bluuebunny/crossref_metadata_2025 huggingface dataset:
Thrombocytopenia Is an Independent Risk Factor for the Prognosis of Thrombotic Microangiopathy in Chinese Patients With Systemic Lupus Erythematosus
Authors: Yang Fan , Tian Junwei , Peng Linyi , Zhang Li , Liu Jia , Tian Xinping , Zhang Wen , Li Mengtao , Zhao Yan , Zhang Fengchun , Zeng Xiaofeng , Wang Li , Leng Xiaomei
Published: November 2021

Objectives: This study aims to describe clinical characteristics and outcome of thrombotic microangiopathy (TMA) in Chinese patients with systemic lupus erythematosus (SLE), and investigate the risk factors.

Methods: We conducted a retrospective single-center cohort and enrolled patients of TMA associated with SLE between January 2015 and December 2018. Demographic characteristics, clinical features, laboratory profiles, therapeutic strategies, and outcomes were collected. The risk factors of TMA in patients with SLE for mortality using multivariate analysis were estimated.

Results: A total of 119 patients with a diagnosis of TMA were enrolled within the study period in our center, and SLE was found in 72 (60.5%) patients. The mean age was 29.2 ± 10.1 and 65 (92.3%) were women. Only 15 patients were found with definite causes, the other 57 cases remained with unclear reasons. Sixty-two patients got improved, while 10 patients died after treatment (mortality rate: 13.9%). Compared with the survival group, the deceased group had a higher prevalence of neuropsychiatric manifestations, infection with two or more sites, increased levels of C-reaction protein (CRP) and D-Dimer, and decreased platelet count. Multivariate analysis showed that the decrease of platelet count is the independent risk factor for in-hospital mortality for TMA in patients with SLE. The receiver operating characteristic (ROC) curve analysis displayed that a cutoff value of <18 × 109/L for platelet count could significantly increase the risk of death.

Conclusions: Thrombotic microangiopathy often occurs in patients with active SLE with high mortality (13.9%), and thrombocytopenia, especially when the platelet count is lower than 18 × 109/L, is the risk factor for death.
Co-conjugation of Virulence Plasmid and KPC Plasmid in a Clinical Klebsiella pneumoniae Strain
Authors: Yang Xuemei , Dong Ning , Liu Xiaoxuan , Yang Chen , Ye Lianwei , Chan Edward Wai-Chi , Zhang Rong , Chen Sheng
Published: November 2021

Carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-HvKP) strains have been increasingly reported, and it is important to understand the evolutionary mechanisms of these highly pathogenic and resistant bacterial pathogens. In this study, we characterized a ST11 carbapenem-resistant K. pneumoniae strain which harbored an IncFIB/IncHI1B type virulence plasmid and an IncFII/IncR type blaKPC–2-bearing plasmid. The virulence plasmid was found to be conjugative and harbored a 35-kbp fragment including aerobactin encoding cluster from virulence plasmid pLVPK and multiple resistance genes, resulting in a mosaic multi-drug resistance and virulence plasmid. This virulence plasmid could be transferred via conjugation to Escherichia coli and K. pneumoniae strains alone as well as together with the blaKPC–2-bearing plasmid. Co-transmission of virulence and blaKPC–2-bearing plasmids would directly convert a classic K. pneumoniae strain into CR-HvKP strain, leading to a sharp increase in the prevalence of CR-HvKP in clinical settings, which poses a great threat to human health.
Propionic Acid and Sodium Benzoate Affected Biogenic Amine Formation, Microbial Community, and Quality of Oat Silage
Authors: Jia Tingting , Yun Ying , Yu Zhu
Published: November 2021

Investigating the microbial communities and biogenic amine (BA) formation in silage is of vital for improving the quality and safety of oat silage. The present study evaluated the effects of propionic acid (P) and sodium benzoate (SB) on the quality properties, microbial communities, and BA formation in oat silage. Oat was harvested at boot stage and ensiled using P and SB as additives in mini silos, followed by 14 days of aerobic exposure. The results showed that P and SB improved fermentation quality of oat silage, increased the lactic acid content, and decreased pH value and ammonia nitrogen content. Putrescine, cadaverine, and tyramine were the dominant BAs in oat silage; spermidine and spermine were not detected. The control silage had the highest content of total biogenic amine (TBA, 2506.7 mg kg–1 DM), and decreased by 51.1 and 57.7% after adding P and SB, respectively. Moreover, a lower putrescine, cadaverine, and tyramine content and undesirable microbes, such as Caproiciproducens, Stenotrophomonas, Herbinix, and Enterobacter genera, were observed in P and SB silages, which was beneficial for oat silage quality. The fungal community of P silage was dominated by Monascus fuliginosus, and the temperature, pH and ammonia nitrogen content increased after exposure to air. Sedimentibacter, Herbinix, Caproiciproducens, Enterobacter, and Escherichia-Shigella were found to be positively correlated with BA formation in oat silage. Overall, P and SB effectively inhibit the undesirable microbes and BA formation in oat silage, the P silage exhibited lower aerobic stability than the SB silage.
Comprehensive Mapping of the Cell Response to Borrelia bavariensis in the Brain Microvascular Endothelial Cells in vitro Using RNA-Seq
Authors: Tkáčová Zuzana , Bhide Katarína , Mochnáčová Evelina , Petroušková Patrícia , Hruškovicová Jana , Kulkarni Amod , Bhide Mangesh
Published: November 2021

Borrelia bavariensiscan invade the central nervous system (CNS) by crossing the blood-brain barrier (BBB). It is predicted thatB. bavariensisevokes numerous signaling cascades in the human brain microvascular endothelial cells (hBMECs) and exploits them to traverse across the BBB. The complete picture of signaling events in hBMECs induced byB. bavariensisremains uncovered. Using RNA sequencing, we mapped 11,398 genes and identified 295 differentially expressed genes (DEGs, 251 upregulated genes and 44 downregulated genes) inB. bavariensischallenged hBMECs. The results obtained from RNA-seq were validated with qPCR. Gene ontology analysis revealed the participation of DEGs in a number of biological processes like cell communication, organization of the extracellular matrix, vesicle-mediated transport, cell response triggered by pattern recognition receptors, antigen processing via MHC class I, cellular stress, metabolism, signal transduction, etc. The expression of several non-protein coding genes was also evoked. In this manuscript, we discuss in detail the correlation between several signaling cascades elicited and the translocation of BBB byB. bavariensis. The data revealed here may contribute to a better understanding of the mechanisms employed byB. bavariensisto cross the BBB.
An Update on Animal Models for Severe Acute Respiratory Syndrome Coronavirus 2 Infection and Countermeasure Development
Authors: Zhang Liang , Chen Shuaiyin , Zhang Weiguo , Yang Haiyan , Jin Yuefei , Duan Guangcai
Published: November 2021

Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a pandemic since March 2020 and led to significant challenges to over 200 countries and regions all over the world. The establishment of highly pathogenic coronavirus animal model is beneficial for the study of vaccines and pathogenic mechanism of the virus. Laboratory mice, Syrian hamsters, Non-human primates and Ferrets have been used to establish animal models of emerging coronavirus infection. Different animal models can reproduce clinical infection symptoms at different levels. Appropriate animal models are of great significance for the pathogenesis of COVID-19 and the research progress related to vaccines. This review aims to introduce the current progress about experimental animal models for SARS-CoV-2, and collectively generalize critical aspects of disease manifestation in humans and increase their usefulness in research into COVID-19 pathogenesis and developing new preventions and treatments.
Novel dTDP-l-Rhamnose Synthetic Enzymes (RmlABCD) From Saccharothrix syringae CGMCC 4.1716 for One-Pot Four-Enzyme Synthesis of dTDP-l-Rhamnose
Authors: Yang Shida , An Xiaonan , Gu Guofeng , Yan Zhenxin , Jiang Xukai , Xu Li , Xiao Min
Published: November 2021

Deoxythymidine diphospho-l-rhamnose (dTDP-l-rhamnose) is used by prokaryotic rhamnosyltransferases as the glycosyl donor for the synthesis of rhamnose-containing polysaccharides and compounds that have potential in pharmaceutical development, so its efficient synthesis has attracted much attention. In this study, we successfully cloned four putative dTDP-l-rhamnose synthesis genes Ss-rmlABCD from Saccharothrix syringae CGMCC 4.1716 and expressed them in Escherichia coli. The recombinant enzymes, Ss-RmlA (glucose-1-phosphate thymidylyltransferase), Ss-RmlB (dTDP-d-glucose 4,6-dehydratase), Ss-RmlC (dTDP-4-keto-6-deoxy-glucose 3,5-epimerase), and Ss-RmlD (dTDP-4-keto-rhamnose reductase), were confirmed to catalyze the sequential formation of dTDP-l-rhamnose from deoxythymidine triphosphate (dTTP) and glucose-1-phosphate (Glc-1-P). Ss-RmlA showed maximal enzyme activity at 37°C and pH 9.0 with 2.5mMMg2+, and the Km and kcat values for dTTP and Glc-1-P were 49.56μM and 5.39s−1, and 117.30μM and 3.46s−1, respectively. Ss-RmlA was promiscuous in the substrate choice and it could use three nucleoside triphosphates (dTTP, dUTP, and UTP) and three sugar-1-Ps (Glc-1-P, GlcNH2-1-P, and GlcN3-1-P) to form nine sugar nucleotides (dTDP-GlcNH2, dTDP-GlcN3, UDP-Glc, UDP-GlcNH2, UDP-GlcN3, dUDP-Glc, dUDP-GlcNH2, and dUDP-GlcN3). Ss-RmlB showed maximal enzyme activity at 50°C and pH 7.5 with 0.02mM NAD+, and the Km and kcat values for dTDP-glucose were 98.60μM and 11.2s−1, respectively. A one-pot four-enzyme reaction system was developed by simultaneously mixing all of the substrates, reagents, and four enzymes Ss-RmlABCD in one pot for the synthesis of dTDP-l-rhamnose and dUDP-l-rhamnose with the maximal yield of 65% and 46%, respectively, under the optimal conditions. dUDP-l-rhamnose was a novel nucleotide-activated rhamnose reported for the first time.
Long Non-Coding RNAs in Epithelial-Mesenchymal Transition of Pancreatic Cancer
Authors: Takahashi Kenji , Taniue Kenzui , Ono Yusuke , Fujiya Mikihiro , Mizukami Yusuke , Okumura Toshikatsu
Published: November 2021

Non-coding RNAs (ncRNAs), or RNA molecules that do not code for proteins, are generally categorized as either small or long ncRNA (lncRNA) and are involved in the pathogenesis of several diseases including many cancers. Identification of a large number of ncRNAs could help to elucidate previously unknown mechanisms in phenotype regulation. Some ncRNAs are encapsulated by extracellular vesicles (EVs) and transferred to recipient cells to regulate cellular processes, including epigenetic and post-transcriptional regulations. Recent studies have uncovered novel molecular mechanisms and functions of lncRNAs in pancreatic ductal adenocarcinoma (PDAC), one of the most intractable cancers that is highly invasive and metastatic. As the epithelial-mesenchymal transition (EMT) triggers tumor cell invasion and migration, clarification of the roles of lncRNA in EMT and tumor cell stemness would be critical for improving diagnostic and therapeutic approaches in metastatic cancers. This review provides an overview of relevant studies on lncRNA and its involvement with EMT in PDAC. Emerging knowledge offers evidence for the dysregulated expression of lncRNAs and essential insights into the potential contribution of both lncRNAs and EVs in the pathogenesis of PDAC. Future directions and new clinical applications for PDAC are also discussed.
Increased 20-HETE Signaling Suppresses Capillary Neurovascular Coupling After Ischemic Stroke in Regions Beyond the Infarct
Authors: Li Zhenzhou , McConnell Heather L. , Stackhouse Teresa L. , Pike Martin M. , Zhang Wenri , Mishra Anusha
Published: November 2021

Neurovascular coupling, the process by which neuronal activity elicits increases in the local blood supply, is impaired in stroke patients in brain regions outside the infarct. Such impairment may contribute to neurological deterioration over time, but its mechanism is unknown. Using the middle cerebral artery occlusion (MCAO) model of stroke, we show that neuronal activity-evoked capillary dilation is reduced by ∼75% in the intact cortical tissue outside the infarct border. This decrease in capillary responsiveness was not explained by a decrease in local neuronal activity or a loss of vascular contractility. Inhibiting synthesis of the vasoconstrictive molecule 20-hydroxyeicosatetraenoic acid (20-HETE), either by inhibiting its synthetic enzyme CYP450 ω-hydroxylases or by increasing nitric oxide (NO), which is a natural inhibitor of ω-hydroxylases, rescued activity-evoked capillary dilation. The capillary dilation unmasked by inhibiting 20-HETE was dependent on PGE2 activation of endoperoxide 4 (EP4) receptors, a vasodilatory pathway previously identified in healthy animals. Cortical 20-HETE levels were increased following MCAO, in agreement with data from stroke patients. Inhibition of ω-hydroxylases normalized 20-HETE levels in vivo and increased cerebral blood flow in the peri-infarct cortex. These data identify 20-HETE-dependent vasoconstriction as a mechanism underlying capillary neurovascular coupling impairment after stroke. Our results suggest that the brain’s energy supply may be significantly reduced after stroke in regions previously believed to be asymptomatic and that ω-hydroxylase inhibition may restore healthy neurovascular coupling post-stroke.
A Descriptive Review of Global Real World Evidence Efforts to Advance Drug Discovery and Clinical Development in Amyotrophic Lateral Sclerosis
Authors: Cook Suzanne F. , Rhodes Thomas , Schlusser Courtney , Han Steve , Chen Chao , Zach Neta , Murthy Venkatesha , Davé Shreya
Published: November 2021

Understanding patient clinical progression is a key gateway to planning effective clinical trials and ultimately enabling bringing treatments to patients in need. In a rare disease like amyotrophic lateral sclerosis (ALS), studies of disease natural history critically depend on collaboration between clinical centers, regions, and countries to enable creation of platforms to allow patients, caregivers, clinicians, and researchers to come together and more fully understand the condition. Rare disease registries and collaborative platforms such as those developed in ALS collect real-world data (RWD) in standardized formats, including clinical and biological specimen data used to evaluate risk factors and natural history of disease, treatment patterns and clinical (ClinROs) and patient- reported outcomes (PROs) and validate novel endpoints. Importantly, these data support the development of new therapeutics by supporting the evaluation of feasibility and design of clinical trials and offer valuable information on real-world disease trajectory and outcomes outside of the clinical trial setting for comparative purposes. RWD may help to accelerate therapy development by identifying and validating outcome measures and disease subpopulations. RWD can also make potential contributions to the evaluation of the safety and effectiveness of new indications for approved products and to satisfy post-approval regulatory and market access requirements. There is a lack of amalgamated information on available registries, databases, and other sources of real-world data on ALS; thus, a global review of all available resources was warranted. This targeted review identifies and describes ALS registries, biobanks and collaborative research networks that are collecting and synthesizing RWD for the purposes of increasing patient awareness and advancing scientific knowledge with the hope of expediting future development of new therapies.
Inhibition of the in vitro Activities of α-Amylase and Pancreatic Lipase by Aqueous Extracts of Amaranthus viridis, Solanum macrocarpon and Telfairia occidentalis Leaves
Authors: Oluwagunwa Olayinka A. , Alashi Adeola M. , Aluko Rotimi E.
Published: November 2021

Inhibition of digestive enzymes such as α-amylase and pancreatic lipase (PL) is a promising therapeutic strategy for the treatment and management of chronic health conditions such as diabetes and obesity. Therefore, the aim of this work was to determine the enzyme inhibitory activity of polyphenol-rich aqueous extracts of Amaranthus viridis (AV), Solanum macrocarpon (SM) and Telfairia occidentalis (TO) leaves, which were harvested from plants produced using multiple urea fertilizer doses (0–80 kg N/ha). Fertilizer application was applied at two time points (at planting or 2 weeks after seedling emergence). Leaf extracts were obtained using aqueous extraction (1:20, leaves:water) for 4 h at 60°C followed by centrifugation and freeze-drying of the supernatant. Results showed that the extracts inhibited α-amylase, and pancreatic lipase dose-dependently with TO extracts having significantly (p < 0.05) higher inhibitory activities for both enzymes. Fluorescence intensity and circular dichroism spectra in the presence and absence of leaf extracts indicate significant changes to the enzyme protein secondary and tertiary conformations. We conclude that the leaf extracts, especially from TO are potential agents for reducing calorie intake as a preventive or treatment tool against chronic diseases such as diabetes and obesity.
Aberrant Cholesterol Metabolism in Ovarian Cancer: Identification of Novel Therapeutic Targets
Authors: He Jiangnan , Siu Michelle K.Y. , Ngan Hextan Y. S. , Chan Karen K. L.
Published: November 2021

Cholesterol is an essential substance in mammalian cells, and cholesterol metabolism plays crucial roles in multiple biological functions. Dysregulated cholesterol metabolism is a metabolic hallmark in several cancers, beyond the Warburg effect. Reprogrammed cholesterol metabolism has been reported to enhance tumorigenesis, metastasis and chemoresistance in multiple cancer types, including ovarian cancer. Ovarian cancer is one of the most aggressive malignancies worldwide. Alterations in metabolic pathways are characteristic features of ovarian cancer; however, the specific role of cholesterol metabolism remains to be established. In this report, we provide an overview of the key proteins involved in cholesterol metabolism in ovarian cancer, including the rate-limiting enzymes in cholesterol biosynthesis, and the proteins involved in cholesterol uptake, storage and trafficking. Also, we review the roles of cholesterol and its derivatives in ovarian cancer and the tumor microenvironment, and discuss promising related therapeutic targets for ovarian cancer.
Pulmonary Complications in Children Following Hematopoietic Cell Transplantation: A Case Report and Review of the Diagnostic Approach
Authors: Elbahlawan Lama , McArthur Jenny , Morin Cara E. , Abdelhafeez Hafeez , McCarville M. Beth , Ruiz Robert E. , Srinivasan Saumini , Qudeimat Amr
Published: November 2021

Pulmonary complications are common in children following hematopoietic cell transplantation (HCT) and contribute to their morbidity and mortality. Early diagnosis is essential for management and prevention of progression of lung injury and damage. In many cases, diagnosis can be challenging and may require diagnostic imaging and more invasive testing such as bronchoscopy and lung biopsy. We report the case of a 12-year-old girl who developed recurrent episodes of acute respiratory failure requiring intensive care unit admission in the post-HCT phase and describe the diagnostic and multidisciplinary approach for her management. In addition, we review the diagnostic approach of pulmonary complications post-HCT and highlight the utility and risks of bronchoscopy and lung biopsy in these children.
The Association Between Placental Residual Blood Volume and Two Placental Transfusion Methods After Delivery at Term
Authors: Hung Tai-Ho , Chuang Ya-Chun , Huang Lulu
Published: November 2021

Background: Despite reports of the beneficial effects, such as increasing hemoglobin level and iron store in the neonatal period, of delayed cord clamping, or umbilical cord milking after delivery in healthy term-born infants, the duration of delayed clamping or rounds of milking in most previous reports were determined arbitrarily and varied widely across different studies.

Methods: We prospectively recruited 80 women with normal singleton pregnancies at 38–40 weeks' gestation. Participants were classified according to the mode of delivery and randomly assigned to either collecting blood from the placenta by umbilical cord drainage (CD) or cord milking (CM), with the placenta left in the uterus. The volume of blood collected, the duration of CD, and the number of rounds of CM were recorded.

Results: Collected placental residual blood volume positively correlated with birth weight, placental weight, and length of the cord. When 80% of the total placental residual blood volume collected was set as the threshold, more than 80% of women who delivered vaginally reached this level within 60 s of CD or seven repetitions of CM. This amount of blood could be obtained within 120 s of CD or after seven repetitions of CM in more than 80% of women who underwent cesarean delivery.

Conclusion: In most women, regardless of birth weight and placental weight, more than 80% of placental residual blood volume could be collected by CD within 60 s after vaginal delivery, 120 s after cesarean delivery, and seven repetitions of CM in both vaginal and cesarean deliveries.
Anticonstriction Effect of MCA in Rats by Danggui Buxue Decoction
Authors: Guo Ying , Zhang Yating , Hou Ya , Guo Pengmei , Wang Xiaobo , Zhang Sanyin , Yang Peng
Published: November 2021

Objective: Danggui Buxue decoction (DBD), consisting of Angelicae Sinensis Radix (ASR) and Astragali Radix (AR), is a famous prescription with the function of antivasoconstriction. This study intends to probe its mechanisms on the relaxation of the middle cerebral artery (MCA).

Methods: Vascular tension of rat MCA was measured using a DMT620 M system. First, the identical series of concentrations of DBD, ASR, and AR were added into resting KCl and U46619 preconstricted MCA. According to the compatibility ratio, their dilatation effects were further investigated on KCl and U46619 preconstricted vessels. Third, four K+ channel blockers were employed to probe the vasodilator mechanism on KCl-contracted MCA. We finally examined the effects of DBD, ASR, and AR on the vascular tone of U46619-contracted MCA in the presence or absence of Ca2+.

Results: Data suggested that DBD, ASR, and AR can relax on KCl and U46619 precontracted MCA with no effects on resting vessels. The vasodilator effect of ASR was greater than those of DBD and AR on KCl-contracted MCA. For U46619-contracted MCA, ASR showed a stronger vasodilator effect than DBD and AR at low concentrations, but DBD was stronger than ASR at high concentrations. Amazingly, the vasodilator effect of DBD was stronger than that of AR at all concentrations on two vasoconstrictors which evoked MCA. The vasodilator effect of ASR was superior to that of DBD at a compatibility ratio on KCl-contracted MCA at low concentrations, while being inferior to DBD at high concentrations. However, DBD exceeded AR in vasodilating MCA at all concentrations. For U46619-constricted MCA, DBD, ASR, and AR had almost identical vasodilation. The dilation of DBD and AR on KCl-contracted MCA was independent of K+ channel blockers. However, ASR may inhibit the K+ channel opening partially through synergistic interactions with Gli and BaCl2. DBD, ASR, and AR may be responsible for inhibiting [Ca2+]out, while ASR and AR can also inhibit [Ca2+]in.

Conclusion: DBD can relax MCA with no effects on resting vessels. The mechanism may be related to ASR’s inhibition of KATP and Kir channels. Meanwhile, the inhibition of [Ca2+]out by DBD, ASR, and AR as well as the inhibition of [Ca2+]in by ASR and AR may contribute to dilate MCA.
The Potential Protective Effect of Iridoid Glycosides Isolated From Osmanthus fragrans Seeds Against the Development of Immune Liver Injury in Mice
Authors: Zhang Yuchen , Xiao Feng , Zhou Qiqi , Diao Tingting , Zhang Meng , Liu Dongyang , Wang Zhuowen , Huang Ting , Wu Yupei , Bai Yuting , Min Qing
Published: November 2021

Objective: The iridoid glycosides were extracted and separated from Osmanthus fragrans seeds, and the potential protective effect of Osmanthus fragrans seed extract on concanavalin A-induced immune liver injury in mice was studied.

Methods:Osmanthus fragrans seeds were extracted by 95% ethanol reflux. Then, the iridoid glycosides were enriched by extraction refined through petroleum ether (60°C–90°C), ethyl acetate, and water-saturated n-butanol in sequence, so as to purify the n-butanol part (Osmanthus fragrans seed’s n-butanol extraction, OFSN) by macroporous resin. Specnuezhenide and Nuezhenoside G13 were used as the reference substances to determine the concentration of iridoid glycosides by HPLC. On this basis, a mouse immune liver injury model was established by tail intravenous concanavalin A (20 mg/kg); the contents of serum ALT, AST, IFN-γ, and TNF-α and the contents of liver tissue MDA and SOD were determined; the pathological changes of the liver by HE staining were observed; and the expression levels of p38MAPK and p-p38mapk in liver tissue were detected by WB.

Results: The linearity, precision, repeatability, recovery, and stability of HPLC all met the requirements by validating with the methodology. The contents of Specnuezhenide and Nuezhenoside G13 in the n-butanol extracts were 39.20% and 39.88%, respectively. Actually, their contents can reach up to 82.56% and 87.9% after being purified by macroporous resin. The results of animal experiments show that OFSN could significantly reduce the liver and spleen index, reduce the ALT and AST contents in plasma and the MDA content in liver tissue, and then increase the SOD content. Besides, OFSN could also reduce the plasma IFN-γ and TNF-α levels. The HE staining result indicates that the pathological changes in the liver tissues of mice treated with OFSN are alleviated to different degrees while the WB result suggests that OFSN could significantly inhibit the expression of p-p38mapk.

Conclusion:Osmanthus fragrans seeds are rich in iridoid glycosides, which has a good protective effect on mouse immune liver injury caused by concanavalin A. The mechanism may be related to inhibiting the phosphorylation of p38MAPK, inhibiting the release of inflammatory mediators, improving the antioxidant capacity of liver cells, and weakening the occurrence of lipid peroxidation.
A Systematic Review Examining the Approaches Used to Estimate Interindividual Differences in Trainability and Classify Individual Responses to Exercise Training
Authors: Bonafiglia Jacob T. , Preobrazenski Nicholas , Gurd Brendon J.
Published: November 2021

Background: Many reports describe statistical approaches for estimating interindividual differences in trainability and classifying individuals as “responders” or “non-responders.” The extent to which studies in the exercise training literature have adopted these statistical approaches remains unclear.

Objectives: This systematic review primarily sought to determine the extent to which studies in the exercise training literature have adopted sound statistical approaches for examining individual responses to exercise training. We also (1) investigated the existence of interindividual differences in trainability, and (2) tested the hypothesis that less conservative thresholds inflate response rates compared with thresholds that consider error and a smallest worthwhile change (SWC)/minimum clinically important difference (MCID).

Methods: We searched six databases: AMED, CINAHL, EMBASE, Medline, PubMed, and SportDiscus. Our search spanned the aerobic, resistance, and clinical or rehabilitation training literature. Studies were included if they used human participants, employed standardized and supervised exercise training, and either: (1) stated that their exercise training intervention resulted in heterogenous responses, (2) statistically estimated interindividual differences in trainability, and/or (3) classified individual responses. We calculated effect sizes (ESIR) to examine the presence of interindividual differences in trainability. We also compared response rates (n = 614) across classification approaches that considered neither, one of, or both errors and an SWC or MCID. We then sorted response rates from studies that also reported mean changes and response thresholds (n = 435 response rates) into four quartiles to confirm our ancillary hypothesis that larger mean changes produce larger response rates.

Results: Our search revealed 3,404 studies, and 149 were included in our systematic review. Few studies (n = 9) statistically estimated interindividual differences in trainability. The results from these few studies present a mixture of evidence for the presence of interindividual differences in trainability because several ESIR values lay above, below, or crossed zero. Zero-based thresholds and larger mean changes significantly (both p < 0.01) inflated response rates.

Conclusion: Our findings provide evidence demonstrating why future studies should statistically estimate interindividual differences in trainability and consider error and an SWC or MCID when classifying individual responses to exercise training.

Systematic Review Registration: [website], identifier [registration number].
Lipid Signaling Modulates the Response to Fumonisin Contamination and Its Source, Fusarium verticillioides, in Maize
Authors: Righetti Laura , Dall’Asta Chiara , Lucini Luigi , Battilani Paola
Published: November 2021

Fumonisin-contaminated maize (Zea mays L.) products are a major health concern because of their toxic effects in humans and animals. Breeding maize for increased mycotoxin resistance is one of the key sustainable strategies for mitigating the effects of fumonisin contamination. Recent studies suggest a link between fumonisin accumulation and plant lipid and oxylipin profiles. However, the data collected so far do not reveal a cause-and-effect relationship. In this study, to decipher the multifactorial nature of mycotoxin resistance and plant–pathogen interaction mechanisms, we examined the oxylipin and complex lipid profiles of two maize hybrids (H21 and H22, the latter showing significantly lower FBs content) grown in the open field in two locations over 3years. Untargeted ultra-high performance liquid chromatography coupled with quadrupole-time-of-flight (UHPLC-Q-TOF), together with chemometrics analysis, successfully distinguished between the two hybrids as having low- and high-level fumonisin contamination. Considering that H21 and H22 were exposed to the same environmental factors, the higher activation of lipid signaling systems in H22 suggests that other routes are enabled in the less susceptible hybrids to limit fumonisin B (FB) accumulation. Our results highlighted the crucial role played by oxylipin and sphingolipid signaling in modulating the complex maize response to F. verticillioides infection. Overall, our results returned a global view on the changes in lipid metabolites related to fumonisin accumulation under open field conditions, and revealed a strong activation of the lipid signaling cascade in maize in the presence of FB1.
Transcriptional Changes in the Developing Rice Seeds Under Salt Stress Suggest Targets for Manipulating Seed Quality
Authors: Lee Choonseok , Chung Chong-Tae , Hong Woo-Jong , Lee Yang-Seok , Lee Jong-Hee , Koh Hee-Jong , Jung Ki-Hong
Published: November 2021

Global sea-level rise, the effect of climate change, poses a serious threat to rice production owing to saltwater intrusion and the accompanying increase in salt concentration. The reclaimed lands, comprising 22.1% of rice production in Korea, now face the crisis of global sea-level rise and a continuous increase in salt concentration. Here, we investigated the relationship between the decrease in seed quality and the transcriptional changes that occur in the developing rice seeds under salt stress. Compared to cultivation on normal land, the japonica rice cultivar, Samgwang, grown on reclaimed land showed a greatly increased accumulation of minerals, including sodium, magnesium, potassium, and sulfur, in seeds and a reduced yield, delayed heading, decreased thousand grain weight, and decreased palatability and amylose content. Samgwang showed phenotypical sensitivity to salt stress in the developing seeds. Using RNA-seq technology, we therefore carried out a comparative transcriptome analysis of the developing seeds grown on reclaimed and normal lands. In the biological process category, gene ontology enrichment analysis revealed that the upregulated genes were closely associated with the metabolism of biomolecules, including amino acids, carboxylic acid, lignin, trehalose, polysaccharide, and chitin, and to stress responses. MapMan analysis revealed the involvement of upregulated genes in the biosynthetic pathways of abscisic acid and melatonin and the relationship of trehalose, raffinose, and maltose with osmotic stress. Interestingly, many seed storage protein genes encoding glutelins and prolamins were upregulated in the developing seeds under salt stress, indicating the negative effect of the increase of storage proteins on palatability. Transcription factors upregulated in the developing seeds under salt stress included, in particular, bHLH, MYB, zinc finger, and heat shock factor, which could act as potential targets for the manipulation of seed quality under salt stress. Our study aims to develop a useful reference for elucidating the relationship between seed response mechanisms and decreased seed quality under salt stress, providing potential strategies for the improvement of seed quality under salt stress.
The Landscape of Alternative Splicing Regulating Potassium Use Efficiency in Nicotiana tabacum
Authors: He Bing , Meng Lin , Tang Lina , Qi Weicong , Hu Fengqin , Lv Yuanda , Song Wenjing
Published: November 2021

Alternative splicing (AS) occurs extensively in eukaryotes as an essential mechanism for regulating transcriptome complexity and diversity, but the AS landscape regulating potassium (K) use efficiency in plants is unclear. In this study, we performed high-throughput transcriptome sequencing of roots and shoots from allopolyploid Nicotiana tabacum under K+ deficiency. Preliminary physiological analysis showed that root system architecture was dramatically changed due to potassium deficiency and that IAA content was significantly reduced in root and shoot. AS analysis showed that a total of 28,179 genes exhibited 54,457 AS events, and 1,510 and 1,732 differentially alternatively spliced (DAS) events were identified in shoots and roots under low K+ stress. Nevertheless, only 120 DAS events occurred in both shoots and roots, implying that most DAS events were tissue-specific. Both in shoot and the root, the proportion of DAS genes in differentially expressed (DE) genes equaled that in non-DE genes, which indicated that AS might play a unique regulatory role in response to low potassium. Gene ontology analysis further indicated that transcription regulation and AS modulation worked independently in response to low K+ stress in tobacco, as their target biological processes were different. Totally 45 DAS transcription factors (TFs) were found, which were involved in 18 TF families. Five Auxin response factor (ARF) TFs were significantly DAS in root, suggesting that response to auxin was probably subject to AS regulation in the tobacco root. Our study shows that AS variation occurs extensively and has a particular regulatory mechanism under K+ deficiency in tobacco. The study also links changes in root system architecture with the changes in AS of ARF TFs, which implied the functional significance of these AS events for root growth and architecture.
Quiet Eye and Computerized Precision Tasks in First-Person Shooter Perspective Esport Games
Authors: Dahl Mats , Tryding Mårten , Heckler Alexander , Nyström Marcus
Published: November 2021

The gaze behavior in sports and other applied settings has been studied for more than 20 years. A common finding is related to the “quiet eye” (QE), predicting that the duration of the last fixation before a critical event is associated with higher performance. Unlike previous studies conducted in applied settings with mobile eye trackers, we investigate the QE in a context similar to esport, in which participants click the mouse to hit targets presented on a computer screen under different levels of cognitive load. Simultaneously, eye and mouse movements were tracked using a high-end remote eye tracker at 300 Hz. Consistent with previous studies, we found that longer QE fixations were associated with higher performance. Increasing the cognitive load delayed the onset of the QE fixation, but had no significant influence on the QE duration. We discuss the implications of our results in the context of how the QE is defined, the quality of the eye-tracker data, and the type of analysis applied to QE data.
Disinhibition of Primitive Reflexes in Attention Deficit and Hyperactivity Disorder: Insight Into Specific Mechanisms in Girls and Boys
Authors: Bob Petr , Konicarova Jana , Raboch Jiri
Published: November 2021

Objective: Cognitive and motor disintegration and other functional disturbances in various neuropsychiatric disorders may be related to inhibitory deficits that may manifest as a persistence or re-expression of primitive reflexes and few recent data suggest that these deficits may occur in Attention Deficit and Hyperactivity Disorder (ADHD).

Methods: We have tested a hypothesis to which extent ADHD symptoms and balance deficits are related to persisting primitive reflexes, such as Asymmetric Tonic Neck Reflex (ATNR) and Symmetric Tonic Neck Reflex (STNR) in 80 medication-naïve children with ADHD (40 boys and 40 girls) in the school age (8–11 years) and compared these data with a control group of 60 children (30 boys and 30 girls).

Results: These data show new finding that ADHD symptoms and balance deficits are strongly and specifically associated with persistent ATNR in girls and STNR in boys.

Conclusions: These results provide first evidence in medical literature that ADHD in girls and boys is specifically related to distinguished neurological developmental mechanisms related to disinhibition of primitive reflexes.
A Longitudinal Study of Parent-Child Interactions and Language Outcomes in Fragile X Syndrome and Other Neurodevelopmental Disorders
Authors: Bush Lauren , Martin Gary E. , Landau Emily , Losh Molly
Published: November 2021

Difficulties with pragmatic language (i.e., language in social contexts, such as conversational ability) are a noted characteristic of the language profiles of both fragile X syndrome (FXS) and autism spectrum disorder (ASD), conditions which show significant phenotypic overlap. Understanding the origins and developmental course of pragmatic language problems in FXS and other developmental conditions associated with language impairment is a critical step for the development of targeted interventions to promote communicative competence across the lifespan. This study examined pragmatic language in the context of parent-child interactions in school-age children with FXS (who did and did not meet ASD criteria on the ADOS;n= 85), idiopathic ASD (n= 32), Down syndrome (DS;n= 38), and typical development (TD;n= 39), and their parents. Parent-child communicative interactions were examined across multiple contexts, across groups, and in relationship to pragmatic language outcomes assessed 2 years later. Results showed both overlapping and divergent patterns across the FXS-ASD and idiopathic ASD child and parent groups, and also highlighted key differences in pragmatic profiles based on situational context, with more pragmatic language difficulties occurring for both ASD groups in less structured interactions. Differences in parental language styles during parent-child interactions were associated with child language outcomes, likely reflecting the complex interplay of discourse style inherent to a parent, with the inevitable influence of child characteristics on parent language as well. Together, findings help delineate the dynamic and multifactorial nature of impaired pragmatic skills among children with FXS and other neurodevelopmental disorders associated with language impairment, with potential implications for the development of targeted interventions for pragmatic communication skills.
The Anticipation of Crime and Corruption Problems Due to the Expansion of Telemedicine: A Study Based on the Korea Medical Crime Investigation System
Authors: Dongkyu Lee
Published: November 2021

The telemedicine system, which has been gradually introduced, has changed dramatically with the outbreak of COVID-19. Now, with the development of related laws and technologies, the introduction of telemedicine will be further accelerated, and like the advent of smartphones, this will become an unstoppable trend of the times. However, just as there are various crimes and corruption problems in the current health system, the introduction of telemedicine may bring other problems. Therefore, it is important to anticipate the types of corruption or crimes that will occur with the introduction of telemedicine. And based on these expectations, we will have an opportunity to properly prepare for the various problems associated with telemedicine.
Investigation of Health Science Students' Knowledge Regarding Healthy Lifestyle Promotion During the Spread of COVID-19 Pandemic: A Randomized Controlled Trial
Authors: Alotaibi Naser , Al-Sayegh Nowall , Nadar Mohammed , Shayea Abdulaziz , Allafi Ahmed , Almari Mohammed
Published: November 2021

Background: Health sciences students as future health care providers, can play a valuable role in protecting societies against the spread of COVID-19 through health promotion and lifestyle modification education. Therefore, proper education of these students is essential.

Objective: This study sought to assess and measure the change of knowledge of health sciences students regarding healthy lifestyle promotion strategies during the spread of the Covid-19 pandemic, after participation in different types of online and social media educational programs.

Methods: In order to serve the purpose of the study, a methodological research design was first used to ensure the validation of the developed scale; the COVID-19 Healthy Lifestyle Promotion Scale (COVID-19 HLPS). The study utilized a four-arm randomized control research design in which the participants were randomly assigned into one of four groups, (1) control group (placebo intervention), (2) brochure group, who received brochures relevant to healthy lifestyle promotion, (3) Instagram group, who received similar information but through Instagram posts, and (4) online interactive educational workshop group, who also received similar information through an online interactive educational workshop.

Results: In total, 155 participants participated in the online and social media intervention programs. There was a significant improvement in the intervention groups in the total knowledge subscale of the healthy promotion strategies compared with the control group (p < 0.001). Overall, the workshop group was the most effective group (effect size = 1.54) followed by the Instagram group (effect size = 0.99) and then the brochure group (effect size = 0.91).

Conclusions: In order to meet the challenges posed by this pandemic, the use of such online and social media interventions is essential and may be the key for health promotion during this pandemic. Health science students, as future health care professionals, can play a fundamental role during the COVID-19 pandemic in disseminating knowledge relevant to healthy lifestyle to their families and communities thus promoting healthy living and behavioral changes. We propose the development of research initiatives at both national and international levels targeting changes within health science curricula that can meet potential challenges of future pandemics, leading to advancement of health care services globally.
Interactive Effects of Enalapril Administration and Novel HIIT Wheel-Bed Training in Aged Rats
Authors: Yang Youfeng , Banerjee Anisha , Sun Yi , Carter Christy S. , Buford Thomas W.
Published: November 2021

Introduction: Growing research suggests that aerobic high-intensity interval training (HIIT) improves cardiovascular function and physical performance compared with moderate intensity continuous training (MICT). However relatively few animal models of HIIT are available to inform about the benefits of this exercise—particularly among older animals. In addition, there is little evidence for how HIIT training interacts with adjuvant pharmacological therapies known to enhance the impact of MCIT in older individuals such as Angiotensin Converting Enzyme (ACE) Inhibitors.

Purpose: The aim of the present study was to establish a HIIT protocol in aged rats based on forced running wheel-bed, and to subsequently (1) establish the feasibility of the HIIT protocol in a proof-of-concept study evaluating interactions between HIIT and (2) the result of combining HIIT + ACE inhibitor treatment using the ACE inhibitor enalapril.

Methods: Two groups of rats were used in this study. The feasibility of using wheel-bed for HIIT training was tested in group one (15- and 30-month-old male rats). In the second group, 37 24-month-old Fisher 344 x Brown Norway male rats were randomly divided into four subgroups: control, enalapril, HIIT training group, and HIIT training combined with enalapril administration. The training and administration lasted for 4 weeks. After the intervention, locomotor activity, exercise tolerance, and grip strength were tested.

Results: Our feasibility study suggested that middle-aged and aged rats were able to successfully complete the HIIT training. In our intervention study, HIIT training alone, regardless of adjuvant enalapril intervention, did raise treadmill exercise tolerance vs. the sedentary condition. Measures of healthspan were not negatively impacted by HIIT training.

Conclusion: The novel HIIT protocol based on forced running wheel-bed was successfully employed in aged rats. We conclude that future studies should compare the results and of multi-modal intervention strategies which include both HIIT and MICT in combination with adjuvant therapies such as enalapril to improve exercise tolerance and other global indices of healthspan.
Pet-Friendly for Whom? An Analysis of Pet Fees in Texas Rental Housing
Authors: Applebaum Jennifer W. , Horecka Kevin , Loney Lauren , Graham Taryn M.
Published: November 2021

Previous studies have underscored the difficulty low-income pet owners often face when attempting to secure affordable rental housing. Further exacerbating this housing disparity are fees charged on top of normal monthly rent to pet owners in “pet-friendly” rental housing. In this study, we aggregated rental housing listings from the twenty most populous cities in Texas, USA from a popular online rental database. We paired the rental listings with census tract information from the American Community Survey in order to investigate economic and racial/ethnic patterns in the spatial distribution of the properties. We find that less expensive pet-friendly listings were more likely to have pet fees charged on top of rent than rental units that were more expensive. Additionally, when pet fee burden was defined as a function of average income by census tract, low-income communities and communities of color were more likely than higher income and predominantly White communities to pay disproportionately higher fees to keep pets in their homes. We also find patterns of spatial inequalities related to pet fee burden by a metric of income inequality by city. The burden of pet rental fees may contribute to both housing insecurity and companion animal relinquishment. We discuss these findings as they relate to inequalities in housing, with particular attention to marginalized and disadvantaged people with pets. We conclude with recommendations for policy and practice.