bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic Trajectory and Clonal Evolution of Multiple Primary Lung Cancer with Lymph Node Metastasis
Authors: Li Chunxiang , Tian He , Wang Yalong , Yang Zhenlin , Chen Ping , Fan Tao , Xiao Chu , Bai Guangyu , Li Lin , Zheng Bo , He Jie
Published: July 2022

Multiple primary lung cancer (MPLC) with lymph node metastasis (LNM) is a rare phenomenon of multifocal lung cancer. The genomic landscapes of MPLC and the clonal evolution pattern between primary lung lesions and lymph node metastasis haven’t been fully illustrated. We performed whole-exome sequencing (WES) on 52 FFPE (Formalin-fixed Paraffin-Embedded) samples from 11 patients diagnosed with MPLC with LNM. Genomic profiling and phylogenetic analysis were conducted to infer the evolutional trajectory within each patient. The top 5 most frequently mutated genes in our study were TTN (76.74%), MUC16 (62.79%), MUC19 (55.81%), FRG1 (46.51%), and NBPF20 (46.51%). For 81.82% of patients (9/11), most genetic alterations harbored by pulmonary tumors were mutually exclusive, suggesting their heterogenous origins. Individually, the genetic profile of lymph node metastatic lesions overlapped with that of multiple lung cancers in different degrees but are more genetically related to specific pulmonary lesions. SETD2 was a potential metastasis biomarker of MPLC. The mean putative neo-antigen number of the primary tumor (646.5) is higher than that of lymph node metastases (300, p = 0.2416). Primary lung tumors and lymph node metastases are highly heterogenous in immune repertoires. Our findings portrayed the comprehensive genomic landscape of MPLC with LNM. We characterized the genomic heterogeneity among different tumors and offered novel clues of the clonal evolution between MPLC and their lymphatic metastases, thus advancing the treatment strategies and preventions of MPLC with LNM.
Periodic solutions to perturbed nonlinear oscillators with memory
Authors: Mariano Paolo Maria , Spadini Marco
Published: July 2022

We consider a general class of nonlinear dynamical systems with memory.We prove under which conditions periodic perturbations allow solutions with the same period. In particular, we consider memory kernels of $\Gamma$-type, which give prominence to critical phenomena in the past.
Self-rated Health Status and Associated Factors in Rural Workers
Authors: Martins Cleodice Alves , Prado Camila Bruneli do , Ferreira Júlia Rabelo Santos , Zandonade Eliana , Bezerra Olívia Maria de Paula Alves , Salaroli Luciane Bresciani
Published: July 2022

Background: Self-rated health status can be considered a good predictor of morbidity and mortality and has been used because of its easy assessment and applicability. The instrument is efficient for understanding sociodemographic, environmental and clinical conditions that may be related to the self-rated health status. Thus, this study aims to analyze the self-assessment of health status in rural workers and its association with socioeconomic characteristics, lifestyle, clinical condition and work characteristics.Methods: This is a cross-sectional study carried out with farmers of both sexes who had agriculture as their main source of income, in the municipality of Santa Maria de Jetibá. A simple and direct question was used: “In general, compared to people your age, how do you rate your own state of health?” to see how they rate their current health status. The independent variables analyzed were socioeconomic, clinical, health and work conditions. The magnitude of the associations was evaluated by means of hierarchical logistic regression in levels. Results: It was found that 42.1% of farmers self-rated their health status as regular or poor. Females had a risk of worse self-rated health (OR=0,705; 95% CI: 0,522 - 0,951), socioeconomic classes C (OR=1,937; 95% CI: 1,009-3,720), D/E (OR= 2,280; 95% CI: 1,178-4,415), the body mass index (OR=1,477; 95% CI: 1,086-2,008), multimorbidity (OR=1,715; 95% CI: 1,201-2,447) and complex multimorbidity (OR=1,738;95% CI: 1,097-2,751). Conclusion: It was concluded that the presence of chronic diseases, socioeconomic status, female gender and overweight were risk factors for a negative self-rated health. The identification of these determinants through self-rated can support the planning of actions aimed at the health of the rural population.Register: This study was approved by the Research Ethics Committee of the Health Sciences Center of the Federal University of Espírito Santo, under protocol number nº. 2091172 (CAAE 52839116.3.0000.5060). All research participants signed the Informed Consent Term.
Assessment of data collection systems for active safety surveillance of vaccines during pregnancy in low- and middle-income countries through key informant’s interviews
Authors: Belizán Maria , Cairoli Federico Rodriguez , Mazzoni Agustina , Goucher Erin , Zaraa Sabra , Matthews Sarah , Pingray Verónica , Stergachis Andy , Xiong Xu , Berrueta Mabel , Buekens Pierre
Published: July 2022

Background: There is an urgent need for active safety surveillance to monitor vaccine exposure during pregnancy in low- and middle-income countries (LMICs). Existing maternal, newborn, and child health (MNCH) data collection systems could serve as platforms for post-marketing active surveillance of maternal immunization safety. To identify sites using existing systems, a thorough assessment should be conducted. Therefore, this study had the objectives to first develop an assessment tool and then to use this tool in sites using MNCH data collection systems through informant interviews.Methods: We conducted a rapid review of the literature to identify frameworks on population health or post-marketing drug surveillance. Four frameworks that met the eligibility criteria were identified and served to develop an assessment tool capable of evaluating sites that could support active monitoring of vaccine safety during pregnancy. We conducted semi-structured interviews in six geographical sites using MNCH data collection systems (DHIS2, INDEPTH, and GNMNHR) to complete the domains included in the assessment tool. Results: We interviewed a total of 9 stakeholders including: central-level systems key informants and/or site level managers from DHIS2 and GNMNHR; DHIS2 in Kampala (Uganda) and Kigali (Rwanda); GNMNHR from Belagavi (​​India) and Lusaka (Zambia); and INDEPTH from Nanoro (Burkina Faso) and Manhica (Mozambique). Similarities among sites were found regarding some domains such as data confidentiality, data management policies, and data quality monitoring. Four of the six sites met some domains to be eligible as potential sites for active surveillance of vaccinations during pregnancy such as routine collection of MNCH individual data, and capability of electronically integrating individual MNCH outcomes with information related to vaccine exposure during pregnancy. Those sites were: Rwanda (DHIS2), Manhica (IN-DEPTH), Lusaka (GNMNHR), and Belagavi (GNMNHR)Conclusion: This study's findings should inform the successful implementation of active safety surveillance of vaccines during pregnancy by integrating the currently used individual MNCH data collection systems in some sites in LMICs.
Direct association of Mg1 with a protease inhibitor confers resistance to rice root-knot nematode
Authors: Wang Xiaomin , Cheng Rui , Xu Daochao , Huang Renliang , Li Haoxing , Jin Liang , Wu Yufeng , Tang Jiuyou , Sun Changhui , Peng Deliang , Chu Chengcai , Guo Xiaoli
Published: July 2022

The rice root-knot nematode (Meloidogyne graminicola) is one of the most destructive pests threatening rice (Oryza sativa L.) production in Asia; however, no rice resistance genes have been cloned. Here, we demonstrate that M. graminicola-resistance gene 1 (Mg1), an R gene highly expressed at the site of nematode invasion, determines resistance against the nematode in several rice varieties. Introgressing Mg1 into susceptible varieties dramatically increases resistance, for which the leucine-rich repeat domain is critical for recognizing root-knot nematode invasion. We also establish the transcriptome and cytological changes that allow a rapid and robust response during the incompatible interaction that occurs in resistant rice upon nematode invasion. Furthermore, we identified a putative protease inhibitor that directly interacts with Mg1 during Mg1-mediated resistance. Our findings provide insight into the molecular basis of nematode resistance as well as valuable resources for developing rice varieties with improved nematode resistance.
Fluid-structure interaction simulation of visceral perfusion and impact of different cannulation methods on aortic dissection
Authors: Lee Gyu-Han , Heo Woon , Lee Youngjin , Kim Tae-Hoon , Huh Hyungkyu , Song Suk-Won , Ha Hojin
Published: July 2022

Hemodynamics in aortic dissection (AD) is closely associated with the risk of aortic aneurysm, coarctation, rupture, hypertension, and malperfusion. Altered blood flow in patients with AD can lead to severe complications such as visceral malperfusion. In this study, we aimed to investigate the effect of cannulation flow on hemodynamics in patients with AD using a fluid-structure interaction simulation. We developed a specific-idealized AD model including intimal tear on descending thoracic aorta. Two different cannulation methods were tested: 1) Axillary cannulation (AC) only through the brachiocephalic trunk, and 2) combined axillary and femoral cannulation (AFC) through the brachiocephalic trunk and the right common iliac artery. The AC was found to develop the pressure difference between the true and false lumens due to the difference of the flow rate through each lumen. This pressure difference collapses the true lumen, disturbing blood flow to the celiac and superior mesenteric arteries. However, in the AFC, the pressure levels between the two lumens were similar, no collapse occurred, and the visceral flow was increased compared to that in the AC. Lastly, the collapse of true lumen was affected by the cannulation flow rate and also stiffness of the intimal flap.
Evaluating heavy metal pollution risks and enzyme activity in areas with intensive hazelnut cultivation under humid ecological conditions
Authors: BAYRAKLI Betül
Published: July 2022

Unlike organic pollutants, heavy metals are often unchanging, non-degradable, and persistent in soil and water. So, they negatively impact the surrounding ecosystems and human health. In this context, the main objectives of this study were to i-) determine some physical, chemical, and biological properties and heavy metal concentrations of different soils in intensive hazelnut cultivation areas under humid ecological conditions; ii-) reveal the heavy metal pollution risks of these areas by their enrichment factor (EF), contamination factor (CF), geo-accumulation index (Igeo), degree of contamination (DC), pollution load index (PLI), and potential ecological risk index (PERI); iii-) analyze the quality of soils contaminated with heavy metals by their total enzyme activity index (TEI) and the geometric mean of enzymatic activities (GMea); iv) explore the correlation between heavy metals and soil enzyme activity indices. According to our results, the average concentrations of heavy metals in the study area ranked as Fe > Mn > Zn > Cr > Ni > Cu > Co > Pb > Cd. Based on EF, the area was evaluated as between deficiency to low enrichment and moderate enrichment for all elements except for Cd. 92.5% of Cd was in the significant enrichment class. Based on CF, the area was in the low to moderate contamination class for all elements except for Cd, with a significant, high contamination risk for Cd. According to Igeo, the area was uncontaminated to moderately contaminated for all elements except Cd, but it was at risk of moderate to strong contamination for Cd. According to DC, 12.5% of the area had a low degree of contamination, 77.5% a moderate degree, and 10% a considerable degree. Besides, for PLI, 12.5% of the area was in the perfection class, 77.5% in the baseline of pollution class, and 10% in the deterioration of site quality class. Nearly 70% of the soils had a low risk for the analyzed ecosystem and the remaining soils (30%) had moderate risk. Moreover, the area had a GMea of 69.97–208 and a TEI of 2.111–5.859. Finally, analyzing the heavy metals and soil enzyme activity indices, show that there is a negative correlation between Ni and GMea (p < 0.01) and TEI (p < 0.05).
Multi-omics reveals the key and specific miRNA-mRNA modules underlying salt tolerance in wild emmer wheat (Triticum dicoccoides L.)
Authors: Yang Guang , Pan Wenqiu , Cao Rui , Guo Qifan , Cheng Yue , Zhao Qinlong , Cui Licao , Nie Xiaojun
Published: July 2022

Background
Salt stress is one of the most destructive environmental factors limiting crop growth and development. MicroRNAs (miRNAs) are a class of conserved endogenous small non-coding RNAs, playing the crucial role in regulating salt response and tolerance in plant. However, the miRNAs in wild emmer wheat, especially the key and specific salt-responsive miRNAs are not well studied.
Results
Here, we performed small RNA, transcriptome, and degradome sequencing of both of salt-tolerance (ST) and salt-sensitive (SS) wild emmer genotypes to identify the miRNA-mRNA modules associating with salt tolerance. Totally, 775 miRNAs, including 361 conserved known miRNAs and 414 novel miRNAs were detected. Differential expression analysis identified 93 salt-responsive miRNAs under salt stress. Combined with RNA-seq and degradome sequencing analysis, 224 miRNA-mRNA modules displayed the complete opposite expression trends between ST and SS genotypes, most of which functionally enriched into ROS homeostasis maintaining, osmotic pressure modulating, and root growth and development. Finally, the qRT-PCR and a large-scale yeast functional screening were also performed to initially validate the expression pattern and function of candidate genes.
Conclusions
This study reported the key and specific miRNA-mRNA modules associated with salt tolerance in wild emmer, which lay the foundation for improving the salt tolerance in cultivated emmer and bread wheat through miRNA engineering approach.
Achieving CD8+ T cell-dependent lethality by targeting cancer USP14 in hepatocellular carcinoma
Authors: Li Binkui , Yuan Yichuan , Niu Yi , Huang Zhenkun , Shi Yunxing , Lin Zhu , Zuo Dinglan , Zhong Chengrui , Li Kai , Yuan Yun-Fei , Guan Xin-Yuan
Published: July 2022

The application of immunotherapies in hepatocellular carcinoma (HCC) have been hindered by resistance to therapeutics. Cancer cell-induced CD8 + T cell dysfunction may account for the failure of tumor immunotherapies. Here, we identified USP14 as an essential driver of cancer cells tolerance to CD8 + T cells through genome-wide screening. scRNA-seq showed that cancer USP14 was frequently upregulated in tumor tissues from patients with HCC. The elevated USP14 was positively correlated with resistance to immunotherapy and poor prognoses. Inhibition of cancer USP14 arrested the growth of HCC with the existence of CD8 + T cells in vivo and in vitro. Furtherly, targeting cancer USP14 boosted immunotherapy efficacy. Mechanistically, the USP14 highly-expressed HCC cells were avidly consumed and outcompeted CD8 + T cells for glucose by stabilizing GLUT1 expression, resulting in CD8 + T cells starving and dysfunction. Collectively, our data defined USP14 as a potential immunotherapy target in HCC.
Comparing the mental health and quality of life of athlete and non-athlete adolescents during the COVID-19 pandemic
Authors: nazari vahid , Dostipasha Morteza , alizadeh shirin , nazari saeed
Published: July 2022

This study was designed to compare the mental health and quality of life of athlete and non-athlete adolescents during the COVID-19 pandemic. The study statistical population included all adolescents aged 14 to 18 years living in Mazandaran province, out of which, 2897 adolescents were randomly selected. We performed an online survey among adolescents in Mazandaran province using GAD-7, PHQ-9, PFABS, and PEDSQL questionnaires. According to the results, athlete adolescents showed lower levels of anxiety and depression and higher quality of life compared to non-athlete adolescents. Moreover, the findings indicated that as the number of practice sessions increases throughout the week, the scores of physical activity and quality of life of athlete adolescents increase and their overall depression and anxiety scores decrease; however, the scores of generalized anxiety, depression, and quality of life among adolescent athletes with different training sessions in a week seem to be equal with no significant difference between them. The present results confirm the positive effect of physical activity on the mental health and quality of life related to the health of student adolescents.
Risk models for predicting diabetes and prediabetes in the first-degree Relatives (FDRs) of patients with type2 diabetic and its comparison with the Finnish Diabetes Risk Score (FINDRIC)
Authors: Shahraki Parisa Khodabandeh , Feizi Awat , Aminorroaya Sima , Ghanbari Heshmatollah , Abyar Majid , Amini Massoud , Aminorroaya Ashraf
Published: July 2022

Introduction: The prevalence of diabetes in Iranian adults is 9.5% with high morbidity and mortality. Here, we aimed to develop a risk model, monitoring the FDRs of patients with type 2 diabetes, who have normal glucose tolerance, to predict the onset of developing diabetes and prediabetes. Methods: A total of n = 1765 FDRs of patients with type 2 diabetes mellitus, who had normal glucose tolerance, were subjected to statistical analysis. Diabetes risk factors including anthropometric indices, physical activity, fast plasma glucose, plasma glucose concentrations two-hour after oral glucose administration, glycosylated hemoglobin, blood pressure, and lipid profile at the baseline were considered as independent variables. Kaplan-Meier, log Rank test, univariate, and multivariable proportional hazard Cox regression were conducted. The optimal cut point for risk score was created according to receiver operating characteristic curve (ROC) analysis. Results: The best diabetes predictability was achieved by a model in which waist to hip ratio, HbA1c, area under oral glucose tolerance curve (OGTT-AUC) and the lipid profile were included. The best prediabetes risk model included HbA1c, OGTT-AUC, systolic blood pressure, and the lipid profile. The predictive efficiencies of models were higher than FPG and HbA1c; however, the predictive efficiency of multivariable models were comparable to OGTT-AUC alone. Additionally, diabetes models and OGTT-AUC showed better performance than FINDRISC.Discussion: We recommend regular tests for FDRs of patients with type 2 diabetes to predict the risk of diabetes and prediabetes by using the OGTT-AUC. As a health check assessment tool, our diabetes models showed a more precise predictor compared to FINDRISC in our population.
An integrative metatranscriptomic analysis reveals differences in enteric methanogenesis mechanisms between cows and goats
Authors: Corral-Jara Karla Fabiola , Ramayo-Caldas Yuliaxis , Bernard Laurence , Martin Cécile , Tournayre Jeremy , Morgavi Diego P. , Popova Milka
Published: July 2022

Background: Reducing enteric methane emissions from farmed ruminants can be achieved by various nutritional strategies. However, it remains unclear to what extent the effects of diet on rumen microbiome are comparable between different ruminant species. In this work, we compared the effects of starch- and/or lipids-rich diets on the rumen microbiome of cows and goats to enhance our understanding of microbial mechanisms of methanogenesis. The study enrolled four Holstein cows and four Alpine goats, conducted simultaneously in a replicate 4×4 Latin square design, receiving the same ration based on grassland hay and concentrate (CTL) or supplemented with corn oil and wheat starch (COS), marine algae powder (MAP) or hydrogenated palm oil (HPO). The microbiome was studied using non-targeted total RNA sequencing. Results: To identify biologically relevant features, we developed a five-step biostatistical pipeline, combining a network-based approach with clustering and supervised model fitting to associate differentially expressed genes (deKEGGs) and Operational Taxonomic Units (deOTUs) with methane emissions. The COS diet induced the highest methane emissions reduction for cows and goats and most profoundly affected the microbiome. With a focus on the COS vs. CTL comparison, the number of deOTUs and deKEGGs in cows (16 and 381) was higher than in goats (10 and 133). Moreover, clustering analysis revealed network topology and functionality differences between ruminant species. In goats, the reduction in methane emissions was strongly associated with genes involved in Carbohydrate metabolism, and genes coding for methylotrophic and hydrogenotrophic pathways of methanogenesis were overrepresented; in cows, only the hydrogenotrophic pathway was prevalent. Further, sPLS analysis identified potential biomarkers characteristic of each ruminant species, such as tetrahydromethanopterin S-methyltransferase and fructose bisphosphate aldolase for cows, and Methanol: coenzyme M methyltransferase, F420-non-reducing hydrogenase for goats. Conclusions:Overall, these results demonstrated a strong influence of the ruminant species on the responses of the rumen microbial community to dietary changes. We observed that the COS diet reduced similarly enteric methane emissions in cows and goats, but the induced shifts in the rumen microbiome were not the same. These results suggest that the host-animal species conditions microbial interactions within the rumen ecosystem.
Habitat Loss for Black Flying Foxes and Implications for Hendra virus
Authors: Baranowski Kelsee , Bharti Nita
Published: July 2022

ContextEnvironmental change impacts natural ecosystems and wildlife populations. In Australia, native forests have been heavily cleared and the local emergence of Hendra virus (HeV) is theorized to be related to environmental change. ObjectivesWe quantified changes in landscape factors for Pteropus alecto, a reservoir host of HeV also called black flying foxes, in sub-tropical Queensland, Australia from 2000-2020. We hypothesized that native winter habitat loss and native remnant forest loss were greatest in areas with the most human population growth.MethodsWe measured the spatiotemporal change in human population size and native ‘remnant’ woody vegetation extent. We assessed changes in the observed P. alecto population and native winter habitats in the 7 bioregions where P. alecto are observed roosting in winter. We assessed changes in the amount of remnant vegetation across bioregions and within 50km foraging buffers around roosts.ResultsHuman populations in these bioregions grew by 1.18M people, mostly within 50km foraging areas around known roosts. Remnant forest extent increased overall, but net growth was observed only in a bioregion with no Pteropus roosts. Winter habitats were continuously lost across all spatial scales. Observed populations of P. alecto declined. ConclusionNative remnant forest loss and winter habitat loss were not directly linked to spatial human population growth. Rather, most remnant vegetation was cleared for indirect human use. We observed forest loss and regrowth in response to state land clearing policies. Expanded flying fox population surveys are needed to better understand how landuse change has impacted P. alecto distribution and Hendra virus spillover.
Dysbiosis: an indicator of COVID-19 severity in critically ill patients
Authors: Cuenca Silvia , Soler Zaida , Serrano-Gomez Gerard , Xie Zixuan , Barquinero Jordi , Roca Joaquim , Sirvent Jose-Maria , Manichanh chaysavanh
Published: July 2022

Background: Research into the association between the microbiome and SARS-CoV-2 infection and acute respiratory distress syndrome remains unclear. Here we examined the dynamics of the gut and respiratory microbiomes in severe COVID-19 cases in need of mechanical ventilation in the intensive care unit (ICU).Methods: We recruited 76 critically ill patients (48 with COVID-19 and 32 without COVID-19) and 17 healthy controls (HCs) and monitored them for up to 4 weeks. We analyzed the bacterial and fungal taxonomic profiles and loads of 232 gut and respiratory samples and we measured blood levels of Interleukin 6, IgG, and IgM in COVID-19 patients.Results: At ICU admission, bacterial composition and load in the gut and respiratory samples were altered in critically ill patients compared to HCs. Six bacterial species could discriminate ICU-COV(+) from ICU-COV(-) cases. During their time in the ICU, all patients experienced increased bacterial and fungal loads, decreased bacterial richness, and progressive changes in bacterial and fungal taxonomic profiles. In ICU-COV(+) patients, Pseudomonas was found positively and Streptococcus negatively correlated with the length of ICU stay. Respiratory bacterial signatures, associated with disease severity and inflammation markers, were predictive of death and a fecal dysbiosis score, associated negatively with PaO2/FiO2 ratio, could be used as an additional indicator for ICU admission.Conclusion: We propose using a high-throughput sequencing approach as an alternative to traditional isolation techniques to monitor the ICU-COV(+) patient infection.
Research on personalized user-centered product improvement based on sentiment mining of online reviews and competitor analysis
Authors: Liu Fang , Li Shugang
Published: July 2022

Online reviews contain a wealth of information about product performance and user sentiment, which can effectively assist manufacturers to make production decisions. Taking abundant online reviews as data, this study mined product attributes and consumer sentiments to analyze users' personalized preferences and the performance of competitive products, and proposed personalized user-centered product improvement strategies for differentiated markets. Specifically, the word2vec technology and the LSTM neural network were applied to develop the sentiment mining method that was suitable for specific product domain, through which the explicit emotional information was extracted from product reviews and the missing emotional information was also predicted combined with the overall sentiment of the review text and the attitude of other consumers. On this basis, the k-means method was applied in this model firstly to segment the users according to their emphasis on product attributes. Then, a preference identification model that describes the relative importance of product attributes was designed according to the utility function and KANO theory, so as to measure consumers’ various preferences of each user group. Finally, combined with the relative performance of product attributes, the traditional IPA model was optimized to determine the improvement priority of attributes for different user groups to meet user preferences in a differentiated way. These work helps enrich the relevant theories and methods of sentiment mining and provides practical guidance for user-centered product improvement.
Machine Learning Model Identifies Genomic Variation in Noise-Induced Hearing Loss via Whole-exome Sequencing
Authors: Fan Boya , Wang Gang , Han Haolun , Li Baowei , Wang Lei , Qu Changbei , Zhang Xiaoli , Liu Hongdan , Sun Zhezhe , Zhou Ying , Zhang Yiyan , Wu Wei
Published: July 2022

Noise-induced hearing loss (NIHL) is related to noise exposure and whether humans suffered from NIHL is also related to different sensitivity to noise. Whole exome sequencing (WES) can detect the genetic mutations of NIHL population so as to find the susceptibility of different people from the genetic level. WES can identify contributing genes, not only find NIHL susceptibility genes, but also divide patient cohort into different subtypes. We conducted a case-control (n = 78, n = 35, respectively) study to find the susceptibility genes of NIHL through WES and stratified the cases into subtypes, so as to achieve the purpose of precision medicine. 73 gene variants were used to train the unsupervised machine learning model which separated the case from the control group and divide the population into two subtypes. Supervised machine learning methods compared the above constructed subgroup classification models. This is the first study to link NIHL with gene variants and has produced a new potential classification method that can be applied to precision medicine in people’s different sensitivity to noise. These observations deserve further study on independent and larger clinical samples in order to provide new information for future research on the susceptibility of NIHL.
Viscosalactone B, a natural LSD1 inhibitor, inhibits proliferation in vitro and in vivo against prostate cancer cells
Authors: Yan Gaobo , Zhang Hongyan , Li Yan , Miao Guoqiang , Liu Xiaolei , Lv Qifan
Published: July 2022

Lysine specific demethylase 1 (LSD1) has been a promising target to treat prostate cancer, and discovery of the novel LSD1 inhibitor has great clinical significance. In this work, viscosalactone B was first identified as a novel LSD1 inhibitor. Viscosalactone B isolated from Withania Somnifera displayed the antiproliferative activity against PC3, DU145, C42B, PC3/MDVR, DU145/MDVR and C42B/MDVR cells with IC50 values of 1.17, 0.72, 3.86, 2.06, 0.96 and 1.15 µM, respectively. It was a selective LSD1 inhibitor with an IC50 value of 970.27 nM and concentration-dependently induced the significant accumulation of LSD1 substrates H3K9me1, H3K9me2 and H3K4me1 against DU145 cells. According to docking studies, it formed hydrogen bonds with Thr11, Lys14 and Arg8. Importantly, it displayed the potent antitumor efficacy in vivo and exhibited no obvious cytotoxicity on the major organs of nude mice. Therefore, viscosalactone B as a novel LSD1 inhibitor is a potential candidate to treat prostate cancer.
The use of Dexmedetomidine in preterm infants: a single academic center experience.
Authors: Hernandez Juan Guillen , Kyllonen Kay , Tumin Dmitry , Rodriguez Ricardo
Published: July 2022

Introduction:
Preterm newborns (PTNB) often require sedation and analgesia. Opioids (OPs) and benzodiazepines (BZDs) have been commonly used but are associated with detrimental effects. Dexmedetomidine (Dex) seems a promising alternative. However, data on dosing, length of therapy and adverse events in extreme PTNB are limited.
Objective
To describe the use of Dex in extreme PTNB in a single academic center
Study Design:
A retrospective cohort study of PTNB receiving Dex for sedation/analgesia from January 1st, 2010, through December 31st, 2018. At The Cleveland Clinic Children's Hospital an urban tertiary academic center with two Level III and one level IV Neonatal Intensive Care Units (NICU) at different campuses. Inclusion criteria were gestational age (GA) < 36 weeks and receipt Dex for > 2 days. Dex dose and length of treatment were recorded. Clinical response was gauged by reviewing Neonatal Pain, Agitation and Sedation Scale (N-PASS) scores for achievement of the goal (≤ 3). Adverse events were recorded as the incidence of hypotension, bradycardia, and respiratory depression.
Results
381 patient charts were reviewed, and 105 patients were included. The birth weight median was 800 grams (range 400–3790); the GA median was 28 weeks (range 22–35). Duration of Dex infusion averaged seven days. Dex dose ranged from 0.2 to 1.2mcg/kg/hour and averaged 0.4mcg/kg/hour. Infants weighing < 1 Kg received a significantly higher Dex dose than infants weighing more or equal to 1 kg (0.5 vs. 0.4mcg/kg/hr, respectively; p = < 0.01). Bradycardia was observed in 35 patients < 1 kg (57%) and in 7 patients > 1 kg (18%) p < 0.01. There was no difference in the incidence of hypotension, fluid resuscitation, or inotropic use between groups defined by birth weight. However, infants < 1 kg required more pharmacological interventions to maintain N-PASS score < 3.
Conclusions
DEX was well tolerated overall and provided adequate sedation to PTNB in this cohort. This is a report of its use in extreme premature infants, providing guidance of dosages, length of therapy, and possible weaning strategies.
Enzymatic polymerization of enantiomeric DOPA into films with enhanced rigidity and stability
Authors: Shen Yuhe , Su Rongxin , Hao Dongzhao , Wang Yuefei , Reches Meital , Chang Heng , Xu Xiaojian , Yu Tao , Li Qing , Zhang Xiaoyu , Wang Yuefei , Qi Wei , He Zhimin
Published: July 2022

L-3,4-dihydroxyphenylalanine (L-DOPA) is an important molecule in the adhesion of mussels, and as an oxidative precursor of natural melanin, it plays an important role in living system. However, the effect of chirality of DOPA monomers on its polymerization and adhesion is still unclear. Here, we investigated the effect of the molecular chirality of DOPA on the properties of the self-assembled films by tyrosinase-induced oxidative polymerization. The kinetics and morphology of pure enantiomers is completely altered upon their co-assembly, allowing the fabrication of layer-to-layer stacked nanostructures and films with improved structural and thermal stability. The different molecular arrangements and self-assembly mechanisms of the L+D-racemic mixtures, whose oxidation products have both increased molecular weight and binding energy, resulting in stronger intermolecular forces and more ordered sheet-stacking arrangements. This leads to the formation of films with a Young's modulus as high as 139 GPa, which is the highest value reported so far for biological materials. This study provides a simple pathway for the fabrication of biomimetic polymeric materials with enhanced physicochemical properties by control the chirality of monomers.
Age-associated B cells are long-lasting effectors that impede latent gHV68 reactivation
Authors: Mouat Isobel C. , Shanina Iryna , Horwitz Marc S.
Published: July 2022

Age-associated B cells (ABCs; CD19+CD11c+T-bet+) are a unique population that are increased in an array of viral infections, though their role during latent infection is largely unexplored. Here, we use murine gammaherpesvirus 68 (γHV68) to demonstrate that ABCs remain elevated long-term during latent infection and express IFNγ and TNF. Using a recombinant γHV68 that is cleared following acute infection, we show that ABCs persist in the absence of latent virus, though their expression of IFNγ and TNF is decreased. With a fluorescent reporter gene-expressing γHV68 we demonstrate that ABCs are infected with γHV68 at similar rates to other previously activated B cells. We find that mice without ABCs display defects in anti-viral IgG2a/c antibodies and are more susceptible to reactivation of γHV68 following virus challenges that typically do not break latency. Together, these results indicate that ABCs are a persistent effector subset during latent viral infection that impedes γHV68 reactivation.
Umbilical cord mesenchymal stem cells and monosialotetrahexosy 1 ganglioside alleviate neuroinflammation in traumatic brain injury
Authors: Fang Yanwei , Qiu Wenna , Li Xin , Jin Qianxu , Yan Hongshan , Yu Ning , Zhao Jianhui , Tan Yi , Zhao Zongmao
Published: July 2022

Neuroinflammation and activated microglia play important role in neuron damage in the traumatic brain injury (TBI). In this study, we determined the effect of human umbilical cord mesenchymal stem cells (UMSCs) combined with monosialotetrahexosy 1 ganglioside (GM1) on the neuroinflammation and polarization of microglia in a rat model of TBI, which was established in male rats using a fluid percussion brain injury device. Rats survived until day 7 after TBI were randomly treated with saline (NS), GM1, UMSCs, and GM1 plus UMSCs. Modified neurological severity score (mNSS) was assessed on days 7 and 14, and the brain tissue of the injured region was collected. Immunofluorescence, RT-PCR, and western blot analysis found that neuroinflammatory cytokines and CD163 protein expression levels in injured brain tissues was significantly decreased rats treated with GM1+UMSCs, GM1, or UMSCs were up-regulated compared with saline-treated rats. iNOS protein expression was down-regulated compared with rats treated with saline. The protein expression levels of NE, NF-200, MAP-2 and β-tubulin III were increased in the injured brain tissues from rats treated with GM1 + UMSCs, or GM1 and UMSCs alone compared with those in the rats treated with NS. The protein expression levels in rats treated with GM1 plus UMSCs was most significant on day 7 following UMSC transplantation. The rats treated with GM1 plus UMSCs had the lowest mNSS compared with that in the other groups. These data suggest that UMSCs and GM1 reduce the neuroinflammation and neurodegeneration through coordinating the polarization state of microglia to promote the recovery of neurological functions in the TBI.
Clinical characteristics of 14 pediatric mycoplasma pneumoniae pneumonia associated thrombosis: A retrospective study
Authors: Fu Y , Zhang TQ , Dong CJ , Xu YS , Dong HQ , Ning J
Published: July 2022

Objective: The aim of the study was to investigate the clinical characteristics and long-term prognosis of Mycoplasma pneumoniae pneumonia (MPP) associated thrombosis,and to improve the understanding of the diagnosis and treatment of the disease.Methods: We retrospectively reviewed the medical records of 14 children with MPP-associated thrombosis between January 2016 and April 2020 at Tianjin Children’s Hospital.Results: The ages of patients were from 3 years old to 12 years old.Among these 14 cases, five cases of pulmonary embolism，two cases of cerebral infarction, one case of splenic infarction, one case of cardiac embolism ,two cases combined cardiac embolism and pulmonary embolism，one case combined internal carotid artery and pulmonary embolism，one case combined internal carotid artery and the cerebral infarction, one case combined cardiac embolism and lower limb artery embolism。All cases had D-dimer rise. After thrombolysis and anticoagulation therapy three cases with cerebral embolism still have neurological sequelae the rest all recovered well.Conclusion: MPP-associated thrombosis can occur in a vessel of any part of the body.Thrombosis-associated symptoms may be complicated and various. Elevated D-Dimer in a child with refractory Mycoplasma pneumoniae pneumonia should raise suspicion for thrombosis.The long-term prognosis of thrombosis was good after timely administration of anticoagulant therapy.
Germline mutations directions are different between introns of the same gene: case study of the gene coding for amyloid-beta precursor protein
Authors: Khrustalev Vladislav Victorovich , Khrustaleva Tatyana Aleksandrovna , Popinako Anna Vladimirovna
Published: July 2022

Amyloid-beta precursor protein (APP) is highly conserved in mammals. This feature allowed us to compare nucleotide usage biases in 4-fold degenerated sites along the length of its coding region for 146 species of mammals and birds in search of fragments with significant deviations. Even though cytosine usage has the highest value in 4-fold degenerated sites in APP coding region from all tested placental mammals, in contrast to marsupial mammals with the bias toward thymine usage, the most frequent germline and somatic mutations in Human APP coding region are C to T and G to A transitions. The same mutational AT-pressure is characteristic for germline mutations in introns of Human APP gene. However, surprisingly, there are several exceptional introns with deviations in germline mutations rates. The most of those introns surround exons with exceptional biases in nucleotide usage in 4-fold degenerated sites. Existence of such fragments in exons 4 and 5, as well as in exon 14, can be connected with the presence of lncRNA genes in complementary strand of DNA. Exceptional nucleotide usage bias in exons 16 and 17 that contain a sequence encoding amyloid-beta peptides can be explained either by the presence of yet unmapped lncRNA(s), or by the autonomous expression of a short mRNA that encodes just C-terminal part of the APP providing an alternative source of amyloid-beta peptides. This hypothesis is supported by the increased rate of T to C transitions in introns 16–17 and 17–18 of Human APP gene relatively to other introns.
Determining farming methods and geographical origin of Chinese rice using NIR combined with chemometrics methods
Authors: Wu Dan , Liu Xing , Bai Bin , Li Jianwu , Wang Ren , Zhang Yin , Deng Qiyun , Huang Huang , Wu Jun
Published: July 2022

This study was conducted to develop fast and nondestructive models for the discrimination of different farming methods and to determine the geographical origin of rice samples from different administrative regions in China using near-infrared (NIR) spectroscopy. Principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) were applied to build the NIR spectral models. Norris smoothing derivative (NSD) and multiplicative scatter correction (MSC) were used as preprocessing methods to reduce the spectral noise and enhance effective information. The results show that it was difficult to distinguish the farming methods with the original spectra plots and PCA score plots except for the rice samples from Heilongjiang Province. In addition, a PLS-DA model combined with NSD preprocessing provided the optimal predictive accuracy of 89.7% for the identification of different farming methods. NSD or MSC preprocessing combined with PLS-DA models provided the best discrimination of the origin traceability. The total accuracy of Northeast China rice samples was 100%, and of the South, East, Central and Southwest China rice samples was 98.2%. The total accuracy of Heilongjiang, Anhui, Jiangsu, Hubei, and Sichuan Provinces were 100%, 98.8%, 95.3%, 95.3%, and 93.6%, respectively. These indicate that NIR combined with PLS-DA and NSD or MSC preprocessing can provide a powerful method to distinguish the different farming methods and geographical origin of Chinese rice.
Lignin, an active component in the corn silk water extract, inhibits glycation
Authors: Sano Aiko , Inoue Yutaka , Suzuki Ryuichiro
Published: July 2022

The formation of advanced glycation end products (AGEs) is associated with aging and diabetic complications such as neuropathy, retinopathy, and nephropathy. Thus, the suppression of AGE formation could prevent and/or treat their related disorders. Corn silk is used as a traditional medicine for the prevention of diabetic complications and treatment of edema in Japan and China. Previous studies revealed the anti-glycation activity of flavonoids in the methanolic extract of corn silk. The anti-glycation activity of the corn silk water extract was higher than that of the methanolic extract; however, the active components of the water extract remained unidentified. In this study, we explored the components showing anti-glycation activity in the corn silk water extract and elucidated their structural characteristics. Remarkable anti-glycation activity was observed in the > 3 kDa fraction. Reversed-phase HPLC analysis of this fraction showed broad peaks characteristic of high-molecular-weight polyphenols. Decomposition reactions did not provide evidence of condensed or acid-hydrolyzable tannins. Therefore, polyphenols contained in the corn silk water extract were considered to be lignins. The 1H- and 13C-NMR and IR spectra of the > 3 kDa fraction were in agreement with the values reported for lignins. Consequently, we concluded that lignin is one of the active components against glycation in the corn silk water extract.
Shared Rules between Planetary Orbits in Multi-planet Systems
Authors: Ma Yong , Wen Xiumei
Published: July 2022

Abstract: Although Mean Motion Resonances (MMRs) only reflect the orbital relations between part planets of some systems, the discovery of MMRs feature has promote the study of the evolution of multi-planet systems. To better study orbital relations between all planets, we calculated planetary observation data of all multi-planet systems with the concept of ratio parameter and deviation rate. In this way, orbital relations between all planets of any system can be displayed in a clearer quantification way, including MMRs planets. Through comparing ratio parameters and counting deviation rates, we found more orbital features and summarized them into the Shared Rules between Planetary Orbits. The Shared Rules describe common regularities between planetary orbits, embodying the essence of logarithmic spiral. From the Shared Rules, we derived related equations and principles. We will show explanations. Although all systems are controlled by the same central gravitation, not every system clearly displays the Shared Rules because of varying disturbances and observation limitations. Calculations show, of the discovered 96 systems containing four and more exoplanets, 83 display the Shared Rules. Of the 335 period ratios consisting of 431 confirmed exoplanets of the 96 systems, 16.12% ratios show the absolute values of the deviation rates bigger than 40 per cent. Big deviation rates usually suggest some influences, imply planetary absence and migration, and affect the display of the Shared Rules. The Shared Rules can help to show planet migration and absence, calculate the orbits of migratory, disappeared and undetected planets, learn about the changes of planetary configurations, and study the evolution of multi-planet systems.
Comparative evaluation of different version of exposure-free Mosquito electrocuting traps and Barrier screen for monitoring densities and biting time phenotypes by malaria and filariasis vectors in Tanzania.
Authors: Githu Victoria , Baravuga Maneno E. , Mbarawa Asiya , Msuya Hajirani M. , Mlacha Yeromin P. , Chaki Prosper P. , Kiware Samson , Mizrai Nosrat , Ferguson Heather M. , Govella Nicodem J.
Published: July 2022

Background
Estimating human exposure to mosquito vectors is crucial for prediction of malaria transmission and intervention impact. Human Landing Catches are often to direct estimate exposure rates; however there has been an increasing move away from this method to exposure-free alternatives such as the Mosquito Electrocuting Traps (MET) and other approaches. While such methods can provide robust and representative values of human exposure and mosquito density; they often still require a human volunteer which poses logistical challenges. Additionally in the case of the MET, the early prototype (METe) required human volunteers to wear protective clothing which could be uncomfortable. We investigated two alternative trapping approaches to address these challenges by comparing the performance of the early MET (METe) prototype to (1) a modified caged MET prototype that offers full protection to users (METc), and (2) a barrier screen trap (BST) designed to passively sample (host seeking and blood-fed) mosquitoes outdoors without requiring a human participant.
Method
The relative performance of the METe, METc and BST were evaluated in a 3x3 Latin Square field experiment design conducted in south-eastern Tanzania over 12 nights. The outcome of interest was the mean nightly mosquito density.
Results
The METc and BST caught similar numbers of Anopheles arabiensis as the METe (RR [95% confidence interval (CI)] = 0.76[0.42–1.39], P = 0.38, and 1.13[0.63–2.04], P = 0.69) respectively. Similarly, the METe caught similar numbers of Culex spp to the METc (RR[95%CI] = 0.87[0.62–1.22], P = 0.42) and BST (0.80[0.57–1.12], P = 0.199). All three trapping methods indicated a similar pattern of biting activity by An. arabiensis and Culex spp; characterized by biting starting in the early evening (18:00–22:00), peaking when people are typically sleeping (22:00–05:00) and dropping drastically toward the morning (05:00–07:00).
Conclusions
The modifications made to the METe design to improve user comfort and remove the need for protective clothing did not result in an underestimation of mosquito vector abundance nor a misrepresentation of their biting-times pattern. Thus, we recommend the METc for use over the METe design. Similarly, to southeast Asia, the BST demonstrated potential for monitoring malaria and filariasis vector densities in Tanzania.