bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti-inflammatory effects of mesenchymal stem cell-derived exosomal microRNA-146a-5p and microRNA-548e-5p on human trophoblast cells
Authors: Yang Changwon , Lim Whasun , Park Junghyun , Park Sunwoo , You Seungkwon , Song Gwonhwa 
Published: September 2019

Abstract
Human umbilical cord mesenchymal stem cells (MSCs) have been reported to improve the migration and invasion of trophoblast cells; however, little is known about whether MSC-derived exosomes and exosomal miRNAs can regulate trophoblast cell properties. In this study, we investigated whether exosomal miRNAs from amniotic fluid-derived MSC (AF-MSC) could regulate the inflammatory response of the human trophoblast cell line HTR8/SVneo. We verified the anti-inflammatory effects of AF-MSCs on lipopolysaccharide (LPS)-induced inflammatory trophoblast cells and found that miR-146a-5p and miR-548e-5p in the AF-MSC–derived exosomes regulate nuclear factor κB, AKT and mitogen-activated protein kinase protein phosphorylation. Furthermore, we found that the transfection of human trophoblast cells with miR-146a-5p and miR-548e-5p inhibitors reduced trophoblast migration (P &lt; 0.05 vs control) and the expression of proliferating cell nuclear antigen, a protein essential for cell proliferation (P &lt; 0.01 vs control). In particular, the miR-548e-5p inhibitor induced apoptosis, while tumor necrosis factor receptor–associated factor 6, a predicted target of miR-146a-5p and miR-548e-5p, was involved in the regulation of oxidative stress in the human trophoblast cells. In a mouse model of LPS-induced preterm birth (PB), miR-146a-5p expression was found to be relatively low in the group in which the effect of AF-MSCs was insignificant. However, this study is limited in that the changes in the expression of some genes in response to AF-MSCs differ between the cell line and mouse model. Collectively, these data show that exosomal miR-146a-5p and miR-548e-5p from AF-MSCs have anti-inflammatory effects on human trophoblast cells and may be novel targets for treating inflammatory diseases and associated problems that occur during pregnancy, such as PB.
Altered DNA ligase activity in human disease
Authors: Tomkinson Alan E , Naila Tasmin , Khattri Bhandari Seema 
Published: September 2019

AbstractThe joining of interruptions in the phosphodiester backbone of DNA is critical to maintain genome stability. These breaks, which are generated as part of normal DNA transactions, such as DNA replication, V(D)J recombination and meiotic recombination as well as directly by DNA damage or due to DNA damage removal, are ultimately sealed by one of three human DNA ligases. DNA ligases I, III and IV each function in the nucleus whereas DNA ligase III is the sole enzyme in mitochondria. While the identification of specific protein partners and the phenotypes caused either by genetic or chemical inactivation have provided insights into the cellular functions of the DNA ligases and evidence for significant functional overlap in nuclear DNA replication and repair, different results have been obtained with mouse and human cells, indicating species-specific differences in the relative contributions of the DNA ligases. Inherited mutations in the human LIG1 and LIG4 genes that result in the generation of polypeptides with partial activity have been identified as the causative factors in rare DNA ligase deficiency syndromes that share a common clinical symptom, immunodeficiency. In the case of DNA ligase IV, the immunodeficiency is due to a defect in V(D)J recombination whereas the cause of the immunodeficiency due to DNA ligase I deficiency is not known. Overexpression of each of the DNA ligases has been observed in cancers. For DNA ligase I, this reflects increased proliferation. Elevated levels of DNA ligase III indicate an increased dependence on an alternative non-homologous end-joining pathway for the repair of DNA double-strand breaks whereas elevated level of DNA ligase IV confer radioresistance due to increased repair of DNA double-strand breaks by the major non-homologous end-joining pathway. Efforts to determine the potential of DNA ligase inhibitors as cancer therapeutics are on-going in preclinical cancer models.
A single ChIP-seq dataset is sufficient for comprehensive analysis of motifs co-occurrence with MCOT package
Authors: Levitsky Victor , Zemlyanskaya Elena , Oshchepkov Dmitry , Podkolodnaya Olga , Ignatieva Elena , Grosse Ivo , Mironova Victoria , Merkulova Tatyana 
Published: September 2019

Abstract
Recognition of composite elements consisting of two transcription factor binding sites gets behind the studies of tissue-, stage- and condition-specific transcription. Genome-wide data on transcription factor binding generated with ChIP-seq method facilitate an identification of composite elements, but the existing bioinformatics tools either require ChIP-seq datasets for both partner transcription factors, or omit composite elements with motifs overlapping. Here we present an universal Motifs Co-Occurrence Tool (MCOT) that retrieves maximum information about overrepresented composite elements from a single ChIP-seq dataset. This includes homo- and heterotypic composite elements of four mutual orientations of motifs, separated with a spacer or overlapping, even if recognition of motifs within composite element requires various stringencies. Analysis of 52 ChIP-seq datasets for 18 human transcription factors confirmed that for over 60% of analyzed datasets and transcription factors predicted co-occurrence of motifs implied experimentally proven protein-protein interaction of respecting transcription factors. Analysis of 164 ChIP-seq datasets for 57 mammalian transcription factors showed that abundance of predicted composite elements with an overlap of motifs compared to those with a spacer more than doubled; and they had 1.5-fold increase of asymmetrical pairs of motifs with one more conservative ‘leading’ motif and another one ‘guided’.
RNAInter in 2020: RNA interactome repository with increased coverage and annotation
Authors: Lin Yunqing , Liu Tianyuan , Cui Tianyu , Wang Zhao , Zhang Yuncong , Tan Puwen , Huang Yan , Yu Jia , Wang Dong 
Published: September 2019

AbstractResearch on RNA-associated interactions has exploded in recent years, and increasing numbers of studies are not limited to RNA–RNA and RNA–protein interactions but also include RNA–DNA/compound interactions. To facilitate the development of the interactome and promote understanding of the biological functions and molecular mechanisms of RNA, we updated RAID v2.0 to RNAInter (RNA Interactome Database), a repository for RNA-associated interactions that is freely accessible at http://www.rna-society.org/rnainter/ or http://www.rna-society.org/raid/. Compared to RAID v2.0, new features in RNAInter include (i) 8-fold more interaction data and 94 additional species; (ii) more definite annotations organized, including RNA editing/localization/modification/structure and homology interaction; (iii) advanced functions including fuzzy/batch search, interaction network and RNA dynamic expression and (iv) four embedded RNA interactome tools: RIscoper, IntaRNA, PRIdictor and DeepBind. Consequently, RNAInter contains &gt;41 million RNA-associated interaction entries, involving more than 450 thousand unique molecules, including RNA, protein, DNA and compound. Overall, RNAInter provides a comprehensive RNA interactome resource for researchers and paves the way to investigate the regulatory landscape of cellular RNAs.
VCAM-1 targeted alpha-particle therapy for early brain metastases
Authors: Corroyer-Dulmont Aurélien , Valable Samuel , Falzone Nadia , Frelin-Labalme Anne-Marie , Tietz Ole , Toutain Jérôme , Soto Manuel Sarmiento , Divoux Didier , Chazalviel Laurent , Pérès Elodie A , Sibson Nicola R , Vallis Katherine A , Bernaudin Myriam 
Published: September 2019

Abstract

Background
Brain metastases (BM) develop frequently in patients with breast cancer. Despite the use of external beam radiotherapy (EBRT), the average overall survival is short (6 months from diagnosis). The therapeutic challenge is to deliver molecularly targeted therapy at an early stage when relatively few metastatic tumor cells have invaded the brain. Vascular cell adhesion molecule 1 (VCAM-1), overexpressed by nearby endothelial cells during the early stages of BM development, is a promising target. The aim of this study was to investigate the therapeutic value of targeted alpha-particle radiotherapy, combining lead-212 (212Pb) with an anti–VCAM-1 antibody (212Pb-αVCAM-1).

Methods
Human breast carcinoma cells that metastasize to the brain, MDA-231-Br-GFP, were injected into the left cardiac ventricle of nude mice. Twenty-one days after injection, 212Pb-αVCAM-1 uptake in early BM was determined in a biodistribution study and systemic/brain toxicity was evaluated. Therapeutic efficacy was assessed using MR imaging and histology. Overall survival after 212Pb-αVCAM-1 treatment was compared with that observed after standard EBRT.

Results
212Pb-αVCAM-1 was taken up into early BM with a tumor/healthy brain dose deposition ratio of 6 (5.52e108 and 0.92e108) disintegrations per gram of BM and healthy tissue, respectively. MRI analyses showed a statistically significant reduction in metastatic burden after 212Pb-αVCAM-1 treatment compared with EBRT (P &lt; 0.001), translating to an increase in overall survival of 29% at 40 days post prescription (P &lt; 0.01). No major toxicity was observed.

Conclusions
The present investigation demonstrates that 212Pb-αVCAM-1 specifically accumulates at sites of early BM causing tumor growth inhibition.
Simulating Episode-Based Bundled Payments for Cranial Neurosurgical Procedures
Authors: Medress Zachary , Ugiliweneza Beatrice , Parker Jonathon , Wang Dengzhi , Burton Eric , Boakye Maxwell , Skirboll Stephen 
Published: September 2019

Abstract

BACKGROUND
Episode-based bundled payments were introduced by Medicare in 2013 as the Bundled Payments for Care Improvement (BPCI) in order to improve care coordination and cost efficiency. BPCI has not yet been applied to cranial neurosurgical procedures.

OBJECTIVE
To determine projected values of episode-based bundled payments when applied to common cranial neurosurgical procedures using retrospective data from a large database.

METHODS
We performed a large retrospective observational study using the MarketScan administrative database to project bundled payment payments for 4 groups of common cranial neurosurgical procedures.

RESULTS
We identified 15 276 procedures that met our inclusion criteria. We observed significant variability between groups, with 90-d bundle projected payments ranging from $ 58,200 for craniotomy for meningioma to $ 102,073 for craniotomy for malignant glioma. We also found significant variability in projected bundled payments within each class of operation. On average, payment for the index hospitalization accounted for 85% of projected payments for a 30-d bundle and 70.5% of projected payments for a 90-d bundle. Multivariable analysis showed that hospital readmission, discharge to postacute care facilities, venous-thrombo-embolism, medical comorbidities, adjuvant therapies, and payer status significantly contributed to projected cranial bundle payments.

CONCLUSION
For the first time, to our knowledge, we project the values of episode-based bundled payments for common vascular and tumor cranial operations. As previously identified in orthopedic procedures, there is significant variability in total bundle payments within each cranial procedure. Compared to spine and orthopedic procedures, postdischarge care significantly impacts total bundle payments in cranial neurosurgery.
Surgical Management of Primary Skull Base Osteosarcomas: Impact of Margin Status and Patterns of Relapse
Authors: Raza Shaan M , Habib Ahmed , Wang Wei-Lien , Gildey Paul W , Conley Anthony P , Nader Marc-Elie , Hanna Ehab Y , Su Shirley Y , DeMonte Franco 
Published: September 2019

Abstract

BACKGROUND
Skull base osteosarcomas are aggressive neoplasms characterized by bony invasion and extracompartmental/extra-osseous soft tissue extension that pose obstacles to achieving complete resection. Management is further complicated by the paucity of data regarding the efficacy of surgery within the treatment paradigm.

OBJECTIVE
To identify the impact of margin status on local progression free survival (PFS) and disease specific survival (DSS).

METHODS
A retrospective review was performed of 36 patients with osteosarcoma who underwent gross total resection with negative margins (R0), or positive margins (R1). Patient demographics, prior treatments, relapse patterns, and survival were collected. Univariate analysis was performed to determine the impact of margin status on the PFS (primary outcome) and DSS (secondary outcome).

RESULTS
R0 resection was achieved in 67%, 25% patients had local recurrence, and 19.4% patients had distant metastasis. In assessing the entire cohort, R0 resections had improved DSS (P = .002) and PFS (P = .04). In chemotherapy-naïve patients, R0 resections also had improved impact on PFS (P = .04) and DSS (P = .027). For radiation-naïve patients, improvements in PFS (P = .026) and DSS (P = .031) were also noted.

CONCLUSION
Skull base osteosarcomas present management challenges in which both local and systemic disease progression is the cause of mortality. Achieving R0 resections significantly improves PFS and DSS in treatment-naïve patients within multimodality treatment paradigms. Salvage surgery may benefit in patients after failing previous radiation and chemotherapy treatments. Further work is needed to determine optimal treatment strategies. These data represent the largest series reported to date.
Efficacy of a Texting Program to Promote Cessation Among Pregnant Smokers: A Randomized Control Trial
Authors: Pollak Kathryn I , Lyna Pauline , Gao Xiaomei , Noonan Devon , Bejarano Hernandez Santiago , Subudhi Sonia , Swamy Geeta K , Fish Laura J 
Published: September 2019

Abstract

Introduction
Smoking during pregnancy poses serious risks to baby and mother. Few disseminable programs exist to help pregnant women quit or reduce their smoking. We hypothesized that an SMS text-delivered scheduled gradual reduction (SGR) program plus support texts would outperform SMS support messages alone.

Methods
We recruited 314 pregnant women from 14 prenatal clinics. Half of the women received theory-based support messages throughout their pregnancy to promote cessation and prevent relapse. The other half received the support messages plus alert texts that gradually reduced their smoking more than 3–5 weeks. We conducted surveys at baseline, end of pregnancy, and 3 months postpartum. Our primary outcome was biochemically validated 7-day point prevalence abstinence at late pregnancy. Our secondary outcome was reduction in cigarettes per day.

Results
Adherence to the SGR was adequate with 70% responding to alert texts to smoke within 60 minutes. Women in both arms quit smoking at the same rate (9%–12%). Women also significantly reduced their smoking from baseline to the end of pregnancy from nine cigarettes to four; we found no arm differences in reduction.

Conclusions
Support text messages alone produced significant quit rates above naturally occurring quitting. SGR did not add significantly to helping women quit or reduce. Sending support messages can reach many women and is low-cost. More obstetric providers might consider having patients who smoke sign up for free texting programs to help them quit.

Implications
A disseminable texting program helped some pregnant women quit smoking.
Clinical Trial Registration number: NCT01995097.
Exercise for Smoking Cessation in Postmenopausal Women: A Randomized, Controlled Trial
Authors: Oncken Cheryl , Allen Sharon , Litt Mark , Kenny Anne , Lando Harry , Allen Alicia , Dornelas Ellen 
Published: September 2019

Abstract

Background
Postmenopausal smokers have difficulty quitting smoking and experience considerable weight gain with smoking cessation. We examined whether adjunctive smoking treatment with exercise, compared to a relaxation control condition, could improve cigarette abstinence, decrease cigarettes smoked per day (CPD), and ameliorate changes in body mass index (BMI) in postmenopausal smokers.

Methods
Women (N = 301) signed informed consent and were randomized to treatment at two sites (Universities of Connecticut and Minnesota). We randomized groups of participants to a comprehensive group treatment program that included 12 weeks of varenicline and either a moderate exercise or relaxation component for 6 months. Participants were followed for a year after medication treatment.

Results
Overall, 17.3% of patients reported carbon monoxide-verified continuous abstinence for the 9- to 12-week period, and 11.6% reported prolonged abstinence at 1 year, with no significant differences between treatment conditions. CPD reported at study visits showed significant main effects for time in weeks, for site, and for treatment. The Exercise condition reported smoking fewer CPD over time, and that advantage widened over time. In terms of BMI, significant effects for time in weeks, and for the interaction of Week × Treatment condition, reflected gradually increasing BMI in these women over time, but with the increase in BMI slower in the Exercise condition.

Conclusions
Exercise, compared to relaxation, was associated with a reduced BMI and CPD in postmenopausal women, but did not increase end of treatment or prolonged abstinence. Further research is needed to devise exercise programs that increase smoking cessation rates in postmenopausal women.

Implications
This study adds to the literature on the effectiveness of a moderate exercise intervention compared to a relaxation control condition as an adjunctive treatment for smoking cessation in postmenopausal women. Our exercise program did not increase end of treatment or prolonged abstinence rates in postmenopausal women; however, there was a beneficial effect on smoking reduction and reduced body mass index. Additional research is needed to devise exercise programs that increase smoking cessation rates in postmenopausal women.
Evaluation of Abuse and Route of Administration of Extended-Release Tapentadol Among Treatment-Seeking Individuals, as Captured by the Addiction Severity Index–Multimedia Version (ASI-MV)
Authors: Vosburg Suzanne K , Beaumont Jared , Dailey-Govoni S Taryn , Butler Stephen F , Green Jody L 
Published: September 2019

AbstractBackgroundTapentadol is a molecule incorporating mu opioid receptor agonism and norepinephrine reuptake inhibition to provide analgesia, with the potential for a lower incidence of gastrointestinal side effects than full mu opioid agonists. Postmarketing surveillance of tapentadol as an active pharmaceutical ingredient has consistently revealed low levels of abuse and diversion.ObjectiveThe purpose of the present study was to further characterize the abuse liability of tapentadol extended-release (ER) by evaluating the prevalence of past 30-day tapentadol ER abuse and reported routes of administration as compared with ER opioids with Food and Drug Administration (FDA) abuse-deterrent labeling (“ADF opioids”) and ER opioids without FDA abuse-deterrent labeling (“non-ADF opioids”).MethodsData were collected from January 2014 through December 2017 from 776 centers located in 43 states throughout the United States using the Addiction Severity Index–Multimedia Version (ASI-MV), an instrument that is integral to the National Addictions Vigilance Intervention and Prevention Program (NAVIPPRO, Inflexxion, an IBH Company, Costa Mesa, CA, USA).ResultsTapentadol ER had lower rates of past 30-day abuse than ADF ER and non-ADF ER opioid comparators, both at a population level and when adjusted for drug utilization. Tapentadol ER was primarily abused orally, although it was also abused through alternate routes of administration. Cumulative rates of tapentadol ER abuse by alternative routes of administration were lower than both ADF and non-ADF ER opioid comparators, although large confidence intervals resulting from the small sample size of reported tapentadol ER use limit firm conclusions.ConclusionsIn summary, tapentadol ER was found to have lower rates of both past 30-day abuse and use via alternate routes of administration, specifically snorting and smoking, than ADF and non-ADF ER comparators.
UNCERTAINTY EVALUATION IN DOSE ASSESSMENT DUE TO SPATIAL DISTRIBUTION OF NORM IN BEACH SANDS OF SOUTHEAST COAST OF INDIA: A PROBABILISTIC APPROACH
Authors: Chandrasekaran S , Sankaran Pillai G , Baskaran R , Venkatraman B 
Published: September 2019

AbstractA study on radionuclide distribution along coastal stretch in high background areas is constantly attracted to many researchers around the world. In the present study, the concentration of radionuclides in beach sands along the southeast coastal region of India has been studied in detail. Concentration of radionuclides is measured using gamma spectrometry at 148 pre-determined locations. It is found that 238U and 232Th concentrations are varying in the range from 3 (BDL) to 298.9 and 1150.2 Bq kg−1, respectively. Concentration of 40K in beach sand varied from 11 to 1743.4 Bq kg−1. The measured activity levels of radionuclides were compared with earlier studies carried out by various researchers in the same region under study. The related radiological parameters of interest were also determined and compared with the internationally recommended values. With an increase in emphasis on quality in dose assessment methods, dose to human population living in the vicinity requires uncertainty evaluation, which is carried out by taking into account variation in the activity values. This study would serve as a baseline radiological mapping for the southeast coast region of India for environmental impact assessment prior to plan of nuclear facility in the future.
Pilot testing an app-based stress management intervention for cancer survivors
Authors: Børøsund Elin , Varsi Cecilie , Clark Matthew M , Ehlers Shawna L , Andrykowski Michael A , Sleveland Hilde Renate Sætre , Bergland Anne , Nes Lise Solberg 
Published: September 2019

Abstract
Psychosocial eHealth intervention programs for cancer survivors are still in their infancy, with inconsistent findings so far in the scientific literature. The aim of this study was to explore system use, usefulness, ease of use, and preliminary effects of Stress Proffen, an app-based cognitive-behavioral stress management intervention for patients with cancer. A feasibility pilot project tested the intervention with cancer survivors (N = 25). The intervention contained (a) one face-to-face introduction session, (b) 10 app-based modules with stress management educational material and exercises, and (c) one follow-up phone call. Post-intervention interviews were conducted and user log-data were extracted. Outcome measures—Perceived Stress Scale (PSS), Anxiety and Depression (Hospital Anxiety and Depression Scale [HADS]), Health-Related Quality of Life (HRQoL; SF-36), and Self-Regulatory Fatigue (SRF-18)—were completed at baseline and post-intervention. Participants were primarily women (84%), age 34–71 (mean 48) and represented a variety of cancer diagnoses (majority breast cancer: 40%). Twenty-two participants completed all (pre–post) questionnaires. Sixteen participants (67%) completed at least 7 of 10 modules within the 8-week study period. Post-intervention interviews described StressProffen as providing a new, appreciated, and easily accessible stress management tool for the cancer survivors. Dependent/paired t-tests showed significant pre–post intervention effects with significant decrease in stress (p = .008), anxiety (p = .019), and self-regulatory fatigue (p = .025), and improved HRQoL (Role Physical, General Health, Vitality, and Role Emotional, all p’s &lt;.01). App-based stress management interventions such as StressProffen can provide appreciated support for cancer survivors, should be easy to use, can provide significant stress reduction, and improve emotional well-being. Further testing in a randomized controlled trial is warranted and is in progress.
Clinicaltrials.gov: NCT0293961.