bluuebunny/crossref_metadata_2025 huggingface dataset:
Bacterial and Host Determinants of Group B Streptococcal Infection of the Neonate and Infant
Authors: Furuta Anna , Brokaw Alyssa , Manuel Gygeria , Dacanay Matthew , Marcell Lauren , Seepersaud Ravin , Rajagopal Lakshmi , Adams Waldorf Kristina
Published: February 2022

Group B streptococci (GBS) are Gram-positive β-hemolytic bacteria that can cause serious and life-threatening infections in neonates manifesting as sepsis, pneumonia, meningitis, osteomyelitis, and/or septic arthritis. Invasive GBS infections in neonates in the first week of life are referred to as early-onset disease (EOD) and thought to be acquired by the fetus through exposure to GBS in utero or to vaginal fluids during birth. Late-onset disease (LOD) refers to invasive GBS infections between 7 and 89 days of life. LOD transmission routes are incompletely understood, but may include breast milk, household contacts, nosocomial, or community sources. Invasive GBS infections and particularly meningitis may result in significant neurodevelopmental injury and long-term disability that persists into childhood and adulthood. Globally, EOD and LOD occur in more than 300,000 neonates and infants annually, resulting in 90,000 infant deaths and leaving more than 10,000 infants with a lifelong disability. In this review, we discuss the clinical impact of invasive GBS neonatal infections and then summarize virulence and host factors that allow the bacteria to exploit the developing neonatal immune system and target organs. Specifically, we consider the mechanisms known to enable GBS invasion into the neonatal lung, blood vessels and brain. Understanding mechanisms of GBS invasion and pathogenesis relevant to infections in the neonate and infant may inform the development of therapeutics to prevent or mitigate injury, as well as improve risk stratification.
TRPC3 Channel Activity and Viability of Purkinje Neurons can be Regulated by a Local Signalosome
Authors: Aslam Naveed , Alvi Farah
Published: February 2022

Canonical transient receptor potential channels (TRPC3) may play a pivotal role in the development and viability of dendritic arbor in Purkinje neurons. This is a novel postsynaptic channel for glutamatergic synaptic transmission. In the cerebellum, TRPC3 appears to regulate functions relating to motor coordination in a highly specific manner. Gain of TRPC3 function is linked to significant alterations in the density and connectivity of dendritic arbor in Purkinje neurons. TRPC3 signals downstream of class I metabotropic glutamate receptors (mGluR1). Moreover, diacylglycerol (DAG) can directly bind and activate TRPC3 molecules. Here, we investigate a key question: How can the activity of the TRPC3 channel be regulated in Purkinje neurons? We also explore how mGluR1 activation, Ca2+influx, and DAG homeostasis in Purkinje neurons can be linked to TRPC3 activity modulation. Through systems biology approach, we show that TRPC3 activity can be modulated by a Purkinje cell (PC)–specific local signalosome. The assembly of this signalosome is coordinated by DAG generation after mGluR1 activation. Our results also suggest that purinergic receptor activation leads to the spatial and temporal organization of the TRPC3 signaling module and integration of its key effector molecules such as DAG, PKCγ, DGKγ, and Ca2+into an organized local signalosome. This signaling machine can regulate the TRPC3 cycling between active, inactive, and desensitized states. Precise activity of the TRPC3 channel is essential for tightly regulating the Ca2+entry into PCs and thus the balance of lipid and Ca2+signaling in Purkinje neurons and hence their viability. Cell-type–specific understanding of mechanisms regulating TRPC3 channel activity could be key in identifying therapeutic targeting opportunities.
Integrating Environment and Aging Research: Opportunities for Synergy and Acceleration
Authors: Malecki Kristen M. C. , Andersen Julie K. , Geller Andrew M. , Harry G. Jean , Jackson Chandra L. , James Katherine A. , Miller Gary W. , Ottinger Mary Ann
Published: February 2022

Despite significant overlaps in mission, the fields of environmental health sciences and aging biology are just beginning to intersect. It is increasingly clear that genetics alone does not predict an individual’s neurological aging and sensitivity to disease. Accordingly, aging neuroscience is a growing area of mutual interest within environmental health sciences. The impetus for this review came from a workshop hosted by the National Academies of Sciences, Engineering, and Medicine in June of 2020, which focused on integrating the science of aging and environmental health research. It is critical to bridge disciplines with multidisciplinary collaborations across toxicology, comparative biology, epidemiology to understand the impacts of environmental toxicant exposures and age-related outcomes. This scoping review aims to highlight overlaps and gaps in existing knowledge and identify essential research initiatives. It begins with an overview of aging biology and biomarkers, followed by examples of synergy with environmental health sciences. New areas for synergistic research and policy development are also discussed. Technological advances including next-generation sequencing and other-omics tools now offer new opportunities, including exposomic research, to integrate aging biomarkers into environmental health assessments and bridge disciplinary gaps. This is necessary to advance a more complete mechanistic understanding of how life-time exposures to toxicants and other physical and social stressors alter biological aging. New cumulative risk frameworks in environmental health sciences acknowledge that exposures and other external stressors can accumulate across the life course and the advancement of new biomarkers of exposure and response grounded in aging biology can support increased understanding of population vulnerability. Identifying the role of environmental stressors, broadly defined, on aging biology and neuroscience can similarly advance opportunities for intervention and translational research. Several areas of growing research interest include expanding exposomics and use of multi-omics, the microbiome as a mediator of environmental stressors, toxicant mixtures and neurobiology, and the role of structural and historical marginalization and racism in shaping persistent disparities in population aging and outcomes. Integrated foundational and translational aging biology research in environmental health sciences is needed to improve policy, reduce disparities, and enhance the quality of life for older individuals.
Emotion Recognition Based on Dynamic Energy Features Using a Bi-LSTM Network
Authors: Zhu Meili , Wang Qingqing , Luo Jianglin
Published: February 2022

Among electroencephalogram (EEG) signal emotion recognition methods based on deep learning, most methods have difficulty in using a high-quality model due to the low resolution and the small sample size of EEG images. To solve this problem, this study proposes a deep network model based on dynamic energy features. In this method, first, to reduce the noise superposition caused by feature analysis and extraction, the concept of an energy sequence is proposed. Second, to obtain the feature set reflecting the time persistence and multicomponent complexity of EEG signals, the construction method of the dynamic energy feature set is given. Finally, to make the network model suitable for small datasets, we used fully connected layers and bidirectional long short-term memory (Bi-LSTM) networks. To verify the effectiveness of the proposed method, we used leave one subject out (LOSO) and 10-fold cross validation (CV) strategies to carry out experiments on the SEED and DEAP datasets. The experimental results show that the accuracy of the proposed method can reach 89.42% (SEED) and 77.34% (DEAP).
Brain Activity Changes in Slow 5 and Slow 4 Frequencies in Patients With Optic Neuritis: A Resting State Functional MRI Study
Authors: Yan Kai , Shi Wen-Qing , Su Ting , Liao Xu-Lin , Wu Shi-Nan , Li Qiu-Yu , Yu Jing , Shu Hui-Ye , Zhang Li-Juan , Pan Yi-Cong , Shao Yi
Published: February 2022

Objective

We used the amplitude of low-frequency fluctuation (ALFF) method to investigate spontaneous brain activity in patients with optic neuritis (ON) in specific frequency bands.

Data and Methods

A sample of 21 patients with ON (13 female and eight male) and 21 healthy controls (HCs) underwent functional magnetic resonance imaging (fMRI) scans in the resting state. We analyzed the ALFF values at different frequencies (slow-4 band: 0.027–0.073 Hz; slow-5 band: 0.01–0.027 Hz) in ON patients and HCs.

Results

In the slow-4 frequency range, compared with HCs, ON patients had apparently lower ALFF in the insula and the whack precuneus. In the slow-5 frequency range, ON patients showed significantly increased ALFF in the left parietal inferior and the left postcentral.

Conclusion

Our results suggest that ON may be involved in abnormal brain function and can provide a basis for clinical research.
We Move or Are We Moved? Unpicking the Origins of Voluntary Movements to Better Understand Semivoluntary Movements
Authors: Virameteekul Sasivimol , Bhidayasiri Roongroj
Published: February 2022

The capacity for voluntary control is seen as essential to human movements; the sense that one intended to move (willing) and those actions were self-generated (self-agency) gives the sense of voluntariness and of being in control. While the mechanisms underlying voluntary movement have long been unclear, recent neuroscientific tools have identified networks of different brain areas, namely, the prefrontal cortex, supplementary motor area, and parietal cortex, that underlie voluntary action. Dysfunction in these brain areas can result in different forms of semivoluntary movement as the borderland of voluntary and involuntary movement where a person may experience a disordered sense of will or agency, and thus the movement is experienced as unexpected and involuntary, for an otherwise voluntary-appearing movement. Tics, functional movement disorders, stereotypies, perseveration, compulsions, utilization behaviors, and motor mannerism have been described elsewhere in the context of psychoses, and are often mistaken for each other. Yet, they reflect an impairment of prefrontal cortices and related circuits rather than simple motor systems, which results in the absence of subjective recognition of the movements, in contrast to other neurological movement disorders where principal abnormalities are located within the basal ganglia and its connections. Therefore, their recognition is clinically important since they are usually associated with neurodevelopmental and neurodegenerative disorders. In this review, we first defined a conceptual framework, from both a neuroanatomical and a neurophysiological point of view, for the generation of voluntary movement. We then examined the evidence linking dysfunctions in different motor pathways to each type of movement disorder. We looked at common semivoluntary movement disorders providing an overview, where possible, of their phenomenology and brain network abnormalities for each condition. We also emphasized important clinical feature similarities and differences to increase recognition of each condition in practice.
OPRA-RS: A Hearing-Aid Fitting Method Based on Automatic Speech Recognition and Random Search
Authors: Gonçalves Braz Libio , Fontan Lionel , Pinquier Julien , Stone Michael A. , Füllgrabe Christian
Published: February 2022

Hearing-aid (HA) prescription rules (such as NAL-NL2, DSL-v5, and CAM2) are used by HA audiologists to define initial HA settings (e.g., insertion gains, IGs) for patients. This initial fitting is later individually adjusted for each patient to improve clinical outcomes in terms of speech intelligibility and listening comfort. During this fine-tuning stage, speech-intelligibility tests are often carried out with the patient to assess the benefits associated with different HA settings. As these tests tend to be time-consuming and performance on them depends on the patient's level of fatigue and familiarity with the test material, only a limited number of HA settings can be explored. Consequently, it is likely that a suboptimal fitting is used for the patient. Recent studies have shown that automatic speech recognition (ASR) can be used to predict the effects of IGs on speech intelligibility for patients with age-related hearing loss (ARHL). The aim of the present study was to extend this approach by optimizing, in addition to IGs, compression thresholds (CTs). However, increasing the number of parameters to be fitted increases exponentially the number of configurations to be assessed. To limit the number of HA settings to be tested, three random-search (RS) genetic algorithms were used. The resulting new HA fitting method, combining ASR and RS, is referred to as “objective prescription rule based on ASR and random search" (OPRA-RS). Optimal HA settings were computed for 12 audiograms, representing average and individual audiometric profiles typical for various levels of ARHL severity, and associated ASR performances were compared to those obtained with the settings recommended by CAM2. Each RS algorithm was run twice to assess its reliability. For all RS algorithms, ASR scores obtained with OPRA-RS were significantly higher than those associated with CAM2. Each RS algorithm converged on similar optimal HA settings across repetitions. However, significant differences were observed between RS algorithms in terms of maximum ASR performance and processing costs. These promising results open the way to the use of ASR and RS algorithms for the fine-tuning of HAs with potential speech-intelligibility benefits for the patient.
Musicality and Age Interaction in Tone Development
Authors: Rhee Nari , Chen Aoju , Kuang Jianjing
Published: February 2022

Vocal pitch, which involves not only F0 but also multiple covarying acoustic cues is central to linguistic perception and production at various levels of prosodic structure. Recent studies on language development have shown that differences in learners' musicality affect the F0 cue development in perception of sentence-level intonation or in prosodic realization of focus. This study aims to contribute toward a fuller understanding of the effect of musicality on linguistic pitch development via a close investigation of the relationship between musicality, age, and lexical tone production covering both F0 and spectral cues in children. Forty-three native Mandarin-speaking children between the ages of 4 and 6 years are recruited to participate in both a semi-spontaneous tone production task and a musicality test. For each age (4, 5, and 6 years) and musicality (below or above the median score of each age group) group, the contrastivity of the four tones is evaluated by performing automatic tone classification using three sets of acoustic cues (F0, spectral cues, and both). It has been found that higher musicality is associated with higher contrastivity of the tones produced at the age of 4 and 5 years, but not at the age of 6 years. These results suggest that musicality promotes earlier development of tone production only in earlier stages of prosodic development; by the age of 6 years, the musicality advantage in tone production subsides.
Dose-Intensified Stereotactic Ablative Radiation for Localized Prostate Cancer
Authors: Chen Lily , Gannavarapu Bhavani S. , Desai Neil B. , Folkert Michael R. , Dohopolski Michael , Gao Ang , Ahn Chul , Cadeddu Jeffrey , Bagrodia Aditya , Woldu Solomon , Raj Ganesh V. , Roehrborn Claus , Lotan Yair , Timmerman Robert D. , Garant Aurelie , Hannan Raquibul
Published: February 2022

Purpose

Stereotactic ablative radiation (SAbR) has been increasingly used in prostate cancer (PCa) given its convenience and cost efficacy. Optimal doses remain poorly defined with limited prospective comparative trials and long-term safety/efficacy data at higher dose levels. We analyzed toxicity and outcomes for SAbR in men with localized PCa at escalated 45 Gy in 5 fractions.

Methods and Materials

This study retrospectively analyzed men from 2015 to 2019 with PCa who received linear-accelerator-based SAbR to 45 Gy in 5 fractions, along with perirectal hydrogel spacer, fiducial placement, and MRI-based planning. Disease control outcomes were calculated from end of treatment. Minimally important difference (MID) assessing patient-reported quality of life was defined as greater than a one-half standard deviation increase in American Urological Association (AUA) symptom score after SAbR.

Results

Two-hundred and forty-nine (249) low-, intermediate-, and high-risk PCa patients with median follow-up of 14.9 months for clinical toxicity were included. Acute urinary grade II toxicity occurred in 20.4% of patients. Acute grade II GI toxicity occurred in 7.3% of patients. For follow-up > 2 years (n = 69), late GU and GI grade ≥III toxicity occurred in 5.8% and 1.5% of patients, respectively. MID was evident in 31.8%, 23.4%, 35.8%, 37.0%, 33.3%, and 26.7% of patients at 3, 6, 12, 24, 36, and 48 months, respectively. The median follow-up for biochemical recurrence was 22.6 months with biochemical failure-free survival of 100% at 1 year (n = 226) and 98.7% for years 2 (n = 113) and 3 (n = 54).

Conclusions

SAbR for PCa at 45 Gy in 5 fractions shows an encouraging safety profile. Prospective studies with longer follow-up are warranted to establish this dose regimen as standard of care for PCa.
Effective Delivery of siRNA-Loaded Nanoparticles for Overcoming Oxaliplatin Resistance in Colorectal Cancer
Authors: Zhou Yue , Zhang Qing , Wang Minjia , Huang Chengzhi , Yao Xueqing
Published: February 2022

Chemotherapy resistance represents a formidable obstacle in advanced or metastatic colorectal cancer (CRC) patients. It is reported that ATPase copper transporting alpha (ATP7A) plays an important role in chemotherapy resistance in CRC. Here, we identified ATP7A as a potentially key gene of OXA resistance in CRC. The patients with higher expression of ATP7A tended to have platinum drug resistance. While the lower expression of ATP7A by siRNA knockdown resulted in enhancement of OXA sensitivity and increased OXA-induced apoptosis. Further, we demonstrated a novel and safe strategy to increase CRC chemosensitivity by delivering siRNA into tumor cells via a novel nanoparticle, DAN. In summary, our study provided a novel nanocarrier-based delivery of ATP7A to interfere in a key gene of chemo-resistance in CRC, which may be a novel therapeutic strategy to overcome chemotherapy resistance in CRC.
Actin Modulation Regulates the Alpha-1-Syntrophin/p66Shc Mediated Redox Signaling Contributing to the RhoA GTPase Protein Activation in Breast Cancer Cells
Authors: Ali Roshia , Mir Hilal Ahmad , Hamid Rabia , Bhat Basharat , Shah Riaz A. , Khanday Firdous A. , Bhat Sahar Saleem
Published: February 2022

SNTA1 signaling axis plays an essential role in cytoskeletal organization and is also implicated in breast cancers. In this study, we aimed to investigate the involvement of actin cytoskeleton in the propagation of SNTA1/p66shc mediated pro-metastatic cascade in breast cancer cells.The effect of actin filament depolymerization on SNTA1-p66Shc interaction and the trimeric complex formation was analyzed using co-immunoprecipitation assays. Immunofluorescence and RhoA activation assays were used to show the involvement of SNTA1-p66Shc interaction in RhoA activation and F-actin organization. Cellular proliferation and ROS levels were assessed using MTT assay and Amplex red catalase assay. The migratory potential was evaluated using transwell migration assay and wound healing assay.We found that cytochalasin D mediated actin depolymerization significantly declines endogenous interaction between SNTA1 and p66Shc protein in MDA-MB-231 cells. Results indicate that SNTA1 and p66Shc interact with RhoA protein under physiological conditions. The ROS generation and RhoA activation were substantially enhanced in cells overexpressing SNTA1 and p66Shc, promoting proliferation and migration in these cells. In addition, we found that loss of SNTA1-p66Shc interaction impaired actin organization, proliferation, and migration in breast cancer cells. Our results demonstrate a novel reciprocal regulatory mechanism between actin modulation and SNTA1/p66Shc/RhoA signaling cascade in human metastatic breast cancer cells.
Perioperative Serum Scoring Systems Predict Early Recurrence and Poor Prognosis of Resectable Pancreatic Cancer
Authors: Li Shengnan , Zhang Gengpu , Lu Yang , Zhao Tiansuo , Gao Chuntao , Liu Weishuai , Piao Yongjun , Chen Yanan , Huang Chongbiao , Chang Antao , Hao Jihui
Published: February 2022

Objective

Some patients with pancreatic ductal adenocarcinoma (PDAC) are prone to rapid recurrence or metastasis after radical resection. However, evaluation methods for effectively identifying these patients are lacking. In this study, we established perioperative serum scoring systems to screen patients with early recurrence and poor prognosis.

Methods

We systematically analysed 44 perioperative serum parameters, including systemic inflammatory parameters, coagulation system parameters, tumor markers, and 18 clinicopathological characteristics of 218 patients with radical resection in our centre. Univariate Cox regression and LASSO regression models were used to screen variables. Kaplan-Meier survival analysis was used to compare relapse-free survival and overall survival. Multivariate Cox regression was used to evaluate the independent risk variables. AUC and C-index were used to reveal the effectiveness of the models. In addition, the effectiveness was also verified in an independent cohort of 109 patients.

Results

Preoperative systemic immune coagulation cascade (SICC) (including increased neutrophil to lymphocyte ratio, decreased lymphocyte to monocyte ratio, increased platelet and fibrinogen) and increased postoperative tumor markers (TMs) (CA199, CEA and CA242) were independent risk factors for early recurrence of resectable pancreatic cancer. On this basis, we established the preoperative SICC score and postoperative TMs score models. The patients with higher preoperative SICC or postoperative TMs score were more likely to have early relapse and worse prognosis. The nomogram based on preoperative SICC, postoperative TMs, CACI, smoking index, vascular cancer embolus and adjuvant chemotherapy can effectively evaluate the recurrence rate (AUC1 year: 0.763, AUC2 year: 0.679, AUC3 year: 0.657) and overall survival rate (AUC1 year: 0.770, AUC3 year: 0.804, AUC5 year: 0.763).

Conclusion

Preoperative SICC and postoperative TMs can help identify resectable PDAC patients with early recurrence and poor prognosis.
Inadequate Bioavailability of Intramuscular Epinephrine in a Neonatal Asphyxia Model
Authors: Berkelhamer Sara K. , Vali Payam , Nair Jayasree , Gugino Sylvia , Helman Justin , Koenigsknecht Carmon , Nielsen Lori , Lakshminrusimha Satyan
Published: February 2022

Background

Over half a million newborn deaths are attributed to intrapartum related events annually, the majority of which occur in low resource settings. While progress has been made in reducing the burden of asphyxia, novel approaches may need to be considered to further decrease rates of newborn mortality. Administration of intravenous, intraosseous or endotracheal epinephrine is recommended by the Newborn Resuscitation Program (NRP) with sustained bradycardia at birth. However, delivery by these routes requires both advanced skills and specialized equipment. Intramuscular (IM) epinephrine may represent a simple, low cost and highly accessible alternative for consideration in the care of infants compromised at birth. At present, the bioavailability of IM epinephrine in asphyxia remains unclear.

Methods

Four term fetal lambs were delivered by cesarean section and asphyxiated by umbilical cord occlusion with resuscitation after 5 min of asystole. IM epinephrine (0.1 mg/kg) was administered intradeltoid after 1 min of positive pressure ventilation with 30 s of chest compressions. Serial blood samples were obtained for determination of plasma epinephrine concentrations by ELISA.

Results

Epinephrine concentrations failed to increase following administration via IM injection. Delayed absorption was observed after return of spontaneous circulation (ROSC) in half of the studies.

Conclusions

Inadequate absorption of epinephrine occurs with IM administration during asphyxial cardiac arrest, implying this route would be ineffective in infants who are severely compromised at birth. Late absorption following ROSC raises concerns for risks of side effects. However, the bioavailability and efficacy of intramuscular epinephrine in less profound asphyxia may warrant further evaluation.
Red Yeast Rice Preparations Reduce Mortality, Major Cardiovascular Adverse Events, and Risk Factors for Metabolic Syndrome: A Systematic Review and Meta−analysis
Authors: Yuan Rong , Yuan Yahui , Wang Lidan , Xin Qiqi , Wang Ya , Shi Weili , Miao Yu , Leng Sean Xiao , Chen Keji , Cong Weihong ,   and BPNMI Consortium
Published: February 2022

Background: Metabolic syndrome (MetS) is characterized by the cooccurrence of obesity, insulin resistance, dyslipidaemia, and hypertension. Red yeast rice (RYR) preparations might be beneficial for the prevention and treatment of MetS.

Objective: To implement a systematic review and meta−analysis to determine whether RYR preparations improve clinical endpoints and reduce risk factors for MetS.

Methods: The PubMed, Cochrane Library, EMBASE, Scopus, China National Knowledge Infrastructure, Chinese VIP Information, and WanFang databases were searched for randomized controlled trials (published up to September 2020), and a meta−analysis was performed using fixed− or random−effects models. The primary outcome measures were mortality and major adverse cardiovascular events (MACEs), and the secondary outcome measures were biochemical parameters of blood glucose, blood lipids, and blood pressure. The registration number is CRD42020209186.

Results: A total of 921 articles were identified, of which 30 articles were included in this article. RYR preparations group demonstrated significant improvements in MetS compared with control group. RYR preparations reduced the mortality and MACEs (RR = 0.62, 95% CI [0.49, 0.78]; RR = 0.54, 95% CI [0.43, 0.66]). In terms of blood glucose metabolism, fasting plasma glucose (FPG) (MD = −0.46 mmol/L, 95% CI [−0.71, −0.22]), haemoglobin A1c (HbA1c) (MD = −0.49, 95% CI [−0.71, −0.26]) and the homeostasis model assessment of insulin resistance (HOMA−IR) (MD = −0.93, 95% CI [−1.64, −0.21]) were decreased. Regarding the lipid metabolism, total cholesterol (TC) (MD = −0.74 mmol/L, 95% CI [−1.02, −0.46]), triglycerides (TG) (MD = −0.45 mmol/L, 95% CI [−0.70, −0.21]), and low−density lipoprotein cholesterol (LDL) (MD = −0.42 mmol/L, 95% CI [−0.78, −0.06]) were decreased, while high−density lipoprotein cholesterol (HDL) (MD = 0.14 mmol/L, 95% CI [0.09, 0.20]) was increased. Regarding blood pressure, the mean arterial pressure (MAP) (MD = −3.79 mmHg, 95% CI [−5.01, −2.57]) was decreased. In addition, RYR preparations did not increase the incidence of adverse reactions (RR = 1.00, 95% CI [0.69, 1.43]).

Conclusion: RYR preparations reduce mortality, MACEs, and multiple risk factors for MetS without compromising safety, which supports its application for the prevention and treatment of MetS. However, additional high−quality studies are needed to provide more evidence for the effect of RYR on MetS due to the heterogeneity in this study.

Systematic Review Registration: www.crd.york.ac.uk/PROSPERO, identifier CRD42020209186
Pharmacokinetics, Tissue Distribution, and Excretion Characteristics of a Radix Polygoni Multiflori Extract in Rats
Authors: Cheng Wenhao , Wu Siyang , Yuan Zheng , Hu Weiyu , Yu Xin , Kang Nianxin , Wang Qiutao , Zhu Mingying , Xia Kexin , Yang Wei , Kang Chen , Zhang Shuofeng , Li Yingfei
Published: February 2022

Although progress has been achieved in the pharmacological activity and toxicity of Radix Polygoni Multiflori (RPM), the chemical basis of its toxicity is still unclear. Here, we performed a multicompound pharmacokinetic analysis and investigated the tissue distribution and excretion characteristics of RPM components after oral administration in rats. The findings demonstrated that the active ingredients of the RPM extract were quickly absorbed after oral administration, with high exposure levels of emodin, 2,3,5,4′-teterahydroxystilbene-2-O-β-D-glucoside (TSG), citreorosein, torachrysone-8-O-glucoside (TG), emodin-8-O-β-D-glucoside (EG), and physcion-8-O-β-D-glucoside (PG). The tissue distributions of emodin, TSG, TG, EG, and PG were high in the liver and kidney. These components were the key contributors to the effectiveness and toxicity of RPM on the liver and kidney. Most of the active ingredients were mainly excreted through feces and bile, while a few were converted into other products in the body and excreted through urine and feces.
Calycosin as a Novel PI3K Activator Reduces Inflammation and Fibrosis in Heart Failure Through AKT–IKK/STAT3 Axis
Authors: Wang Xiaoping , Li Weili , Zhang Yawen , Sun Qianbin , Cao Jing , Tan NanNan , Yang Shuangjie , Lu Linghui , Zhang Qian , Wei Peng , Ma Xiao , Wang Wei , Wang Yong
Published: February 2022

Aim: Inflammation and fibrosis have been shown to be critical factors in heart failure (HF) progression. Calycosin (Cal) is the major active component of Astragalus mongholicus Bunge and has been reported to have therapeutic effects on the cardiac dysfunction after myocardial infarction. However, whether Cal could ameliorate myocardial infarction (MI)-induced inflammation and fibrosis and precise mechanisms remain uncertain. The aim of this study is to explore the role of Cal in HF and to clarify the underlying mechanisms.

Methods: For in vivo experiments, rats underwent left anterior descending artery ligation for heart failure model, and the cardioprotective effects of Cal were measured by echocardiographic assessment and histological examination. RNA-seq approach was applied to explore potential differential genes and pathways. For further mechanistic study, proinflammatory-conditioned media (conditioned media)-induced H9C2 cell injury model and TGFβ-stimulated cardiac fibroblast model were applied to determine the regulatory mechanisms of Cal.

Results: In the in vivo experiments, echocardiography results showed that Cal significantly improved heart function. GO and reactome enrichment revealed that inflammation and fibrosis pathways are involved in the Cal-treated group. KEGG enrichment indicated that the PI3K–AKT pathway is enriched in the Cal-treated group. Further experiments proved that Cal alleviated cardiomyocyte inflammatory responses evidenced by downregulating the expressions of phosphorylated IκB kinase α/β (p-IKKα/β), phosphorylated nuclear factor kapa B (p-NFκB), and tumor necrosis factor α (TNFα). Besides, Cal effectively attenuated cardiac fibrosis through the inhibitions of expressions and depositions of collagen I and collagen III. In the in vitro experiments, the phosphatidylinositol three kinase (PI3K) inhibitor LY294002 could abrogate the anti-inflammation and antifibrosis therapeutic effects of Cal, demonstrating that the cardioprotective effects of Cal were mediated through upregulations of PI3K and serine/threonine kinase (AKT).

Conclusion: Cal inhibited inflammation and fibrosis via activation of the PI3K–AKT pathway in H9C2 cells, fibroblasts, and heart failure in postacute myocardial infarction rats.
The Role of Vitamin D in COVID-19 and the Impact of Pandemic Restrictions on Vitamin D Blood Content
Authors: Tomaszewska Agata , Rustecka Agnieszka , Lipińska-Opałka Agnieszka , Piprek Rafal P. , Kloc Małgorzata , Kalicki Bolesław , Kubiak Jacek Z.
Published: February 2022

Vitamin D is a hormone regulating the immune system and playing a pivotal role in responses to microbial infections. It regulates inflammatory processes by influencing the transcription of immune-response genes in macrophages, T cells, and dendritic cells. The proven role of vitamin D in many infectious diseases of the respiratory tract indicated that vitamin D should also play a role in SARS-CoV-2 infection. Vitamin D inhibits cytokine storm by switching the pro-inflammatory Th1 and Th17 to the anti-inflammatory Th2 and Treg response. Vitamin D is therefore expected to play a role in preventing, relieving symptoms, or treating SARS-CoV-2 infection symptoms, including severe pneumonia. There are several possible mechanisms by which vitamin D may reduce the risk of COVID-19 infection, such as induction of the transcription of cathelicidin and defensin. Also a nongenomic antiviral action of vitamin D and lumisterol, the molecule closely related to vitamin D, was reported. Despite this enormous progress, currently, there is still insufficient scientific evidence to support the claim that vitamin D supplementation may help treat COVID-19 infection. The pandemic restrictions were also shown to impact vitamin D uptake by limiting exposure to sunlight.
IL7R Is Correlated With Immune Cell Infiltration in the Tumor Microenvironment of Lung Adenocarcinoma
Authors: Wang Xin , Chang Shujian , Wang Teng , Wu Ruirong , Huang Zebo , Sun Junjie , Liu Jingjing , Yu Yan , Mao Yong
Published: February 2022

Tumor microenvironment plays an important role in the development, progression, and prognosis of lung adenocarcinoma. Exploring new biomarkers based on the immune microenvironment of lung adenocarcinoma can effectively predict the prognosis and provide effective clinical treatment. In this study, we used the ESTIMATE algorithm to score the immune and stromal components in lung adenocarcinoma data downloaded from the TCGA database. The result showed that the immune/stromal score was associated with clinical features and prognosis of lung adenocarcinoma patients. Interleukin-7 receptor (IL7R) is an important prognostic biomarker identified by intersection analysis of protein-protein interaction networks and Cox regression survival analysis. According to TCGA and Oncomine database analysis, IL7R expression in adenocarcinoma tissues was significantly lower than that in normal lung tissues and was further verified in clinical tissue samples. Survival analysis showed IL7R was an independent prognostic factor of lung adenocarcinoma. IL7R expression was positively correlated with the overall survival and progression-free survival of lung adenocarcinoma patients and negatively correlated with tumor size. Our results suggest that IL7R inhibits tumor growth by regulating the proportion of immune infiltrating cells in the tumor immune microenvironment. IL7R could be a beneficial prognostic marker in patients with lung adenocarcinoma and has great potential in immune therapy.
Dichotomous Role of Tumor Necrosis Factor in Pulmonary Barrier Function and Alveolar Fluid Clearance
Authors: Lucas Rudolf , Hadizamani Yalda , Enkhbaatar Perenlei , Csanyi Gabor , Caldwell Robert W. , Hundsberger Harald , Sridhar Supriya , Lever Alice Ann , Hudel Martina , Ash Dipankar , Ushio-Fukai Masuko , Fukai Tohru , Chakraborty Trinad , Verin Alexander , Eaton Douglas C. , Romero Maritza , Hamacher Jürg
Published: February 2022

Alveolar-capillary leak is a hallmark of the acute respiratory distress syndrome (ARDS), a potentially lethal complication of severe sepsis, trauma and pneumonia, including COVID-19. Apart from barrier dysfunction, ARDS is characterized by hyper-inflammation and impaired alveolar fluid clearance (AFC), which foster the development of pulmonary permeability edema and hamper gas exchange. Tumor Necrosis Factor (TNF) is an evolutionarily conserved pleiotropic cytokine, involved in host immune defense against pathogens and cancer. TNF exists in both membrane-bound and soluble form and its mainly -but not exclusively- pro-inflammatory and cytolytic actions are mediated by partially overlapping TNFR1 and TNFR2 binding sites situated at the interface between neighboring subunits in the homo-trimer. Whereas TNFR1 signaling can mediate hyper-inflammation and impaired barrier function and AFC in the lungs, ligand stimulation of TNFR2 can protect from ventilation-induced lung injury. Spatially distinct from the TNFR binding sites, TNF harbors within its structure a lectin-like domain that rather protects lung function in ARDS. The lectin-like domain of TNF -mimicked by the 17 residue TIP peptide- represents a physiological mediator of alveolar-capillary barrier protection. and increases AFC in both hydrostatic and permeability pulmonary edema animal models. The TIP peptide directly activates the epithelial sodium channel (ENaC) -a key mediator of fluid and blood pressure control- upon binding to its α subunit, which is also a part of the non-selective cation channel (NSC). Activity of the lectin-like domain of TNF is preserved in complexes between TNF and its soluble TNFRs and can be physiologically relevant in pneumonia. Antibody- and soluble TNFR-based therapeutic strategies show considerable success in diseases such as rheumatoid arthritis, psoriasis and inflammatory bowel disease, but their chronic use can increase susceptibility to infection. Since the lectin-like domain of TNF does not interfere with TNF’s anti-bacterial actions, while exerting protective actions in the alveolar-capillary compartments, it is currently evaluated in clinical trials in ARDS and COVID-19. A more comprehensive knowledge of the precise role of the TNFR binding sites versus the lectin-like domain of TNF in lung injury, tissue hypoxia, repair and remodeling may foster the development of novel therapeutics for ARDS.
Ploidy Testing of Blastocoel Fluid for Screening May Be Technically Challenging and More Invasive Than That of Spent Cell Culture Media
Authors: Shi Wenhao , Zhao Zhenghao , Xue Xia , Li Qian , Yao Yaxin , Wang Dongyang , Wang Jing , Lu Sijia , Shi Juanzi
Published: February 2022

Background

Recent studies have demonstrated that both blastocoel fluid (BF) and spent cell culture media (SCM) have potential as materials for non-invasive or less-invasive pre-implantation genetic analysis. BF may allow more opportunity to obtain cell-free DNA from the inner cell mass (ICM), and it has a lower risk of containing contaminant DNA from cumulus cells, sperm and culture media. There are no data regarding the ICM as a gold standard to evaluate the chromosome constitution of BF or SCM for embryo liquid biopsy.

Methods

Two hundred eighteen donated human blastocysts were warmed and cultured in blastocyst culture media for 18–24 h. The corresponding SCM was collected, and only clear ICM was biopsied in blastocysts; otherwise, the whole blastocyst (WB) was biopsied. Quantitative PCR was performed to determine the DNA levels in the SCM and BF before and after amplification. ChromInst was used to amplify BF/SCM and blastocyst DNA before sequencing. Chromosomal copy number variation (CNV) was investigated to evaluate the chromosome constitution.

Results

In total, 212 blastocysts were available for SCM and BF collection. The technical success rates (next-generation sequencing data) were 100 and 69.8% (148/212) for SCM and BF, respectively. Among the 148 blastocysts with both SCM and BF data, 101 were euploid and 47 were aneuploid based on ICM (n = 89) or WB (n = 59) analysis as the gold standard. Among all blastocysts, SCM was comparable to BF [specificity: 80.2 versus 61.4% (P = 0.005, χ2 test); sensitivity: 91.5 versus 87.2% (P = 0.738, χ2 test); negative predictive value (NPV): 95.3 versus 91.2% (P = 0.487, χ2 test); positive predictive value (PPV): 68.3% versus 51.3% (P = 0.042, χ2 test)]. The SCM and BF samples were 83.8% (124/148) and 69.6% (103/148) concordant with the corresponding ICM/WB samples when only two categories, euploid or aneuploid/mosaic, were grouped to calculate the concordance.

Conclusions

Compared with BF, SCM has superior diagnostic performance, and it is non-invasive for embryos.

Clinical Trial Registration

[http://www.chictr.org.cn], identifier [ChiCTR-BPD-17014087].
Action Understanding Promoted by Interoception in Children: A Developmental Model
Authors: Zhou Hui , Gao Qiyang , Chen Wei , Wei Qiaobo
Published: February 2022

Action understanding of children develops from simple associative learning to mentalizing. With the rise of embodied cognition, the role of interoception in action observation and action understanding has received more attention. From a developmental perspective, this study proposes a novel developmental model that explores how interoception promotes action understanding of children across ages. In early infancy, most actions observed in infants come from interactions with their caregivers. Babies learn about action effects through automatic interoceptive processing and interoceptive feedback. Interoception in early infancy is not fully developed, such as the not fully developed gastrointestinal tract and intestinal nervous system. Therefore, in early infancy, action understanding is based on low-level and original interoceptive information. At this stage, after observing the actions of others, infants can create mental representations or even imitate actions without external visual feedback, which requires interoception to provide internal reference information. By early childhood, children begin to infer action intentions of other people by integrating various types of information to reach the mentalizing level. Interoception processing requires the integration of multiple internal signals, which promotes the information integration ability of children. Interoception also provides inner information for reasoning about action intention. This review also discussed the neural mechanisms of interoception and possible ways by which it could promote action understanding of children. In early infancy, the central autonomic neural network (CAN) automatically processes and responds to the actions of caregivers on infants, providing interoceptive information for action understanding of infants. In infancy, the growth of the somatomotor system provides important internal reference information for observing and imitating the actions of infants. In early childhood, the development of interoception of children facilitates the integration of internal and external information, which promotes the mentalization of action understanding of children. According to the proposed developmental model of action understanding of children promoted by interoception, there are multilevel and stage-dependent characteristics that impact the role of interoception in action understanding of children.
The Mediating Role of Critical Thinking Abilities in the Relationship Between English as a Foreign Language Learners’ Writing Performance and Their Language Learning Strategies
Authors: Esmaeil Nejad Maryam , Izadpanah Siros , Namaziandost Ehsan , Rahbar Behzad
Published: February 2022

Recent developments in the field of education have led to a renewed interest in the mediating role of critical thinking abilities (CTA) in the relationship between language learning strategies and the intermediate English as a Foreign Language (EFL) learners’ writing performance. Oxford Placement Test (OPT) was run to homogenize the participants, and 100 intermediate learners out of 235 were selected. Then, two valid questionnaires of Ricketts’ Critical Thinking Disposition and Oxford’s Strategy Inventory for Language Learning were administered. Having administered the questionnaires, the researchers asked the participants to sit for a writing test. The data collected from the questionnaires and as well as the scores of their writing performances were analyzed through SPSS (25.00). The results showed a significant relationship between (a) learning strategies and learners’ writing performances, (b) the sub-sets of learning strategies and learners’ writing performances, and (c) CTA and learners’ learning strategies. However, CTA did not play a mediating role in the relationship between intermediate EFL learners’ learning strategies and writing performance. Based on the results of the study, one might also conclude that strategies seemed to play a more important role in the performance of learners especially their writing performances. Therefore, this study had useful contributions for students, teachers, and curriculum designers. Findings of this research could assist teachers to be aware of learners’ strategies in learning writing and help their students to be responsive to using learning strategies in their learning process and create a satisfactory learning context for using learning strategies. Therefore, learners were able to become independent and feel responsibility for their own learning. Secondly, curriculum developers could take advantage of the findings to include learning strategies training into the curriculum. As a result, students were able to use strategies in their learning process more easily and finally, the results might pave the way for improving the research findings.
Self-Care as a Method to Cope With Suffering and Death: A Participatory Action-Research Aimed at Quality Improvement
Authors: Buonaccorso Loredana , Tanzi Silvia , Sacchi Simona , Alquati Sara , Bertocchi Elisabetta , Autelitano Cristina , Taberna Eleonora , Martucci Gianfranco
Published: February 2022

Introduction

Palliative care is an emotionally and spiritually high-demanding setting of care. The literature reports on the main issues in order to implement self-care, but there are no models for the organization of the training course. We described the structure of training on self-care and its effects for a Hospital Palliative Care Unit.

Method

We used action-research training experience based mostly on qualitative data. Thematic analysis of data on open-ended questions, researcher’s field notes, oral and written feedback from the trainer and the participants on training outcomes and satisfaction questionnaires were used.

Results

Four major themes emerged: (1) “Professional role and personal feelings”; (2) “Inside and outside the team”; (3) “Do I listen to my emotions in the care relationship?”; (4) “Death: theirs vs. mine.” According to participants’ point of view and researchers’ observations, the training course resulted in ameliorative adjustments of the program; improved skills in self-awareness of own’s emotions and sharing of perceived emotional burden; practicing “compassionate presence” with patients; shared language to address previously uncharted aspects of coping; allowing for continuity of the skills learned; translation of the language learned into daily clinical practices through specific facilitation; a structured staff’s support system for emotional experiences.

Discussion

Self-care is an important enabler for the care of others. The core of our intervention was to encourage a meta-perspective in which the trainees developed greater perspicacity pertaining to their professional role in the working alliance and also recognizing the contribution of their personal emotions to impasse experienced with patients.