bluuebunny/crossref_metadata_2025 huggingface dataset:
Evidence of Genomic Diversification in a Natural Symbiotic Population Within Its Host
Authors: Bongrand Clotilde , Koch Eric , Mende Daniel , Romano Anna , Lawhorn Susannah , McFall-Ngai Margaret , DeLong Edward F. , Ruby Edward G.
Published: March 2022

Planktonic cells of the luminous marine bacteriumVibrio fischeriestablish themselves in the light-emitting organ of each generation of newly hatchedEuprymna scolopesbobtail squid. A symbiont population is maintained within the 6 separated crypts of the organ for the ∼9-month life of the host. In the wild, the initial colonization step is typically accomplished by a handful of planktonicV. fischericells, leading to a species-specific, but often multi-strain, symbiont population. Within a few hours, the inoculating cells proliferate within the organ’s individual crypts, after which there is evidently no supernumerary colonization. Nevertheless, every day at dawn, the majority of the symbionts is expelled, and the regrowth of the remaining ∼5% of cells provides a daily opportunity for the population to evolve and diverge, thereby increasing its genomic diversity. To begin to understand the extent of this diversification, we characterized the light-organ population of an adult animal. First, we used 16S sequencing to determine that species in theV. fischericlade were essentially the only ones detectable within a field-caughtE. scolopes. Efforts to colonize the host with a minor species that appeared to be identified,V. litoralis, revealed that, although some cells could be imaged within the organ, they were <0.1% of the typicalV. fischeripopulation, and did not persist. Next, we determined the genome sequences of seventy-two isolates from one side of the organ. While all these isolates were associated with one of three clusters ofV. fischeristrains, there was considerable genomic diversity within this natural symbiotic population. Comparative analyses revealed a significant difference in both the number and the presence/absence of genes within each cluster; in contrast, there was little accumulation of single-nucleotide polymorphisms. These data suggest that, in nature, the light organ is colonized by a small number ofV. fischeristrains that can undergo significant genetic diversification, including by horizontal-gene transfer, over the course of ∼1500 generations of growth in the organ. When the resulting population of symbionts is expelled into seawater, its genomic mix provides the genetic basis for selection during the subsequent environmental dispersal, and transmission to the next host.
Selective Cleavage at CCA Ends and Anticodon Loops of tRNAs by Stress-Induced RNases
Authors: Akiyama Yasutoshi , Lyons Shawn M. , Fay Marta M. , Tomioka Yoshihisa , Abe Takaaki , Anderson Paul J. , Ivanov Pavel
Published: March 2022

Stress-induced tRNA cleavage has been implicated in various cellular processes, where tRNA fragments play diverse regulatory roles. Angiogenin (ANG), a member of the RNase A superfamily, induces cleavage of tRNAs resulting in the formation of tRNA-derived stress-induced RNAs (tiRNAs) that contribute to translational reprogramming aiming at cell survival. In addition to cleaving tRNA anticodon loops, ANG has been shown to cleave 3′-CCA termini of tRNAs in vitro, although it is not known whether this process occurs in cells. It has also been suggested that tiRNAs can be generated independently of ANG, although the role of other stress-induced RNases in tRNA cleavage is poorly understood. Using gene editing and biochemical approaches, we examined the involvement of ANG in stress-induced tRNA cleavage by focusing on its cleavage of CCA-termini as well as anticodon loops. We show that ANG is not responsible for CCA-deactivation under sodium arsenite (SA) treatment in cellulo, and although ANG treatment significantly increases 3′-tiRNA levels in cells, the majority of 3′-tiRNAs retain their 3′-CCA termini. Instead, other RNases can cleave CCA-termini in cells, although with low efficiency. Moreover, in the absence of ANG, other RNases are able to promote the production of tiRNAs in cells. Depletion of RNH1 (an endogenous inhibitor of RNase A superfamily) promotes constitutively-produced tiRNAs and CCA-deactivated tRNAs in cells. Interestingly, SA treatment in RNH1-depleted cells did not increase the amount of tiRNAs or CCA-deactivated tRNAs, suggesting that RNase A superfamily enzymes are largely responsible for SA-induced tRNA cleavage. We show that interplay between stress-induced RNases cause targeting tRNAs in a stress-specific manner in cellulo.
Proteomic Identification of a Gastric Tumor ECM Signature Associated With Cancer Progression
Authors: Moreira Ana M. , Ferreira Rui M. , Carneiro Patrícia , Figueiredo Joana , Osório Hugo , Barbosa José , Preto John , Pinto-do-Ó Perpétua , Carneiro Fátima , Seruca Raquel
Published: March 2022

The extracellular matrix (ECM) plays an undisputable role in tissue homeostasis and its deregulation leads to altered mechanical and biochemical cues that impact cancer development and progression. Herein, we undertook a novel approach to address the role of gastric ECM in tumorigenesis, which remained largely unexplored. By combining decellularization techniques with a high-throughput quantitative proteomics approach, we have performed an extensive characterization of human gastric mucosa, uncovering its composition and distribution among tumor, normal adjacent and normal distant mucosa. Our results revealed a common ECM signature composed of 142 proteins and indicated that gastric carcinogenesis encompasses ECM remodeling through alterations in the abundance of 24 components, mainly basement membrane proteins. Indeed, we could only identify one de novo tumor-specific protein, the collagen alpha-1(X) chain (COL10A1). Functional analysis of the data demonstrated that gastric ECM remodeling favors tumor progression by activating ECM receptors and cellular processes involved in angiogenesis and cell-extrinsic metabolic regulation. By analyzing mRNA expression in an independent GC cohort available at the TGCA, we validated the expression profile of 12 differentially expressed ECM proteins. Importantly, the expression of COL1A2, LOX and LTBP2 significantly correlated with high tumor stage, with LOX and LTBP2 further impacting patient overall survival. These findings contribute for a better understanding of GC biology and highlight the role of core ECM components in gastric carcinogenesis and their clinical relevance as biomarkers of disease prognosis.
Assessment of Greenhouse Tomato Anthesis Rate Through Metabolomics Using LASSO Regularized Linear Regression Model
Authors: Siriwach Ratklao , Matsuzaki Jun , Saito Takeshi , Nishimura Hiroshi , Isozaki Masahide , Isoyama Yosuke , Sato Muneo , Arita Masanori , Akaho Shotaro , Higashide Tadahisa , Yano Kentaro , Hirai Masami Yokota
Published: March 2022

While the high year-round production of tomatoes has been facilitated by solar greenhouse cultivation, these yields readily fluctuate in response to changing environmental conditions. Mathematic modeling has been applied to forecast phenotypes of tomatoes using environmental measurements (e.g., temperature) as indirect parameters. In this study, metabolome data, as direct parameters reflecting plant internal status, were used to construct a predictive model of the anthesis rate of greenhouse tomatoes. Metabolome data were obtained from tomato leaves and used as variables for linear regression with the least absolute shrinkage and selection operator (LASSO) for prediction. The constructed model accurately predicted the anthesis rate, with an R2value of 0.85. Twenty-nine of the 161 metabolites were selected as candidate markers. The selected metabolites were further validated for their association with anthesis rates using the different metabolome datasets. To assess the importance of the selected metabolites in cultivation, the relationships between the metabolites and cultivation conditions were analyzedviacorrespondence analysis. Trigonelline, whose content did not exhibit a diurnal rhythm, displayed major contributions to the cultivation, and is thus a potential metabolic marker for predicting the anthesis rate. This study demonstrates that machine learning can be applied to metabolome data to identify metabolites indicative of agricultural traits.
Mild Cognitive Impairment Subtypes Are Associated With Peculiar Gait Patterns in Parkinson’s Disease
Authors: Amboni Marianna , Ricciardi Carlo , Cuoco Sofia , Donisi Leandro , Volzone Antonio , Ricciardelli Gianluca , Pellecchia Maria Teresa , Santangelo Gabriella , Cesarelli Mario , Barone Paolo
Published: March 2022

Background

Mild cognitive impairment (MCI) is frequent in Parkinson’s disease (PD) and represents a risk factor for the development of dementia associated with PD (PDD). Since PDD has been associated with disability, caregiver burden, and an increase in health-related costs, early detection of MCI associated with PD (PD-MCI) and its biomarkers is crucial.

Objective

Given that gait is considered a surrogate marker for cognitive decline in PD, the aim of this study was to compare gait patterns in PD-MCI subtypes in order to verify the existence of an association between specific gait features and particular MCI subtypes.

Methods

A total of 67 patients with PD were consecutively enrolled and assessed by an extensive clinical and cognitive examination. Based on the neuropsychological examination, patients were diagnosed as patients with MCI (PD-MCI) and without MCI (no-PD-MCI) and categorized in MCI subtypes. All patients were evaluated using a motion capture system of a BTS Bioengineering equipped with six IR digital cameras. Gait of the patients was assessed in the ON-state under three different tasks (a single task and two dual tasks). Statistical analysis included the t-test, the Kruskal–Wallis test with post hoc analysis, and the exploratory correlation analysis.

Results

Gait pattern was poorer in PD-MCI vs. no-PD-MCI in all tasks. Among PD-MCI subtypes, multiple-domain PD-MCI and amnestic PD-MCI were coupled with worse gait patterns, notably in the dual task.

Conclusion

Both the magnitude of cognitive impairment and the presence of memory dysfunction are associated with increased measures of dynamic unbalance, especially in dual-task conditions, likely mirroring the progressive involvement of posterior cortical networks.
Mendelian Randomization Analysis Suggests No Associations of Herpes Simplex Virus Infections With Multiple Sclerosis
Authors: Zhang Wan , Wu Pengfei , Yin Rui , Sun Meichen , Zhang Rongsen , Liao Xiaoyao , Lin Yuhong , Lu Hui
Published: March 2022

Previous studies have suggested an association between infection with herpes simplex virus (HSV) and liability to multiple sclerosis (MS), but it remains largely unknown whether the effect is causal. We performed a two-sample Mendelian randomization (MR) study to explore the relationship between genetically predicted HSV infection and MS risk. Genetic instrumental variables for diagnosed infections with HSV (p < 5 × 10–6) were retrieved from the FinnGen study, and single nucleotide polymorphisms associated with circulating immunoglobulin G (IgG) levels of HSV-1 and HSV-2 and corresponding summary-level statistics of MS were obtained from genome-wide association studies of the European-ancestry. Inverse-variance weighted MR was employed as the primary method and multiple sensitivity analyses were performed. Genetically proxied infection with HSV was not associated with the risk of MS (odds ratio [OR], 0.96; 95% confidence interval [CI], 0.90–1.02; p = 0.22) per one-unit increase in log-OR of herpes viral infections. MR results provided no evidence for the relationship between circulating HSV-1 IgG levels and MS risks (OR = 0.91; 95% CI, 0.81–1.03; p = 0.37), and suggested no causal effect of HSV-2 IgG (OR = 1.04; 95% CI, 0.96–1.13; p = 0.32). Additional sensitivity analyses confirmed the robustness of these null findings. The MR study did not support the causal relationship between genetic susceptibly to HSV and MS in the European population. Further studies are still warranted to provide informative knowledge, and triangulating evidence across multiple lines of evidence are necessary to plan interventions for the treatment and prevention of MS.
What Can Make the Difference Between Chronotypes in Sleep Duration? Testing the Similarity of Their Homeostatic Processes
Authors: Putilov Arcady A. , Donskaya Olga G.
Published: March 2022

The two-process conceptualization of sleep-wake regulation suggests that the biological underpinnings of the differences between morning and evening types in sleep timing and duration might be related to either the circadian process or the homeostatic process or both. The purpose of this report was to test whether morning and evening types might have similar homeostatic processes to achieve such ultimate goal of homeostatic sleep regulation as taking an adequate amount of sleep on free days. Weekend and weekday rise- and bedtimes reported for 50 paired samples of morning and evening types were averaged and simulated with a model of sleep-wake regulation. In morning and evening types of the same age, the homeostatic components of the sleep-wake regulation were found to be identical. Therefore, the difference in the circadian process between chronotypes of similar age can account for the observed differences between them in sleep timing and duration on weekdays and weekends. It was also demonstrated that the model-based simulations might have practical implications for informing an individual about the extent of unrecoverable reduction of his/her sleep on weekdays.
Lateral Hypothalamic Orexin Neurons Mediate the Reward Effects of Pain Relief Induced by Electroacupuncture
Authors: Wang Can , Chen Meiyu , Qin Chuan , Qu Xiaoyi , Shen Xueyong , Liu Sheng
Published: March 2022

The reward of pain relief caused by acupuncture has been found to be clinically significant. However, the molecular mechanisms underlying acupuncture-induced reward of pain relief in chronic pain remain unclear and have not been analyzed in suitable preclinical models. Here, we investigated whether acupuncture could potentially induce the reward of pain relief and orexin neuronal signaling in the lateral hypothalamus (LH) and exhibit a possible role in electroacupuncture (EA)-induced reward in spared nerve injury (SNI) rats. Therefore, by using conditioned place preference (CPP) paradigm, we noticed that EA induced the preference for cues associated with EA-induced pain relief in the early, but not late, phase of chronic pain. These observations were different from the immediate antihyperalgesic effects of EA. c-Fos/orexin double labeling revealed that EA stimulation on 14 days but not on 28 days after SNI modeling activated greater numbers of c-Fos positive orexin neurons in the LH after the CPP test. Moreover, the administration of an orexin-A antagonist in the LH significantly blocked the reward effects of pain relief induced by EA. Furthermore, by using cholera toxin b subunit combined with c-Fos detection, we found that the orexin circuit from the LH to the nucleus accumbens (NAc) shell was significantly activated after EA induced CPP. Microinjection of the orexin antagonist into the NAc shell substantially attenuated the CPP induced by EA. Intravenous injection of low-dose orexin-A together with EA resulted in significantly greater antihyperalgesia effects and CPP scores. Together, these findings clearly demonstrated that LH orexin signaling could potentially play a critical role in the reward effects of pain relief induced by acupuncture. The observations of the present study extended our understanding of orexin signaling in the LH and its role in EA-induced reward, providing new insights into the mechanisms of acupuncture analgesia.
Hearing Loss Increases Inhibitory Effects of Prefrontal Cortex Stimulation on Sound Evoked Activity in Medial Geniculate Nucleus
Authors: De Vis Chenae , Barry Kristin M. , Mulders Wilhelmina H. A. M.
Published: March 2022

Sensory gating is the process whereby irrelevant sensory stimuli are inhibited on their way to higher cortical areas, allowing for focus on salient information. Sensory gating circuitry includes the thalamus as well as several cortical regions including the prefrontal cortex (PFC). Defective sensory gating has been implicated in a range of neurological disorders, including tinnitus, a phantom auditory perception strongly associated with cochlear trauma. Recently, we have shown in rats that functional connectivity between PFC and auditory thalamus, i.e., the medial geniculate nucleus (MGN), changes following cochlear trauma, showing an increased inhibitory effect from PFC activation on the spontaneous firing rate of MGN neurons. In this study, we further investigated this phenomenon using a guinea pig model, in order to demonstrate the validity of our finding beyond a single species and extend data to include data on sound evoked responses. Effects of PFC electrical stimulation on spontaneous and sound-evoked activity of single neurons in MGN were recorded in anaesthetised guinea pigs with normal hearing or hearing loss 2 weeks after acoustic trauma. No effect, inhibition and excitation were observed following PFC stimulation. The proportions of these effects were not different in animals with normal hearing and hearing loss but the magnitude of effect was. Indeed, hearing loss significantly increased the magnitude of inhibition for sound evoked responses, but not for spontaneous activity. The findings support previous observations that PFC can modulate MGN activity and that functional changes occur within this pathway after cochlear trauma. These data suggest hearing loss can alter sensory gating which may be a contributing factor toward tinnitus development.
Modulation of TLR/NF-κB/NLRP Signaling by Bioactive Phytocompounds: A Promising Strategy to Augment Cancer Chemotherapy and Immunotherapy
Authors: Fakhri Sajad , Moradi Seyed Zachariah , Yarmohammadi Akram , Narimani Fatemeh , Wallace Carly E. , Bishayee Anupam
Published: March 2022

Background

Tumors often progress to a more aggressive phenotype to resist drugs. Multiple dysregulated pathways are behind this tumor behavior which is known as cancer chemoresistance. Thus, there is an emerging need to discover pivotal signaling pathways involved in the resistance to chemotherapeutic agents and cancer immunotherapy. Reports indicate the critical role of the toll-like receptor (TLR)/nuclear factor-κB (NF-κB)/Nod-like receptor pyrin domain-containing (NLRP) pathway in cancer initiation, progression, and development. Therefore, targeting TLR/NF-κB/NLRP signaling is a promising strategy to augment cancer chemotherapy and immunotherapy and to combat chemoresistance. Considering the potential of phytochemicals in the regulation of multiple dysregulated pathways during cancer initiation, promotion, and progression, such compounds could be suitable candidates against cancer chemoresistance.

Objectives

This is the first comprehensive and systematic review regarding the role of phytochemicals in the mitigation of chemoresistance by regulating the TLR/NF-κB/NLRP signaling pathway in chemotherapy and immunotherapy.

Methods

A comprehensive and systematic review was designed based on Web of Science, PubMed, Scopus, and Cochrane electronic databases. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed to include papers on TLR/NF-κB/NLRP and chemotherapy/immunotherapy/chemoresistance by phytochemicals.

Results

Phytochemicals are promising multi-targeting candidates against the TLR/NF-κB/NLRP signaling pathway and interconnected mediators. Employing phenolic compounds, alkaloids, terpenoids, and sulfur compounds could be a promising strategy for managing cancer chemoresistance through the modulation of the TLR/NF-κB/NLRP signaling pathway. Novel delivery systems of phytochemicals in cancer chemotherapy/immunotherapy are also highlighted.

Conclusion

Targeting TLR/NF-κB/NLRP signaling with bioactive phytocompounds reverses chemoresistance and improves the outcome for chemotherapy and immunotherapy in both preclinical and clinical stages.
Lipidomic Analysis Reveals the Protection Mechanism of GLP-1 Analogue Dulaglutide on High-Fat Diet-Induced Chronic Kidney Disease in Mice
Authors: Yeung Martin Ho Yin , Leung Ka Long , Choi Lai Yuen , Yoo Jung Sun , Yung Susan , So Pui-Kin , Wong Chi-Ming
Published: March 2022

Many clinical studies have suggested that glucagon-like peptide-1 receptor agonists (GLP-1RAs) have renoprotective properties by ameliorating albuminuria and increasing glomerular filtration rate in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) by lowering ectopic lipid accumulation in the kidney. However, the mechanism of GLP-1RAs was hitherto unknown. Here, we conducted an unbiased lipidomic analysis using ultra-high-performance liquid chromatography/electrospray ionization-quadrupole time-of-flight mass spectrometry (UHPLC/ESI-Q-TOF-MS) and matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) to reveal the changes of lipid composition and distribution in the kidneys of high-fat diet-fed mice after treatment with a long-acting GLP-1RA dulaglutide for 4 weeks. Treatment of dulaglutide dramatically improved hyperglycemia and albuminuria, but there was no substantial improvement in dyslipidemia and ectopic lipid accumulation in the kidney as compared with controls. Intriguingly, treatment of dulaglutide increases the level of an essential phospholipid constituent of inner mitochondrial membrane cardiolipin at the cortex region of the kidneys by inducing the expression of key cardiolipin biosynthesis enzymes. Previous studies demonstrated that lowered renal cardiolipin level impairs kidney function via mitochondrial damage. Our untargeted lipidomic analysis presents evidence for a new mechanism of how GLP-1RAs stimulate mitochondrial bioenergetics via increasing cardiolipin level and provides new insights into the therapeutic potential of GLP-1RAs in mitochondrial-related diseases.
Efficacy and Safety of Ojeok-San Plus Saengmaek-San for Gastroesophageal Reflux-Induced Chronic Cough: A Pilot, Randomized, Double-Blind, Placebo-Controlled Trial
Authors: Lyu Yee Ran , Kim Kwan-Il , Yang Changsop , Jung So-Young , Kwon O Jin , Jung Hee-Jae , Lee Jun-Hwan , Lee Beom-Joon
Published: March 2022

Introduction: Gastroesophageal reflux-induced chronic cough (GERC) is one of the most common etiologies of chronic cough. Despite the growing prevalence and interest in GERC, no effective treatment is currently available. In our study, we used a combination of herbal medicines, Ojeok-san (OJS) plus Saengmaek-san (SMS), for the treatment of GERC.

Methods: We conducted a pilot, randomized, placebo-controlled, parallel-arm, single-center clinical trial to assess the feasibility of our study protocol, as our study is the first herbal medicine trial for GERC. All enrolled participants were randomly assigned to either the intervention or placebo group in a 1:1 ratio and were administered trial drugs three times a day for 6 weeks, with an evaluation visit performed every 2 weeks for their efficacy and safety assessment until the follow-up visit (week 8). We evaluated the severity and frequency of cough, cough-specific quality of life, airway hypersensitivity, and reflux-related gastrointestinal symptoms, as well as pattern identification, to investigate the complex mechanisms of reflux cough syndrome.

Results: A total of 30 participants were enrolled, and 25 completed the study at Kyung Hee University Korean Medicine Hospital from 26 December 2018 to 31 May 2021. OJS plus SMS significantly improved the cough diary score (CDS), cough visual analog scale, Korean version of the Leicester Cough Questionnaire, Hull Airway Reflux Questionnaire, and Gastrointestinal Symptom Rating Scale after the treatment compared to the baseline. Notably, OJS plus SMS showed significant efficacy in the daytime and total CDS compared with the placebo. Only one adverse event was observed during the trial, and no serious adverse events occurred. Additionally, we achieved successful results in feasibility outcomes by exceeding the ratio of 80%.

Conclusion: We confirmed the feasibility of our trial design and demonstrated the potential of OJS plus SMS in relieving the severity of cough and GI symptoms in GERC patients with safe and successful feasibility results. We anticipate that our study results will be used as the basis for further large-scale, well-designed, confirmatory trials to evaluate the safety and efficacy of OJS plus SMS in GERC.

Clinical Trial Registration: [https://cris.nih.go.kr], identifier WHO International Clinical Trials Registry Platform, Clinical Research Information Service [KCT0003115].
Improvement of the Detection Sensitivity for Tunable Diode Laser Absorption Spectroscopy: A Review
Authors: Lin Shan , Chang Jun , Sun Jiachen , Xu Peng
Published: March 2022

Tunable Diode Laser Absorption Spectroscopy (TDLAS), a trace gas sensing technology based on infrared absorption spectroscopy, has been developed rapidly in the past few decades. The advantages of low cost and easy miniaturization could be applied in real-time monitoring. As an important factor, the detection sensitivity of TDLAS has been improved by a variety of methods. In this review paper, the important advances in TDLAS detection sensitivity are discussed, including the selection of absorption lines, the improvement of diode lasers, the design of effective optical paths, data demodulation, and the suppression of background interference. For gases with high application values, such as CH4, CO2, and NO, we summarize the detection sensitivity that the existing TDLAS system has been achieved, combined with the above-improved process. However, considering the principle of infrared absorption, the increase in detection sensitivity could reach an ultra-limit. Therefore, the hypothesis of the sensitivity limit of TDLAS is proposed at the end of the paper, through the quantization analysis.
Photoplethysmogram Analysis and Applications: An Integrative Review
Authors: Park Junyung , Seok Hyeon Seok , Kim Sang-Su , Shin Hangsik
Published: March 2022

Beyond its use in a clinical environment, photoplethysmogram (PPG) is increasingly used for measuring the physiological state of an individual in daily life. This review aims to examine existing research on photoplethysmogram concerning its generation mechanisms, measurement principles, clinical applications, noise definition, pre-processing techniques, feature detection techniques, and post-processing techniques for photoplethysmogram processing, especially from an engineering point of view. We performed an extensive search with the PubMed, Google Scholar, Institute of Electrical and Electronics Engineers (IEEE), ScienceDirect, and Web of Science databases. Exclusion conditions did not include the year of publication, but articles not published in English were excluded. Based on 118 articles, we identified four main topics of enabling PPG: (A) PPG waveform, (B) PPG features and clinical applications including basic features based on the original PPG waveform, combined features of PPG, and derivative features of PPG, (C) PPG noise including motion artifact baseline wandering and hypoperfusion, and (D) PPG signal processing including PPG preprocessing, PPG peak detection, and signal quality index. The application field of photoplethysmogram has been extending from the clinical to the mobile environment. Although there is no standardized pre-processing pipeline for PPG signal processing, as PPG data are acquired and accumulated in various ways, the recently proposed machine learning-based method is expected to offer a promising solution.
No Differences Between 12 Weeks of Block- vs. Traditional-Periodized Training in Performance Adaptations in Trained Cyclists
Authors: Almquist Nicki Winfield , Eriksen Hanne Berg , Wilhelmsen Malene , Hamarsland Håvard , Ing Steven , Ellefsen Stian , Sandbakk Øyvind , Rønnestad Bent R. , Skovereng Knut
Published: March 2022

The purpose of this study was to compare the effects of 12 weeks load-matched block periodization (BP, n = 14), using weekly concentration of high- (HIT), moderate- (MIT), and low- (LIT) intensity training, with traditional periodization (TP, n = 16) using a weekly, cyclic progressive increase in training load of HIT-, MIT-, and LIT-sessions in trained cyclists (peak oxygen uptake: 58 ± 8 ml·kg−1·min−1). Red blood cell volume increased 10 ± 16% (p = 0.029) more in BP compared to TP, while capillaries around type I fibers increased 20 ± 12% (p = 0.002) more in TP compared to BP from Pre to Post12. No other group differences were found in time-trial (TT) performances or muscular-, or hematological adaptations. However, both groups improved 5 and 40-min TT power by 9 ± 9% (p < 0.001) and 8 ± 9% (p < 0.001), maximal aerobic power (Wmax) and power output (PO) at 4 mmol·L−1 blood lactate (W4mmol), by 6 ± 7 (p = 0.001) and 10 ± 12% (p = 0.001), and gross efficiency (GE) in a semi-fatigued state by 0.5 ± 1.1%-points (p = 0.026). In contrast, GE in fresh state and VO2peak were unaltered in both groups. The muscle protein content of β-hydroxyacyl (HAD) increased by 55 ± 58% in TP only, while both TP and BP increased the content of cytochrome c oxidase subunit IV (COXIV) by 72 ± 34%. Muscle enzyme activities of citrate synthase (CS) and phosphofructokinase (PFK) were unaltered. TP increased capillary-to-fiber ratio and capillary around fiber (CAF) type I by 36 ± 15% (p < 0.001) and 17 ± 8% (p = 0.025), respectively, while BP increased capillary density (CD) by 28 ± 24% (p = 0.048) from Pre to Post12. The present study shows no difference in performance between BP and “best practice”-TP of endurance training intensities using a cyclic, progressively increasing training load in trained cyclists. However, hematological and muscle capillary adaptations may differ.
CCL5 Suppresses Klotho Expression via p-STAT3/DNA Methyltransferase1-Mediated Promoter Hypermethylation
Authors: Liu QiFeng , Li ShaSha , Yu LiXia , Yin XiaoYa , Liu Xi , Ye JianMing , Lu GuoYuan
Published: March 2022

Background

Enhanced inflammation and reduced Klotho are common features in chronic kidney disease (CKD). Inflammation induces DNA hypermethylation. This study assessed the performance of inflammatory marker C-C motif chemokine 5 (CCL5) in epigenetic regulation of Klotho expression.

Methods

Fifty CKD patients and 25 matched controls were enrolled, and serum CCL5 level, sKlotho level, and DNA methylation were evaluated in these subjects. A renal interstitial fibrosis (RIF) model with CKD was induced in mice via unilateral ureteral obstruction (UUO) in vivo and human proximal tubular epithelial (HK-2) cells treated with CCL5 in vitro. 5-aza-2′-deoxycytidine (5-Aza), a DNA methyltransferase inhibitor was given to UUO mice. Hematoxylin and eosin (HE) and Masson trichrome staining were adopted to evaluate renal pathological changes. Methylation-specific PCR was performed to assess DNA methylation of Klotho promoter in the peripheral blood leucocytes (PBLs) from CKD patients and obstructive kidney from UUO mice. CCL5, Klotho, and DNA methyltransferases (DNMTs) were determined by ELISAs, immunofluorescence, or western blotting. HK-2 cells were exposed to CCL5 with or without 5-Aza and stattic, a p-signal transducer and activator of transcription 3 (STAT3) inhibitor, and expressions of p-STAT3, DNMT1, and Klotho were determined by western blotting.

Results

CCL5 upregulation concomitant with Klotho downregulation in serum and global DNA methylation in PBLs were observed in CKD samples. UUO contributed to severe renal interstitial fibrosis and enhanced expressions of fibrotic markers. Moreover, UUO increased the CCL5 level, induced Klotho promoter methylation, suppressed Klotho level, activated p-STAT3 signaling, and upregulated DNMT1 level. A similar observation was made in HK-2 cells treated with CCL5. More importantly, 5-Aza inhibited UUO-induced Klotho hypermethylation, reversed Klotho, downregulated p-STAT3 expressions, and ameliorated RIF in vivo. The consistent findings in vitro were also obtained in HK-2 cells exposed to 5-Aza and stattic.

Conclusion

The CCL5/p-STAT3/DNMT1 axis is implicated in epigenetic regulation of Klotho expression in CKD. This study provides novel therapeutic possibilities for reversal of Klotho suppression by CKD.
Pollinator-Mediated Selection on Floral Traits of Primula tibetica Differs Between Sites With Different Soil Water Contents and Among Different Levels of Nutrient Availability
Authors: Wu Yun , Duan Xuyu , Tong Zhaoli , Li Qingjun
Published: March 2022

Abiotic environmental factors are predicted to affect plant traits and the intensity of plant-pollinator interactions. However, knowledge of their potential effects on pollinator-mediated selection on floral traits is still limited. We separately estimated the effects of soil water (two sites with different soil water contents) and N-P-K nutrient availability (different levels of nutrient addition) on pollinator-mediated selection on floral traits of Primula tibetica (an insect-pollinated perennial herbaceous species). Our results demonstrated that floral traits, plant reproductive success and pollinator-mediated selection on floral traits varied between sites with different soil water contents and among different levels of nutrient addition. The strength of pollinator-mediated selection was stronger at the site with low soil water content than at the site with high soil water content, and first decreased and then increased with increasing N-P-K nutrient addition. Our results support the hypothesis that abiotic environmental factors influence the importance of pollinators in shaping floral evolution.
Self-Assessed Digital Competences of Romanian Teachers During the COVID-19 Pandemic
Authors: Hatos Adrian , Cosma Mirela-Lăcrimioara , Clipa Otilia
Published: March 2022

Studies on the determinants of school results have shown that they depend largely on the context of learning. Concerning the pandemic, teachers have been forced to find online teaching methods, which leads us to the central issue of this study of whether the effectiveness of online education depends on teachers’ digital skills. Therefore, in this study, we analyzed the perceived digital competences of Romanian pre-tertiary cycle teachers about their professional status, school location, gender, age, taught field, and prior participation in training for online teaching. Using data from 3,419 self-completed questionnaires in an online survey of teachers performed at the beginning of the global lockdown in March 2020, we have built two reliable measures of perceived digital skills, namely the Self-Assessed Multimedia and Online Skills Score (SMOS) and the Self-Assessed Digital Office Skills Score (SDOS), which were the dependent variables in our study. Hierarchical linear regressions were used to test the hypotheses regarding the variations of dependent variables, measuring the two concepts of self-assessed digital skills (SMOS and SDOS). These concepts underlined that both decrease with age and are positively affected by prior attendance at training sessions for online teaching skills and by having ICT and informatics as a taught subject field. However, teachers of all specialties are relatively significantly less skilled in this field. The most important results concern the impact of gender and professional status on the teachers’ self-assessed digital competences. In summary, it appears that self-assessed office digital skills are a specialism demonstrated mainly by female teachers, while multimedia and online skills are perceived by teachers to be a “male” domain. Simultaneously, net of the other variables, a higher status within the teaching profession correlates positively with perceived office digital skills. Lastly, implications for future research, as well as for educational interventions and policies, are discussed.
Ivermectin and the Integrity of Healthcare Evidence During COVID-19
Authors: O'Mathúna Dónal P.
Published: March 2022

The COVID-19 pandemic has been characterized by a lack of clear evidence to guide healthcare professionals, the public and policymakers. The resulting uncertainty, coupled with changing guidelines as additional evidence became available, added to the stress and anxiety reported by decision-makers. Research results are key to providing evidence to guide healthcare decisions. Important questions have arisen about whether various interventions are safe and effective. The evidence found guides those making treatment decisions, and influences those selecting interventions for further evaluation in research studies. As the COVID-19 pandemic intensified, the effectiveness and safety of many pharmaceuticals was queried. Ivermectin will be used to explore the ethics of how healthcare evidence must be critically appraised, even, or especially, during a pandemic. This drug is alleged to be effective in treating COVID-19, with various studies and systematic reviews finding supportive evidence. Some of these have now been linked to concerns about fraud or poor research reporting. This article will focus on the scientific literature and how apparently fraudulent studies were published and influenced treatment decisions, on-going research and public health guidelines. Research evidence is critical during emergencies like pandemics, but urgency should not overtake ethical responsibilities to critically appraise (or evaluate) studies as they become available. These responsibilities apply in various ways to editors, peer-reviewers, news media reporters, and those making treatment decisions, including clinicians, policymakers and the general public. While research article authors have the primary ethical responsibility to reject fraudulent or inaccurate claims, the readers of health research must carefully evaluate all publications. To detect and reject fraudulent healthcare claims, readers need critical appraisal skills that match their level of engagement with those articles. The core principles of critical appraisal will be described in the article, and how they can be adapted for different types of readers. Exemplar tools that develop critical appraisal skills will be noted, with reviews of ivermectin's efficacy explored as examples. As stakeholders in healthcare evidence are increasingly able to identify well-conducted and ethical research they will simultaneously be able to spot and reject fraudulent reports and prevent them from influencing healthcare decisions.
In vitro Dissolution Testing and Pharmacokinetic Studies of Silymarin Solid Dispersion After Oral Administration to Healthy Pigs
Authors: Xu Ying , Li Jie , He Bing , Feng Tingsong , Liang Lijie , Huang Xianhui
Published: March 2022

We evaluated the pharmacokinetics of silymarin solid dispersion in pigs to determine whether silybin bioavailability would be increased over that of a silymarin premix. In vitro dissolution testing was conducted using dissolution apparatus 1 (baskets) at 100 rpm at 37 ± 0.5°C in pH 1.2 HCl, pH 6.8 phosphate, and pH 4.3 acetate buffers containing 0.5% Tween-80. In vivo pharmacokinetics were studied using 16 healthy pigs (Yorkshire × Landrace) that were randomly assigned to two groups. Silymarin as solid dispersion and premix dosage forms were administered directly by stomach tubes at 50 mg kg−1 silybin. In vitro dissolution of silybin for the premix was 35.02, 35.90, and 38.70% in these buffers, respectively. In contrast, silybin dissolution in solid dispersions was increased to 82.92, 87.48, and 99.70%, respectively. Silymarin solid dispersion administered at a single dose resulted in a peak concentration (Cmax) of 1,190.02 ± 246.97 ng ml−1 with the area under the curve (AUC0−∞) at 1,299.19 ± 67.61 ng ml−1 h. These parameters for the premix groups were 411.35 ± 84.92 ng ml−1 and 586.82 ± 180.99 ng ml−1 h, respectively. The Cmax and AUC0−∞ values for the solid dispersion were about twice that of the premix and were consistent with the in vitro dissolution data.
Long-Term Visitation Value for Deep Exploration in Sparse-Reward Reinforcement Learning
Authors: Parisi Simone , Tateo Davide , Hensel Maximilian , D’Eramo Carlo , Peters Jan , Pajarinen Joni
Published: March 2022

Reinforcement learning with sparse rewards is still an open challenge. Classic methods rely on getting feedback via extrinsic rewards to train the agent, and in situations where this occurs very rarely the agent learns slowly or cannot learn at all. Similarly, if the agent receives also rewards that create suboptimal modes of the objective function, it will likely prematurely stop exploring. More recent methods add auxiliary intrinsic rewards to encourage exploration. However, auxiliary rewards lead to a non-stationary target for the Q-function. In this paper, we present a novel approach that (1) plans exploration actions far into the future by using a long-term visitation count, and (2) decouples exploration and exploitation by learning a separate function assessing the exploration value of the actions. Contrary to existing methods that use models of reward and dynamics, our approach is off-policy and model-free. We further propose new tabular environments for benchmarking exploration in reinforcement learning. Empirical results on classic and novel benchmarks show that the proposed approach outperforms existing methods in environments with sparse rewards, especially in the presence of rewards that create suboptimal modes of the objective function. Results also suggest that our approach scales gracefully with the size of the environment.
Non-Invasive Systems and Methods Patents Review Based on Electrocardiogram for Diagnosis of Cardiovascular Diseases
Authors: Flores Nellyzeth , Reyna Marco , Avitia Roberto , Cardenas-Haro Jose , Garcia-Gonzalez Conrado
Published: March 2022

Cardiovascular disease (CVD) is a global public health problem. It is a disease of multifactorial origin, and with this characteristic, having an accurate diagnosis of its incidence is a problem that health personnel face every day. That is why having all the indispensable tools to achieve optimal results is of utmost importance. Time is an essential factor when identifying heart problems, specialists look for and develop options to improve this aspect, which requires a thorough analysis of the patient, electrocardiograms being the factor standard for diagnosis and monitoring of patients. In this paper, we review patents and combined systems for the analysis of existing electrocardiogram signals, specific to cardiovascular diseases. All these methods and equipment have the purpose of giving an accurate diagnosis and a prediction of the presence of CVD in patients with positive risk factors. These are considered as the first diagnostic option, based on the guidelines already established in the field of preventive cardiology. The methodology consists of the searching of specific electrocardiography and cardiovascular disease subjects, taking as a reference the use of various patent databases. A total of 2634 patents were obtained in the consulted databases. Of that total, only 30 patents that met all the previous criteria were considered; furthermore, a second in-depth review of their information was conducted. It is expected that studying and reviewing these patents will allow us to know the variety of tools available for the different pathologies that make up CVD, not only for its immediate diagnosis because, as mentioned, the time factor is decisive for the best forecast but also to allow us to follow up on all the cases that arise, being able to provide a better quality of life to patients with CVD or even being able to lead them to a full recovery.
Effects of Climate Change on Climate Suitability of Green Orange Planting in Hainan Island, China
Authors: Chen Yanxi , Ren Lixuan , Lou Yunsheng , Tang Liling , Yang Jianzhou , Su Lei
Published: March 2022

Hainan Island is endowed with unique climatic and geographical conditions in China. Green orange is a characteristic fruit and plays an important role in local agricultural production of the island. However, few studies have been available regarding the climatic suitability index of green orange planting suitable regions in the island. Based on 30 years (1980 to 2019) of climatic data from 19 meteorological stations in the island, this study established spatial analysis models with topographical data, land use and GIS spatial analysis. Based on climate suitability function, this study established the climate suitability models of temperature, sunshine, precipitation, accumulated temperature and comprehensive suitability model for green orange planting. The Climate suitability index model for green orange planting suitable zoning areas was developed using a natural point segmentation method, and future climate change scenarios were adopted for evaluating the trends of climate suitable areas. The results revealed that the most suitable areas for planting green orange are mainly located at the eastern central region in the island. The climate suitability index ranged from 0.9 to 1.0 in the most suitable regions. The suitable area is mainly distributed in the eastern part, most of the central and western parts of the island, with the climate suitability index ranging from 0.7–0.9. However, the population density in the area is large, and the planting land is limited. The sub-suitable area is mainly located in the coastal areas of the western island, and the high-altitude areas in the central and western regions of the island, with the climate suitability index varying from 0.4 to 0.7. The unsuitable area is mainly distributed in the central mountainous area, with the climate suitability index being 0.0–0.4. The suitability of temperature showed decreasing trend, and the suitability of precipitation gradually moved from the east to the central region under future climate change scenarios. This study is helpful in promoting the development and utilization of agricultural resources and the fine zoning of green orange planting climate suitability in the island.
A Case Study for Decentralized Heat Storage Solutions in the Agroindustry Sector Using Phase Change Materials
Authors: Simão Carlos , Murta-Pina João , Oliveira João Pedro , Coelho Luís , Pássaro João , Ferreira Diogo , Reboredo Fernando , Jorge Tiago , Figueiredo Pedro
Published: March 2022

The development of thermal energy storage solutions (TES) in agroindustry allows reduction of production costs and improvement of operation sustainability. Such solutions require high storage capacity and the ability to adapt to existing equipment. The use of phase change materials (PCMs), which are able to store thermal energy as latent heat, creates new opportunities for heat storage solutions (LHS, latent heat storage) with higher energy density and improved performance when compared to sensible heat storage. New architectures are envisaged where heat storage is distributed throughout the production chain, creating prospects for the integration of renewable generation and recovery of industrial heat waste. This work aims to investigate the benefits of decentralized thermal storage architecture, directly incorporating PCM into the existing equipment of an agroindustry production line. To assess the feasibility and potential gain in the adoption of this TES/LHS distributed solution, a tempering and mixing equipment for food granules is selected as a case study, representing a larger cluster operating under the operation paradigm of water jacket heating. The behavior of the equipment, incorporating an inorganic PCM, is modeled and analyzed in the ANSYS Fluent software. Subsequently, a prototype is instrumented and used in laboratory tests, allowing for data collection and validation of the simulation model. This case study presents a demonstration of the increase in storage capacity and the extension of the discharge process when compared to a conventional solution that uses water for sensible heat storage.