bluuebunny/crossref_metadata_2025 huggingface dataset:
Joint hemorrhage accelerates cartilage degeneration in a rat immobilized knee model
Authors: Sogi Yasuhito , Yabe Yutaka , Hagiwara Yoshihiro , Tsuchiya Masahiro , Onoda Yoshito , Sekiguchi Takuya , Itaya Nobuyuki , Yoshida Shinichiro , Yano Toshihisa , Suzuki Kazuaki , Onoki Takahiro , Itoi Eiji
Published: November 2020

Background

Joint hemorrhage is caused by trauma, ligament reconstruction surgery, and bleeding disorders such as hemophilia. Recurrence of hemorrhage in the joint space induces hemosiderotic synovitis and oxidative stress, resulting in both articular cartilage degeneration and arthropathy. Joint immobilization is a common treatment option for articular fractures accompanied by joint hemorrhage. Although joint hemorrhage has negative effects on the articular cartilage, there is no consensus on whether a reduction in joint hemorrhage would effectively prevent articular cartilage degeneration. The purpose of this study was to investigate the effect of joint hemorrhage combined with joint immobilization on articular cartilage degeneration in a rat immobilized knee model.

Methods

The knee joints of adult male rats were immobilized at the flexion using an internal fixator from 3 days to 8 weeks. The rats were randomly divided into the following groups: immobilized blood injection (Im-B) and immobilized-normal saline injection (Im-NS) groups. The cartilage was evaluated in two areas (contact and non-contact areas). The cartilage was used to assess chondrocyte count, Modified Mankin score, and cartilage thickness. The total RNA was extracted from the cartilage in both areas, and the expression of metalloproteinase (MMP)-8,MMP-13, interleukin (IL)-1β, and tumor necrosis factor (TNF)-α was measured by quantitative real-time polymerase chain reaction.

Results

The number of chondrocytes in the Im-B group significantly decreased in both areas, compared with that in the Im-NS group. Modified Mankin score from 4 to 8 weeks of the Im-B group was significantly higher than that of the Im-NS group only in the contact area. The expression ofMMP-8andMMP-13from 2 to 4 weeks andTNF-αfrom 2 to 8 weeks significantly increased in the Im-B group compared with those in the Im-NS group, but there was no significant difference inIL-1βexpression.

Conclusions

The results showed that joint hemorrhage exacerbated immobilization-induced articular cartilage degeneration. Drainage of a joint hemorrhage or avoidance of loading may help prevent cartilage degeneration during joint immobilization with a hemorrhage.
Reliability and validity of pelvic floor muscle strength assessment using the MizCure perineometer
Authors: Abe-Takahashi Yui , Kitta Takeya , Ouchi Mifuka , Okayauchi Minori , Chiba Hiroki , Higuchi Madoka , Togo Mio , Shinohara Nobuo
Published: November 2020

Background

The purpose of this study was to clarify the reliability and validity of pelvic floor muscle (PFM) strength assessment using the MizCure perineometer in healthy women.

Methods

Twenty healthy women (age 20–45 years) participated in this study. The vaginal pressure measured using the MizCure and validated Peritron perineometers were repeated during PFM contraction in the supine and standing positions. All women were evaluated twice by examiners 1 and 2. Following the measurements in the first session (Test 1), they were repeated after an interval of between 2 and 6 weeks (Test 2). Within- and between-session intra- and inter-rater reliabilities in vaginal pressure were analyzed using intraclass correlation coefficients (ICC) (1, 1) and (2, 1), respectively. Validity was assessed by Pearson’s product-moment correlation coefficient and Spearman’s rank correlation analysis.

Results

Within-session intra-rater reliabilities for both examiners 1 and 2 for all vaginal pressures in Tests 1 and 2 were 0.90–0.96 for both perineometers. Between-session intra-rater reliability for the MizCure was 0.72–0.79 for both positions for examiner 1, and 0.63 in the supine position and 0.80 in the standing position for examiner 2. Inter-rater reliability for Test 1 was 0.91 in the supine position and 0.87 in the standing position for the MizCure. The vaginal pressures using the MizCure and Peritron were significantly associated with the supine position (r = 0.68, P < .001) and the standing position (rs = 0.82, P < .001).

Conclusion

MizCure perineometer is a validated tool to measure PFM strength in both supine and standing positions in healthy nulliparous women.
Intensive and pharmacological care in times of COVID-19: A “special ethics” for emergency?
Authors: Marinelli Enrico , Busardò Francesco Paolo , Zaami Simona
Published: November 2020

Background

The Authors have laid out an analysis of Italian COVID-19 confirmed data and fatality rates, pointing out how a dearth of health care resources in northern regions has resulted in hard, ethically challenging decisions in terms of granting patient access to intensive care units (ICU).

Main text

Having to make such decisions certainly entails substantial difficulties, and that has led many health care professional to seek ethical guidance. The Italian Society of Anesthesia, Analgesia, Resuscitation and Intensive Care (SIAARTI) has attempted to meet that growing need by a set of recommendations, applying “clinical soundness” as a beacon standard; that approach tends to prioritize patients with higher life expectancy, which could be characterized as a “moderately utilitarian” approach. Yet, such a selection has engendered daunting ethical quandaries. The authors believe it can only be warranted and acceptable if rooted in a transparent decision-making process and verifiable, reviewed criteria. Moreover, the authors have stressed how clinical experimentation in a pandemic setting is a subtext of great interest from an ethical perspective. In Italy, no drug therapy and trials were undertaken for COVID-19 patients for a rather long period of time. When the epidemic was already circulating, an intervention proved necessary on the system of administrative procedures, aimed at expediting the authorization and validation of protocols, then bogged down by bureaucracy. A new system has since been instituted by a government decree that was signed about one month after the first Covid-19 case was officially recorded in the country. Such a swift implementation, which took just a few weeks, is noteworthy and proves that clinical trials can be initiated in a timely fashion, even with a pandemic unfolding. The concerted, action of supportive care and RCTs is the only way to attain effective forms of treatments for COVID-19 and any other future outbreak.

Conclusions

The authors have arrived at the conclusion that the most effective and ethically sound response on the part of any national health care system would be to adequately reconfigure its organizational mechanisms, by making clinical trials and all related administrative procedures consistent with the current state of emergency.
Identification of an IRF10 gene in common carp (Cyprinus carpio L.) and analysis of its function in the antiviral and antibacterial immune response
Authors: Zhu Yaoyao , Shan Shijuan , Zhao Huaping , Liu Rongrong , Wang Hui , Chen Xinping , Yang Guiwen , Li Hua
Published: November 2020

Background

Interferon (IFN) regulatory factors (IRFs), as transcriptional regulatory factors, play important roles in regulating the expression of type I IFN and IFN- stimulated genes (ISGs) in innate immune responses. In addition, they participate in cell growth and development and regulate oncogenesis.

Results

In the present study, the cDNA sequence of IRF10 in common carp (Cyprinus carpio L.) was characterized (abbreviation, CcIRF10). The predicted protein sequence of CcIRF10 shared 52.7–89.2% identity with other teleost IRF10s and contained a DNA-binding domain (DBD), a nuclear localization signal (NLS) and an IRF-associated domain (IAD). Phylogenetic analysis showed that CcIRF10 had the closest relationship with IRF10 of Ctenopharyngodon idella. CcIRF10 transcripts were detectable in all examined tissues, with the highest expression in the gonad and the lowest expression in the head kidney. CcIRF10 expression was upregulated in the spleen, head kidney, foregut and hindgut upon polyinosinic:polycytidylic acid (poly I:C) and Aeromonas hydrophila stimulation and induced by poly I:C, lipopolysaccharide (LPS) and peptidoglycan (PGN) in peripheral blood leucocytes (PBLs) and head kidney leukocytes (HKLs) of C. carpio. In addition, overexpression of CcIRF10 was able to decrease the expression of the IFN and IFN-stimulated genes PKR and ISG15.

Conclusions

These results indicate that CcIRF10 participates in antiviral and antibacterial immunity and negatively regulates the IFN response, which provides new insights into the IFN system of C. carpio.
A multi-parametric prognostic model based on clinical features and serological markers predicts overall survival in non-small cell lung cancer patients with chronic hepatitis B viral infection
Authors: Chen Shulin , Huang Hanqing , Liu Yijun , Lai Changchun , Peng Songguo , Zhou Lei , Chen Hao , Xu Yiwei , He Xia
Published: November 2020

Background

To establish and validate a multi-parametric prognostic model based on clinical features and serological markers to estimate the overall survival (OS) in non-small cell lung cancer (NSCLC) patients with chronic hepatitis B viral (HBV) infection.

Methods

The prognostic model was established by using Lasso regression analysis in the training cohort. The incremental predictive value of the model compared to traditional TNM staging and clinical treatment for individualized survival was evaluated by the concordance index (C-index), time-dependent ROC (tdROC) curve, and decision curve analysis (DCA). A prognostic model risk score based nomogram for OS was built by combining TNM staging and clinical treatment. Patients were divided into high-risk and low-risk subgroups according to the model risk score. The difference in survival between subgroups was analyzed using Kaplan–Meier survival analysis, and correlations between the prognostic model, TNM staging, and clinical treatment were analysed.

Results

The C-index of the model for OS is 0.769 in the training cohorts and 0.676 in the validation cohorts, respectively, which is higher than that of TNM staging and clinical treatment. The tdROC curve and DCA show the model have good predictive accuracy and discriminatory power compare to the TNM staging and clinical treatment. The prognostic model risk score based nomogram show some net clinical benefit. According to the model risk score, patients are divided into low-risk and high-risk subgroups. The difference in OS rates is significant in the subgroups. Furthermore, the model show a positive correlation with TNM staging and clinical treatment.

Conclusions

The prognostic model showed good performance compared to traditional TNM staging and clinical treatment for estimating the OS in NSCLC (HBV+) patients.
Hsa_circ_0004831 serves as a blood-based prognostic biomarker for colorectal cancer and its potentially circRNA-miRNA-mRNA regulatory network construction
Authors: Xing Linlin , Xia Mengyan , Jiao Xin , Fan Ling
Published: November 2020

Background

Colorectal cancer (CRC) is a common malignant tumor with unsatisfactory overall prognosis. CircRNAs could be promising prognostic biomarkers in cancers, and play important role in the process of tumorigenesis and progression. Here, we explored the role of hsa_circ_0004831 in blood extracellular vesicles and its prognostic value in CRC.

Methods

The circRNA and mRNA expression level matrix in extracellular vesicles of CRC and normal samples were obtained from the exoRBase database. The corresponding miRNA expression level matrix in extracellular vesicles was downloaded from the BBCancer database. Differentially expressed circRNAs, miRNAs and mRNAs were identified using the limma package of R software at the cut-off criteria of fold change (FC) > 2 and adj. p < 0.05. RT-qPCR assay was conducted to measure hsa_circ_0004831 expression level in CRC blood samples. A circRNA-miRNA-mRNA regulatory network of hsa_circ_0004831 was constructed based on competitive endogenous RNA mechanism and differentially expressed genes. The mRNAs co-expressed with hsa_circ_0004831 were screened at the cut-off criteria of pearson |r| > 0.3 and p < 0.05. Gene set enrichment analysis (GSEA) based on co-expressed mRNAs was used to explore the potential molecular function of hsa_circ_0004831.

Results

Differentially expressed circRNAs, miRNAs and mRNAs were identified and hsa_circ_0004831 had a FC value of 3.92 in CRC blood extracellular vesicles. The RT-qPCR assay showed that the hsa_circ_0004831 was up-regulated in CRC blood samples. The overall survival analysis found that high expression of hsa_circ_0004831 was linked with poorer prognosis. Finally, a circRNA-miRNA-mRNA regulatory network of hsa_circ_0004831 was constructed based on down-regulated miR-4326 and 12 up-regulated mRNAs. GSEA indicated that mRNAs co-expressed with hsa_circ_0004831 were involved in EMT, WNT and p53 signaling pathways.

Conclusions

The study confirmed the up-regulation of hsa_circ_0004831 in CRC, and it may act as a vital prognostic biomarker. The circRNA-miRNA-mRNA regulatory network of hsa_circ_0004831 could be used to uncover the tumorigenesis and progression of CRC.
Evaluation of in vivo anti-malarial potential of omidun obtained from fermented maize in Ibadan, Nigeria
Authors: Omeiza Favour O. , Ademowo George O. , Ayeni Funmilola A.
Published: November 2020

Background

The menace of resistance to anti-malarial drugs is a great challenge to malaria control, necessitating the search for new anti-malarial agents. This search has led to the exploration of natural products for efficacy in malaria therapy.Omidunis the supernatant of fermenting maize (ogi) slurry that has been widely investigated and reported to possess several health benefits and it is used traditionally as solvent for preparing anti-malarial herbs. However, there is no information on the anti-malarial activity ofomidunitself. This study was conducted to investigate the prophylactic, curative and suppressive anti-malarial potential ofomidun.

Methods

Experimental mice in the curative group were infected with 1 × 106cells ofPlasmodium bergheistrain ANKA and treated with either 0.2 ml ofomiduncontaining 3 × 109 cfu/ml of viable lactic acid bacteria or 0.2 ml of 5 mg/kg of chloroquine (positive control) or 0.2 ml of saline (negative control) for 4 days from day 3 post infection. The prophylactic group of mice were pre-treated with eitheromidun, chloroquine or saline for 4 days before infection withP. berghei, while the suppressive group was treated withomidunor chloroquine or saline and infected withP. bergheisimultaneously. A group of mice were uninfected but treated (withomidunand control samples), while a final group was uninfected and untreated (controls). Parasitaemia and histopathology analysis were done in all groups.

Results

The curative and suppressive groups showed a significant difference between theomidun-treated mice (100% parasitaemia reduction) and the untreated mice (54.5% parasitaemia increase). There was no significance difference between theomiduntreatment and chloroquine (positive control) treatment in suppressive group as both treatment had 100% parasitaemia reduction. Theomidunprophylactic treatment however did not show any parasitaemia suppression, but a significant difference was observed between theomiduntreatment (85% increase) and the chloroquine (positive control) treatment (100% reduction) in the group.Omiduntreatment is non-toxic to the kidney.

Conclusion

This study provides scientific evidence supportingomidunusage in the treatment of malaria. Consequently, further work may yield the specific component ofomidunresponsible for the anti-malarial activity.
Vitamin D and Covid-19: an update on evidence and potential therapeutic implications
Authors: Murdaca Giuseppe , Pioggia Giovanni , Negrini Simone
Published: November 2020

The world is now experiencing its third major epidemic of coronavirus (CoV) infections began in Wuhan, Hubei, China, in late 2019 and named COVID-19. After an initial explosive outbreak of pneumonia of unknown etiology in China, the disease spread first to neighboring Asian countries and then worldwide. Patients with COVID-19 presented with a constellation of symptoms such as fever, dry cough, dyspnea, sore throat, and nasal congestion and radiological findings showed bilateral lung glassy opacities. Vitamin D has many mechanisms by which it reduces the risk of microbial infection and death, including physical barrier, cellular natural immunity, and adaptive immunity. Vitamin D supplementation has shown favorable effects in viral infections including influenza and HIV. The effects of vitamin D supplementation during covid 19 infection remain controversial. Looking ahead, clinical studies are needed to define better cut offs for vitamin D levels and, finally, which dosage is the best.
Analysis of risk factors and prevention strategies for functional delayed gastric emptying in 1243 patients with distal gastric cancer
Authors: Pang Tao , Yin Xiao-Yi , Cui Hang-Tian , Lu Zheng-Mao , Nie Ming-Ming , Yin Kai , Fang Guo-En , Luo Tian-Hang , Xue Xu-Chao
Published: November 2020

Background

Analysis of the risk factors associated with functional delayed gastric emptying after distal gastric cancer surgery to provide a basis for further reduction of the incidence of this complication.

Methods

Total of 1382 patients with distal gastric cancer from January 2016 to October 2018 were enrolled. Correlation analysis was performed in 53 patients with FDGE by logistic regression. Subgroup risk analysis was performed in 114 patients with preoperative pyloric obstruction. A Pearson Chi-square analysis was used to compare categorical variables between normal distribution groups. Meanwhile, a t test was used to compare continuous variables between groups. Odds ratio (OR) was used for comparison of the two groups, and it was summarized with its 95% confidence interval (CI) and p value using logistic regression.

Result

In multivariable analysis, age (OR 1.081, 95% CI, 1.047–1.117), BMI (OR 1.233, 95% CI, 1.116–1.363), preoperative pyloric obstruction (OR 3.831, 95% CI, 1.829–8.023), smaller volume of residual stomach (OR 1.838, 95% CI, 1.325–6.080), and anastomosis in greater curvature perpendicular (OR 3.385, 95% CI, 1.632–7.019) and in greater curvature parallel (OR 2.375, 95% CI, 0.963–5.861) were independent risk factors of FDGE. In the preoperative pyloric obstruction group, higher BMI (OR 1.309, 95% CI, 1.086–1.579) and preoperative obstruction time (OR 1.054, 95% CI, 1.003–1.108) were independent risk factors of FDGE and preoperative gastrointestinal decompression (OR 0.231, 95% CI, 0.068–0.785) was independent protective factor of FDGE.

Conclusion

Adequate gastrointestinal decompression should be performed before the operation to reduce the incidence of postoperative gastroparesis in patients with preoperative pyloric obstruction. We also could improve the surgical methods to reduce the occurrence of FDGE, such as controlling the size of the residual stomach, ensuring blood supply. Especially selecting an appropriate stapler and anastomosis during the anastomosis process, the occurrence of FDGE can be reduced.
Adding team-based financial incentives to the Carrot Rewards physical activity app increases daily step count on a population scale: a 24-week matched case control study
Authors: Pearson Emma , Prapavessis Harry , Higgins Christopher , Petrella Robert , White Lauren , Mitchell Marc
Published: November 2020

Background

Mobile health applications (mHealth apps) targeting physical inactivity have increased in popularity yet are usually limited by low engagement. This study examined the impact of adding team-based incentives (Step Together Challenges, STCs) to an existing mHealth app (Carrot Rewards) that rewarded individual physical activity achievements.

Methods

A 24-week quasi-experimental study (retrospective matched pairs design) was conducted in three Canadian provinces (pre-intervention: weeks 1–12; intervention: weeks 13–24). Participants who used Carrot Rewards and STCs (experimental group) were matched with those who used Carrot Rewards only (controls) on age, gender, province and baseline mean daily step count (±500 steps/d). Carrot Rewards users earned individual-level incentives (worth $0.04 CAD) each day they reached a personalized daily step goal. With a single partner, STC users could earn team incentives ($0.40 CAD) for collaboratively reaching individual daily step goals 10 times in seven days (e.g., Partner A completes four goals and Partner B completes six goals in a week).

Results

The main analysis included 61,170 users (mean age = 32 yrs.; % female = 64). Controlling for pre-intervention mean daily step count, a significant difference in intervention mean daily step count favoured the experimental group (p < 0.0001; ηp2 = 0.024). The estimated marginal mean group difference was 537 steps per day, or 3759 steps per week (about 40 walking min/wk). Linear regression suggested a dose-response relationship between the number of STCs completed (app engagement) and intervention mean daily step count (adjusted R2 = 0.699) with each new STC corresponding to approximately 200 more steps per day.

Conclusion

Despite an explosion of physical activity app interest, low engagement leading to small or no effects remains an industry hallmark. In this paper, we found that adding modest team-based incentives to the Carrot Rewards app increased mean daily step count, and importantly, app engagement moderated this effect. Others should consider novel small-teams based approaches to boost engagement and effects.
The epidemiology of postnatal depression in Ethiopia: a systematic review and meta-analysis
Authors: Duko Bereket , Wolde Dereje , Alemayehu Yonas
Published: November 2020

Background

Postnatal depression is among the common mental health problems that occur during the postnatal period. However, it is left undiagnosed in low- and middle-income countries including Ethiopia. Therefore, this systematic review and meta-analysis aimed to systematically summarize the available evidence on the epidemiology of postnatal depression in Ethiopia and suggest recommendations for future clinical practice.

Methods

The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was followed to conduct this systematic review and meta-analysis. We searched PubMed, SCOPUS, EMBASE and Google Scholar databases for the relevant articles that assessed the prevalence of postnatal depression in Ethiopia. We used a random-effect model to conduct a meta-analysis. We conducted a subgroup and sensitivity analysis to explore the source of heterogeneity. Cochrane Q- and the I2-test were used to check the heterogeneity of the included studies. The presence of publication bias was also checked by visual inspection of symmetry and Egger's test.

Results

The pooled estimated prevalence of postnatal depression in Ethiopia was 20.1% (95% CI 12.7–30.2). The pooled prevalence of postnatal depression in the studies that were conducted in community settings and used the Patient Health Questionnaire to assess postnatal depression [16.6% (95% CI 8.90–28.99)] was lower than the prevalence in studies based in institutions and that used the Edinburgh Postnatal Depression Scale [23.2% (95% CI 14.50–28.5)]. Further, in a leave-one-out sensitivity analysis the prevalence of postnatal depression ranges between 15.4% and 25.4%. Unplanned pregnancy [AOR = 3.46, 95% CI (2.37–5.04)], age between 15–24 years [AOR = 1.72, 95% CI (1.11–2.68)], marital problems [AOR = 3.07, 95% CI (2.36–3.99)], experiencing the death of infant [AOR = 3.41, 95% CI (1.91–6.09)] and history of substance use [AOR = 3.47, 95% CI (2.17–5.56)] were associated with the increased odds of postnatal depression in Ethiopia.

Conclusion

The prevalence of postnatal depression in Ethiopia was high. Therefore, the concerned body should give due attention to improve reproductive health services through early detection of risk factors of postnatal depression.
Phylogenetic analysis and clinical characteristics of the co-occurring mutations in HA and NA genes of influenza A(H1N1)pdm09 viruses during 2015–2017 in Beijing, China
Authors: Liu Yafen , Wang Yue , Liu Baiyi , Cong Xu , Ji Ying , Guo Xiaolin , Gao Yan
Published: November 2020

Background

Influenza A(H1N1)pdm09 viruses have undergone rapid evolution, and in recent years the complementary and antagonistic effects of HA and NA have gathered more attentions; however, the effects of co-occurring mutations in HA and NA on the patients’ clinical characteristics are still poorly understood. In this study, we analyzed molecular epidemiology and evolution of A(H1N1) pdm09, explored co-occurring mutations of HA and NA, and investigated effect of co-occurring mutations on patients’ clinical features.

Methods

A(H1N1)pdm09 was confirmed by reverse transcription-polymerase chain reaction. HA and NA genes were sequenced and phylogenetically analyzed. Clinical characteristics of the co-occurring mutations were analyzed statistically.

Results

By analyzing the HA and NA gene sequences of 33 A(H1N1)pdm09 viruses during the 2015–2017 influenza season, we found that all the viruses shared high similarities to each other and the HA genes of these viruses exclusively belonged to subclade 6B.1A. Several unreported substitutions in HA and NA proteins were observed, furthermore, co-occurring mutations of HA-V169T, A278S, E508G, D518E and NA-V67I were detected in 30.3% (10/33) A(H1N1)pdm09 virus strains when comparing with vaccine strains A/California/07/2009 and A/Michigan/45/2015 (H1N1). Sore throat was significantly associated with co-occurring mutations in HA and NA of A(H1N1)pdm09 (χ2,P < 0.05).

Conclusions

Co-occurring mutations in HA and NA were detected in A(H1N1)pdm09 isolated during 2015–2017 in Beijing. Symptomatically, sore throat was associated with co-occurring mutations in HA and NA of A(H1N1)pdm09. Therefore, studying the effect and mechanism of co-occurring mutations in HA and NA on patients’ clinical features is of note needed.
Water hardness influenced variations in reproductive potential of two freshwater fish species; Poecilia reticulata and Betta splendens
Authors: Krishnakumar Abarna , Patrick Anton E. S. , Jayawardena Uthpala A.
Published: November 2020

Objective

Hardness of water in the form of CaCO3affects reproductive potential in various fish species, differently. This study evaluates the effect of water hardness on growth and reproduction of two aquarium fishes,Poecilia reticulata(Ovo-viviparous sp.) andBetta splendens(Oviparous sp.) by growing them under 150 (control), 320, 540 and 900 ppm CaCO3levels in semi natural aquaria.

Results

Growth increased with increasing water hardness, reporting a significant progress ofP. reticulata(p = 0.005) at 900 ppm. Similarly, the reproductive potential ofP. reticulatawas improved significantly, recording the highest fecundity (16.22 ± 3.90) and Gonadosomatic Index (GSI-2.48 ± 0.6) at 900 ppm. However, inB. splendenswater hardness adversely affected the reproduction by resulting a significantly low hatchability and disturbed bubble nests at 900 ppm, compared to the largest bubble nest formed at the control condition (108.58 ± 16.19 cm2). Thus, the study revealed differential effects of water hardness on reproductive potential of the test species, by increasing the potential ofP. reticulatawhile decreasing that ofB. splendens. Though larval survival was affected in both species, larval growth was improved significantly inP. reticulataat 900 ppm level. Understanding reproductive potential of aquarium fishes in natural waters is crucial for their management purposes.
High-fat diet-induced and genetically inherited obesity differentially alters DNA methylation profile in the germline of adult male rats
Authors: Deshpande Sharvari S. , Nemani Harishankar , Arumugam Gandhimathi , Ravichandran Avinash , Balasinor Nafisa H.
Published: November 2020

Background

Paternal obesity has been associated with reduced live birth rates. It could lead to inheritance of metabolic disturbances to the offspring through epigenetic mechanisms. However, obesity is a multifactorial disorder with genetic or environmental causes. Earlier we had demonstrated differential effects of high-fat diet-induced obesity (DIO) and genetically inherited obesity (GIO) on metabolic, hormonal profile, male fertility, and spermatogenesis using two rat models. The present study aimed to understand the effect of DIO and GIO on DNA methylation in male germline, and its subsequent effects on the resorbed (post-implantation embryo loss) and normal embryos. First, we assessed the DNA methylation enzymatic machinery in the testis by Real-Time PCR, followed global DNA methylation levels in spermatozoa and testicular cells by ELISA and flow cytometry, respectively. Further, we performed Methylation Sequencing in spermatozoa for both the groups. Sequencing data in spermatozoa from both the groups were validated using Pyrosequencing. Expression of the differentially methylated genes was assessed in the resorbed and normal embryos sired by the DIO group using Real-Time PCR for functional validation.

Results

We noted a significant decrease in Dnmt transcript and global DNA methylation levels in the DIO group and an increase in the GIO group. Sequencing analysis showed 16,966 and 9113 differentially methylated regions in the spermatozoa of the DIO and GIO groups, respectively. Upon pathway analysis, we observed genes enriched in pathways involved in embryo growth and development namely Wnt, Hedgehog, TGF-beta, and Notch in spermatozoa for both the groups, the methylation status of which partially correlated with the gene expression pattern in resorbed and normal embryos sired by the DIO group.

Conclusion

Our study reports the mechanism by which diet-induced and genetically inherited obesity causes differential effects on the DNA methylation in the male germline that could be due to a difference in the white adipose tissue accumulation. These differences could either lead to embryo loss or transmit obesity-related traits to the offspring in adult life.
Amyloid biomarkers as predictors of conversion from mild cognitive impairment to Alzheimer’s dementia: a comparison of methods
Authors:   for the Alzheimer Disease Neuroimaging Initiative, Sörensen Arnd , Blazhenets Ganna , Schiller Florian , Meyer Philipp Tobias , Frings Lars
Published: November 2020

Background

Amyloid-β (Aβ) PET is an established predictor of conversion from mild cognitive impairment (MCI) to Alzheimer’s dementia (AD). We compared three PET (including an approach based on voxel-wise Cox regression) and one cerebrospinal fluid (CSF) outcome measures in their predictive power.

Methods

Datasets were retrieved from the ADNI database. In a training dataset (N = 159), voxel-wise Cox regression and principal component analyses were used to identify conversion-related regions (Cox-VOI and AD conversion-related pattern (ADCRP), respectively). In a test dataset (N = 129), the predictive value of mean normalized 18F-florbetapir uptake (SUVR) in AD-typical brain regions (composite SUVR) or the Cox-VOI and the pattern expression score (PES) of ADCRP and CSF Aβ42/Aβ40 as predictors were compared by Cox models (corrected for age and sex).

Results

All four Aβ measures were significant predictors (p < 0.001). Prediction accuracies (Harrell’s c) showed step-wise significant increases from Cox-SUVR (c = 0.71; HR = 1.84 per Z-score increase), composite SUVR (c = 0.73; HR = 2.18), CSF Aβ42/Aβ40 (c = 0.75; HR = 3.89) to PES (c = 0.77; HR = 2.71).

Conclusion

The PES of ADCRP is the most predictive Aβ PET outcome measure, comparable to CSF Aβ42/Aβ40, with a slight but statistically significant advantage.
Genetic associations of in vivo pathology influence Alzheimer’s disease susceptibility
Authors:   for the KBASE Research Group, Seo Jieun , Byun Min Soo , Yi Dahyun , Lee Jun Ho , Jeon So Yeon , Shin Seong A. , Kim Yu Kyeong , Kang Koung Mi , Sohn Chul-Ho , Jung Gijung , Park Jong-Chan , Han Sun-Ho , Byun Jayoung , Mook-Jung Inhee , Lee Dong Young , Choi Murim
Published: November 2020

Introduction

Although the heritability of sporadic Alzheimer’s disease (AD) is estimated to be 60–80%, addressing the genetic contribution to AD risk still remains elusive. More specifically, it remains unclear whether genetic variants are able to affect neurodegenerative brain features that can be addressed by in vivo imaging techniques.

Methods

Targeted sequencing analysis of the coding and UTR regions of 132 AD susceptibility genes was performed. Neuroimaging data using 11C-Pittsburgh Compound B positron emission tomography (PET), 18F-fluorodeoxyglucose PET, and MRI that are available from the KBASE (Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer’s disease) cohort were acquired. A total of 557 participants consisted of 336 cognitively normal (CN) adults, 137 mild cognitive impairment (MCI), and 84 AD dementia (ADD) groups.

Results

We called 5391 high-quality single nucleotide variants (SNVs) on AD susceptibility genes and selected significant associations between variants and five in vivo AD pathologies: (1) amyloid β (Aβ) deposition, (2) AD-signature region cerebral glucose metabolism (AD-Cm), (3) posterior cingulate cortex (PCC) cerebral glucose metabolism (PCC-Cm), (4) AD-signature region cortical thickness (AD-Ct), and (5) hippocampal volume (Hv). The association analysis for common variants (allele frequency (AF) > 0.05) yielded several novel loci associated with Aβ deposition (PIWIL1-rs10848087), AD-Cm (NME8-rs2722372 and PSEN2-rs75733498), AD-Ct (PSEN1-rs7523) and, Hv (CASS4-rs3746625). Meanwhile, in a gene-based analysis for rare variants (AF < 0.05), cases carrying rare variants in LPL, FERMT2, NFAT5, DSG2, and ITPR1 displayed associations with the neuroimaging features. Exploratory voxel-based brain morphometry between the variant carriers and non-carriers was performed subsequently. Finally, we document a strong association of previously reported APOE variants with the in vivo AD pathologies and demonstrate that the variants exert a causal effect on AD susceptibility via neuroimaging features.

Conclusions

This study provides novel associations of genetic factors to Aβ accumulation and AD-related neurodegeneration to influence AD susceptibility.
High-throughput screening identifies histone deacetylase inhibitors that modulate GTF2I expression in 7q11.23 microduplication autism spectrum disorder patient-derived cortical neurons
Authors: Cavallo Francesca , Troglio Flavia , Fagà Giovanni , Fancelli Daniele , Shyti Reinald , Trattaro Sebastiano , Zanella Matteo , D’Agostino Giuseppe , Hughes James M. , Cera Maria Rosaria , Pasi Maurizio , Gabriele Michele , Lazzarin Maddalena , Mihailovich Marija , Kooy Frank , Rosa Alessandro , Mercurio Ciro , Varasi Mario , Testa Giuseppe
Published: November 2020

Background

Autism spectrum disorder (ASD) is a highly prevalent neurodevelopmental condition affecting almost 1% of children, and represents a major unmet medical need with no effective drug treatment available. Duplication at 7q11.23 (7Dup), encompassing 26–28 genes, is one of the best characterized ASD-causing copy number variations and offers unique translational opportunities, because the hemideletion of the same interval causes Williams–Beuren syndrome (WBS), a condition defined by hypersociability and language strengths, thereby providing a unique reference to validate treatments for the ASD symptoms. In the above-indicated interval at 7q11.23, defined as WBS critical region, several genes, such as GTF2I, BAZ1B, CLIP2 and EIF4H, emerged as critical for their role in the pathogenesis of WBS and 7Dup both from mouse models and human studies.

Methods

We performed a high-throughput screening of 1478 compounds, including central nervous system agents, epigenetic modulators and experimental substances, on patient-derived cortical glutamatergic neurons differentiated from our cohort of induced pluripotent stem cell lines (iPSCs), monitoring the transcriptional modulation of WBS interval genes, with a special focus on GTF2I, in light of its overriding pathogenic role. The hits identified were validated by measuring gene expression by qRT-PCR and the results were confirmed by western blotting.

Results

We identified and selected three histone deacetylase inhibitors (HDACi) that decreased the abnormal expression level of GTF2I in 7Dup cortical glutamatergic neurons differentiated from four genetically different iPSC lines. We confirmed this effect also at the protein level.

Limitations

In this study, we did not address the molecular mechanisms whereby HDAC inhibitors act on GTF2I. The lead compounds identified will now need to be advanced to further testing in additional models, including patient-derived brain organoids and mouse models recapitulating the gene imbalances of the 7q11.23 microduplication, in order to validate their efficacy in rescuing phenotypes across multiple functional layers within a translational pipeline towards clinical use.

Conclusions

These results represent a unique opportunity for the development of a specific class of compounds for treating 7Dup and other forms of intellectual disability and autism.
Secretory phospholipase A2-X (Pla2g10) is a novel progesterone receptor target gene exclusively induced in uterine luminal epithelium for uterine receptivity in mice
Authors: Park Hee Kyoung , Park So Hee , Lee Miji , Kim Gyeong Ryeong , Park Mira , Yang Seung Chel , Kim Yeon Sun , Lim Hyunjung J. , Kim Hye-Ryun , Song Haengseok
Published: November 2020

Background

Aberration of estrogen (E2) and/or progesterone (P4) signaling pathways affects expression of their target genes, which may lead to failure of embryo implantation and following pregnancy. Although many target genes of progesterone receptors (PRs) have been identified in uterine stroma, only a few PR targets have been reported in the epithelium. Secretory phospholipase A2-(PLA2)-X, a member of the PLA2family that releases arachidonic acids for the synthesis of prostaglandins that are important for embryo implantation, is dysregulated in the endometrium of patients suffering from repeated implantation failure. However, it is not clear whether sPLA2-X is directly regulated by ovarian steroid hormones for embryo implantation in the uterus.

Result

P4induced thePla2g10encoding of secretory PLA2-X in the apical region of uterine LE of ovariectomized mice via PR in both time- and dose-dependent manners, whereas E2significantly inhibited it. This finding is consistent with the higher expression ofPla2g10at the diestrus stage, when P4is elevated during the estrous cycle, and at P4-treated delayed implantation. The level ofPla2g10on day 4 of pregnancy (day 4) was dramatically decreased on day 5, when PRs are absent in the LE. Luciferase assays of mutagenesis in uterine epithelial cells demonstrated that four putative PR response elements in aPla2g10promoter region are transcriptionally active forPla2g10. Intrauterine delivery of small interfering RNA forPla2g10on day 3 significantly reduced the number of implantation sites, reinforcing the critical function(s) ofPla2g10for uterine receptivity in mice.

Conclusions

Pla2g10is a novel PR target gene whose expression is exclusively localized in the apical region of the uterine LE for uterine receptivity for embryo implantation in mice.
A secure data deduplication system for integrated cloud-edge networks
Authors: P. G. Shynu , R. K. Nadesh , Menon Varun G. , P. Venu , Abbasi Mahdi , Khosravi Mohammad R.
Published: November 2020

Data redundancy is a significant issue that wastes plenty of storage space in the cloud-fog storage integrated environments. Most of the current techniques, which mainly center around the static scenes, for example, the backup and archive systems, are not appropriate because of the dynamic nature of data in the cloud or integrated cloud environments. This problem can be effectively reduced and successfully managed by data deduplication techniques, eliminating duplicate data in cloud storage systems. Implementation of data deduplication (DD) over encrypted data is always a significant challenge in an integrated cloud-fog storage and computing environment to optimize the storage efficiently in a highly secured manner. This paper develops a new method using Convergent and Modified Elliptic Curve Cryptography (MECC) algorithms over the cloud and fog environment to construct secure deduplication systems. The proposed method focuses on the two most important goals of such systems. On one side, the redundancy of data needs to be reduced to its minimum, and on the other hand, a robust encryption approach must be developed to ensure the security of the data. The proposed technique is well suited for operations such as uploading new files by a user to the fog or cloud storage. The file is first encrypted using the Convergent Encryption (CE) technique and then re-encrypted using the Modified Elliptic Curve Cryptography (MECC) algorithm. The proposed method can recognize data redundancy at the block level, reducing the redundancy of data more effectively. Testing results show that the proposed approach can outperform a few state-of-the-art methods of computational efficiency and security levels.
New viral biogeochemical roles revealed through metagenomic analysis of Lake Baikal
Authors: Coutinho F. H. , Cabello-Yeves P. J. , Gonzalez-Serrano R. , Rosselli R. , López-Pérez M. , Zemskaya T. I. , Zakharenko A. S. , Ivanov V. G. , Rodriguez-Valera F.
Published: November 2020

Background

Lake Baikal is the largest body of liquid freshwater on Earth. Previous studies have described the microbial composition of this habitat, but the viral communities from this ecosystem have not been characterized in detail.

Results

Here, we describe the viral diversity of this habitat across depth and seasonal gradients. We discovered 19,475 bona fide viral sequences, which are derived from viruses predicted to infect abundant and ecologically important taxa that reside in Lake Baikal, such as Nitrospirota, Methylophilaceae, and Crenarchaeota. Diversity analysis revealed significant changes in viral community composition between epipelagic and bathypelagic zones. Analysis of the gene content of individual viral populations allowed us to describe one of the first bacteriophages that infect Nitrospirota, and their extensive repertoire of auxiliary metabolic genes that might enhance carbon fixation through the reductive TCA cycle. We also described bacteriophages of methylotrophic bacteria with the potential to enhance methanol oxidation and the S-adenosyl-L-methionine cycle.

Conclusions

These findings unraveled new ways by which viruses influence the carbon cycle in freshwater ecosystems, namely, by using auxiliary metabolic genes that act upon metabolisms of dark carbon fixation and methylotrophy. Therefore, our results shed light on the processes through which viruses can impact biogeochemical cycles of major ecological relevance.
Antimicrobial use and production system shape the fecal, environmental, and slurry resistomes of pig farms
Authors: Mencía-Ares Oscar , Cabrera-Rubio Raúl , Cobo-Díaz José Francisco , Álvarez-Ordóñez Avelino , Gómez-García Manuel , Puente Héctor , Cotter Paul D. , Crispie Fiona , Carvajal Ana , Rubio Pedro , Argüello Héctor
Published: November 2020

Background

The global threat of antimicrobial resistance (AMR) is a One Health problem impacted by antimicrobial use (AMU) for human and livestock applications. Extensive Iberian swine production is based on a more sustainable and eco-friendly management system, providing an excellent opportunity to evaluate how sustained differences in AMU impact the resistome, not only in the animals but also on the farm environment. Here, we evaluate the resistome footprint of an extensive pig farming system, maintained for decades, as compared to that of industrialized intensive pig farming by analyzing 105 fecal, environmental and slurry metagenomes from 38 farms.

Results

Our results evidence a significantly higher abundance of antimicrobial resistance genes (ARGs) on intensive farms and a link between AMU and AMR to certain antimicrobial classes. We observed differences in the resistome across sample types, with a higher richness and dispersion of ARGs within environmental samples than on those from feces or slurry. Indeed, a deeper analysis revealed that differences among the three sample types were defined by taxa-ARGs associations. Interestingly, mobilome analyses revealed that the observed AMR differences between intensive and extensive farms could be linked to differences in the abundance of mobile genetic elements (MGEs). Thus, while there were no differences in the abundance of chromosomal-associated ARGs between intensive and extensive herds, a significantly higher abundance of integrons in the environment and plasmids, regardless of the sample type, was detected on intensive farms.

Conclusions

Overall, this study shows how AMU, production system, and sample type influence, mainly through MGEs, the profile and dispersion of ARGs in pig production.
Bioequivalence of levamlodipine besylate tablets in healthy Chinese subjects: a single-dose and two-period crossover randomized study
Authors: Li Xin , Wang Chenjing , Li Ting , Liu Yanping , Liu Shuqin , Tao Ye , Ma Yaping , Gao Xiaomeng , Cao Yu
Published: November 2020

Background

Levamlodipine, a calcium channel blocker, has been show act as a cardiovascular drug. To compare the pharmacokinetic parameters between levamlodipine (test formulation) at a single dose of 5 mg and amlodipine (reference formulation) at a single dose of 10 mg, the bioequivalence study was carried out.

Methods

A single-dose randomized, open-label, two-period crossover study was designed in healthy Chinese subjects. 48 subjects were divided into fasted and fed groups equally. The subjects randomly received the test or reference formulations at the rate of 1:1. Following a 21-day washout period, the alternative formulations were received. The blood samples were collected at 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 24, 36, 48, 72, 96, 120, 144, 168 h later. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was applied to determine the plasma concentrations of levamlodipine. Adverse events were recorded.

Results

The 90% confidence intervals (CIs) of the ratio of geometric means (GMRs) of Cmax, AUC0-t, and AUC0-∞ under both fasted and fed conditions were within the prespecified bioequivalence limits between 80 ~ 125%. Under fasted conditions, 24 subjects were enrolled and completed the study. The mean Cmax was (2.70 ± 0.49) ng/mL, AUC0-t was (141.32 ± 36.24) ng × h/mL and AUC0-∞ was (157.14 ± 45.65) ng × h/mL after a single dose of 5 mg levamlodipine. The mean Cmax was (2.83 ± 0.52) ng/mL, AUC0-t was (153.62 ± 33.96) ng × h/mL and AUC0-∞ was (173.05 ± 41.78) ng × h/mL after a single dose of 10 mg amlodipine. Under fed conditions, 24 subjects were enrolled and completed the study. The mean Cmax was (2.73 ± 0.55) ng/mL, AUC0-t was (166.93 ± 49.96) ng × h/mL and AUC0-∞ was (190.99 ± 70.89) ng × h/mL after a single dose of 5 mg levamlodipine. The mean Cmax was (2.87 ± 0.81) ng/mL AUC0-t was (165.46 ± 43.58) ng × h/mL and AUC0-∞ was (189.51 ± 64.70) ng × h/mL after a single dose of 10 mg amlodipine. Serious adverse event was not observed.

Conclusion

The trial confirmed that levamlodipine at a single dose of 5 mg and amlodipine at a single dose of 10 mg were bioequivalent under both fasted condition and fed condition.

Trial registration

Cinicaltrials, NCT04411875. Registered 3 June 2020 - Retrospectively registered