bluuebunny/crossref_metadata_2025 huggingface dataset:
Putative Nucleotide-Based Second Messengers in the Archaeal Model Organisms Haloferax volcanii and Sulfolobus acidocaldarius
Authors: Braun Frank , Recalde Alejandra , Bähre Heike , Seifert Roland , Albers Sonja-Verena
Published: November 2021

Research on nucleotide-based second messengers began in 1956 with the discovery of cyclic adenosine monophosphate (3′,5′-cAMP) by Earl Wilbur Sutherland and his co-workers. Since then, a broad variety of different signaling molecules composed of nucleotides has been discovered. These molecules fulfill crucial tasks in the context of intracellular signal transduction. The vast majority of the currently available knowledge about nucleotide-based second messengers originates from model organisms belonging either to the domain of eukaryotes or to the domain of bacteria, while the archaeal domain is significantly underrepresented in the field of nucleotide-based second messenger research. For several well-stablished eukaryotic and/or bacterial nucleotide-based second messengers, it is currently not clear whether these signaling molecules are present in archaea. In order to shed some light on this issue, this study analyzed cell extracts of two major archaeal model organisms, the euryarchaeon Haloferax volcanii and the crenarchaeon Sulfolobus acidocaldarius, using a modern mass spectrometry method to detect a broad variety of currently known nucleotide-based second messengers. The nucleotides 3′,5′-cAMP, cyclic guanosine monophosphate (3′,5′-cGMP), 5′-phosphoadenylyl-3′,5′-adenosine (5′-pApA), diadenosine tetraphosphate (Ap4A) as well as the 2′,3′-cyclic isomers of all four RNA building blocks (2′,3′-cNMPs) were present in both species. In addition, H. volcanii cell extracts also contain cyclic cytosine monophosphate (3′,5′-cCMP), cyclic uridine monophosphate (3′,5′-cUMP) and cyclic diadenosine monophosphate (3′,5′-c-di-AMP). The widely distributed bacterial second messengers cyclic diguanosine monophosphate (3′,5′-c-di-GMP) and guanosine (penta-)/tetraphosphate [(p)ppGpp] could not be detected. In summary, this study gives a comprehensive overview on the presence of a large set of currently established or putative nucleotide-based second messengers in an eury- and a crenarchaeal model organism.
Litter Decomposition of Imperata cylindrica in a Copper Tailing Areas With Different Restoration History: Fungal Community Dynamics and Driving Factors
Authors: Jia Tong , Wang Xuerong , Guo Tingyan , Chai Baofeng
Published: November 2021

Microorganisms drive litter decomposition while maintaining the chemical cycle of ecosystems. We used the dominant vegetation (Imperata cylindrica) in the mining area selected for this study for this experiment to explore fungal community characteristics, key fungal groups, and their associative driving factors during I. cylindrica litter decomposition. Maximum litter C/N values occurred 100days after the commencement of the decomposition experiment during all different recovery years in this copper tailings area. Heavy metals in litter [copper (Cu), zinc (Zn), plumbum (Pb), and cadmium (Cd)] accumulated gradually with decomposition. The dominant fungal phyla observed in the community were Ascomycota and Basidiomycota, while the classes Sordariomycetes and Eurotiomycetes significantly increased as litter decomposition progressed. Degrees of connectivity and interaction between fungal communities were highest during the early litter decomposition stage. Sordariomycetes, Dothideomycetes, and Leotiomycetes all played critical roles in maintaining fungal community relationships. The effect of physicochemical properties and enzyme activities in I. cylindrica litter was significant on the dominant fungi, while driving factors that affected fungal communities differed over different recovery stages. Total nitrogen (TN), heavy metals, pH, and enzyme activities in the little were significantly correlated with fungal community composition. Litter properties throughout the litter decomposition process mainly affected the dynamics of the fungal community structure. The main environmental factors that affected fungal community structure were copper content and pH. Dichotomopilus, Trichoderma, Knufia, Phialophora, Oxyporus, and Monocillium, which all played important roles in litter decomposition, positively correlated with heavy metals, sucrase, and catalase. Finally, results from this study will help us better clarify litter decomposition mechanisms in degraded ecosystems as well as provide a scientific basis for improving species cycling and nutrient transformation efficiency in mining ecosystems.
Histone Acetyltransferases and Deacetylases Are Required for Virulence, Conidiation, DNA Damage Repair, and Multiple Stresses Resistance of Alternaria alternata
Authors: Ma Haijie , Li Lei , Gai Yunpeng , Zhang Xiaoyan , Chen Yanan , Zhuo Xiaokang , Cao Yingzi , Jiao Chen , Gmitter Fred G. , Li Hongye
Published: November 2021

Histone acetylation, which is critical for transcriptional regulation and various biological processes in eukaryotes, is a reversible dynamic process regulated by HATs and HDACs. This study determined the function of 6 histone acetyltransferases (HATs) (Gcn5, RTT109, Elp3, Sas3, Sas2, Nat3) and 6 histone deacetylases (HDACs) (Hos2, Rpd3, Hda1, Hos3, Hst2, Sir2) in the phytopathogenic fungus Alternaria alternata by analyzing targeted gene deletion mutants. Our data provide evidence that HATs and HDACs are both required for mycelium growth, cell development and pathogenicity as many gene deletion mutants (ΔGcn5, ΔRTT109, ΔElp3, ΔSas3, ΔNat3, ΔHos2, and ΔRpd3) displayed reduced growth, conidiation or virulence at varying degrees. In addition, HATs and HDACs are involved in the resistance to multiple stresses such as oxidative stress (Sas3, Gcn5, Elp3, RTT109, Hos2), osmotic stress (Sas3, Gcn5, RTT109, Hos2), cell wall-targeting agents (Sas3, Gcn5, Hos2), and fungicide (Gcn5, Hos2). ΔGcn5, ΔSas3, and ΔHos2 displayed severe growth defects on sole carbon source medium suggesting a vital role of HATs and HDACs in carbon source utilization. More SNPs were generated in ΔGcn5 in comparison to wild-type when they were exposed to ultraviolet ray. Moreover, ΔRTT109, ΔGcn5, and ΔHos2 showed severe defects in resistance to DNA-damaging agents, indicating the critical role of HATs and HDACs in DNA damage repair. These phenotypes correlated well with the differentially expressed genes in ΔGcn5 and ΔHos2 that are essential for carbon sources metabolism, DNA damage repair, ROS detoxification, and asexual development. Furthermore, Gcn5 is required for the acetylation of H3K4. Overall, our study provides genetic evidence to define the central role of HATs and HDACs in the pathological and biological functions of A. alternata.
TMS-EEG Biomarkers of Amnestic Mild Cognitive Impairment Due to Alzheimer’s Disease: A Proof-of-Concept Six Years Prospective Study
Authors: Ferreri Florinda , Guerra Andrea , Vollero Luca , Ponzo David , Määtta Sara , Könönen Mervi , Vecchio Fabrizio , Pasqualetti Patrizio , Miraglia Francesca , Simonelli Ilaria , Corbetta Maurizio , Rossini Paolo Maria
Published: November 2021

Background: Early and affordable identification of subjects with amnestic mild cognitive impairment (aMCI) who will convert to Alzheimer’s disease (AD) is a major scientific challenge.

Objective: To investigate the neurophysiological hallmarks of sensorimotor cortex function in aMCI under the hypothesis that some may represent the plastic rearrangements induced by neurodegeneration, hence predictors of future conversion to AD. We sought to determine (1) whether the sensorimotor network shows peculiar alterations in patients with aMCI and (2) if sensorimotor network alterations predict long-term disease progression at the individual level.

Methods: We studied several transcranial magnetic stimulation (TMS)-electroencephalogram (EEG) parameters of the sensorimotor cortex in a group of patients with aMCI and followed them for 6 years. We then identified aMCI who clinically converted to AD [prodromal to AD-MCI (pAD-MCI)] and those who remained cognitively stable [non-prodromal to AD-MCI (npAD-MCI)].

Results: Patients with aMCI showed reduced motor cortex (M1) excitability and disrupted EEG synchronization [decreased intertrial coherence (ITC)] in alpha, beta and gamma frequency bands compared to the control subjects. The degree of alteration in M1 excitability and alpha ITC was comparable between pAD-MCI and npAD-MCI. Importantly, beta and gamma ITC impairment in the stimulated M1 was greater in pAD-MCI than npAD-MCI. Furthermore, an additional parameter related to the waveform shape of scalp signals, reflecting time-specific alterations in global TMS-induced activity [stability of the dipolar activity (sDA)], discriminated npAD-MCI from MCI who will convert to AD.

Discussion: The above mentioned specific cortical changes, reflecting deficit of synchronization within the cortico-basal ganglia-thalamo-cortical loop in aMCI, may reflect the pathological processes underlying AD. These changes could be tested in larger cohorts as neurophysiological biomarkers of AD.
Characteristics of Neural Network Changes in Normal Aging and Early Dementia
Authors: Watanabe Hirohisa , Bagarinao Epifanio , Maesawa Satoshi , Hara Kazuhiro , Kawabata Kazuya , Ogura Aya , Ohdake Reiko , Shima Sayuri , Mizutani Yasuaki , Ueda Akihiro , Ito Mizuki , Katsuno Masahisa , Sobue Gen
Published: November 2021

To understand the mechanisms underlying preserved and impaired cognitive function in healthy aging and dementia, respectively, the spatial relationships of brain networks and mechanisms of their resilience should be understood. The hub regions of the brain, such as the multisensory integration and default mode networks, are critical for within- and between-network communication, remain well-preserved during aging, and play an essential role in compensatory processes. On the other hand, these brain hubs are the preferred sites for lesions in neurodegenerative dementias, such as Alzheimer’s disease. Disrupted primary information processing networks, such as the auditory, visual, and sensorimotor networks, may lead to overactivity of the multisensory integration networks and accumulation of pathological proteins that cause dementia. At the cellular level, the brain hub regions contain many synapses and require a large amount of energy. These regions are rich in ATP-related gene expression and had high glucose metabolism as demonstrated on positron emission tomography (PET). Importantly, the number and function of mitochondria, which are the center of ATP production, decline by about 8% every 10 years. Dementia patients often have dysfunction of the ubiquitin-proteasome and autophagy-lysosome systems, which require large amounts of ATP. If there is low energy supply but the demand is high, the risk of disease can be high. Imbalance between energy supply and demand may cause accumulation of pathological proteins and play an important role in the development of dementia. This energy imbalance may explain why brain hub regions are vulnerable to damage in different dementias. Here, we review (1) the characteristics of gray matter network, white matter network, and resting state functional network changes related to resilience in healthy aging, (2) the mode of resting state functional network disruption in neurodegenerative dementia, and (3) the cellular mechanisms associated with the disruption.
A Platform for Cognitive Monitoring of Neurosurgical Patients During Hospitalization
Authors: Ashmaig Omer , Hamilton Liberty S. , Modur Pradeep , Buchanan Robert J. , Preston Alison R. , Watrous Andrew J.
Published: November 2021

Intracranial recordings in epilepsy patients are increasingly utilized to gain insight into the electrophysiological mechanisms of human cognition. There are currently several practical limitations to conducting research with these patients, including patient and researcher availability and the cognitive abilities of patients, which limit the amount of task-related data that can be collected. Prior studies have synchronized clinical audio, video, and neural recordings to understand naturalistic behaviors, but these recordings are centered on the patient to understand their seizure semiology and thus do not capture and synchronize audiovisual stimuli experienced by patients. Here, we describe a platform for cognitive monitoring of neurosurgical patients during their hospitalization that benefits both patients and researchers. We provide the full specifications for this system and describe some example use cases in perception, memory, and sleep research. We provide results obtained from a patient passively watching TV as proof-of-principle for the naturalistic study of cognition. Our system opens up new avenues to collect more data per patient using real-world behaviors, affording new possibilities to conduct longitudinal studies of the electrophysiological basis of human cognition under naturalistic conditions.
Isolation-Induced Ultrasonic Vocalization in Environmental and Genetic Mice Models of Autism
Authors: Shekel Itay , Giladi Shaked , Raykin Eynav , Weiner May , Chalifa-Caspi Vered , Lederman Dror , Kofman Ora , Golan Hava M.
Published: November 2021

Studies in rodent models suggest that calls emitted by isolated pups serve as an early behavioral manifestation of communication deficits and autistic like behavior. Previous studies in our labs showed that gestational exposure to the pesticide chlorpyrifos (CPF) and the Mthfr-knock-out mice are associated with impaired social preference and restricted or repetitive behavior. To extend these studies, we examine how pup communication via ultrasonic vocalizations is altered in these ASD models. We implemented an unsupervised hierarchical clustering method based on the spectral properties of the syllables in order to exploit syllable classification to homogeneous categories while avoiding over-categorization. Comparative exploration of the spectral and temporal aspects of syllables emitted by pups in two ASD models point to the following: (1) Most clusters showed a significant effect of the ASD factor on the start and end frequencies and bandwidth and (2) The highest percent change due to the ASD factor was on the bandwidth and duration. In addition, we found sex differences in the spectral and temporal properties of the calls in both control groups as well as an interaction between sex and the gene/environment factor. Considering the basal differences in the characteristics of syllables emitted by pups of the C57Bl/6 and Balb/c strains used as a background in the two models, we suggest that the above spectral-temporal parameters start frequency, bandwidth, and duration are the most sensitive USV features that may represent developmental changes in ASD models.
Assessment of Isocitrate Dehydrogenase 1 Genotype and Cell Proliferation in Gliomas Using Multiple Diffusion Magnetic Resonance Imaging
Authors: Xie Yan , Li Shihui , Shen Nanxi , Gan Tongjia , Zhang Shun , Liu Weiyin Vivian , Zhu Wenzhen
Published: November 2021

Objectives: To compare the efficacy of parameters from multiple diffusion magnetic resonance imaging (dMRI) for prediction of isocitrate dehydrogenase 1 (IDH1) genotype and assessment of cell proliferation in gliomas.

Methods: Ninety-one patients with glioma underwent diffusion weighted imaging (DWI), multi-b-value DWI, and diffusion kurtosis imaging (DKI)/neurite orientation dispersion and density imaging (NODDI) on 3.0T MRI. Each parameter was compared between IDH1-mutant and IDH1 wild-type groups by Mann–Whitney U test in lower-grade gliomas (LrGGs) and glioblastomas (GBMs), respectively. Further, performance of each parameter was compared for glioma grading under the same IDH1 genotype. Spearman correlation coefficient between Ki-67 labeling index (LI) and each parameter was calculated.

Results: The diagnostic performance was better achieved with apparent diffusion coefficient (ADC), slow ADC (D), fast ADC (D∗), perfusion fraction (f), distributed diffusion coefficient (DDC), heterogeneity index (α), mean diffusivity (MD), mean kurtosis (MK), and intracellular volume fraction (ICVF) for distinguishing IDH1 genotypes in LrGGs, with statistically insignificant AUC values from 0.750 to 0.817. In GBMs, no difference between the two groups was found. For IDH1-mutant group, all parameters, except for fractional anisotropy (FA) and D∗, significantly discriminated LrGGs from GBMs (P < 0.05). However, for IDH1 wild-type group, only ADC statistically discriminated the two (P = 0.048). In addition, MK has maximal correlation coefficient (r = 0.567, P < 0.001) with Ki-67 LI.

Conclusion: dMRI-derived parameters are promising biomarkers for predicting IDH1 genotype in LrGGs, and MK has shown great potential in assessing glioma cell proliferation.
N-Terminal Pro-brain Natriuretic Peptide Is Associated With Hemorrhagic Transformation and Poor Outcomes in Patients With Stroke Treated With Intravenous Thrombolysis
Authors: Zhang Ke-Jia , Jin Hang , Xu Rui , Zhang Peng , Guo Zhen-Ni , Yang Yi
Published: November 2021

Background: N-terminal pro-brain natriuretic peptide (NT-proBNP) levels are a promising biomarker for predicting stroke outcomes; however, their prognostic validity is not well-understood in patients who have undergone intravenous thrombolysis. This study was designed to evaluate the prognostic value of NT-proBNP levels in patients with acute ischemic stroke treated with intravenous thrombolysis.

Methods: Patients with ischemic stroke who underwent intravenous thrombolysis between April 2015 and December 2020 were analyzed. Demographic information, information related to intravenous thrombolysis, medical history, and laboratory test results were collected. Outcomes, such as hemorrhagic transformation, early neurologic deterioration, poor 3-month functional outcomes, and 3-month mortality were recorded. Correlations between NT-proBNP levels and the above outcomes were analyzed, an individualized prediction model based on NT-proBNP levels for functional outcomes was developed, and a nomogram was drafted.

Results: A total of 404 patients were included in the study. Elevated NT-proBNP levels were independently associated with hemorrhagic transformation, poor 3-month functional outcomes, and 3-month mortality, while early neurological deterioration was not. An association between NT-proBNP levels and hemorrhagic transformation was noted. An individualized prediction model for poor functional outcomes was established, which was composed of ln(NT-proBNP), National Institutes of Health Stroke Scale (NIHSS), and baseline glucose, with good discrimination [area under the curve (AUC) 0.764] and calibration (P > 0.05).

Conclusion: To the best of our knowledge, this is the first report on the association between NT-proBNP levels and hemorrhagic transformation in patients who have undergone intravenous thrombolysis. The 3-month functional outcomes and mortality were found to be associated with NT-proBNP levels. An individualized prediction model based on NT-proBNP levels to predict the 3-month functional outcomes was established. Our results suggest that NT-proBNP levels could be used as a prognostic biomarker in patients with acute ischemic stroke treated with intravenous thrombolysis.
Involvement of Gut Microbiota in the Development of Psoriasis Vulgaris
Authors: Sun Chaonan , Chen Ling , Yang Huan , Sun Hongjiang , Xie Zhen , Zhao Bei , Jiang Xuemei , Qin Bi , Shen Zhu
Published: November 2021

Objectives: Psoriasis is a common chronic recurrent dermatitis. Accumulating observations show gut microbiota dysbiosis in psoriasis. We intend to further investigate the relationship between intestinal microbiota and psoriasis development.

Design: We first performed an epidemiological investigation on differences of gastrointestinal discomfort symptoms between patients with psoriasis and general population. Then variation of gut microbiota in patients with psoriasis (un)treated with acitretin plus narrow-band ultraviolet B (NB-UVB) was analyzed by 16S rRNA sequencing. We last compared recovery status and vital cytokines (lesion and intestine) of mouse psoriasiform models, which were transplanted with fecal microbiota from patients with psoriasis or healthy controls.

Results: (1) About 85.5% of patients with psoriasis vs. 58.1% of healthy controls presented with at least one gastrointestinal symptom. The prevalence of investigated symptoms (e.g., abdominal distension and constipation) were significantly higher in patients, compared with controls (p < 0.05). Passing flatus and constipation were significantly correlated with psoriasis (p < 0.05 in both cases). (2) The abundance of Ruminococcaceae family, Coprococcus_1 genus, and Blautia genus were decreased with psoriasis improvement (p < 0.05, respectively), which had been demonstrated significantly increased in psoriasis. (3) Mice receiving psoriatic microbes transplantation showed delayed recovery of psoriasiform dermatitis and less reduction of interleukin (IL)-17A than those receiving healthy microbiota or blank control (p < 0.05 and p < 0.01, respectively).

Conclusion: Multiple evidence we provided here preliminarily demonstrates the involvement of gut microbiota in the different degree of psoriasis activity. The strategy based on overall microbial communities is expected to be a promising supplementary for long-term management of psoriasis.
Effects of Microcurrent on Oxygen Saturation by Controlling Rectus Abdominis Activity in Preterm Infant With Desaturation During Feeding: A Pilot Study
Authors: Kwon Dong Rak , Kwon Dae Gil , Jeong Ji Eun
Published: November 2021

Objective:To determine whether a portable microcurrent therapy device (PMTD) of the rectus abdominis muscles is effective for treating desaturation during feeding in preterm infants and to evaluate the association between initial electrical activity of respiratory muscle and long-term development delay.

Methods:Twenty preterm infants with desaturation during feeding were recruited. Respiratory muscle activity was quantified by calculating the root mean square (RMS) of the electromyography. All preterm infants received a 30 min PMTD application to the rectus abdominis and diaphragm daily for 2 weeks. RMS of diaphragm and rectus abdominis, feeding volume, frequency of desaturation during feeding at baseline (pre-PMTD) and 1, 2 week post-PMTD were measured. The number of days it took to treat desaturation after PMTD was measured. A Denver developmental screening test was performed and infants were divided into 3 groups: (1) normal; (2) caution; and (3) delayed at 3months after PMTD.

Results:The desaturation during feeding of all the preterm infants subsided after PMTD and the mean days took to treat desaturation was 25.4 ± 14.2 days. The RMS of diaphragm, rectus abdominis, and frequency of desaturation during feeding were significantly decreased and the feeding volume was significantly increased after PMTD (p< 0.01). The mean treatment duration for desaturation was negatively correlated with RMS of rectus abdominis at baseline and 1 week post-PMTD, respectively (Pearson's correlation coefficient = −0.461,−0.514,p-value = 0.047, 0.029). RMS of rectus abdominis of Group 3 is lower than that of group 1 and 2 (p< 0.01).

Conclusions:This pilot study showed that the microcurrent therapy of rectus abdominis is an efficient therapy for the treatment of preterm infants with desaturation during feeding, especially preterm infants with higher activity of the rectus abdominis. In preterm infants with lower rectus abdominis activity, longer time is required to treat desaturation by microcurrent therapy and developmental delay is observed at months post-treatment.
Occult Kidney Dysfunction in Children With Transfusion-Dependent Thalassemia
Authors: Mohd Zikre Nurwahida , Muhamad Nor A. , Eng Caroline S. Y. , Zailanalhuddin Nur E. , Lai Charles D. , Foo Jen C. , Yap Suet L. , Ariffin Hany , Abu Bakar Karmila
Published: November 2021

Background: Thalassemia is the commonest hemoglobinopathy in Southeast Asia. Kidney dysfunction is an underreported sequelae in children with thalassemia. We conducted a retrospective study to identify the prevalence of and predisposing factors for kidney dysfunction in children with transfusion-dependent thalassemia (TDT).

Method: Abnormal kidney function was defined as children with a glomerular filtration rate (GFR) of <90 ml/min/1.73 m2 or a decline in GFR of >20 ml/min/1.73 m2 or presence of nephrotic range proteinuria within 3 years of commencing regular (every ≤6 weeks) red cell transfusion. Data analyzed were age at diagnosis of thalassemia, number of transfusion-years, iron chelation therapy, serum ferritin, and pre-transfusion hemoglobin levels.

Results: Eighty-one children were studied. Mean age was 11.72 ± 5.275 years. Thirty out of 81 (37%) demonstrated abnormal kidney function. Evidence of glomerular hyperfiltration was seen in 29/81 patients (25.85%) at their last clinic visit. This fraction was doubled [48/81 (59.3%)] when the cohort was tracked back by 3 years from the last clinic encounter. Age at diagnosis (RR, 1.157; 95% CI, 1.014–1.319; p = 0.03) and duration of receiving transfusions (RR, 0.984; 95% CI, 0.974–0.994; p = 0.001) were associated with increased risk of developing abnormal kidney function.

Conclusion: Abnormal kidney function in children with TDT may be overlooked by medical personnel without active screening measures. Children receiving regular red cell transfusions require systematic surveillance to enable early detection of kidney dysfunction and timely implementation of appropriate therapeutic interventions.
Examining the Relationship Between Community Integration and Mental Health Characteristics of Individuals With Childhood Acquired Neurological Disability
Authors: Nguyen Christine , Leung Abigail , Lauzon Andrea , Bayley Mark T. , Langer Laura L. , Luong Dorothy , Munce Sarah E. P.
Published: November 2021

Background: Many individuals with cerebral palsy (CP) or acquired brain injury (ABI) are at higher risk of lowered psychosocial functioning, poor mental health outcomes and decreased opportunities for community integration (CI) as they transition to adulthood. It is imperative to understand the characteristics of those at highest risk of dysfunction so that targeted interventions can be developed to reduce the impact.

Methods: This quantitative, cross-sectional study examines current patients of the Living Independently Fully Engaged [(LIFEspan) Service], a tertiary outpatient hospital-based clinic. The Patient Health Questionnaire-4 (PHQ-4) and the Community Integration Questionnaire (CIQ) were administered to participants. Personal health information was also collected from participants' health charts, and participant interviews. Associations of sex and condition with the outcomes of screening for further assessment of depression, screening for further assessment of anxiety, and CI were calculated using t-tests and Chi-square tests.

Results: 285 participants completed standardized screening tools for depression and anxiety (PHQ-4) and 283 completed the Community Integration Questionnaire (CIQ). Mean age was 23.4 (4.2) years; 59% were diagnosed with CP, 41% diagnosed with ABI, and 56% were male. A moderate proportion of the sample screened positive for further assessment of anxiety (28%) and depression (16%), and the overall mean score on the CIQ for the sample was 15.8 (SD 5.1). Participants that screened positive for further assessment of depression and anxiety on the PHQ-4 had lower scores on the Social Integration subscale of the CIQ (p = 0.04 and p = 0.036, respectively). Females were found to have significantly higher community integration than males (p = 0.0011) and those diagnosed with ABI were found to have significantly higher community integration than those with CP (p = 0.009), respectively. A weak negative association was found between age for the total sample and overall PHQ-4 score (p = 0.0417). Presence of an intellectual or learning disability/challenge was associated with a lower CIQ score (p = 0.0026).

Conclusions: This current study, highlights the need for further research to explore the unique needs and barriers faced by this population. This study may inform assessments and interventions to support the mental health and community integration of this population.
Population Pharmacokinetics of Polymyxin B in Obese Patients for Resistant Gram-Negative Infections
Authors: Wang Peile , Zhang Qiwen , Feng Min , Sun Tongwen , Yang Jing , Zhang Xiaojian
Published: November 2021

Polymyxin B is an effective but potentially nephrotoxic antibiotic that is commonly used to treat resistant Gram-negative infections. As a weight-based dosing drug, obese patients may be at a high risk of nephrotoxicity. However, the pharmacokinetics and dosing recommendations for this population are currently lacking. This study aimed to describe the polymyxin B population pharmacokinetics and to evaluate pharmacokinetic/pharmacodynamics (PK/PD) target attainment for obese patients. This study included 26 patients (body mass index, BMI >30) who received polymyxin B for ≥3 days. The total body weight (TBW) ranged from 75 to 125 kg, and the BMI ranged from 30.04 to 40.35. A two-compartment model adequately described the data using Phoenix NLME software. Monte Carlo simulation was used to assess polymyxin B exposure and the probability of target attainment (PTA). As a result, body weight had no significant effect on polymyxin B pharmacokinetics. According to model-based simulation, adjusted body weight (ABW)-based regimens had a high probability of achieving optimal exposure with minimal toxicity risk by comparing TBW and ideal body weight (IBW)-based regimens. The fixed dose of 125 mg or 150 mg q12h had a high toxicity risk. PTA results showed that TBW, IBW, and ABW-based regimens had similar PTA values. Therefore, for obese patients, ABW-based regimens but with a daily dose <250 mg have a high likelihood of achieving an AUCss,24h of 50–100 mg h/L and attaining PK/PD targets with the MIC ≤0.5 mg/L.
Paeonol Attenuated Vascular Fibrosis Through Regulating Treg/Th17 Balance in a Gut Microbiota-Dependent Manner
Authors: Shi Xiaoyan , Huang Hanwen , Zhou Min , Liu Yarong , Wu Hongfei , Dai Min
Published: November 2021

Background: Paeonol (Pae) is a natural phenolic compound isolated from Cortex Moutan, which exhibits anti-atherosclerosis (AS) effects. Our previous work demonstrated that gut microbiota plays an important role during AS treatment as it affects the efficacy of Pae. However, the mechanism of Pae in protecting against vascular fibrosis as related to gut microbiota has yet to be elucidated.

Objective: To investigate the antifibrosis effect of Pae on AS mice and demonstrate the underlying gut microbiota-dependent mechanism.

Methods: ApoE-/- mice were fed with high-fat diet (HFD) to replicate the AS model. H&E and Masson staining were used to observe the plaque formation and collagen deposition. Short-chain fatty acid (SCFA) production was analyzed through LC-MS/MS. The frequency of immune cells in spleen was phenotyped by flow cytometry. The mRNA expression of aortic inflammatory cytokines was detected by qRT-PCR. The protein expression of LOX and fibrosis-related indicators were examined by western blot.

Results: Pae restricted the development of AS and collagen deposition. Notably, the antifibrosis effect of Pae was achieved by regulating the gut microbiota. LC-MS/MS data indicated that the level of SCFAs was increased in caecum contents. Additionally, Pae administration selectively upregulated the frequency of regulatory T (Treg) cells as well as downregulated the ratio of T helper type 17 (Th17) cells in the spleen of AS mice, improving the Treg/Th17 balance. In addition, as expected, Pae intervention can significantly downregulate the levels of proinflammatory cytokines IL-1β, IL-6, TNF-α, and IL-17 in the aorta, and upregulate the levels of anti-inflammatory factor IL-10, a marker of Treg cells. Finally, Pae’s intervention in the gut microbiota resulted in the restoration of the balance of Treg/Th17, which indirectly downregulated the protein expression level of LOX and fibrosis-related indicators (MMP-2/9 and collagen I/III).

Conclusion: Pae attenuated vascular fibrosis in a gut microbiota-dependent manner. The underlying protective mechanism was associated with the improved Treg/Th17 balance in spleen mediated through the increased microbiota-derived SCFA production. Collectively, our results demonstrated the role of Pae as a potential gut microbiota modulator to prevent and treat AS.
Rapid-Onset Anti-Stress Effects of a Kappa-Opioid Receptor Antagonist, LY2795050, Against Immobility in an Open Space Swim Paradigm in Male and Female Mice
Authors: Baynard Caroline , Prisinzano Thomas E. , Butelman Eduardo R.
Published: November 2021

The kappa-opioid receptor (KOR) / dynorphin system is implicated with behavioral and neurobiological effects of stress exposure (including heavy exposure to drugs of abuse) in translational animal models. Thus some KOR-antagonists can decrease the aversive, depressant-like and anxiety-like effects caused by stress exposure. The first generation of selective KOR-antagonists have slow onsets (hours) and extremely long durations of action (days-weeks), in vivo. A new generation of KOR antagonists with rapid onset and shorter duration of action can potentially decrease the effects of stress exposure in translational models, and may be of interest for medication development. This study examined the rapid onset anti-stress effects of one of the shorter acting novel KOR-antagonists (LY2795050, (3-chloro-4-(4-(((2S)-2-pyridin-3-ylpyrrolidin-1-yl)methyl) phenoxy)benzamide)) in a single-session open space swim (OSS) stress paradigm (15 min duration), in adult male and female C57BL/6 J mice. LY2795050 (0.32 mg/kg, i.p.) had rapid onset (within 15 min) and short duration (<3 h) of KOR-antagonist effects, based on its blockade of the locomotor depressant effects of the KOR-agonist U50,488 (10 mg/kg). LY2795050 (0.32 mg/kg), when administered only 1 min prior to the OSS stress paradigm, decreased immobility in males, but not females. With a slightly longer pretreatment time (15 min), this dose of LY2795050 decreased immobility in both males and females. A 10-fold smaller dose of LY2795050 (0.032 mg/kg) was inactive in the OSS, showing dose-dependence of this anti-stress effect. Overall, these studies show that a novel KOR-antagonist can produce very rapid onset anti-immobility effects in this model of acute stress exposure.
Analysis of Antibiotic Consumption by AWaRe Classification in Shandong Province, China, 2012–2019: A Panel Data Analysis
Authors: Yin Jia , Li Hongyu , Sun Qiang
Published: November 2021

Introduction: This study aims to examine the changes in trends and patterns of clinical consumption of antibiotics in Shandong, China based on Access, Watch, and Reserve (AWaRe) Classification after 10-years national antibiotic stewardship.

Methods: Antibiotic consumption data of all health care institutions for the period of 2012–2019 were obtained from the Drug Centralized Bidding Procurement System of Shandong. Shandong is a province that has the second-largest population in China. Five of the 16 cities in Shandong were high-income areas (HIAs) and the other 11 cities were grouped into upper-middle-income areas (UMIAs). The main outcome measures were the antibiotic consumption rates (DDD per 1,000 inhabitants per day, DID) and the proportions of different groups of antibiotics.

Results: The overall antibiotic consumption rate increased from 12.859–15.802 DID between 2012 and 2014, then continuously decreased to 9.771 DID in 2019. The consumption rate of access, watch, and reserve antibiotics have reduced since 2014 with a compound annual growth rate of −10.1, −9.0, and −8.1%, respectively. During 2012–2019, the access group proportion reduced from 50.0 to 44.9%, while the proportion of the watch group increased from 42 to 45.2%. The antibiotic consumption rate increased from 2012 to 2019 (from 7.38 to 9.12 DID) in the HIAs but sharply decreased in the UMIAs from 2014 to 2019 (from 17.94 to 10.05 DID). The watch antibiotics had the highest proportion of consumption in the HIAs (55.3% in 2019), while the access group had the highest proportion of consumption in the UMIA (49.5% in 2019).

Conclusion: The antibiotic stewardship policies launched in the last 10 years have contributed to reducing the clinical antibiotic consumption in Shandong. These policies have different effects on areas with different economic levels. The pattern of antibiotic consumption is still inappropriate in China as the watch group of antibiotics was consumed the most.
Partially Coherent Illumination Based Point-Diffraction Digital Holographic Microscopy Study Dynamics of Live Cells
Authors: Zhuo Kequn , Wang Yu , Wang Yang , Wen Kai , Liu Min , Ma Ying , Zheng Juanjuan , Gao Peng
Published: November 2021

This paper presents a partially coherent point-diffraction digital holographic microscopy (PC-pDHM) prototype and demonstrates its application in label-free imaging of the dynamic processes of live cells. In PC-pDHM, the light scattered by a rotating diffuser is coupled into a multi-mode fiber, and the output light is used as the partially coherent illumination (PCI), which reduces the speckle noise significantly in PC-pDHM. A polarization-grating is used to remold the object and the reference waves, and the fringe contrast of the generated hologram can be adjusted by changing the polarization of the illumination wave. Using the PC-pDHM prototype, transparent samples and notably the dynamic processes of live cells were imaged with high contrast and in a label-free manner, discovering the pathological mechanisms of biology in the cellular and sub-cellular levels.
Functional Organization of Sequence Motifs in Diverse Transit Peptides of Chloroplast Proteins
Authors: Jeong Jinseung , Hwang Inhwan , Lee Dong Wook
Published: November 2021

Although the chloroplasts in plants are characterized by an inherent genome, the chloroplast proteome is composed of proteins encoded by not only the chloroplast genome but also the nuclear genome. Nuclear-encoded chloroplast proteins are synthesized on cytosolic ribosomes and post-translationally targeted to the chloroplasts. In the latter process, an N-terminal cleavable transit peptide serves as a targeting signal required for the import of nuclear-encoded chloroplast interior proteins. This import process is mediated via an interaction between the sequence motifs in transit peptides and the components of the TOC/TIC (translocon at the outer/inner envelope of chloroplasts) translocons. Despite a considerable diversity in primary structures, several common features have been identified among transit peptides, including N-terminal moderate hydrophobicity, multiple proline residues dispersed throughout the transit peptide, preferential usage of basic residues over acidic residues, and an absence of N-terminal arginine residues. In this review, we will recapitulate and discuss recent progress in our current understanding of the functional organization of sequence elements commonly present in diverse transit peptides, which are essential for the multi-step import of chloroplast proteins.
Optimizing RNAi-Target by Nicotiana benthamiana-Soybean Mosaic Virus System Drives Broad Resistance to Soybean Mosaic Virus in Soybean
Authors: Jiang Hua , Li Kai , Gai Junyi
Published: November 2021

Soybean mosaic virus (SMV) is a prevalent pathogen of soybean (Glycine max). Pyramiding multiple SMV-resistance genes into one individual is tedious and difficult, and even if successful, the obtained multiple resistance might be broken by pathogen mutation, while targeting viral genomeviahost-induced gene silencing (HIGS) has potential to explore broad-spectrum resistance (BSR) to SMV. We identified five conserved target fragments (CTFs) fromS1toS5using multiple sequence alignment of 30 SMV genome sequences and assembled the corresponding target-inverted-repeat constructs (TIRs) from S1-TIR to S5-TIR. Since the inefficiency of soybean genetic transformation hinders the function verification of batch TIRs in SMV-resistance, theNicotiana benthamiana-chimeric-SMV andN. benthamiana-pSMV-GUS pathosystems combined withAgrobacterium-mediated transient expression assays were invented and used to test the efficacy of these TIRs. From that, S1-TIR assembled from 462 bp CTF-S1with 92% conservation rate performed its best on inhibiting SMV multiplication. Accordingly, S1-TIR was transformed into SMV-susceptible soybeanNN1138-2, the resistant-healthy transgenic T1-plants were then picked outviadetached-leaf inoculation assay with the stock-plants continued for progeny reproduction (T1dual-utilization). All the four T3transgenic progenies showed immunity to all the inoculated 11 SMV strains under individual or mixed inoculation, achieving a strong BSR. Thus, optimizing target for HIGSviatransientN. benthamiana-chimeric-SMV andN. benthamiana-pSMV-GUS assays is crucial to drive robust resistance to SMV in soybean and the transgenic S1-TIR-lines will be a potential breeding source for SMV control in field.
In Case of an Emergency: The Development and Effects of a Digital Intervention for Coping With Distress in Norway During the COVID-19 Pandemic
Authors: Nordgreen Tine , Nordby Emilie Sektnan , Myklebost Sunniva Burok , Flobak Eivind , Kahlon Smiti
Published: November 2021

Background: The COVID-19 pandemic and its consequences has been found to negatively affect the general population’s psychological well-being.

Objective: The objectives of this paper are to report on the development and clinical effects of a self-guided Internet-delivered intervention for adults in Norway who suffer from mild to moderate psychological distress during the COVID-19 pandemic.

Methods: The participants, recruited between April and December 2020, were randomized to receive a new treatment module either every third or every fifth day. The clinical outcomes were self-reported depressive and anxiety symptoms and change in positive and negative emotions.

Results: A total of 1256 individuals accessed the pre-screening survey, 407 were eligible and 92 provided contact information, where 82 were included in the study, n = 44 in the 3-day group and n = 38 in the 5-day group. Overall, the statistical analyses showed a significant decrease in depressive and anxiety symptoms and an increase in positive emotions, with small and moderate within group effect sizes. No significant differences between the groups were identified in clinical outcomes or adherence.

Conclusion: These findings indicate that psychological distress in the general population during the COVID-19 pandemic may be reduced through the use of a scalable self-guided Internet-delivered intervention. Furthermore, the lack of significant differences between the 5-day and 3-day group may indicate that the intervention can be delivered at a more intensive pace without negatively affecting treatment outcomes. The results need to be interpreted with caution as the sample was self-selected, as well as the lack of passive control group. Hence the results may be attributed to external factors.
“I Just Find It Easier to Let Go of Anger”: Reflections on the Ways in Which Yoga Influences How Young People Manage Their Emotions
Authors: Hagen Ingunn , Skjelstad Solbjørg , Nayar Usha Sidana
Published: November 2021

In this article we discuss how young people experienced a school-based yoga intervention. We pay particular attention to how yoga provides a space for young people to deal with their emotions. We base our discussion on qualitative data from young people in Norway who participated in the European research project “Hippocampus: Promoting Mental Health and Wellbeing among Young People through Yoga.” The qualitative results are based on experiences described by these young people in individual semi-structured interviews and in diaries or logs. Our data include nine interviews performed in the spring of 2019 with young people of Norwegian and refugee background in their late teens and early twenties. There were also 133 logs noted by the students exposed to the yoga intervention. In the qualitative interviews, young people talk about yoga and emotional management, improved sleep habits, and regulation. They also report improved ability to regulate and cope with stress. Yoga seemed especially beneficial for refugee trauma. In this article, we have chosen to focus on the utterances of young people about emotions, as those were quite dominant in our data, especially in the interview material. We have identified instances of emotional regulation, but also of emotional processes and changes of emotions, all of which were related to these young students practicing yoga. The impact of yoga on emotions illustrates the potential of yoga to improve the well-being and mental health of young people.
Shared Representations in Athletes: Segmenting Action Sequences From Taekwondo Reveals Implicit Agreement
Authors: Stadler Waltraud , Kraft Veit S. , Be’er Roee , Hermsdörfer Joachim , Ishihara Masami
Published: November 2021

How do athletes represent actions from their sport? How are these representations structured and which knowledge is shared among experts in the same discipline? To address these questions, the event segmentation task was used. Experts in Taekwondo and novices indicated how they would subjectively split videos of Taekwondo form sequences into meaningful units. In previous research, this procedure was shown to unveil the structure of internal action representations and to be affected by sensorimotor knowledge. Without specific instructions on the grain size of segmentation, experts tended to integrate over longer episodes which resulted in a lower number of single units. Moreover, in accordance with studies in figure-skating and basketball, we expected higher agreement among experts on where to place segmentation marks, i.e., boundaries. In line with this hypothesis, significantly more overlap of boundaries was found within the expert group as compared to the control group. This was observed even though the interindividual differences in the selected grain size were huge and expertise had no systematic influence here. The absence of obvious goals or objects to structure Taekwondo forms underlines the importance of shared expert knowledge. Further, experts might have benefited from sensorimotor skills which allowed to simulate the observed actions more precisely. Both aspects may explain stronger agreement among experts even in unfamiliar Taekwondo forms. These interpretations are descriptively supported by the participants’ statements about features which guided segmentation and by an overlap of the group’s agreed boundaries with those of an experienced referee. The study shows that action segmentation can be used to provide insights into structure and content of action representations specific to experts. The mechanisms underlying shared knowledge among Taekwondoists and among experts in general are discussed on the background of current theoretic frameworks.