revealed significant motor and cognitive dysfunction in pMCAO rats, respectively. Magnetic resonance angiography presented abnormal intracranial arteries in pMCAO rats with reduced signal intensity of the anterior cerebral artery, anterior communicating cerebral artery, internal carotid artery, and increased basilar artery vessel signal compared with sham rats. Arterial spin labeling confirmed the decreased cerebral blood flow in the infarcted sensorimotor cortex and striatum. Structural T2-weighted imaging and T2 mapping showed brain atrophy and elevation of T2 value in the gray (sensorimotor cortex, striatum) and white (external capsule, internal capsule) matter of pMCAO rats. The results from diffusion tensor imaging (DTI) corresponded well with LFB staining showing reduced relative FA accompanied with increased relative AD and RD in the gray and white matter of pMCAO rats compared with sham rats. Fiber tracking derived from DTI further observed significantly reduced fiber density and length in the corresponding brain regions of pMCAO rats compared with sham rats. Specially, the DTI parameters (especially FA) in the relevant gray matter and white matter significantly correlated with the behavior performance in the gait and MWM tests.

Conclusion

Collectively, the gray and white matter damages could be non-invasively monitored in pMCAO rats by multimodal MRI. DTI-derived parameters, particularly the FA, might be a good imaging index to stage gray and white matter damages associated with post-stroke motor and cognitive impairments.
Endovascular Treatment of Large or Giant Basilar Artery Aneurysms Using the Pipeline Embolization Device: Complications and Outcomes
Authors: Ge Huijian , Chen Xiheng , Liu Kai , Zhao Yang , Zhang Longhui , Liu Peng , Jiang Yuhua , He Hongwei , Lv Ming , Li Youxiang
Published: March 2022

Background

This study aimed to investigate clinical and angiographic outcomes of Pipeline embolization device (PED) treatment of large or giant basilar artery (BA) aneurysms and examine associated factors.

Methods

Clinical and angiographic data of 29 patients (18 men, 11 women) with large or giant BA aneurysms were retrospectively examined. Mean age was 44.1 ± 21.2 years (range, 30–68). Mean aneurysm size was 22.2 ± 8.3 mm (range, 12.0–40.1).

Results

Mean angiographic follow-up was 18.3 ± 3.4 months (range, 4.5–60). The rate of adequate aneurysmal occlusion (O'Kelly–Marotta grade C–D) was 87%. The overall complication rate was 44.8%; most complications (84.6%) occurred in the periprocedural period. Univariable comparison of patients who did and did not develop complications showed significant differences in aneurysm size (p < 0.01), intra-aneurysmal thrombus (p = 0.03), and mean number of PEDs used (p = 0.02). Aneurysm size (odds ratio, 1.4; p = 0.04) was an independent risk factor for periprocedural complications in multivariable analysis. Mean clinical follow-up was 23.5 ± 3.2 months (range, 0.1–65). Nine patients (31%) had a poor clinical outcome (modified Rankin scale score ≥3) at last follow-up, including 7 patients who died. Univariable comparisons between patients with favorable and unfavorable clinical outcomes showed that aneurysm size (p = 0.009) and intra-aneurysmal thrombus (p = 0.04) significantly differed between the groups. Multivariable analysis showed that aneurysm size (odds ratio, 1.1; p = 0.04) was an independent risk factor for poor clinical outcome.

Conclusion

PED treatment of large or giant BA aneurysms is effective and can achieve a satisfactory long-term occlusion rate. However, the treatment complications are not negligible. Aneurysm size is the strongest predictor of perioperative complications and poor clinical outcome.
Are Clinical Impairments Related to Kinematic Gait Variability in Children and Young Adults With Cerebral Palsy?
Authors: Tabard-Fougère Anne , Rutz Dionys , Pouliot-Laforte Annie , De Coulon Geraldo , Newman Christopher J. , Armand Stéphane , Wegrzyk Jennifer
Published: March 2022

Intrinsic gait variability (GV), i.e., fluctuations in the regularity of gait patterns between repetitive cycles, is inherent to the sensorimotor system and influenced by factors such as age and pathology. Increased GV is associated with gait impairments in individuals with cerebral palsy (CP) and has been mainly studied based on spatiotemporal parameters. The present study aimed to describe kinematic GV in young people with CP and its associations with clinical impairments [i.e., passive range of motion (pROM), muscle weakness, reduced selective motor control (selectivity), and spasticity]. This retrospective study included 177 participants with CP (age range 5–25 years; Gross Motor Function Classification System I-III) representing 289 clinical gait analyses [n = 172 for unilateral CP (uCP) vs. 117 for bilateral CP (bCP)]. As variability metrics, Root Mean Square Deviation (RMSD) for nine lower-limb kinematic parameters and Gait Standard Deviation (GaitSD) – as composite score of the kinematic parameters – were computed for the affected (unilateral = uCP) and most affected side (bilateral = bCP), respectively, as defined by clinical scores. GaitSD was then computed for the non/less-affected side for between leg comparisons. Uni- and multivariate linear regressions were subsequently performed on GaitSD of the affected/most affected side with all clinical impairments (composite scores) as independent variables. Highest RMSD were found in the transverse plane (hip, pelvis), for distal joints in the sagittal plane (knee, ankle) and for foot progression. GaitSD was not different between uCP and bCP (affected/most affected side) but higher in the non-affected vs. affected side in uCP. GaitSD was associated with age (p < 0.001), gait deviation index (GDI) (p < 0.05), muscle weakness (p < 0.001), selectivity (p < 0.05), and pROM (p < 0.001). After adjustment for age and GDI, GaitSD remained associated with muscle weakness (uCP: p = 0.003, bCP: p < 0.001) and selectivity (bCP: p = 0.024). Kinematic GV can be expressed as global indicator of variability (GaitSD) in young people with CP given the strong correlation of RMSD for lower-limb kinematic parameters. In terms of asymmetry, increased variability of the non-affected vs. affected side may indicate contralateral compensation mechanisms in uCP. Notably muscle weakness (uCP, bCP) and selectivity (bCP) – but not spasticity – were associated with GaitSD. Further studies need to explore the clinical relevance of kinematic GV in CP to support the interpretation of clinical gait analyses and therapeutic decision-making.
Task-Based Functional Connectivity and Blood-Oxygen-Level-Dependent Activation During Within-Scanner Performance of Lumbopelvic Motor Tasks: A Functional Magnetic Resonance Imaging Study
Authors: Jordon Max K. , Stewart Jill Campbell , Silfies Sheri P. , Beattie Paul F.
Published: March 2022

There are a limited number of neuroimaging investigations into motor control of the lumbopelvic musculature. Most investigation examining motor control of the lumbopelvic musculature utilize transcranial magnetic stimulation (TMS) and focus primarily on the motor cortex. This has resulted in a dearth of knowledge as it relates to how other regions of the brain activate during lumbopelvic movement. Additionally, task-based functional connectivity during lumbopelvic movements has not been well elucidated. Therefore, we used functional magnetic resonance imaging (fMRI) to examine brain activation and ROI-to-ROI task-based functional connectivity in 19 healthy individuals (12 female, age 29.8 ± 4.5 years) during the performance of three lumbopelvic movements: modified bilateral bridge, left unilateral bridge, and right unilateral bridge. The whole brain analysis found robust, bilateral activation within the motor regions of the brain during the bilateral bridge task, and contralateral activation of the motor regions during unilateral bridging tasks. Furthermore, the ROI-to-ROI analysis demonstrated significant connectivity of a motor network that included the supplemental motor area, bilateral precentral gyrus, and bilateral cerebellum regardless of the motor task performed. These data suggest that while whole brain activation reveals unique patterns of activation across the three tasks, functional connectivity is very similar. As motor control of the lumbopelvic area is of high interest to those studying low back pain (LBP), this study can provide a comparison for future research into potential connectivity changes that occur in individuals with LBP.
Stochastic Motion Stimuli Influence Perceptual Choices in Human Participants
Authors: Fard Pouyan R. , Bitzer Sebastian , Pannasch Sebastian , Kiebel Stefan J.
Published: March 2022

In the study of perceptual decision making, it has been widely assumed that random fluctuations of motion stimuli are irrelevant for a participant’s choice. Recently, evidence was presented that these random fluctuations have a measurable effect on the relationship between neuronal and behavioral variability, the so-called choice probability. Here, we test, in a behavioral experiment, whether stochastic motion stimuli influence the choices of human participants. Our results show that for specific stochastic motion stimuli, participants indeed make biased choices, where the bias is consistent over participants. Using a computational model, we show that this consistent choice bias is caused by subtle motion information contained in the motion noise. We discuss the implications of this finding for future studies of perceptual decision making. Specifically, we suggest that future experiments should be complemented with a stimulus-informed modeling approach to control for the effects of apparent decision evidence in random stimuli.
Prognostic Implications of Molecular Subtypes in Primary Small Cell Lung Cancer and Their Correlation With Cancer Immunity
Authors: Qi Jing , Zhang Jiaqi , Liu Ningbo , Zhao Lujun , Xu Bo
Published: March 2022

Introduction

Small cell lung cancer (SCLC) has recently been characterized as heterogeneous tumors due to consensus nomenclature for distinct molecular subtypes on the basis of differential expression of four transcription markers (ASCL1, NEUROD1, POU2F3, and YAP1). It is necessary to validate molecular subtype classification in primary SCLC tumors by immunohistochemical (IHC) staining and investigate its relevance to survival outcomes.

Methods

Using a large number of surgically resected primary SCLC tumors, we assessed the mRNA and protein levels of the four subtype markers (ASCL1, NEUROD1, POU2F3 and YAP1) in two independent cohorts, respectively. Next, molecular subtypes defined by the four subtype markers was conducted to identify the association with clinicopathologic characteristics, survival outcomes, the expression of classic neuroendocrine markers, and molecules related to tumor immune microenvironment.

Results

Samples were categorized into four subtypes based on the relative expression levels of the four subtype markers, yielding to ASCL1, NEUROD1, POU2F3 and YAP1 subtypes, respectively. The combined neuroendocrine differentiation features were more prevalent in either ASCL1 or NEUROD1 subtypes. Kaplan-Meier analyses found that patients with tumors of the YAP1 subtype and ASCL1 subtype obtained the best and worst prognosis on both mRNA and IHC levels, respectively. Based on multivariate Cox proportional-hazards regression model, molecular subtype classification determined by IHC was identified as an independent indicator for survival outcomes in primary SCLC tumors. Correlation analyses indicated that the four subtype markers in SCLC cancer cells were interacted with its tumor immune microenvironment. Specifically, tumors positive for YAP1 was associated with fewer CTLA4+ T cell infiltration, while more immune-inhibitory receptors (FoxP3,PD1, and CTLA4) and fewer immune-promoting receptor (CD8) were found in tumors positive for ASCL1.

Conclusions

We validated the new molecular subtype classification and clinical relevance on both mRNA and protein levels from primary SCLC tumors. The molecular subtypes determined by IHC could be a pre-selected effective biomarker significantly influenced on prognosis in patients with SCLC, which warrants further studies to provide better preventative and therapeutic options for distinct molecular subtypes.
Dosimetric and Clinical Risk Factors for the Development of Maxillary Osteoradionecrosis in Adenoid Cystic Carcinoma (ACC) Patients Treated With Carbon Ion Radiotherapy
Authors: Vischioni Barbara , Russo Stefania , Meuli Martino , Bonora Maria , Ronchi Sara , Ingargiola Rossana , Camarda Anna Maria , Imparato Sara , Preda Lorenzo , Ciocca Mario , Molinelli Silvia , Orlandi Ester
Published: March 2022

Background

The present study aims to evaluate dosimetric and clinical risk factors for the development of maxillary osteoradionecrosis (ORN) in head and neck adenoid cystic carcinoma (ACC) patients treated with carbon ion radiotherapy (CIRT).

Methods

Clinical data and treatment plans of ACC patients, consecutively treated from January 2013 to September 2016 within the phase II clinical trial CNAO S9/2012/C, were retrospectively reviewed. ORN and other treatment-related toxicity were graded according to the Common Terminology Criteria for Adverse Events (CTACE), version 4.0. The maxillary bone was contoured on the planning CT, and only patients receiving more than 10% of the prescription dose at their maxilla were considered for the analysis (67 patients). The volumes of maxilla receiving doses from 10 Gy (RBE) to 60 Gy (RBE) (VD), with an increment of 10 Gy (RBE), and additional clinical factors were correlated to the incidence of ORN with univariate analysis (Chi-square test). The logistic regression model was subsequently applied for multivariate analysis. Treatment plans calculated with a local effect model (LEM)-based optimization were recalculated with the modified microdosimetric kinetic model (MKM), and compared with literature data from the Japanese experience.

Results

The median time interval from the start of CIRT to ORN appearance was 24 months (range, 8–54 months). Maxillary ORN was observed in 11 patients (16.4%). Grade 1 ORN was observed in 2 patients (18.1%), G2 in 4 (36.3%), G3 in 4 (36.3%) and G4 in 1 (9.3%). From univariate analysis, the site of the tumor, the presence of teeth within the PTV and acute mucositis correlated with the development of maxillary ORN. VD were significantly higher for all the dose levels tested in patients with maxillary ORN than patients without necrosis, according to both radiobiological models. The multivariate analysis showed that V60 significantly correlated with ORN risk.

Conclusion

The volume of maxilla irradiated with high dose values was relevant for ORN development in our cohort of ACC patients. These results are in line with previously published data obtained with a different radiobiological model. Our findings might be helpful to prevent the risk of ORN in patients receiving CIRT.
Effects of Stable Vagus Nerve Stimulation Efficacy on Autistic Behaviors in Ten Pediatric Patients With Drug Resistant Epilepsy: An Observational Study
Authors: Wang Zhiyan , Yuan Xing , Zhang Qian , Wen Jialun , Cheng Tungyang , Qin Xiaoya , Ji Taoyun , Shu Xiaomei , Jiang Yuwu , Liao Jianxiang , Hao Hongwei , Li Luming , Wu Ye
Published: March 2022

Vagus nerve stimulation (VNS) is a safe and effective therapy for pediatric patients with drug-resistant epilepsy (DRE). However, in children with DRE, the effects of VNS on autistic behaviors remain controversial. We retrospectively collected data from 10 children with DRE who underwent VNS implantation and regular parameter regulation in three pediatric epilepsy centers, and completed the behavioral assessments, including the autistic behavior checklist and the child behavior checklist, at follow-ups 1 (mean 2.16 years) and 2 (mean 2.98 years). The 10 children maintained stable seizure control between the two follow-ups. Their autistic behaviors, especially in language, social and self-help, were reduced at follow-up 2 compared to follow-up 1 (p = 0.01, p = 0.01, respectively). Moreover, these improvements were not associated with their seizure control, whether it was positive or negative. These results suggested that the VNS had a positive effect on autistic behaviors, which provided a preliminary clinical basis that VNS may benefit to younger children with DRE comorbidity autism spectrum disorder (ASD).
Therapeutic Effects of Berberine on Liver Fibrosis are associated With Lipid Metabolism and Intestinal Flora
Authors: Liu Xianzhi , Wang Lifu , Tan Siwei , Chen Zebin , Wu Bin , Wu Xiaoying
Published: March 2022

Liver cirrhosis is a form of liver fibrosis resulting from chronic hepatitis caused by various liver diseases, such as viral hepatitis, alcoholic liver damage, nonalcoholic steatohepatitis, autoimmune liver disease, and by parasitic diseases such as schistosomiasis. Liver fibrosis is the common pathological base and precursors of cirrhosis. Inflammation and disorders of lipid metabolism are key drivers in liver fibrosis. Studies have determined that parts of the arachidonic acid pathway, such as its metabolic enzymes and biologically active products, are hallmarks of inflammation, and that aberrant peroxisome proliferator-activated receptor gamma (PPARγ)-mediated regulation causes disorders of lipid metabolism. However, despite the ongoing research focus on delineating the mechanisms of liver fibrosis that underpin various chronic liver diseases, effective clinical treatments have yet to be developed. Berberine (BBR) is an isoquinoline alkaloid with multiple biological activities, such as anti-inflammatory, anti-bacterial, anti-cancer, and anti-hyperlipidemic activities. Many studies have also found that BBR acts via multiple pathways to alleviate liver fibrosis. Furthermore, the absorption of BBR is increased by nitroreductase-containing intestinal flora, and is strengthened via crosstalk with bile acid metabolism. This improves the oral bioavailability of BBR, thereby enhancing its clinical utility. The production of butyrate by intestinal anaerobic bacteria is dramatically increased by BBR, thereby amplifying butyrate-mediated alleviation of liver fibrosis. In this review, we discuss the effects of BBR on liver fibrosis and lipid metabolism, particularly the metabolism of arachidonic acid, and highlight the potential mechanisms by which BBR relieves liver fibrosis through lipid metabolism related and intestinal flora related pathways. We hope that this review will provide insights on the BBR-based treatment of liver cirrhosis and related research in this area, and we encourage further studies that increase the ability of BBR to enhance liver health.
A Systematic Review and Meta-Analysis of the Efficacy and Safety of Xinbao Pill in Chronic Heart Failure
Authors: Wang Yuanping , Liu Yuntao , Liu Zhongqiu , Cheng Yuanyuan , Wang Dawei
Published: March 2022

Objective: This study aimed to clarify the efficacy and safety of Xinbao pill (XBP) as an adjunctive treatment for chronic heart failure (CHF).

Methods: Randomized controlled trials (RCTs) on the efficacy and safety of XBP in the treatment of CHF were searched from the six databases. The risk of bias assessment tool recommended by Cochrane Handbook 5.1 were used to assess the methodological quality of the included studies. RevMan 5.3 software was used for meta-analysis. The subgroup and sensitivity analyses were also performed. The grading recommendations assessment, development, and evaluation (GRADE) technique were used to assess the evidence’s certainty.

Results: Nine RCTs with a total of 882 patients were identified in this study. The meta-analysis demonstrated that XBP as adjunctive therapy was superior to conventional medicine alone for the treatment of CHF in improving the left ventricular ejection fraction (LVEF; MD = 5.34; 95% CI 4.68 to 5.99; p < 0.001), the total effective rate (RR = 1.21; 95% CI, 1.14 to 1.29; p < 0.001), the cardiac output (MD = 0.56; 95% CI 0.42 to 0.70; p < 0.001), the stroke volume (MD = 3.42; 95% CI 2.03 to 4.81; p < 0.001) and the 6-min walking distance (6-MWD; MD = 31.95; 95% CI 21.83 to 42.06; p < 0.001), meanwhile reducing the left ventricular end-diastolic diameter (LVEDD; MD = −3.22; 95% CI −4.03 to −2.42; p < 0.001) and left ventricular end-systolic dimension (LVESD; MD = −2.93; 95% CI −3.80 to −2.06; p < 0.001). Regarding safety, a total of 2.4% (11/456) adverse reactions occurred in the XBP groups while 3.9% (18/456) in the control group. The outcomes’ evidentiary quality ranged from “very low” to “moderate”.

Conclusion: This study indicated that XBP as adjunctive therapy combined with conventional medicine seemed to be safe and more effective than conventional medicine alone in treating CHF. However, due to the poor methodological quality of the included RCTs, further well-designed RCTs are required to confirm the efficacy and safety of XBP.
SLC35B4 Stabilizes c-MYC Protein by O-GlcNAcylation in HCC
Authors: Jiang Tao , Yang Jinghong , Yang Huohong , Chen Wancheng , Ji Kaiyuan , Xu Yang , Yu Lili
Published: March 2022

UDP-GlcNAc is a sugar substrate necessary for the O-GlcNAcylation of proteins. SLC35B4 is one of the nucleotide sugar transporters that transport UDP-GlcNAc and UDP-xylose into the endoplasmic reticulum and Golgi apparatus for glycosylation. The roles of SLC35B4 in hepatocellular carcinoma (HCC) tumorigenesis remain unknown. We find that the expression levels of SLC35B4 are higher in HCC tissues than adjacent non-tumor tissues. SLC35B4 is important for the proliferation and tumorigenesis of HCC cells. Mechanistically, SLC35B4 is important for the O-GlcNAc modification of c-Myc and thus the stabilization of c-Myc, which is required for HCC tumorigenesis. Therefore, SLC35B4 is a promising therapeutic target for treating HCC.
Smart Dielectric Barrier Discharge Plasma Decontamination: Spatially Targeted Decontamination With Actuated Ozone Distribution
Authors: Choudhury Bhaswati , Portugal Sherlie , Roy Subrata , Mastro Emma , Johnson Judith A.
Published: March 2022

This study introduces spatially targeted decontamination using a synergistic combination of dielectric barrier discharge (DBD) flow actuation and ozone generation. Here, we relate the spatial distribution of local microbial decontaminations in an enclosure to that of local ozone concentrations caused by DBD ozone generation and flow actuation using two reactors with contrasting flow actuation, the Fan and Comb reactors, run at equal power of 1 ± 0.03 W for 3.5 min. Deviations in ozone concentrations and reductions of Escherichia coli on contaminated coupons over two planes were used to quantify the utilization capacity of the generated ozone to simultaneously disinfect regions of a surface placed in the planes. Results show that uniform ozone consumption by a contaminated target, i.e., targeted decontamination, lowers ozone requirements, exposure times, and reactor energy consumption for its disinfection. Furthermore, a significant positive correlation was found between local decontamination and ozone concentrations with Pearson’s correlation, ρ (34) = 0.64; p < 0.001. Simulated ozone distribution using an experiment integrated simulation method, governed by DBD reactor geometry induced flow actuation and ozone reaction rates, is also presented for predicting DBD actuated spatial decontamination distribution. Our study shows an innovative approach of applying DBD plasma reactors for decontamination using flow actuation and ozone generation to achieve targeted killing with maximized ozone utilization lowering overall ozone dosage requirements, energy requirements, and exposure times.
Species Diversity Regulates Ecological Strategy Spectra of Forest Vegetation Across Different Climatic Zones
Authors: Han Xin , Xu Yue , Huang Jihong , Zang Runguo
Published: March 2022

Ecological strategy is the tactics employed by species in adapting to abiotic and biotic conditions. The ecological strategy spectrum is defined as the relative proportion of species in different ecological strategy types within a community. Determinants of ecological strategy spectrum of plant community explored by most previous studies are about abiotic factors. Yet, the roles of biotic factors in driving variations of ecological strategy spectra of forest communities across different geographic regions remains unknown. In this study, we established 200 0.04-ha forest dynamics plots (FDPs) and measured three-leaf functional traits of tree and shrub species in four forest vegetation types across four climatic zones. Based on Grime’s competitor, stress-tolerator, ruderal (CSR) triangular framework, and the StrateFy method, we categorized species into four ecological strategy groups (i.e., C-, S-, Int-, and R-groups) and related the ecological spectra of the forests to three species diversity indices [i.e., species richness, Shannon-Wiener index, and stem density (stem abundance)]. Linear regression, redundancy analysis, and variance partition analysis were utilized for assessing the roles of species diversity in regulating ecological strategy spectra of forest communities across different climatic zones. We found that the proportion of species in the C- and Int-groups increased, while the proportion of species in the S-group decreased, with the increase of three indices of species diversity. Among the three species diversity indices, stem abundance played the most important role in driving variations in ecological strategy spectra of forests across different climatic zones. Our finding highlights the necessity of accounting for biotic factors, especially stem abundance, in modeling or predicting the geographical distributions of plant species with varied ecological adaptation strategies to future environmental changes.