bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcriptomics- and metabolomics-based integration analyses revealed the potential pharmacological effects and functional pattern of in vivo Radix Paeoniae Alba administration
Authors: Wang Sining , Chen Huihua , Zheng Yufan , Li Zhenyu , Cui Baiping , Zhao Pei , Zheng Jiali , Lu Rong , Sun Ning
Published: May 2020

Background

Radix Paeoniae Alba (RPA) and other natural medicines have remarkable curative effects and are widely used in traditional Chinese Medicine (TCM). However, due to their multi-component and multi-target characteristics, it is difficult to study the detailed pharmacological mechanisms for those natural medicines in vivo. Therefore, their real effects on organisms is still uncertain.

Methods

RPA was selected as research object, the present study was designed to study the complex mechanisms of RPA in vivo by integrating and interpreting the transcriptomic based RNA-seq and metabolomic based NMR spectrum after RPA administration in mice. A variety of dimension-reduction algorithms and classifier models were applied to the processing of high-throughput data.

Results

Among serum metabolites, the contents of PC and glucose were significantly increased, while the contents of various amino acids, lipids and their metabolites were significantly decreased in mice after RPA administration. Based on the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, differential analysis showed that the liver was the site where RPA exerted a significant effect, which confirmed the rationality of “meridian tropism” in the theory in TCM. In addition, RPA played a role in lipid metabolism by regulating genes encoding enzymes of the glycerolipid metabolism pathway, such as 1-acyl-sn-glycerol-3-phosphate acyltransferase (Agpat), phosphatidate phosphatase (Lpin), phospholipid phosphatase (Plpp) and endothelial lipase (Lipg). We also found that RPA regulates several substance addiction pathways in the brain, such as the cocaine addiction pathway, and the related targets were predicted based on the sequencing data from pathological model in the GEO database. The overall effective pattern of RPA was intuitively presented with a multidimensional radar map through a self-designed model which found that liver and brain were mainly regulated by RPA compared with the traditional meridian tropism theory.

Conclusions

Overall this study expanded the potential application of RPA and provided possible targets and directions for further mechanism study, meanwhile, it also established a multi-dimensional evaluation model to represent the overall effective pattern of TCM for the first time. In the future, such study based on the high-throughput data sets can be used to interpret the theory of TCM and to provide a valuable research model and clinical medication reference for the TCM researchers and doctors.
Prophylactic treatment of rapamycin ameliorates naturally developing and episode -induced heterotopic ossification in mice expressing human mutant ACVR1
Authors: Maekawa Hirotsugu , Kawai Shunsuke , Nishio Megumi , Nagata Sanae , Jin Yonghui , Yoshitomi Hiroyuki , Matsuda Shuichi , Toguchida Junya
Published: May 2020

Background

Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal-dominant disease characterized by heterotopic ossification (HO) in soft tissues and caused by a mutation of the ACVR1A/ALK2 gene. Activin-A is a key molecule for initiating the process of HO via the activation of mTOR, while rapamycin, an mTOR inhibitor, effectively inhibits the Activin-A-induced HO. However, few reports have verified the effect of rapamycin on FOP in clinical perspectives.

Methods

We investigated the effect of rapamycin for different clinical situations by using mice conditionally expressing human mutant ACVR1A/ALK2 gene. We also compared the effect of rapamycin between early and episode-initiated treatments for each situation.

Results

Continuous, episode-independent administration of rapamycin reduced the incidence and severity of HO in the natural course of FOP mice. Pinch-injury induced HO not only at the injured sites, but also in the contralateral limbs and provoked a prolonged production of Activin-A in inflammatory cells. Although both early and injury-initiated treatment of rapamycin suppressed HO in the injured sites, the former was more effective at preventing HO in the contralateral limbs. Rapamycin was also effective at reducing the volume of recurrent HO after the surgical resection of injury-induced HO, for which the early treatment was more effective.

Conclusion

Our study suggested that prophylactic treatment will be a choice of method for the clinical application of rapamycin for FOP.
Causes and risk factors for common mental illnesses: the beliefs of paediatric hospital staff in the United Arab Emirates
Authors: Slewa-Younan Shameran , Nguyen Thomas P. , Al-Yateem Nabeel , Rossiter Rachel Cathrine , Robb Walter
Published: May 2020

Background

Children and adolescents with chronic physical health conditions are vulnerable to poor mental health outcomes. The measurement of mental health literacy of health professionals working with such populations is important because of their role in promoting early and appropriate help-seeking. This study sought to determine the beliefs regarding the causes of and risks factors for three types of mental illnesses amongst health professionals in United Arab Emirates.

Method

A culturally validated mental health literacy survey presenting three vignettes of fictional characters meeting diagnostic criteria for posttraumatic stress disorder, depression with suicidal thoughts and psychosis was distributed. The survey measured health care professionals’ beliefs regarding the causes of and risk factors for these disorders.

Results

A total of 317 health care professional (> 90% nurses) were surveyed from across the UAE. Although 43.8% correctly endorsed exposure to a ‘traumatic event’ as the most likely cause for developing posttraumatic stress disorder, there was a more limited understanding of the contribution of biopsychosocial factors to the development of the mental illness, particularly for psychosis. Participant socio-demographic variables were associated with attributions of religious or spiritual beliefs and personal weakness as causal and/or vulnerability factors in the development of depression with suicidal thoughts and psychosis.

Conclusions

Efforts to improve mental health systems and health care providers in UAE and other similar Middle Eastern countries requires targeted mental health literacy programs that seek to integrate biopsychosocial models of mental illness and their treatment with the positive aspects of religious and cultural beliefs that are dominant in this region.
Emerging therapeutic agents for advanced non-small cell lung cancer
Authors: Chen Ruqin , Manochakian Rami , James Lauren , Azzouqa Abdel-Ghani , Shi Huashan , Zhang Yan , Zhao Yujie , Zhou Kexun , Lou Yanyan
Published: May 2020

Advanced non-small cell lung cancer (NSCLC) is the most common type of lung cancer, with a poor prognosis and no known cure. Survival time is often short because of limited treatment options. Recent advances in targeted therapy and immunotherapy have changed the landscape for the treatment of advanced NSCLC. In the last 10 years, the US Food and Drug Administration (FDA) has approved more than 17 new medications for this devastating disease and more are coming. Molecular and immunogenic testing makes personalized medicine possible for patients with advanced NSCLC. The new medications provide promising efficacy and safety resulting in improved long-term survival for a significant number of patients. In this review, we summarize the recent advances in advanced/metastatic NSCLC therapeutics with a specific focus on first in-human or early-phase I/II clinical trials. These drugs either offer better alternatives to current standard drugs in the same class or are a completely new class of drugs with novel mechanisms of action. Advances are divided into (1) targeted agents, (2) antibody-drug conjugates, and (3) immunotherapies. Finally, we present a brief review of the emerging agents and ongoing clinical studies.
RNA-binding protein MSI2 isoforms expression and regulation in progression of triple-negative breast cancer
Authors: Li Ming , Li An-qi , Zhou Shu-ling , Lv Hong , Wei Ping , Yang Wen-tao
Published: May 2020

Background

The RNA-binding protein Musashi-2 (MSI2) has been implicated in the tumorigenesis and tumor progression of some human cancers. MSI2 has also been reported to suppress tumor epithelial-to-mesenchymal transition (EMT) progression in breast cancer, and low MSI2 expression is associated with poor outcomes for breast cancer patients; however, the underlying mechanisms have not been fully investigated. This study investigated the expression and phenotypic functions of two major alternatively spliced MSI2 isoforms (MSI2a and MSI2b) and the potential molecular mechanisms involved in triple-negative breast cancer (TNBC) progression.

Methods

The Illumina sequencing platform was used to analyze the mRNA transcriptomes of TNBC and normal tissues, while quantitative reverse transcription-polymerase chain reaction and immunohistochemistry validated MSI2 isoform expression in breast cancer tissues. The effects of MSI2a and MSI2b on TNBC cells were assayed in vitro and in vivo. RNA immunoprecipitation (RIP) and RNA sequencing were performed to identify the potential mRNA targets of MSI2a, and RIP and luciferase analyses were used to confirm the mRNA targets of MSI2.

Results

MSI2 expression in TNBC tissues was significantly downregulated compared to that in normal tissues. In TNBC, MSI2a expression was associated with poor overall survival of patients. MSI2a overexpression in vitro and in vivo inhibited TNBC cell invasion as well as extracellular signal-regulated kinase 1/2 (ERK1/2) activity. However, MSI2b overexpression had no significant effects on TNBC cell migration. Mechanistically, MSI2a expression promoted TP53INP1 mRNA stability by its interaction with the 3′-untranslated region of TP53INP1 mRNA. Furthermore, TP53INP1 knockdown reversed MSI2a-induced suppression of TNBC cell invasion, whereas ectopic expression of TP53INP1 and inhibition of ERK1/2 activity blocked MSI2 knockdown-induced TNBC cell invasion.

Conclusions

The current study demonstrated that MSI2a is the predominant functional isoform of MSI2 proteins in TNBC, that its downregulation is associated with TNBC progression and poor prognosis and that MSI2a expression inhibited TNBC invasion by stabilizing TP53INP1 mRNA and inhibiting ERK1/2 activity. Overall, our study provides new insights into the isoform-specific roles of MSI2a and MSI2b in the tumor progression of TNBC, allowing for novel therapeutic strategies to be developed for TNBC.
A systematic review of biomarkers multivariately associated with acute respiratory distress syndrome development and mortality
Authors: van der Zee Philip , Rietdijk Wim , Somhorst Peter , Endeman Henrik , Gommers Diederik
Published: May 2020

Background

Heterogeneity of acute respiratory distress syndrome (ARDS) could be reduced by identification of biomarker-based phenotypes. The set of ARDS biomarkers to prospectively define these phenotypes remains to be established.

Objective

To provide an overview of the biomarkers that were multivariately associated with ARDS development or mortality.

Data sources

We performed a systematic search in Embase, MEDLINE, Web of Science, Cochrane CENTRAL, and Google Scholar from inception until 6 March 2020.

Study selection

Studies assessing biomarkers for ARDS development in critically ill patients at risk for ARDS and mortality due to ARDS adjusted in multivariate analyses were included.

Data extraction and synthesis

We included 35 studies for ARDS development (10,667 patients at risk for ARDS) and 53 for ARDS mortality (15,344 patients with ARDS). These studies were too heterogeneous to be used in a meta-analysis, as time until outcome and the variables used in the multivariate analyses varied widely between studies. After qualitative inspection, high plasma levels of angiopoeitin-2 and receptor for advanced glycation end products (RAGE) were associated with an increased risk of ARDS development. None of the biomarkers (plasma angiopoeitin-2, C-reactive protein, interleukin-8, RAGE, surfactant protein D, and Von Willebrand factor) was clearly associated with mortality.

Conclusions

Biomarker data reporting and variables used in multivariate analyses differed greatly between studies. Angiopoeitin-2 and RAGE in plasma were positively associated with increased risk of ARDS development. None of the biomarkers independently predicted mortality. Therefore, we suggested to structurally investigate a combination of biomarkers and clinical parameters in order to find more homogeneous ARDS phenotypes.

PROSPERO identifier

PROSPERO, CRD42017078957
Hemophagocytic lymphohistiocytosis in critically ill patients: diagnostic reliability of HLH-2004 criteria and HScore
Authors: Knaak Cornelia , Nyvlt Peter , Schuster Friederike S. , Spies Claudia , Heeren Patrick , Schenk Thomas , Balzer Felix , La Rosée Paul , Janka Gritta , Brunkhorst Frank M. , Keh Didier , Lachmann Gunnar
Published: May 2020

Background

Hemophagocytic lymphohistiocytosis (HLH) is a rare though often fatal hyperinflammatory syndrome mimicking sepsis in the critically ill. Diagnosis relies on the HLH-2004 criteria and HScore, both of which have been developed in pediatric or adult non-critically ill patients, respectively. Therefore, we aimed to determine the sensitivity and specificity of HLH-2004 criteria and HScore in a cohort of adult critically ill patients.

Methods

In this further analysis of a retrospective observational study, patients ≥ 18 years admitted to at least one adult ICU at Charité – Universitätsmedizin Berlin between January 2006 and August 2018 with hyperferritinemia of ≥ 500 μg/L were included. Patients’ charts were reviewed for clinically diagnosed or suspected HLH. Receiver operating characteristics (ROC) analysis was performed to determine prediction accuracy.

Results

In total, 2623 patients with hyperferritinemia were included, of whom 40 patients had HLH. We found the best prediction accuracy of HLH diagnosis for a cutoff of 4 fulfilled HLH-2004 criteria (95.0% sensitivity and 93.6% specificity) and HScore cutoff of 168 (100% sensitivity and 94.1% specificity). By adjusting HLH-2004 criteria cutoffs of both hyperferritinemia to 3000 μg/L and fever to 38.2 °C, sensitivity and specificity increased to 97.5% and 96.1%, respectively. Both a higher number of fulfilled HLH-2004 criteria [OR 1.513 (95% CI 1.372–1.667); p <  0.001] and a higher HScore [OR 1.011 (95% CI 1.009–1.013); p <  0.001] were significantly associated with in-hospital mortality.

Conclusions

An HScore cutoff of 168 revealed a sensitivity of 100% and a specificity of 94.1%, thereby providing slightly superior diagnostic accuracy compared to HLH-2004 criteria. Both HLH-2004 criteria and HScore proved to be of good diagnostic accuracy and consequently might be used for HLH diagnosis in critically ill patients.

Clinical trial registration

The study was registered with www.ClinicalTrials.gov (NCT02854943) on August 1, 2016.
The Disruptive bEhavior manageMEnt ANd prevention in hospitalized patients using a behaviORal intervention team (DEMEANOR) study protocol: a pragmatic, cluster, crossover trial
Authors:   for the Vanderbilt Learning Healthcare System Investigators, Vanderbilt University, Morrison Jay , Hasselblad Michele , Kleinpell Ruth , Buie Reagan , Ariosto Deborah , Hardiman Erin , Osborn Stephen W. , Lindsell Christopher J.
Published: May 2020

Background

Disruptive behavior in hospitalized patients has become a priority area of safety concern for clinical staff, and also has consequences for patient management and hospital course. Proactive screening and intervention of patients with behavioral comorbidities has been reported to reduce disruptive behavior in some settings, but it has not been studied in a rigorous way.

Methods

The Disruptive bEhavior manageMEnt ANd prevention in hospitalized patients using a behaviORal intervention team (DEMEANOR) study is a pragmatic, cluster, crossover trial that is being conducted. Each month, the behavioral intervention team, comprising a psychiatric-mental health advanced practice nurse and a clinical social worker, with psychiatrist consultation as needed, rotates between an adult medicine unit and a mixed cardiac unit at Vanderbilt University Medical Center in Nashville, TN, USA. The team proactively screens patients upon admission, utilizing a protocol which includes a comprehensive chart review and, if indicated, a brief interview, seeking to identify those patients who possess risk factors indicative of either a potential psychological barrier to their own clinical progress or a potential risk for exhibiting disruptive, aggressive, or self-injurious behavior during their hospitalization. Once identified, the team provides interventions aimed at mitigating these risks, educates and supports the patient care teams (nurses, physicians, and others), and assists non-psychiatric staff in the management of patients who require behavioral healthcare. Patients who are both admitted to and discharged from either unit are included in the study. Anticipated enrollment is approximately 1790 patients. The two primary outcomes are (1) a composite of objective measures related to the patients’ disruptive, threatening, or acting out behaviors, and (2) staff self-reported comfort with and confidence in their ability to manage patients exhibiting disruptive, threatening, or acting out behavior. Secondary outcomes include patient length of stay, patient attendant (sitter) use, and the unit nursing staff retention.

Discussion

This ongoing trial will provide evidence on the real-world effectiveness of a proactive behavioral intervention to prevent disruptive, threatening, or acting out events in adult hospitalized patients.

Trial registration

ClinicalTrials.gov: NCT03777241. Registered on 14 December 2018.
The effectiveness of an electronic pain management programme for the working population with chronic pain: study protocol for a randomized controlled trial
Authors: Tang Shuk Kwan , Tse Mimi Mun Yee , Leung Sau Fong , Fotis Theofanis
Published: May 2020

Background

Chronic pain is highly prevalent in the working population. People tend to attempt self-initiated treatments to manage their pain. The self-efficacy of behavioural change is a suitable model for guiding the development of an electronic pain management programme (ePain). The aim in this study is to develop ePain and to evaluate its effectiveness at improving pain self-efficacy, reducing pain intensity and negative emotions, and increasing quality of life.

Methods

This study will be a randomized controlled trial. ePain will take the form of a 6-week online pain management programme. Participants will be aged 15 years or above, have chronic pain, and be employed. They must complete the baseline questionnaire and will be randomized into intervention and control groups. They will receive notifications to encourage their participation in ePain and complete the evaluation questionnaires. They will complete the process evaluation at week 3, the post assessment at week 6, and the follow-up assessment at week 12. The study will focus on pain self-efficacy; pain situations; negative emotions including levels of depression, anxiety, and stress; and quality of life. The participants’ opinions of ePain will be collected as feedback. Data will be analysed on an intention-to-treat basis and generalized estimating equations will be used to investigate the time-averaged difference and differences at each follow-up time.

Discussion

The study will provide information about the pain situations of online users in the working population. The participants will benefit from improvements in pain self-efficacy, pain situations, emotional status, and quality of life. The study will illustrate whether online learning is an effective intervention for improving the pain self-efficacy of the working population.

Trial registration

ClinicalTrials.gov, NCT03718702. Registered on 23 October 2018.
Comparison of blogshots with plain language summaries of Cochrane systematic reviews: a qualitative study and randomized trial
Authors: Buljan Ivan , Tokalić Ružica , Roguljić Marija , Zakarija-Grković Irena , Vrdoljak Davorka , Milić Petra , Puljak Livia , Marušić Ana
Published: May 2020

Background

Cochrane, an organization dedicated to the production and dissemination of high-quality evidence on health, endeavors to reach consumers by developing appropriate summary formats of its systematic reviews. However, the optimal type of presentation of evidence to consumers is still unknown.

Objective

The aim of this study was to investigate consumer preferences for different summary formats of Cochrane systematic reviews (CSRs), using both qualitative and quantitative approaches.

Methods

Initially, we conducted three focus groups with medical students (n = 7), doctors (n = 4), and patients (n = 9) in 2017 to explore their health information search habits and preferences for CSR summary formats. Based on those findings, we conducted a randomized trial with medical students at the University of Split School of Medicine, Croatia, and with patients from three Dalmatian family practices to determine whether they prefer CSR blogshots (n = 115) or CSR plain language summaries (PLSs; n = 123).

Results

Participants in the focus groups favored brief and explicit CSR summary formats with fewer numbers. Although we found no difference in participants’ preferences for a specific summary format in the overall sample, subgroup analysis showed that patients preferred blogshots over PLSs in comparison to medical students (P = 0.003, eta squared effect size η2 = 0.04).

Conclusion

CSR summaries should be produced in a format that meets the expectations and needs of consumers. Use of blogshots as a summary format could enhance the dissemination of CSRs among patients.

Trial registration

The trial was registered in ClinicalTrials.gov, NCT03542201. Registered on May 31st 2018.
Interactions between Schistosoma haematobium group species and their Bulinus spp. intermediate hosts along the Niger River Valley
Authors: Pennance Tom , Allan Fiona , Emery Aidan , Rabone Muriel , Cable Jo , Garba Amadou Djirmay , Hamidou Amina Amadou , Webster Joanne P. , Rollinson David , Webster Bonnie L.
Published: May 2020

Background

Urogenital schistosomiasis, caused by infection with Schistosoma haematobium, is endemic in Niger but complicated by the presence of Schistosoma bovis, Schistosoma curassoni and S. haematobium group hybrids along with various Bulinus snail intermediate host species. Establishing the schistosomes and snails involved in transmission aids disease surveillance whilst providing insights into snail-schistosome interactions/compatibilities and biology.

Methods

Infected Bulinus spp. were collected from 16 villages north and south of the Niamey region, Niger, between 2011 and 2015. From each Bulinus spp., 20–52 cercariae shed were analysed using microsatellite markers and a subset identified using the mitochondrial (mt) cox1 and nuclear ITS1 + 2 and 18S DNA regions. Infected Bulinus spp. were identified using both morphological and molecular analysis (partial mt cox1 region).

Results

A total of 87 infected Bulinus from 24 sites were found, 29 were molecularly confirmed as B. truncatus, three as B. forskalii and four as B. globosus. The remaining samples were morphologically identified as B. truncatus (n = 49) and B. forskalii (n = 2). The microsatellite analysis of 1124 cercariae revealed 186 cercarial multilocus genotypes (MLGs). Identical cercarial genotypes were frequently (60%) identified from the same snail (clonal populations from a single miracidia); however, several (40%) of the snails had cercariae of different genotypes (2–10 MLG’s) indicating multiple miracidial infections. Fifty-seven of the B. truncatus and all of the B. forskalii and B. globosus were shedding the Bovid schistosome S. bovis. The other B. truncatus were shedding the human schistosomes, S. haematobium (n = 6) and the S. haematobium group hybrids (n = 13). Two B. truncatus had co-infections with S. haematobium and S. haematobium group hybrids whilst no co-infections with S. bovis were observed.

Conclusions

This study has advanced our understanding of human and bovid schistosomiasis transmission in the Niger River Valley region. Human Schistosoma species/forms (S. haematobium and S. haematobium hybrids) were found transmitted only in five villages whereas those causing veterinary schistosomiasis (S. bovis), were found in most villages. Bulinus truncatus was most abundant, transmitting all Schistosoma species, while the less abundant B. forskalii and B. globosus, only transmitted S. bovis. Our data suggest that species-specific biological traits may exist in relation to co-infections, snail-schistosome compatibility and intramolluscan schistosome development.
Epigenetic deregulation of lamina-associated domains in Hutchinson-Gilford progeria syndrome
Authors: Köhler Florian , Bormann Felix , Raddatz Günter , Gutekunst Julian , Corless Samuel , Musch Tanja , Lonsdorf Anke S. , Erhardt Sylvia , Lyko Frank , Rodríguez-Paredes Manuel
Published: May 2020

Background

Hutchinson-Gilford progeria syndrome (HGPS) is a progeroid disease characterized by the early onset of age-related phenotypes including arthritis, loss of body fat and hair, and atherosclerosis. Cells from affected individuals express a mutant version of the nuclear envelope protein lamin A (termed progerin) and have previously been shown to exhibit prominent histone modification changes.

Methods

Here, we analyze the possibility that epigenetic deregulation of lamina-associated domains (LADs) is involved in the molecular pathology of HGPS. To do so, we studied chromatin accessibility (Assay for Transposase-accessible Chromatin (ATAC)-see/-seq), DNA methylation profiles (Infinium MethylationEPIC BeadChips), and transcriptomes (RNA-seq) of nine primary HGPS fibroblast cell lines and six additional controls, two parental and four age-matched healthy fibroblast cell lines.

Results

Our ATAC-see/-seq data demonstrate that primary dermal fibroblasts from HGPS patients exhibit chromatin accessibility changes that are enriched in LADs. Infinium MethylationEPIC BeadChip profiling further reveals that DNA methylation alterations observed in HGPS fibroblasts are similarly enriched in LADs and different from those occurring during healthy aging and Werner syndrome (WS), another premature aging disease. Moreover, HGPS patients can be stratified into two different subgroups according to their DNA methylation profiles. Finally, we show that the epigenetic deregulation of LADs is associated with HGPS-specific gene expression changes.

Conclusions

Taken together, our results strongly implicate epigenetic deregulation of LADs as an important and previously unrecognized feature of HGPS, which contributes to disease-specific gene expression. Therefore, they not only add a new layer to the study of epigenetic changes in the progeroid syndrome, but also advance our understanding of the disease’s pathology at the cellular level.
Metabolic syndrome is associated with better quality of sleep in the oldest old: results from the “Mugello Study”
Authors:   the Mugello Study Working Group, Laudisio Alice , Giovannini Silvia , Finamore Panaiotis , Navarini Luca , Margiotta Domenico Paolo Emanuele , Vannetti Federica , Macchi Claudio , Coraci Daniele , Imbimbo Isabella , Molino-Lova Raffaello , Loreti Claudia , Antonelli Incalzi Raffaele , Zuccalà Giuseppe , Padua Luca
Published: May 2020

Background and aims

Reduced sleep quality is common in advanced age. Poor sleep quality is associated with adverse outcomes, chiefly cardiovascular, in young and middle-aged subjects, possibly because of its association with metabolic syndrome (MetS). However, the correlates of sleep quality in oldest populations are unknown. We evaluated the association of sleep quality with MetS in a cohort of subjects aged 90+.

Methods and results

We analysed data of 343 subjects aged 90+ living in the Mugello area (Tuscany, Italy). Quality of sleep was assessed using the Pittsburgh Sleep Quality Assessment Index (PSQI). Good quality of sleep was defined by a PSQI score < 5. MetS was diagnosed according to the National Cholesterol Education Program’s ATP-III criteria; 83 (24%) participants reported good quality of sleep. MetS was diagnosed in 110 (24%) participants. In linear and logistic models, MetS was inversely associated with PSQI score ((B = − 1.04; 95% CI − 2.06 to − .03; P = .044), with increased probability of good sleep quality (OR = 2.52; 95% CI 1.26–5.02; P = .009), and with a PSQI below the median (OR = 2.11; 95% CI 1.11–3.40, P = .022), after adjusting. None of the single components of MetS were associated with PSQI (all P values > .050). However, an increasing number of MetS components was associated with increasing probability of good quality of sleep (P for trend = .002), and of PSQI below the median (P for trend = .007). Generalized Additive Model analysis documented no smoothing function suggestive of nonlinear association between PSQI and MetS.

Conclusion

Our results confirm a high prevalence of poor sleep quality in oldest age; however, in these subjects, MetS seems to be associated with better sleep quality. Additional larger, dedicated studies are required to confirm our results, and, if so, to identify the subsystems involved and the potential therapeutic implications of such an association.
Phenotyping individuals with newly-diagnosed type 2 diabetes at risk for all-cause mortality: a single centre observational, prospective study
Authors: Biancalana Edoardo , Parolini Federico , Mengozzi Alessandro , Solini Anna
Published: May 2020

Background

Type 2 diabetes (T2D) shows a high mortality rate, dependent on disease duration, comorbidities and glucose control over time. Data on patients with short disease duration are scanty.

Methods

We prospectively followed a cohort of newly-diagnosed T2D patients referring to a single diabetes centre, treated according to the international guidelines and checked every 6–12 months. All-cause mortality and major cardiovascular (CV) events were registered.

Results

289 patients out of 3019 consecutive first attendances matched inclusion criteria and were included in the observation. Mean follow-up was 51.2 months. At 31 December 2018, 253 patients were alive and 36 deceased. At baseline, deceased individuals were older, with lower eGFR and lower uric acid, higher prevalence of atrial fibrillation. During the follow-up, 18 non-fatal CV events were adjudicated; patients with incident CV disease (CVD) differed at baseline for sex, previous history of CVD and retinopathy, higher use of secretagogues and lower use of metformin. At multivariate analysis, age and previous CVD were the only independent determinants of all-cause mortality and incident CVD, respectively. In deceased individuals, eGFR slope was markedly unstable and ΔeGFR at the end of the follow-up was higher (p < 0.001), and predicted mortality.

Conclusion

Newly-diagnosed T2D patients followed according to the best clinical practice show a mortality rate similar to that reported in more complicated patients with longer disease duration; none of the clinical and biochemical variables commonly measured at baseline can predict mortality or incident CVD; early metformin use seems to be associated with no risk of prevalent or incident retinopathy.
Study on biodegradation kinetics of di-2-ethylhexyl phthalate by newly isolated halotolerant Ochrobactrum anthropi strain L1-W
Authors: Nshimiyimana Jean Bosco , Khadka Sujan , Zou Piao , Adhikari Sanjib , Proshad Ram , Thapa Alina , Xiong Li
Published: May 2020

Objective

Di-2-ethylhexyl phthalate (DEHP) pollution is one of the major environmental concerns all over the world. This research aimed at studying the biodegradation kinetics of DEHP by a newly isolated bacterial strain. Water and sediment samples were collected from Wuhan South Lake and potent bacterial isolates were screened for DEHP degradation, characterized by biochemical, physiological, morphological and 16S rDNA gene sequencing, and optimized under suitable pH, temperature, NaCl and DEHP concentrations. DEHP and its metabolites were quantified by High Performance Liquid Chromatography and their degradation kinetics were studied.

Results

The newly isolated bacterium was identified as Ochrobactrum anthropi strain L1-W with 99.63% similarity to Ochrobactrum anthropi ATCC 49188. It was capable of utilizing DEHP as the carbon source. The optimum growth temperature, pH, DEHP and NaCl concentration for the strain L1-W were 30 °C, 6, 400 mg/L and 10 g/L respectively. Strain L1-W was capable of degrading almost all (98.7%) of DEHP when the initial concentration was 200 mg/L within a period of 72 h. Besides, it was also found capable of degrading five other phthalates, thus making it a possible candidate for bioremediation of phthalates in the environmental settings.
Structure-based screening of chemical libraries to identify small molecules that are likely to bind with the SET and RING-associated (SRA) domain of Ubiquitin-like, PHD and Ring Finger-containing 1 (UHRF1)
Authors: Patnaik Debasis
Published: May 2020

Objectives

UHRF1 is a multi-domain protein that recognizes both histone and DNA modification marks on chromatin. UHRF1 is involved in various cellular processes that lead to tumorigenesis and thus attracted considerable attention as a potential anti-cancer drug target. The SRA domain is a unique to the UHRF family. SRA domain recognizes 5-methylcytosine in hemimethylated DNA and necessary for maintenance DNA methylation mediated by DNMT1. Small molecules capable of interacting with the SRA domain may reduce aberrant methylation levels by preventing the interaction of 5-methylcytosine with the SRA domain and thereby blocking substrate access to the catalytic center of DNMT1. The data were collected to identify and predict an initial set of small molecules that are expected to bind to the SRA domain.

Data description

Nearly 2.4 million molecules from various chemical libraries were screened with the SRA domain of UHRF1 using Schrodinger’s Small Molecule Drug Discovery Suite. The data is available in the form of a methodology presentation, MS Excel files listing the top hits, and Maestro pose viewer files that provide visualization of how the identified ligands interact with the SRA domain.
Transgenerational inheritance of fetal alcohol exposure adverse effects on immune gene interferon-ϒ
Authors: Gangisetty Omkaram , Palagani Ajay , Sarkar Dipak K.
Published: May 2020

Background

Alcohol exposures in utero have been shown to alter immune system functions in the offspring which persists into adulthood. However, it is not apparent why the in utero alcohol effect on the immune system persists into adulthood of fetal alcohol-exposed offspring. The objective of this study was to determine the long-term effects of fetal alcohol exposure on the production of interferon-ϒ (IFN-ϒ), a cytokine known to regulate both innate and adaptive immunity.

Methods

Isogenic Fisher 344 rats were bred to produce pregnant dams, which were fed with a liquid diet containing 6.7% alcohol between gestation days 7 and 21 and pair-fed with an isocaloric liquid diet or fed ad libitum with rat chow; their male and female offspring were used for the study. F1-F3 generation rats were used when they were 2 to 3 months old. Fetal alcohol exposure effects on the Ifn-ɣ gene was determined by measuring the gene promoter methylation and mRNA and protein expression in the spleen. Additionally, transgenerational studies were conducted to evaluate the germline-transmitted effects of fetal alcohol exposure on the Ifn-ɣ gene.

Results

Fetal alcohol exposure reduced the expression of Ifn-ɣ mRNA and IFN-ϒ protein while it increased the proximal promoter methylation of the Ifn-ɣ gene in both male and female offspring during the adult period. Transgenerational studies revealed that the reduced levels of Ifn-ɣ expression and increased levels of its promoter methylation persisted only in F2 and F3 generation males derived from the male germ line.

Conclusion

Overall, these findings provide the evidence that fetal alcohol exposures produce an epigenetic mark on the Ifn-ɣ gene that passes through multiple generations via the male germ line. These data provide the first evidence that the male germ line transmits fetal alcohol exposure's adverse effects on the immune system.
Symphony of epigenetic and metabolic regulation—interaction between the histone methyltransferase EZH2 and metabolism of tumor
Authors: Zhang Tengrui , Gong Yueqing , Meng Hui , Li Chen , Xue Lixiang
Published: May 2020

Increasing evidence has suggested that epigenetic and metabolic alterations in cancer cells are highly intertwined. As the master epigenetic regulator, enhancer of zeste homolog 2 (EZH2) suppresses gene transcription mainly by catalyzing the trimethylation of histone H3 at lysine 27 (H3K27me3) and exerts highly enzymatic activity in cancer cells. Cancer cells undergo the profound metabolic reprogramming and manifest the distinct metabolic profile. The emerging studies have explored that EZH2 is involved in altering the metabolic profiles of tumor cells by multiple pathways, which cover glucose, lipid, and amino acid metabolism. Meanwhile, the stability and methyltransferase activity of EZH2 can be also affected by the metabolic activity of tumor cells through various mechanisms, including post-translational modification. In this review, we have summarized the correlation between EZH2 and cellular metabolic activity during tumor progression and drug treatment. Finally, as a promising target, we proposed a novel strategy through a combination of EZH2 inhibitors with metabolic regulators for future cancer therapy.
Cell therapy approaches to autism: a review of clinical trial data
Authors: Price Jack
Published: May 2020

A number of clinical trials of cell therapies for autism spectrum disorder have been conducted, and some have published their outcomes. This review considers the data that have emerged from this small set of published trials, evaluates their success, and proposes further steps that could be taken if this field of endeavour is to be pursued further. A number of reservations arise from this tranche of studies, specifically the absence of identified therapeutic targets, and deficiencies in the therapeutic approach that is being employed. If this therapeutic direction is to be pursued further, then additional pre-clinical studies are recommended that might lead to improvements in patient stratification, biomarkers, the defined mode of action, and the preparation and identification of the therapeutic cells themselves.
Broken-crescent sign at CT indicates impending aortic rupture in patients with acute aortic intramural hematoma
Authors: Ko Sheung-Fat , Lu Chia-Yin , Sheu Jiunn-Jye , Yip Hon-Kan , Huang Chung-Cheng , Ng Shu-Hang
Published: May 2020

Background

This retrospective study evaluated the computed tomography (CT) features and clinical implications of a novel broken-crescent sign in patients with acute aortic intramural hematoma (IMH).

Methods

Out of 104 patients with aortic IMH encountered in our institution between 2003 and 2018, nine patients exhibited a positive broken-crescent sign, which was defined as a focal defect within the hyper-attenuating crescentic IMH on unenhanced CT, corresponding to a smooth out-bulging of the aortic lumen on enhanced study. The clinical findings, CT features, and outcomes of these nine patients were analyzed.

Results

Of five males and four females (age range 48–84 years, mean 69.7 years), six had type A and three had type B IMH. Five patients who had medical treatment and stable status for 1 to 3 days suffered sudden death, two of whom showed ascending aortic rupture with hemopericardium in one and adventitial tear with outward spillage of IMH in another at follow-up CT. The other four patients had early surgical or endovascular management survived; two demonstrated ascending aorta ecchymosis with adventitial tear and intact intima at surgery. Our results support the supposition that aortic IMH complicated with adventitial tear and partial outward seepage of IMH may generate a broken-crescent sign in CT. Despite initially stable clinical status, the residual intact inner aortic wall carries a high risk of sudden aortic rupture.

Conclusions

In patients with acute aortic IMH, identification of a broken-crescent sign in CT is highly suggestive of impending aortic rupture, and early aggressive treatment is mandatory.
Stem cell therapy: a potential approach for treatment of influenza virus and coronavirus-induced acute lung injury
Authors: Du Jiang , Li Han , Lian Jie , Zhu Xinxing , Qiao Liang , Lin Juntang
Published: May 2020

Acute lung injury (ALI), an increasingly devastating human disorder, is characterized by a multitude of lung changes arising from a wide variety of lung injuries. Viral infection is the main cause of morbidity and mortality in ALI and acute respiratory distress syndrome (ARDS) patients. In particular, influenza virus, coronavirus, and other respiratory viruses circulate in nature in various animal species and can cause severe and rapidly spread human infections. Although scientific advancements have allowed for rapid progress to be made to understand the pathogenesis and develop therapeutics after each viral pandemic, few effective methods to treat virus-induced ALI have been described. Recently, stem cell therapy has been widely used in the treatment of various diseases, including ALI. In this review, we detail the present stem cell-based therapeutics for lung injury caused by influenza virus and the outlook for the future state of stem cell therapy to deal with emerging influenza and coronaviruses.
Intracellular functions of RNA-binding protein, Musashi1, in stem and cancer cells
Authors: Forouzanfar Mahboobeh , Lachinani Liana , Dormiani Kianoush , Nasr-Esfahani Mohammad Hossein , Gure Ali Osmay , Ghaedi Kamran
Published: May 2020

RNA-binding protein, musashi1 (MSI1), is a main protein in asymmetric cell division of the sensory organ precursor cells, whereas its expression is reported to be upregulated in cancers. This protein is a critical element in proliferation of stem and cancer stem cells, which acts through Wnt and Notch signaling pathways. Moreover, MSI1 modulates malignancy and chemoresistance of lung cancer cells via activating the Akt signaling. Due to the main role of MSI1 in metastasis and cancer development, MSI1 would be an appropriate candidate for cancer therapy. Downregulation of MSI1 inhibits proliferation of cancer stem cells and reduces the growth of solid tumors in several cancers. On the other hand, MSI1 expression is regulated by microRNAs in such a way that several different tumor suppressor miRNAs negatively regulate oncogenic MSI1 and inhibit migration and tumor metastasis. The aim of this review is summarizing the role of MSI1 in stem cell proliferation and cancer promotion.
TATA box-binding protein-related factor 3 drives the mesendoderm specification of human embryonic stem cells by globally interacting with the TATA box of key mesendodermal genes
Authors: Liang He , Zhang Peng , Bai Hua-Jun , Huang Jijun , Yang Huang-Tian
Published: May 2020

Background

Mesendodermal formation during early gastrulation requires the expression of lineage-specific genes, while the regulatory mechanisms during this process have not yet been fully illustrated. TATA box-binding protein (TBP) and TBP-like factors are general transcription factors responsible for the transcription initiation by recruiting the preinitiation complex to promoter regions. However, the role of TBP family members in the regulation of mesendodermal specification remains largely unknown.

Methods

We used an in vitro mesendodermal differentiation system of human embryonic stem cells (hESCs), combining with the microarray and quantitative polymerase chain reaction (qRT-PCR) analysis, loss of function and gain of function to determine the function of the TBP family member TBP-related factor 3 (TRF3) during mesendodermal differentiation of hESCs. The chromatin immunoprecipitation (ChIP) and biochemistry analysis were used to determine the binding of TRF3 to the promoter region of key mesendodermal genes.

Results

The mesendodermal differentiation of hESCs was confirmed by the microarray gene expression profile, qRT-PCR, and immunocytochemical staining. The expression of TRF3 mRNA was enhanced during mesendodermal differentiation of hESCs. The TRF3 deficiency did not affect the pluripotent marker expression, alkaline phosphatase activity, and cell cycle distribution of undifferentiated hESCs or the expression of early neuroectodermal genes during neuroectodermal differentiation. During the mesendodermal differentiation, the expression of pluripotency markers decreased in both wild-type and TRF3 knockout (TRF3−/−) cells, while the TRF3 deficiency crippled the expression of the mesendodermal markers. The reintroduction of TRF3 into the TRF3−/− hESCs rescued inhibited mesendodermal differentiation. Mechanistically, the TRF3 binding profile was significantly shifted to the mesendodermal specification during mesendodermal differentiation of hESCs based on the ChIP-seq data. Moreover, ChIP and ChIP-qPCR analysis showed that TRF3 was enriched at core promoter regions of mesendodermal developmental genes, EOMESODERMIN, BRACHYURY, mix paired-like homeobox, and GOOSECOID homeobox, during mesendodermal differentiation of hESCs.

Conclusions

These results reveal that the TBP family member TRF3 is dispensable in the undifferentiated hESCs and the early neuroectodermal differentiation. However, it directs mesendodermal lineage commitment of hESCs via specifically promoting the transcription of key mesendodermal transcription factors. These findings provide new insights into the function and mechanisms of the TBP family member in hESC early lineage specification.
Improvement in circulating endothelial progenitor cells pool after cardiac resynchronization therapy: increasing the list of benefits
Authors: Cristóvão Gonçalo , Milner James , Sousa Pedro , Ventura Miguel , Cristóvão João , Elvas Luís , Paiva Artur , Gonçalves Lino , Ribeiro Carlos Fontes , António Natália
Published: May 2020

Background

Recent studies suggest that circulating endothelial progenitor cells (EPCs) may influence the response to cardiac resynchronization therapy (CRT). The aim of this study was to evaluate the effect of CRT on EPC levels and to assess the impact of EPCs on long-term clinical outcomes.

Population and methods

Prospective study of 50 patients submitted to CRT. Two populations of circulating EPCs were quantified previously to CRT implantation: CD34+KDR+ and CD133+KDR+ cells. EPC levels were reassessed 6 months after CRT. Endpoints during the long-term follow-up were all-cause mortality, heart transplantation, and hospitalization for heart failure (HF) management.

Results

The proportion of non-responders to CRT was 42% and tended to be higher in patients with an ischemic vs non-ischemic etiology (64% vs 35%, p = 0.098). Patients with ischemic cardiomyopathy (ICM) showed significantly lower CD34+KDR+ EPC levels when compared to non-ischemic dilated cardiomyopathy patients (DCM) (0.0010 ± 0.0007 vs 0.0030 ± 0.0024 cells/100 leukocytes, p = 0.032). There were no significant differences in baseline EPC levels between survivors and non-survivors nor between patients who were rehospitalized for HF management during follow-up or not. At 6-month follow-up, circulating EPC levels were significantly higher than baseline levels (0.0024 ± 0.0023 vs 0.0047 ± 0.0041 CD34+KDR+ cells/100 leukocytes, p = 0.010 and 0.0007 ± 0.0004 vs 0.0016 vs 0.0013 CD133+/KDR+ cells/100 leukocytes, p = 0.007).

Conclusions

Patients with ICM showed significantly lower levels of circulating EPCs when compared to their counterparts. CRT seems to improve the pool of endogenously circulating EPCs and reduced baseline EPC levels seem not to influence long-term outcomes after CRT.

Graphical abstract