bluuebunny/crossref_metadata_2025 huggingface dataset:
Bioinformatics profiling integrating a three immune-related long non-coding RNA signature as a prognostic model for clear cell renal cell carcinoma
Authors: Jiang Yuanbin , Gou Xin , Wei Zongjie , Tan Jianyu , Yu Haitao , Zhou Xiang , Li Xinyuan
Published: May 2020

Background

Renal cell carcinoma (RCC) is one of the most common aggressive malignant tumors in urogenital system, and the clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal carcinoma. Immune related long non-coding RNAs (IRlncRs) plentiful in immune cells and immune microenvironment (IME) are potential in evaluating prognosis and assessing the effects of immunotherapy. A completed and meaningful IRlncRs analysis based on abundant ccRCC gene samples from The Cancer Genome Atlas (TCGA) will provide insight in this field.

Methods

Based on the TCGA dataset, we integrated the expression profiles of IRlncRs and overall survival (OS) in the 611 ccRCC patients. The immune score of each sample was calculated based on the expression level of immune-related genes and used to identify the most meaningful IRlncRs. Survival-related IRlncRs (sIRlncRs) was estimated by calculating the algorithm of difference and COX regression analysis in ccRCC patients. Based on the median immune-related risk score (IRRS) developed from the screened sIRlncRs, the high-risk and low-risk components were distinguished. Functional annotation was detected by gene set enrichment analysis (GSEA) and principal component analysis (PCA), and the immune composition and purity of the tumor was evaluated by microenvironment cell population records. The expression levels of three sIRlncRs were verified in various tissues and cell lines.

Results

A total of 39 IRlncRs were collected by Pearson correlation analyses among immune score and the lncRNA expression. A total of 7 sIRlncRs were significantly associated with the clinical outcomes of ccRCC patients. Three sIRlncRs (ATP1A1-AS1, IL10RB-DT and MELTF-AS1) with the most significant prognostic values were enrolled to build the IRRS model in which the OS of in the high-risk group was shorter than that in the low-risk group. The IRRS was identified as an independent prognosis factor and correlated with the OS. The high-risk group and low-risk group illustrated different distributions in PCA and different immune status in GSEA. Besides, we found the more significant expression in certain ccRCC cell lines and tumor tissues of ccRCC patients compared with the HK-2 and adjacent tissues respectively. Additionally, the expression levels of lncR-MELTF-AS1 and IL10RB-DT were remarkably enhanced along the more advanced T-stages, but the lncR-ATP1A1-AS1 showed the inverse gradient.

Conclusion

Our results demonstrate some sIRlncRs with remark clinical relevance show the latent monitoring and prognosis values for ccRCC patients and may provide new insight in immunological researches and treatment strategies of ccRCC patients.
Biological effects of selective COX-2 inhibitor NS398 on human glioblastoma cell lines
Authors: Palumbo Paola , Lombardi Francesca , Augello Francesca Rosaria , Giusti Ilaria , Dolo Vincenza , Leocata Pietro , Cifone Maria Grazia , Cinque Benedetta
Published: May 2020

Background

Cyclooxygenase-2 (COX-2), an inflammation-associated enzyme, has been implicated in tumorigenesis and progression of glioblastoma (GBM). The poor survival of GBM was mainly associated with the presence of glioma stem cells (GSC) and the markedly inflammatory microenvironment. To further explore the involvement of COX-2 in glioma biology, the effects of NS398, a selective COX-2 inhibitor, were evaluated on GSC derived from COX-2 expressing GBM cell lines, i.e., U87MG and T98G, in terms of neurospheres’ growth, autophagy, and extracellular vesicle (EV) release.

Methods

Neurospheres’ growth and morphology were evaluated by optical and scanning electron microscopy. Autophagy was measured by staining acidic vesicular organelles. Extracellular vesicles (EV), released from neurospheres, were analyzed by transmission electron microscopy. The autophagic proteins Beclin-1 and LC3B, as well as the EV markers CD63 and CD81, were analyzed by western blotting. The scratch assay test was used to evaluate the NS398 influence on GBM cell migration.

Results

Both cell lines were strongly influenced by NS398 exposure, as showed by morphological changes, reduced growth rate, and appearance of autophagy. Furthermore, the inhibitor led to a functional change of EV released by neurospheres. Indeed, EV secreted by NS398-treated GSC, but not those from control cells, were able to significantly inhibit adherent U87MG and T98G cell migration and induced autophagy in recipient cells, thus leading to effects quite similar to those directly caused by NS398 in the same cells.

Conclusion

Despite the intrinsic diversity and individual genetic features of U87MG and T98G, comparable effects were exerted by the COX-2 inhibitor NS398 on both GBM cell lines. Overall, our findings support the crucial role of the inflammatory-associated COX-2/PGE2 system in glioma and glioma stem cell biology.
RETRACTED ARTICLE: Neuron tau-targeting biomimetic nanoparticles for curcumin delivery to delay progression of Alzheimer’s disease
Authors: Gao Chunhong , Chu Xiaoyang , Gong Wei , Zheng Jinpeng , Xie Xiangyang , Wang Yuli , Yang Meiyan , Li Zhiping , Gao Chunsheng , Yang Yang
Published: May 2020

Background

Although many therapeutic strategies for Alzheimer’s disease (AD) have been explored, these strategies are seldom used in the clinic. Therefore, AD therapeutic research is still urgently needed. One major challenge in the field of nanotherapeutics is to increase the selective delivery of drugs to a targeted location. Herein, we devised and tested a strategy for delivery of nanoparticles to neurons to inhibit tau aggregation by directly targeting p-tau.

Results

Curcumin (CUR) is loaded onto red blood cell (RBC) membrane-coated PLGA particles bearing T807 molecules attached to the RBC membrane surface (T807/RPCNP). With the advantage of the suitable physicochemical properties of the PLGA nanoparticles and the unique biological functions of the RBC membrane, the RPCNP are stabilized and promote sustained CUR release, which provided improved biocompatibility and resulted in long-term presence in the circulation. Under the synergistic effects of T807, T807/RPCNP can not only effectively penetrate the blood–brain barrier (BBB), but they also possess high binding affinity to hyperphosphorylated tau in nerve cells where they inhibit multiple key pathways in tau-associated AD pathogenesis. When CUR was encapsulated, our data also demonstrated that CUR-loaded T807/RPCNP NPs can relieve AD symptoms by reducing p-tau levels and suppressing neuronal-like cells death both in vitro and in vivo. The memory impairment observed in an AD mouse model is significantly improved following systemic administration of CUR-loaded T807/RPCNP NPs.

Conclusion

Intravenous neuronal tau-targeted T807-modified novel biomimetic nanosystems are a promising clinical candidate for the treatment of AD.
Barriers to and recommendations for take-home naloxone distribution: perspectives from opioid treatment programs in New Mexico
Authors: Salvador Julie G. , Sussman Andrew L. , Takeda Mikiko Y. , Katzman William G. , Moya Balasch Monica , Katzman Joanna G.
Published: May 2020

Background

Naloxone is a safe and effective medication to help reverse opioid overdose. Providing take-home naloxone to patients in opioid treatment settings is a critical step to reducing opioid overdose deaths. In New Mexico, a US state with one of the highest rates of opioid overdose deaths, legislation was passed in 2017 (House Bill 370) to support take-home naloxone, and followed by naloxone training of Opioid Treatment Program staff to increase distribution.

Methods

Naloxone training was offered to all New Mexico Opioid Treatment Programs along with a baseline survey to assess current practices and barriers to take-home naloxone distribution. Focus groups were conducted approximately 1 year post-training with staff at a subset of the trained Opioid Treatment Programs to assess the impact of the legislation and training provided.

Results

Baseline survey results show most Opioid Treatment Program staff were unfamiliar with House Bill 370, reported conflicting understandings of their agency’s current take-home naloxone practices, and reported a number of barriers at the patient, agency, and policy level. Follow-up focus groups revealed support for House Bill 370 but persistent barriers to its implementation at the patient, agency, and policy level including patient receptivity, cost of naloxone, staff time, and prohibitive pharmacy board regulations.

Conclusions

In spite of targeted legislation and training, provision of take-home naloxone at remained low. This is alarming given the need for this lifesaving medication among the Opioid Treatment Program patient population, and high opioid death rate in New Mexico. Locally, important next steps include clarifying regulatory guidelines and supporting policy/billing changes to offset costs to Opioid Treatment Programs. Globally, additional research is needed to identify the prevalence of take-home naloxone distribution in similar settings, common barriers, and best practices that can be shared to increase access to this vital lifesaving medication in this critical context.
Validation and clinical interpretation of the St George’s respiratory questionnaire for COPD (SGRQ-C) after adaptation to Malaysian language and culture, in patients with COPD
Authors: Rehman Anees ur , Hassali Mohamed Azmi Ahmad , Harun Sabariah Noor , Abbas Sameen , Muneswarao Jaya , Ali Irfhan Ali Bin Hyder , Hussain Rabia
Published: May 2020

Background

Cultural differences affect the administration and results of health status questionnaires. “Cross cultural adaptation” ensures retention of psychometric properties such as validity and reliability at an item and/or scale level.

Objective

To develop a Malaysian version of St George’s respiratory COPD specific questionnaire (SGRQ-CM), to evaluate the full spectrum of psychometric properties (reliability, validity and responsiveness), to test the factor structure and to assess minimum clinically important difference for the SGRQ-CM, to be used in population of Malaysia.

Methodology

SGRQ-C was translated to Bahasa Malaysia using a standard protocol. 240 COPD patients were included in the study. All patients were followed-up for six months. Construct validity, internal consistency, item convergent validity, test-retest ability, responsiveness, factor analysis and MCID of the Malaysian version of SGRQ-C to be used in population of Malaysia were evaluated.

Results

The Cronbach alpha coefficient and intraclass correlation coefficients (ICC) for SGRQ-CM were reported as 0.87, and 0.88 respectively. Correlation of SGRQ-CM with CAT, EQ-5D-5 L, mMRC dyspnea scales and FEV1%predicted were reported as 0.86, − 0.82, 0.72 and − 0.42 respectively. Correlation coefficient between the subscales and other clinical and health status measures ranged from r = − 0.35 to r = − 0.87. The MCID was reported as 5.07 (− 2.54–12.67).

Conclusion

The Malaysian version of SGRQ-C has a good psychometric property comparable to those of the original version and has a strong evidence of validity, reliability and responsiveness towards disease severity in Malaysian COPD patients. It can be recommended as a reliable quality of life measure for future research.
Effect of Letrozole on sperm parameters, chromatin status and ROS level in idiopathic Oligo/Astheno/Teratozoospermia
Authors: Kooshesh Leila , Bahmanpour Soghra , Zeighami Shahriar , Nasr-Esfahani Mohammad Hussain
Published: May 2020

Background

This study investigates the effect of letrozole on hormone profiles, semen parameters, body mass index (BMI), degree of oxidative stress and sperm chromatin integrity in men with idiopathic oligo/astheno/teratozoospermia (iOAT) and T:E2 ratio ≤ 10.

Materials and methods

This study is a longitudinal, prospective, interventional and open-labelled clinical trial. Semen samples were collected from 20 iOAT men with low serum testosterone (T) to estradiol (E2) ratio (T:E2 ratio ≤ 10). The participants were treated with 2.5 mg letrozole orally per day for 3 months. Then, sperm parameters, hormone profiles, BMI, chromatin integrity and intracellular reactive oxygen species (ROS) level were assessed pre- and post- treatment. The chromatin integrity was evaluated by assessment of DNA fragmentation (with TUNEL assay) and protamine deficiency (with Chromomycin A3, CMA3). Also, the intracellular ROS levels were investigated by 2′, 7′-dichlorodihydrofluorescein diacetate (DCFH-DA) staining. Finally, the differences between the parameters evaluated before and after letrozole treatment were analyzed with the t-test and the Wilcoxon signed-rank test.

Results

Sperm concentration, percentage of sperm motility and its normal morphology increased significantly after letrozole treatment. Moreover, serum testosterone level increased but estradiol level decreased significantly following treatment. The mean of T:E2 ratio improved 1600%. Also, letrozole treatment significantly reduced the percentage of sperm TUNEL positivity and sperm CMA3 positivity. While no significant difference was observed between intracellular ROS levels and BMI before and after treatment. Finally, as a notable result, four spontaneous pregnancies (20%) were achieved after treatment.

Conclusions

Letrozole treatment can effectively increase spontaneous pregnancies by improving sperm parameters and sperm chromatin integrity in men with iOAT and T:E2 ratio ≤ 10.

Trial registration

Trial registration: IRCT, IRCT20191030045283N1. Registered 16 November 2019 - Retrospectively registered, https://fa.irct.ir/user/trial/43484/view
Clinical application and evaluation of metagenomic next-generation sequencing in suspected adult central nervous system infection
Authors: Zhang Yi , Cui Peng , Zhang Hao-Cheng , Wu Hong-Long , Ye Ming-Zhi , Zhu Yi-Min , Ai Jing-Wen , Zhang Wen-Hong
Published: May 2020

Background

Accurate etiology diagnosis is crucial for central nervous system infections (CNS infections). The diagnostic value of metagenomic next-generation sequencing (mNGS), an emerging powerful platform, remains to be studied in CNS infections.

Methods

We conducted a single-center prospective cohort study to compare mNGS with conventional methods including culture, smear and etc. 248 suspected CNS infectious patients were enrolled and clinical data were recorded.

Results

mNGS reported a 90.00% (9/10) sensitivity in culture-positive patients without empirical treatment and 66.67% (6/9) in empirically-treated patients. Detected an extra of 48 bacteria and fungi in culture-negative patients, mNGS provided a higher detection rate compared to culture in patients with (34.45% vs. 7.56%, McNemar test, p < 0.0083) or without empirical therapy (50.00% vs. 25.00%, McNemar test, p > 0.0083). Compared to conventional methods, positive percent agreement and negative percent agreement was 75.00% and 69.11% separately. mNGS detection rate was significantly higher in patients with cerebrospinal fluid (CSF) WBC > 300 * 106/L, CSF protein > 500 mg/L or glucose ratio ≤ 0.3. mNGS sequencing read is correlated with CSF WBC, glucose ratio levels and clinical disease progression.

Conclusion

mNGS showed a satisfying diagnostic performance in CNS infections and had an overall superior detection rate to culture. mNGS may held diagnostic advantages especially in empirically treated patients. CSF laboratory results were statistically relevant to mNGS detection rate, and mNGS could dynamically monitor disease progression.
Retraction Note to: TREM-1 associated macrophage polarization plays a significant role in inducing insulin resistance in obese population
Authors: Subramanian Saravanan , Pallati Pradeep K. , Sharma Poonam , Agrawal Devendra K. , Nandipati Kalyana C.
Published: May 2020

An amendment to this paper has been published and can be accessed via the original article.
Effect of aging on the transcriptomic changes associated with the expression of the HERV-K (HML-2) provirus at 1q22
Authors: Autio Arttu , Nevalainen Tapio , Mishra Binisha H. , Jylhä Marja , Flinck Heini , Hurme Mikko
Published: May 2020

Background

The human genome contains remnants of ancient retroviral infections called human endogenous retroviruses (HERV). Their expression is often observed in several diseases of autoimmune or inflammatory nature. However, the exact biological mechanisms induced by HERVs are still poorly understood. We have previously shown that several HERVs of the HERV-K (HML-2) family are strongly transcribed in the peripheral blood mononuclear cells (PBMC) derived from young and old individuals. To examine the potential functional consequences of HERV-K (HML-2) expression, we have now analyzed the correlation of its expression with age-associated changes in the transcriptome using gene set enrichment analysis (GSEA). We focused our analysis on the HERV-K (HML-2) provirus at 1q22, also known as ERVK-7.

Results

The genes strongly correlating with the expression of HERV-K (HML-2) provirus at 1q22 expression were found to be almost entirely different in young and old individuals. The number of genes strongly correlating (Pearson correlation coefficient ≥ 0.7) with 1q22 expression was 946 genes in the old and 435 in the young, of which only 41 genes correlated strongly in both. Consequently, the related gene ontology (GO) biological processes were different. In the older individuals, many of the highest correlating processes relate to the function of neutrophils.

Conclusions

The results of this work suggest that the biological processes associated with the expression of HERV-K (HML-2) provirus at 1q22 are different in the blood of young and old individuals. Specifically, a strong association was found in the older individuals between neutrophil activity and the expression of the HERV-K (HML-2) provirus at 1q22. These findings offer insight into potential effects of altered HERV expression in older individuals.
Factors associated with exclusive breastfeeding at hospital discharge: a study using data from the Georgian Birth Registry
Authors: Lande Marie Sigstad , Nedberg Ingvild Hersoug , Anda Erik Eik
Published: May 2020

Background

The World Health Organization recommends exclusive breastfeeding for six months, defined as no other solids or liquids besides breast milk and essential vitamins or medicines. Data about exclusive breastfeeding are limited in Georgia, and the information that exist are provided by national surveys, that present inconsistent numbers. Georgia has recently established a national birth registry, which includes information about early postpartum breastfeeding. The objective of this study was to identify factors associated with exclusive breastfeeding of term newborns at hospital discharge in Georgia, using national registry data.

Methods

All live, singleton, term births registered in the Georgian Birth Registry in November and December 2017 were included, with a final study sample of 7134 newborns. Newborns exclusively breastfed at hospital discharge were compared with those who were not, and potential factors were assessed with logistic regression analysis. Hospital discharge normally occurred between 2 and 5 days postpartum.

Results

The study identified several factors associated with nonexclusive breastfeeding of term newborns at hospital discharge in Georgia: maternal higher education compared to secondary education or less (Adjusted Odds Ratio [AOR] 0.75; 95% CI 0.59, 0.97), caesarean delivery compared to vaginal or assisted vaginal delivery (AOR 0.47; 95% CI 0.37, 0.60), birthweight < 2500 g compared to 3000–3499 g (AOR 0.51; 95% CI 0.27, 0.97), and admission to neonatal intensive care unit after delivery (AOR 0.02; 95% CI 0.02, 0.03). None of the following factors were associated with exclusive breastfeeding at discharge: mother’s age, marital status, Body Mass Index (BMI), parity, in vitro fertilization, maternal intrapartum complications and the sex of the newborn.

Conclusions

To the authors’ knowledge, this is the first time determinants of exclusive breastfeeding at hospital discharge have been studied in Georgia. Several factors associated with nonexclusive breastfeeding at discharge were identified, most noteworthy were caesarean delivery and admission to neonatal intensive care unit. These findings are of importance to the Georgian health authorities and maternal/child non-governmental organizations.
Feasibility investigation of uniportal video-assisted thoracoscopic anatomical lung resection for pulmonary sequestration
Authors: Sun Yungang , Shao Feng , Zhang Qiang , Wang Zhao
Published: May 2020

Background

Uniportal video-assisted thoracic surgery (UVATS) technique has been increasingly used for many thoracic diseases. Whether UVATS has equivalent or better perioperative outcomes for pulmonary sequestration (PS) patients remains controversial. Our study aimed to evaluate the feasibility of UVATS in anatomical lung resection for pulmonary sequestration.

Methods

A total of 24 patients with PS including fifteen males and nine females with the mean age of 40 (range, 18–65) years old, who had received completely UVATS anatomical lung resection for PS in Nanjing Chest Hospital between January 2016 and December 2018 were retrospectively reviewed. Related clinical data were retrieved from hospital records and analyzed.

Results

All 24 patients had been treated with the UAVTS approach successfully without aberrant artery ruptured or massive hemorrhage, and no patients died during the perioperative period. Overall mean surgery time was 102 mins (range, 55–150 min), the mean blood loss was 94 ml (range, 10-300 ml), the mean days of chest tube maintained were 4 days (range,1-10 days), and the mean postoperative hospitalization days was 6 days (range,2-11 days). All patients were cured, without cough, fever, hemoptysis, and so on, associated with PS, occurring during the average follow-up of 17 months (range, 3-35 months).

Conclusions

Our preliminary results revealed that anatomical lung resection by UVATS is a safe and feasible mini-invasive technique for PS patients, which might be associated with less postoperative pain, reduced paresthesia, better cosmetic results, and faster recovery.
The novel immunomodulatory biologic LMWF5A for pharmacological attenuation of the “cytokine storm” in COVID-19 patients: a hypothesis
Authors: Thomas Gregory , Frederick Elizabeth , Hausburg Melissa , Goldberg Laura , Hoke Marshall , Roshon Michael , Mains Charles , Bar-Or David
Published: May 2020

Background

A common complication of viral pulmonary infections, such as in the ongoing COVID-19 pandemic, is a phenomenon described as a “cytokine storm”. While poorly defined, this hyperinflammatory response results in diffuse alveolar damage. The low molecular weight fraction of commercial human serum albumin (LMWF5A), a novel biologic in development for osteoarthritis, demonstrates beneficial in vitro immunomodulatory effects complimentary to addressing inflammation, thus, we hypothesize that LMWF5A could improve the clinical outcomes of COVID-19 by attenuating hyperinflammation and the potential development of a cytokine storm.

Presentation of the hypothesis

A variety of human in vitro immune models indicate that LMWF5A reduces the production of pro-inflammatory cytokines implicated in cytokine storm associated with COVID-19. Furthermore, evidence suggests LMWF5A also promotes the production of mediators required for resolving inflammation and enhances the barrier function of endothelial cultures.

Testing the hypothesis

A randomized controlled trial, to evaluate the safety and efficacy of nebulized LMWF5A in adults with Acute Respiratory Distress Syndrome (ARDS) secondary to COVID-19 infection, was developed and is currently under review by the Food and Drug Administration.

Implications of hypothesis

If successful, this therapy may attenuate the cytokine storm observed in these patients and potentially reduce mortality, increase ventilation free days, improve oxygenation parameters and consequently lessen the burden on patients and the intensive care unit.

Conclusions

In conclusion, in vitro findings suggest that the immunomodulatory effects of LMWF5A make it a viable candidate for treating cytokine storm and restoring homeostasis to the immune response in COVID-19.
A potential method of identifying stroke and other intracranial lesions in a prehospital setting
Authors: Saviluoto Anssi , Harve-Rytsälä Heini , Lääperi Mitja , Kirves Hetti , Jäntti Helena , Nurmi Jouni
Published: May 2020

Background

Identifying stroke and other intracranial lesions in patients with a decreased level of consciousness may be challenging in prehospital settings. Our objective was to investigate whether the combination of systolic blood pressure, heart rate and age could be used to identify intracranial lesions.

Methods

We conducted a retrospective case-control study including patients with a decreased level of consciousness who had their airway secured during prehospital care. Patients with intracranial lesions were identified based on the final diagnoses at the end of hospitalization. We investigated the ability of systolic blood pressure, heart rate and age to identify intracranial lesions and derived a decision instrument.

Results

Of 425 patients, 127 had an intracranial lesion. Patients with a lesion were characterized by higher systolic blood pressure, lower heart rate and higher age (P < 0.0001 for all). A systolic blood pressure ≥ 140 mmHg had an odds ratio (OR) of 3.5 (95% confidence interval [CI] 1.7 to 7.0), and > 170 mmHg had an OR of 8.2 (95% CI 4.5–15.32) for an intracranial lesion (reference: < 140 mmHg). A heart rate < 100 beats/min had an OR of 3.4 (95% CI 2.0 to 6.0, reference: ≥100). Age 50–70 had an OR of 4.1 (95% CI 2.0 to 9.0), and > 70 years had an OR of 10.2 (95% CI 4.8 to 23.2), reference: < 50. Logarithms of ORs were rounded to the nearest integer to create a score with 0–2 points for age and blood pressure and 0–1 for heart rate, with an increasing risk for an intracranial lesion with higher scores. The area under the receiver operating characteristics curve for the instrument was 0.810 (95% CI 0.850–0.890).

Conclusions

An instrument combining systolic blood pressure, heart rate and age may help identify stroke and other intracranial lesions in patients with a decreased level of consciousness in prehospital settings.

Trial registration

Not applicable.
Lausanne medical dispatch centre’s response to COVID-19
Authors: Dami Fabrice , Berthoz Vincent
Published: May 2020

The COVID-19 crisis is an unprecedented event. It is therefore essential for dispatch centres to share their experiences while the crisis is underway, similar to hospitals, so that we will all benefit from feedback.

This letter to the editor describes the Lausanne dispatch centre response to COVID-19 and the lessons learned so far.
Genetics of atrioventricular canal defects
Authors: Pugnaloni Flaminia , Digilio Maria Cristina , Putotto Carolina , De Luca Enrica , Marino Bruno , Versacci Paolo
Published: May 2020

Atrioventricular canal defect (AVCD) represents a quite common congenital heart defect (CHD) accounting for 7.4% of all cardiac malformations. AVCD is a very heterogeneous malformation that can occur as a phenotypical cardiac aspect in the context of different genetic syndromes but also as an isolated, non-syndromic cardiac defect. AVCD has also been described in several pedigrees suggesting a pattern of familiar recurrence. Targeted Next Generation Sequencing (NGS) techniques are proved to be a powerful tool to establish the molecular heterogeneity of AVCD.

Given the complexity of cardiac embryology, it is not surprising that multiple genes deeply implicated in cardiogenesis have been described mutated in patients with AVCD. This review attempts to examine the recent advances in understanding the molecular basis of this complex CHD in the setting of genetic syndromes or in non-syndromic patients.
Microcirculatory perfusion disturbances following cardiopulmonary bypass: a systematic review
Authors: den Os Matthijs M. , van den Brom Charissa E. , van Leeuwen Anoek L. I. , Dekker Nicole A. M.
Published: May 2020

Background

Microcirculatory perfusion disturbances are associated with increased morbidity and mortality in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). Technological advancements made it possible to monitor sublingual microcirculatory perfusion over time. The goal of this review is to provide an overview of the course of alterations in sublingual microcirculatory perfusion following CPB. The secondary goal is to identify which parameter of sublingual microcirculatory perfusion is most profoundly affected by CPB.

Methods

PubMed and Embase databases were systematically searched according to PRISMA guidelines and as registered in PROSPERO. Studies that reported sublingual microcirculatory perfusion measurements before and after onset of CPB in adult patients undergoing cardiac surgery were included. The primary outcome was sublingual microcirculatory perfusion, represented by functional capillary density (FCD), perfused vessel density (PVD), total vessel density (TVD), proportion of perfused vessels (PPV), and microvascular flow index (MFI).

Results

The search identified 277 studies, of which 19 fulfilled all eligibility criteria. Initiation of CPB had a profound effect on FCD, PVD, or PPV. Seventeen studies (89%) reported one or more of these parameters, and in 11 of those studies (65%), there was a significant decrease in these parameters during cardiac surgery; the other 6 studies (35%) reported no effect. In 29% of the studies, FCD, PVD, or PPV normalized by the end of cardiac surgery, and in 24% percent of the studies, this effect lasted at least 24 h. There was no clear effect of CPB on TVD and a mixed effect on MFI.

Conclusion

CPB during cardiac surgery impaired sublingual microcirculatory perfusion as reflected by reduced FCD, PVD, and PPV. Four studies reported this effect at least 24 h after surgery. Further research is warranted to conclude on the duration of CPB-induced microcirculatory perfusion disturbances and the relationship with clinical outcome.

Trial registration

PROSPERO, CRD42019127798
Insecticide susceptibility of the sand fly leishmaniasis vector Phlebotomus argentipes in Sri Lanka
Authors: Pathirage Dulani R. K. , Karunaratne S. H. P. Parakrama , Senanayake Sanath C. , Karunaweera Nadira D.
Published: May 2020

Background

Leishmania donovani-induced and sand fly-transmitted leishmaniasis is a growing health problem in Sri Lanka. Limited knowledge on biological and behavioral characteristics of probable vector Phlebotomus argentipes hinders disease control. Here, insecticide susceptibility patterns of P. argentipes were investigated with exploration of probable underlying resistance mechanisms.

Methods

Adult sand flies were collected using standard cattle baited net traps and CDC light traps from selected sites in four districts. Adult F1 progeny of P. argentipes were exposed to different concentrations of DDT, malathion, deltamethrin and propoxur using WHO susceptibility bioassay kits. Post-1-h knockdown and post-24-h mortality were recorded and analyzed. Metabolic enzyme activity and the sensitivity of the acetylcholinesterase target-site were determined by biochemical assays using wild-caught flies. Extracted fly DNA samples were tested for the presence of knockdown-resistance (kdr) type mutations.

Results

The LC100 values for DDT, malathion, propoxur and deltamethrin were 0.8–1.5%, 0.9–2.0%, 0.017–0.03% and 0.007% respectively. Insecticide-susceptibility levels were higher than the discriminating dosages established for Aedes mosquitoes, except for malathion. The lowest susceptibility levels (except for deltamethrin) were detected in the Mamadala population, whereas the highest levels were detected in the Mirigama population. The percentage of knocked-down sand flies was < 75% at any tested concentration, including those, which exhibited 100% mortality after 24 h. Elevated activity levels of glutathione S-transferase (3%, 7%, 12.5% and 14%) and esterase (2%, 5%, 5.5% and 6.5%) were detected in flies that originated from Mirigama, Pannala, Thalawa and Mamadala respectively, while monooxygenase quantities remained below the cut-off level. Ten to 34.5% of flies were heterozygous for acetylcholinesterases target-site insensitivity, associated with organophosphate and carbamate resistance. Pyrethroid-resistance-associated L1014F kdr-type mutation in the voltage gated sodium channel gene was detected in 30/53 flies.

Conclusions

Populations of P. argentipes in Sri Lanka are largely susceptible to common insecticides, except for malathion (used extensively in the past for malaria control). Their insecticide susceptibility appears negatively associated with past malaria endemicity of the study sites, with signs of early insecticide tolerance. Presence of insecticide target site insensitivity in a notable proportion of flies and enhanced insecticide metabolizing enzyme activities imply potential future challenges for leishmaniasis control, with a call for urgent proactive measures for its containment.
Predominant risk factors for tick-borne co-infections in hunting dogs from the USA
Authors: Mahachi Kurayi , Kontowicz Eric , Anderson Bryan , Toepp Angela J. , Lima Adam Leal , Larson Mandy , Wilson Geneva , Grinnage-Pulley Tara , Bennett Carolyne , Ozanne Marie , Anderson Michael , Fowler Hailie , Parrish Molly , Saucier Jill , Tyrrell Phyllis , Palmer Zachary , Buch Jesse , Chandrashekar Ramaswamy , Scorza Breanna , Brown Grant , Oleson Jacob J. , Petersen Christine A.
Published: May 2020

Background

Both incidence and geographical range of tick-borne disease has increased across the USA. Similar to people, dogs are hosts for Anaplasma spp., Babesia spp., Ehrlichia spp. and Borrelia burgdorferi. Dogs also share our homes and beds, making them both a sentinel for the ticks in our backyards but also increasing our exposure to ticks. Measures to better track, prevent, and/or treat tick-borne diseases in companion animals can lead to better control and prevention of human tick-borne disease. This study identifies demographic and co-infection risk factors for canine seropositivity to tick-borne infections in a cohort of hunting dogs across the USA.

Results

Human patterns of tick-borne disease co-infection in the USA have been predominantly driven by the geographical distribution of the tick vector. Dogs who tested seropositive for Anaplasma spp. were 1.40 times more likely (P = 0.0242) to also test seropositive for Babesia spp. and vice versa (1.60 times more likely, P = 0.0014). Dogs living in the West had 5% lower risk (P = 0.0001) for Ehrlichia spp. seropositivity compared to other regions. Controlling for age and Anaplasma spp. seroprevalence, dogs in all three other regions were 2.30 times more likely (P = 0.0216) to test seropositive for B. burgdorferi than dogs in the West. Dogs seropositive for B. burgdorferi were 1.60 times more likely (P = 0.0473) to be seropositive for Anaplasma spp.

Conclusions

Tick geographical distributions have a prominent impact on the regional distribution of hunting dog exposure to tick-borne diseases. Education concerning regional tick prevalence and disease risk is important for everyone, but particularly dog owners, regarding ticks in their region and protection from infection and co-infection of tick-borne pathogens as they travel or move with their dogs. Dogs are sentinel species for human exposure to ticks, and as such surveillance of canine tick-borne infections and understanding the probability that these infections might be seen together as co-infections helps predict emerging areas where people are more likely to be exposed as well.
Scanning electron microscopy of Onchocerca fasciata (Filarioidea: Onchocercidae) adults, microfilariae and eggs with notes on histopathological findings in camels
Authors: Ghahvei Younes , Mirzaei Mohammad , Hashemnia Shadi , Golchin Mehdi , Kheirandish Reza , Uni Shigehiko , Mendoza-Roldan Jairo Alfonso , Otranto Domenico , Sazmand Alireza
Published: May 2020

Background

Onchocerca fasciatais a prevalent filarial species in camelids of Asia and Africa forming nodules in the skin of dromedary and Bactrian camels. In spite of recent advances in the biology and epidemiology of this nematode species, a relatively scant number of studies have focussed on the morphology of this parasite. The main objective of this study was to describe morphological characteristics of adults, microfilariae and eggs ofO. fasciataby scanning electron microscopy (SEM), staining and histology.

Methods

From April 2016 to March 2017 dromedary camels (n = 456) were inspected for infection withO. fasciatain a slaughterhouse in Kerman (south of Iran). Adult worms in nodules were isolated by digestion of nodules in collagenase and used for SEM. Skin nodules were also fixed, sectioned and stained with hematoxylin and eosin for histopathology. Skin microfilariae that were isolated from tissues surrounding the nodules were confirmed asO. fasciataby sequencing of the cytochromecoxidase subunit 1 (cox1) and12SrRNA genes and used for SEM and Giemsa staining.

Results

Single or multipleO. fasciatanodules (1.2–2.2 cm in diameter and 507–845 mg in weight) were found in 30.3% of the examined camels. SEM analysis helped identify 18 papillae in the caudal region of the male. Discontinuous longitudinal cuticular crests were observed in the posterior region of the male. In female nematodes, the ridges had a rounded shape with a height/width ratio of 7/16 in longitudinal sections. Unsheathed skin microfilariae with a rounded anterior extremity measured 210.7 × 2.5 μm on average. Developed eggs containing microfilariae measured 35.9 × 31.0 μm and their smooth shell surface had characteristic tongue-like appendages. In addition to inflammatory reactions surrounding the parasites, accumulation of intracellular ceroid pigment, golden-yellow to brown in colour, was observed within macrophages upon histopathological examination.

Conclusions

We found longitudinal crests on the surface of the posterior region of the male nematode. Measurements of the main morphological features of microfilariae and eggs, and the shape index of ridges (height/width) in female nematodes are described for the first time.
Divergent domains of 28S ribosomal RNA gene: DNA barcodes for molecular classification and identification of mites
Authors: Zhao Yae , Zhang Wan-Yu , Wang Rui-Ling , Niu Dong-Ling
Published: May 2020

Background

The morphological and molecular identification of mites is challenging due to the large number of species, the microscopic size of the organisms, diverse phenotypes of the same species, similar morphology of different species and a shortage of molecular data.

Methods

Nine medically important mite species belonging to six families, i.e.Demodex folliculorum,D. brevis,D. canis,D. caprae,Sarcoptes scabiei canis,Psoroptes cuniculi,Dermatophagoides farinae,Cheyletus malaccensisandOrnithonyssus bacoti, were collected and subjected to DNA barcoding. Sequences ofcox1,16Sand12SmtDNA, as well as ITS,18Sand28SrDNA from mites were retrieved from GenBank and used as candidate genes. Sequence alignment and analysis identified28SrDNA as the suitable target gene. Subsequently, universal primers of divergent domains were designed for molecular identification of 125 mite samples. Finally, the universality of the divergent domains with high identification efficiency was evaluated in Acari to screen DNA barcodes for mites.

Results

Domains D5 (67.65%), D6 (62.71%) and D8 (77.59%) of the28SrRNA gene had a significantly higher sequencing success rate, compared to domains D2 (19.20%), D3 (20.00%) and D7 (15.12%). The successful divergent domains all matched the closely-related species in GenBank with an identity of 74–100% and a coverage rate of 92–100%. Phylogenetic analysis also supported this result. Moreover, the three divergent domains had their own advantages. D5 had the lowest intraspecies divergence (0–1.26%), D6 had the maximum barcoding gap (10.54%) and the shortest sequence length (192–241 bp), and D8 had the longest indels (241 bp). Further universality analysis showed that the primers of the three divergent domains were suitable for identification across 225 species of 40 families in Acari.

Conclusions

This study confirmed that domains D5, D6 and D8 of28SrDNA are universal DNA barcodes for molecular classification and identification of mites.28SrDNA, as a powerful supplement forcox1 mtDNA 5’-end 648-bp fragment, recommended by the International Barcode of Life (IBOL), will provide great potential in molecular identification of mites in future studies because of its universality.
Effectiveness of a modified group cognitive behavioral therapy program for anxiety in children with ASD delivered in a community context
Authors: Solish Abbie , Klemencic Nora , Ritzema Anne , Nolan Vicki , Pilkington Martha , Anagnostou Evdokia , Brian Jessica
Published: May 2020

Background

Youth with autism spectrum disorder (ASD) experience high rates (approximately 50–79%) of comorbid anxiety problems. Given the significant interference and distress that excessive anxiety can cause, evidence-based intervention is necessary in order to reduce long-term negative effects. Cognitive behavioral therapy (CBT) has demonstrated efficacy for treating anxiety disorders across the lifespan, both in individual and group formats. Recently, modified CBT programs for youth with ASD have been developed, showing positive outcomes. To date, these modified CBT programs have primarily been evaluated in controlled research settings.

Methods

The current community effectiveness study investigated the effectiveness of a modified group CBT program (Facing Your Fears) delivered in a tertiary care hospital and across six community-based agencies providing services for youth with ASD. Data were collected over six years (N= 105 youth with ASD; ages 6–15 years).

Results

Hospital and community samples did not differ significantly, except in terms of age (hospitalM= 10.08 years; communityM= 10.87 years). Results indicated significant improvements in anxiety levels from baseline to post-treatment across measures, with medium effect sizes. An attempt to uncover individual characteristics that predict response to treatment was unsuccessful.

Conclusions

Overall, this study demonstrated that community implementation of a modified group CBT program for youth with ASD is feasible and effective for treating elevated anxiety.
Quantitative prediction of selectivity between the A1 and A2A adenosine receptors
Authors: Burggraaff Lindsey , van Vlijmen Herman W. T. , IJzerman Adriaan P. , van Westen Gerard J. P.
Published: May 2020

The development of drugs is often hampered due to off-target interactions leading to adverse effects. Therefore, computational methods to assess the selectivity of ligands are of high interest. Currently, selectivity is often deduced from bioactivity predictions of a ligand for multiple targets (individual machine learning models). Here we show that modeling selectivity directly, by using the affinity difference between two drug targets as output value, leads to more accurate selectivity predictions. We test multiple approaches on a dataset consisting of ligands for the A1 and A2A adenosine receptors (among others classification, regression, and we define different selectivity classes). Finally, we present a regression model that predicts selectivity between these two drug targets by directly training on the difference in bioactivity, modeling the selectivity-window. The quality of this model was good as shown by the performances for fivefold cross-validation: ROC A1AR-selective 0.88 ± 0.04 and ROC A2AAR-selective 0.80 ± 0.07. To increase the accuracy of this selectivity model even further, inactive compounds were identified and removed prior to selectivity prediction by a combination of statistical models and structure-based docking. As a result, selectivity between the A1 and A2A adenosine receptors was predicted effectively using the selectivity-window model. The approach presented here can be readily applied to other selectivity cases.
Proteomic analysis revealed T cell hyporesponsiveness induced by Haemonchus contortus excretory and secretory proteins
Authors: Lu Mingmin , Tian Xiaowei , Yang Zhang , Wang Wenjuan , Tian Ai-Ling , Li Charles , Yan Ruofeng , Xu Lixin , Song Xiaokai , Li Xiangrui
Published: May 2020

Haemonchus contortus has evolved highly integrated and sophisticated mechanisms to promote coexistence with hosts. The excretory-secretory (ES) products generated by this parasite contribute to the regulation of the host immune response to facilitate immune evasion and induce chronicity, but the proteins responsible for this process and the exact cellular mechanisms have yet to be defined. In this study, we identified 114 H. contortus ES proteins (HcESPs) interacting with host T cells and 15 T cell binding receptors via co-immunoprecipitation and shotgun liquid chromatography-tandem mass spectrometry analysis. Based on bioinformatics analysis, we demonstrated that HcESPs could inhibit T cell viability, induce cell apoptosis, suppress T cell proliferation and cause cell cycle arrest. Furthermore, the stimulation of HcESPs exerted critical control effects on T cell cytokine production profiles, predominantly promoting the secretion of interleukin (IL)-10, IL-17A and transforming growth factor-β1 and inhibiting IL-2, IL-4 and interferon-γ production. Collectively, these findings may provide insights into the interaction between ES proteins and key host effector cells, enhancing our understanding of the molecular mechanism underlying parasite immune evasion and providing new clues for novel vaccine development.
Stability analysis by fixed point theorems for a class of non-linear Caputo nabla fractional difference equation
Authors: Butt Rabia Ilyas , Abdeljawad Thabet , ur Rehman Mujeeb
Published: May 2020

Fractional difference equations have become important due to their qualitative properties and applications in discrete modeling. Stability analysis of solutions is one of the most widely used qualitative properties with tremendous applications. In this paper, we investigate the existence and stability results for a class of non-linear Caputo nabla fractional difference equations. To obtain the existence and stability results, we use Schauder’s fixed point theorem, the Banach contraction principle and Krasnoselskii’s fixed point theorem. The analysis of the theoretical results depends on the structure of nabla discrete Mittag-Leffler functions. An example is provided to illustrate the theoretical results.
Chaotic triopoly game: a congestion case
Authors: Askar S. S. , Al-khedhairi A.
Published: May 2020

In this paper, we propose a simple network consisting of only two nodes and two paths. The first node, which is called the source, has three competing firms that send their quantities of load via the two paths to the second node, called the destination node. The static game that describes the reaction among the three firms is constructed. The Nash equilibrium point of the static game is discussed. Assuming a gradient firm based rule we investigate the dynamic game which has the same Nash equilibrium as in the static game. The local stability conditions of the Nash equilibrium are obtained in terms of the reactivity parameters among the firms and the nonlinear costs functions adopted by those firms. The obtained results are supported by a numerical simulation that in turn gives routes where Nash equilibrium may lose its stability. The simulation shows that Nash equilibrium loses its stability via flip and fold bifurcations and then chaos exists.